ON DIABETES MELLITUS
INTRODUCTION
This fascinating illness afflicts over 170 million people, a number that is expected to double by the year 2030. It consumes over 5% of the NHS healthcare budget and its various afflictions lead to a vastly increased use of hospital beds. It affects over 12% of Middle Eastern and Asian peoples and is therefore worthy of our greatest attention.
I have heard it being said that having diabetes is worse than having cancer or HIV, and although this may be said in just pure frustration, there may be an element of truth in that. It is a disease of glucose utilisation, and since all body cells require glucose, all of them are afflicted by it. This contrasts with cancer, usually a disease of a single organ, or HIV, a disease of the CD4 cells of the immune system. Aretaeus, a Cappadocian physician of the second century vividly characterized it as “being a melting-down of the flesh and limbs into urine” and coined the term diabetes, meaning ‘to run through’.
Diabetes occurs when we have a lack of (type 1), or deficient action (type 2) of the hormone insulin, which is involved in many different biochemical processes, including protein synthesis, lipid and carbohydrate metabolism. Some types of diabetes are secondary to increased antagonism of insulin, such as thyrotoxicosis, Cushing’s syndrome and phaeochromocytoma, but most are primary, due to insulin-related problems.
EPIDEMIOLOGY OF DIABETES
One of the saddest things about diabetes is that it is more prevalent in the poor, and affects them in the worst manner with the most complications. A BBC report recently stated:
“Britain's poorest communities are 2.5 times more likely to develop Type 2 diabetes than the general population, research suggests. They are also 3.5 times more likely to develop serious complications of diabetes, including heart disease.”
Overall it is a common disorder, and is increasing in incidence. The table above shows the current prevalence of diabetes in many parts of the world, with over 10% of Hong Kong, Pakistanis and Czechs, and a ridiculously high prevalence among Egyptians and Cubans too. The following table illustrates how things will worsen within the next few decades:
But by far, the highest prevalence of diabetes is in the Pima Indians, native American Indians who live in Arizona and Mexico – with a prevalence of 21%. The study of this population has taught us much about diabetes, most importantly, one of the biggest risk factors for type II diabetes – the sudden shift in diet from traditional agricultural goods towards processed foods. The more Westernised Arizona Pimans are those primarily affected, and the genetically similar Pimas in Mexico have virtually no type 2 diabetes. The rising incidence of diabetes around the world can be attributed to the rise of obesity, and the increasing inactivity (due to the comfortable lives we lead) and reliance on processed foods.
The Arab world is increasingly afflicted by diabetes and its ills, which can be explained by the thrifty genotype hypothesis. As explained by Raz et al (2008):
“This phenomenon of shifting disease patterns, termed epidemiological transition, initially occurred in developed countries and subsequently spread to developing nations. Arthur Koestler coined the term 'Coca- colonization' to describe the impact of the lifestyle of Western societies on developing countries. The devastating results of intrusion by Western society into the lives of traditional living indigenous communities can now be seen across the globe”.
Having introduced syphilis and tuberculosis to the developing word in the 19th century, the West has introduced diabetes everywhere else. Does the answer for modern civilization still lie in the Western civilization, with so much mental and physical illness around? There is so much good in it no doubt, but anyone looking deeply into it, will find that all the basic ideas of any quality in the Western world are embodies, to an even greater extent.
In addition, the great poverty that afflicts some leads to lack of education, and a further misunderstanding and poor treatment of the condition. Because it is a chronic condition, with poverty, appropriate drugs are not bought as they are too expensive, and traditional herbal remedies are used. For instance, in the Gaza Strip, where the annual income (for those lucky enough to work) is just under £350 a year, people are resorting to pomegranate seeds and chamomile for treatment, and the management of the condition is careless, with no monitoring facilities, a crucial aspect of its care. This sad truth illustrates the importance of justice, social equality and even distribution of wealth in medical care, things which can only be found in a fair society governed by wisdom and truth.
There are many famous diabetics out there, what I would like to focus here on some of its more interesting victims, whose stories may teach us something about the condition.
FAMOUS DIABETICS
With regards to aetiology, knowledge that former Egyptian president Jamal Abdel Nasser had diabetes, and possibly slipped into a diabetic coma before he died would help us recall two points – the high prevalence of the disease among Egyptians, and the existence of secondary cause of diabetes; his biographers insist that he had haemochromatosis, although his physician, Alsaway Habib recently published his memoirs and, “He denies that Nasser (1918-1970) had slipped into a diabetic coma before his death. Nor did Nasser suffer from bronzed diabetes as once published in the local press. "Nasser suffered from the ordinary type of adult diabetes," says Dr Habib.”
One of the more recent victims is Halle Berry, the American award winning actress. Her story highlights one of the problems that celebrities can cause to the health awareness of people, and how misinformed they can be.
Halle Berry is a type 1 diabetic – in other words dependent on insulin. She has made many fascinating comments on the condition, like "Diabetes turns out to be a gift. It gave me strength and toughness because I had to face reality, no matter how uncomfortable or painful it was", and interesting stories, like her diagnosis, when she “lay dangerously ill in a diabetic coma for a week before waking to a life that would never be the same again”. As a result of this, she became a spokesperson for Novo Nordisk, the pharmaceutical company specialising in diabetic products.
But it is terrifying when such celebrities make comments on therapeutic aspects of a disease. On 6th of November 2007, the ABC News Channel reported Berry to have said, "I've managed to wean myself off insulin, so now I'd like to put myself in the Type 2 category". As everyone knows, this is nonsense, and what Berry is saying is suicidal. I very much doubt that Berry actually said that, because she remains with us to this day. But what her story highlights is that one should always take celebrities comments on the treatment of disease with a pinch of salt. Symptoms yes, management no. The damage that actors and actresses can cause by making statements such as these in our celebrity culture could be devastating.
Another celebrity whose story I am tempted to discuss here is the Honorary Vice President of ‘Diabetes UK’, the great British oarsman and Olympic champion Sir Steve Redgrave, the only person ever to have won gold medals at five consecutive games. But I have opted to discuss his case in the section on ulcerative colitis, since that is a rarer disease, with fewer famous victims that I can think of.
Talking of Diabetes UK, the creation of this excellent charity society which provides a lot of patient support and guidance as well as funding for scientific research and publications over the disease, was due to the efforts of two great men, both diabetic and both very influential.
The story of Robert Daniel Lawrence, the ENT surgeon is so fascinating that his version is quoted in full in that excellent pharmacology book, ‘Clinical Pharmacology’, by Bennett and Brown (2005). I will do the same:
“Many doctors, after they have developed a disease, take up the speciality in it... But that was not so with me. I was studying for surgery when diabetes took me up. The great book of Joslin said that by starving you might live four years with luck. [He went to Italy and, whilst his health was declining there, he received a letter from a biochemist friend which said] there was something called 'insulin' appearing with a good name in Canada, what about going there and getting it. I said 'No thank you; I've tried too many quackeries for diabetes; I'll wait and see'. Then I got peripheral neuritis ...So when [the friend] cabled me and said, 'I've got insulin — it works — come back quick', I responded, arrived at King's College Hospital,London, and went to the laboratory as soon as it opened ... It was all experimental for [neither of us] knew a thing about it... So we decided to have 20 units a nice round figure. I had a nice breakfast. I had bacon and eggs and toast made on the Bunsen. I hadn't eaten bread for months and months ... by 3 o'clock in the afternoon my urine was quite sugar free. That hadn't happened for many months. So we gave a cheer for Banting and Best.But at 4 pm I had a terrible shaky feeling and a terrible sweat and hunger pain. That was my first experience of hypoglycaemia. We remembered that Banting and Best had described an overdose of insulin in dogs. So I had some sugar and a biscuit and soon got quite well, thank you"
The disease changed Lawrence’s life entirely, and he devoted all his time to research on the condition and the care of its patients. He set up a clinic which quickly became overcrowded, and this is where Herbert George Wells comes in. The great creator of science of fiction was also a diabetic and a patient of Lawrence. The details were summarised by Curnow (2002):
“The number of people with diabetes attending the clinic doubled within four years, conditions were crowded and the equipment was inadequate. The hospital authorities supported Lawrence’s request to make a personal appeal to his more wealthy private patients to fund improvements to the facilities available to outpatients, and possibly build a small unit for in-patients. HG Wells, who had been referred to Lawrence in 1931, was one of the patients Lawrence approached. Wells donated half a crown, saying he was not a wealthy man and believed that the appeal should be of interest to all people with diabetes, and offered to write to The Times to involve a wider audience. The letter to ‘The Select Company of Diabetics – for the Benefit of Their Cult’ was published on 19th April 1933. He ended it saying, "I am a little surprised we have not already formed a Diabetic Association to watch over and extend this most benign branch of medicine to which we owe our lives" (Br J Diabetes Vasc Dis 2002;2:469–72).
In 1934, the ‘Diabetic Association’ was founded, with RD Lawrence as the Chairman and HG Wells the President of the Association, with the nominated Vice Presidents including Professor FG Banting and Dr CH Best and two diabetic well-known novelists, GDH Cole and Hugh Walpole.
I cannot help but digress and talk a little about H G Wells, who was one of the best writers of both fiction and non fiction of the 20th century. There are an abundant number of biographies of the great man, to which I would like to refer the kind reader, for he is a most interesting person.
For the medical man, Wells is interesting for several reasons. Firstly, because of his diabetes, and his massive contribution to the creation of the ‘Diabetic Association’ (now Diabetes UK) together with Lawrence, as explained above. Indeed, the first time it was revealed to me that Wells was diabetic was while reading a very moving letter of his to the great Bertrand Russell, who incorporated it in his ‘Autobiography’, one of the most beautiful books I have ever read. An extract from the letter, written the year before his death in 1946, says a lot about the impact diabetes can have on one’s life:
“I have been ill & I keep ill. I am President of the Diabetic Society and diabetes keeps one in and out, in and out of bed every two hours or so. This exhausts, and this vast return to chaos which is called the peace, the infinite meanness of great masses of my fellow creatures, the wickedness of organised religion give me a longing for a sleep that will have no awakening. There is a long history of heart failure on my paternal side but modern palliatives are very effective holding back that moment of release. Sodium bicarbonate keeps me in a grunting state of protesting endurance. But while I live I have to live and I owe a lot to the decaying civilisation which has anyhow kept alive enough of the spirit of scientific devotion to stimulate my curiosity and make me its debtor.”
Secondly, because of his very interesting ideas regarding future health care. Wells was a great historian, and he illustrated this with his tour-de-force, ‘An Outline of History’, a 1324 page work that was the most popular book sold in America after its publication (after the Bible). Backed with this huge historical expertise, he gave some marvellous visions of how the future may turn out to be, and in one work, ‘An Englishman Looks At The World’, he envisages a system that seems to predate the GMC and NHS by many years:
“In that extravagant world of which I dream, in which people will live in delightful cottages and ground rents will serve instead of rates, and everyone will have a chance of being happy--in that impossible world all doctors will be members of one great organisation for the public health, with all or most of their income guaranteed to them: I doubt if there will be any private doctors at all.
Heaven forbid I should seem to write a word against doctors as they are. Daily I marvel at the wonders the general practitioner achieves, having regard to the difficulties of his position.
But I cannot hide from myself, and I do not intend to hide from anyone else, my firm persuasion that the services the general practitioner is able to render us are not one-tenth so effectual as they might be if, instead of his being a private adventurer, he were a member of a sanely organised public machine. Consider what his training and equipment are, consider the peculiar difficulties of his work, and then consider for a moment what better conditions might be invented, and perhaps you will not think my estimate of one-tenth an excessive understatement in this matter.”
How nice is it to see praise of the general practitioner, at a time when he or she is regarded, somewhat unfairly, as a second class physician!
Moving on from Wells, who has taught us so much, we can move smoothly to another British genius, who shared much with Wells – his creativity and invention, disbelief in God, faith in eugenics (which is almost inextricably intertwined) and last but not least, his diabetes. It’s the great inventor of the telephone, Alexander Graham Bell.
I will not deal here with the full biographical details of this great man, his numerous struggles and tragedies, his many success stories, and his great romanticism and his love and marriage to his deaf student Mabel Hubbard. But I will focus on what I regard as interesting from the medical point of view.
Robert V. Bruce writes in his biography, ‘Bell: Alexander Graham Bell and the Conquest of Solitude’:
“By 1915 Bell himself was in the grip of that incurable and (in pre-insulin days) perilous condition, diabetes. He had occasion for somber thought now in his sessions of nocturnal solitude. He could not have been deaf to the meaning of what was upon him. Diabetes had been the death of his uncle David 14 years before, but Bell's motto was 'keep on fighting'”.
He was later diagnosed with pernicious anaemia, which is a recognized association with diabetes, although not with type 2 diabetes, which is what Bell likely had (no one with type 1 diabetes survives without insulin to the age of 75). And although it is stated in many places that Bell died of pernicious anaemia, including in the Wikipaedia article on him, I feel that is unlikely to be the case. Although it sounds paradoxical, diabetes, particularly when uncared for is a more pernicious than the pernicious disease!
It is clear that Bell’s diabetes was uncared for, for obvious reasons. Firstly, he lived in the pre-insulin age – he was unlucky to have died in the same year Banting and Best discovered insulin, although it would be difficult to foresee if their treatment would have made any difference to him had he survived. For example, he developed neuropathy, as Charlotte Gray discloses in her biography of Bell, ‘Reluctant Genius’ (pages 418-419) – he was able to keep on wiggling “his toes, even though he had lost sensation in them. None of his family realized that the loss of sensation was an indication that he had pernicious anemia". (Although giving a clever possibility, it will never be known which one it is that led to his peripheral neuropathy). Neuropathy happens after years of damage, as we will soon see.
There was an absence of the routine care we now have for diabetes (which has been formulated after many years of intensive research into its most appropriate management). Knowing the above, Bell would have surely benefited from seeing a chiropodist, something all diabetics of today are routinely familiar with. He would have also possibly benefited from a dietitian, but by sounds of things, he would have probably been, as are most diabetics, pretty non-compliant with their recipes. As Bruce illustrates in the aforementioned biography:
“Always a hearty eater, Bell broke loose now and then from the coils of medical caution and, to the distress of his family, defied restrictions on starch and sugar. “Melville," he would say to his grandson as they walked by a redolent bakeshop on Wisconsin Avenue, "would you like some apple pie?" Bell himself would then join in the snack. "Don't you say a word to your grandmother," he would caution the boy. But when he toyed with his dinner, Mabel would notice. "Alec, you stopped in that bakeshop, I know." Ignoring the smoke screen of an exciting story, she would keep after him until he confessed like a small boy caught out. Charles Thompson kept an eye on the state of the refrigerator, but one night Bell made a raid, washed the china, and brushed up every crumb. Called to treat his acute indigestion, the doctor extracted the confession, "To go downstairs at three in the morning, load up on Smithfield ham, cold potatoes, macaroni cheese, and then go right to bed is the most ridiculous thing imaginable, " said the doctor severely; "that meal might have put an end to you, sir" "Well, as it is," said Bell, "the game was worth the candle. It was the best meal I've enjoyed in an age"!”
In knowing that Alexander Graham Bell had type 2 diabetes we will immediately dispel the idea that type 2 diabetes is a twentieth century phenomenon. It is not, although it certainly has increased in prevalence since. Indeed, the two different types of diabetes were distinguished as early as 1875, by Apollinaire Bouchardat in his book on glycosuria (Kiple, 2003).
In addition, the story of his doctor suspecting that “Bell’s diabetes had affected his liver” reveals a very clever insight into diabetes, which has only recently been recognized. Liver disease is now thought to be a not uncommon cause of problems in diabetics. Indeed, it is now felt that NASH, non-alcoholic steatohepatitis, the commonest liver pathology seen in diabetics is now a not uncommon cause of progressive chronic liver injury overall (Evans et al, 2002).
Quite smoothly, history moves us on to discuss one of Bell’s close associates, Thomas Edison, the great American inventor. If Bell invented the telephone, it was Edison who made improved on it greatly and made it the technological masterpiece that it is today. He devised a mouthpiece for it that contained carbon powder, which when compressed, carried more current than when not compressed. As the sound waves compressed and decompressed it, the electric current fluctuated accordingly.
Edison died of complications of diabetes aged 84, namely renal failure. In ‘Edison - Inventing the Century’, Neil Baldwin describes the experience of his physician:
“Dr. Howe had a challenging patient in Thomas Edison - a totally deaf, eighty-four-year-old-man who did not bathe more than once a week, but did not believe in exercise, still (by his own account) "chewed tobacco continuously" and smoked several cigars a fay, and whose only foods were milk and the occasional glass of orange juice... In later years, Edison also suffered from diabetes and Bright's disease”.
Bright’s disease is the old name for renal failure. He died uraemic on October 18th 1931. One can see how Edison would have benefited, like Bell, from attending a dietitian, and having smoking cessation advice. And unlike his Scottish counterpart, he would have been more likely to heed their advice. After all, wasn’t Edison the one who famously said:
“The doctor of the future will give no medicine, but will interest her or his patients in the care of the human frame, in a proper diet, and in the cause and prevention of disease”?
Now let us move on to diabetes itself.
DIABETES – THOUGHTS ON PATHOPHYSIOLOGY
One of the biggest lessons of diabetes, is that it induces a feeling of appreciation of normal metabolism. The primitive human being, by virtue of instinct, knows that through lack of food and water, oxygen and warmth, he will die. We know this death is caused by cardiac arrest, and treating these three, if present, is part of the established cardiac arrest management algorithm (namely hypothermia, hypoxia, hypovolaemia). We always pierce the patient’s finger to check his blood glucose (in any comatose patient, including that due to a cardiac arrest). Both hypoglycaemia and hyperglycaemia are sinister and are treated aggressively, and what is important to realise is that they are both forms of ‘body starvation’ – not just hypoglycaemia. Whereas in hypoglycaemia, the body is starved of fuel, in diabetic hyperglycaemia, the body is starved of glucose utilisation, and in a desperate attempt, tries to consume other fuels, fats and proteins, which is only possible for a short while without severe consequences, which we shall discuss later. What is important to realise too is that hyperglycaemia not only leads to metabolic consequences, but also to hypovolaemia. This is because of the increased urine output and intracellular fluid loss due to osmotic shift. Indeed, in a patient with severe uncontrolled hyperglycaemia, such as diabetic ketoacidosis or HONK (hyperosmolar non-ketotic diabetic coma), it is dehydration that kills them, not the hyperglycaemia per se.
Normal glucose regulation is maintained by several complex mechanisms. After any carbohydrate meal, the pancreas responds by releasing insulin from its beta cells (islets of Langerhans). This serves to stop gluconeogenesis and glycogenolysis, and stimulate glycogen synthesis (stimulating the enzyme glycogen synthase) by the liver (as well as glycerol for triglyceride synthesis), and shifts glucose intracellularly (via GLUT-4 receptors) into skeletal muscles and adipose tissue. Note that the liver does not need insulin to get glucose into its cells. It enters simply via a concentration gradient.
Why should this be the case? Perhaps the body is being economical with its insulin, knowing that the insulin is required for the insulin-induced stimulation of glycogen synthase and triglyceride synthesis. I do not know, but am sure there is a clever reason behind it.
One of the fascinating facts is that the brain, which consumes about 80% of the glucose utilised at rest in the fasting state, it too, like the liver, does not depend on insulin to get to it. The brain has exclusive GLUT-3 receptors. Now, imagine if the brain depended on insulin. This would be a disaster for all type 1 diabetics, who would quickly go into a coma and die once their pancreas is overwhelmed by the disease.
Now we mentioned above a fact that everyone knows – after a high carbohydrate meal, the pancreas releases insulin. What we fail to realise and appreciate is that, these four words – ‘the pancreas releases insulin’ is one of the most majestic events of the cosmos. This is not an exaggeration, as I will explain below. Perhaps because we are see so many diabetic patients in hospital and in general practice that we regard it all as monotonous, and so we do not reflect on or appreciate this majesty. But let me break away and begin reflecting on this process like an intelligent child, and prove my point.
To begin with – the pancreas needs to detect the glucose cells. Harun Yahya summarises this amazing process as follows, “First, the pancreas cells would find and distinguish the sugar molecules from among all the millions of other molecules in your blood. Moreover, they would count the sugar molecules to decide if the number were too high or too low. Amazingly, cells too small for the eye to see, without eyes, hands, or a brain know the correct proportion of sugar molecules in a fluid.” The glucose enters the beta cells by facilitated diffusion through the glucose transporter, GLUT-2. Although the majority of human cells require insulin to shift insulin into them, the pancreas, like the liver, doesn’t. It is a basic rule of the human body that an organ synthesising a chemical or hormone is never itself dependent on it. It is a form of altruism.
Within the beta cells, glucose is metabolised to produce ATP. This ATP closes ATP-dependent potassium channels present in the beta cell membrane, which then depolarises the cell, causing calcium entry, which stimulates exocytosis of insulin. Sulphonylurea drugs, like gliclazide act like ATP here, inhibiting the ATP-dependent potassium channels.
The insulin is synthesised as a large molecule – called pre-proinsulin. The reason for this is that it includes a signal peptide, called C-peptide, which is important for directing its proper folding and movement through the Golgi apparatus where it is synthesised (Kaufmann, p.240). Just before storage this is converted to insulin and C-peptide.
Unfortunately, for reasons of space, we will not be able to talk about many of these magnificent processes which we are passing by here without much reflection. ATP manufature, depolarisation, insulin (protein) synthesis, exocytosis and cleavage. But the details may be found in any decent biochemistry textbook. I preferred Stryer back in the day.
Once insulin is secreted into the bloodstream it exerts its action by binding to receptors primarily in the liver, muscle and adipose tissue; these are tyrosine kinase linked receptors which when bound to insulin result in a conformational change and autophosphorylation, and phosphorylation of IRS (insulin receptor substrate) proteins which activates intracellular signal cascades and enzymes.
The actions of insulin are summarised in the table below:
Following discussion of insulin’s roles, Harun Yahya concluded wondering, “How can it be that cells without a brain, nervous system, eyes or ears can manage to make such a complex calculation and carry out their function perfectly? How can these unconscious cells formed by the coming together of proteins and fat molecules do things too complicated for humans to achieve? What is the source of this remarkable awareness demonstrated by these unconscious molecules? Surely all of these delicate operations taking place in our bodies show us the existence and power of God Who rules over the universe and all living things.” I wish I were the first to say that!
So insulin’s main role is in glucose homeostasis, and indeed, it is the only hormone in the human body that lowers blood glucose, whereas several other hormones can raise it. Why is this the case? As one researcher postulates, “Our body has no back-up system if insulin stops working. Why would that be, do you think? Does it not strike you as odd that in the fabulous system that is our body there is no back-up system for insulin, when our body tends to have all kinds of fall-back plans if something should fail? Perhaps it is worth looking at the question through the eyes of primitive humankind. Not having lived at that time I can't be certain, but I would imagine that there would have been times of limited food, and being able to increase blood sugar levels would have been critically important in order to fuel the body when there was very little or no food being consumed. Just like many other animals, in the spring and summer when fruit, plants and grains were available, it was advantageous to have insulin store some fat to aid chances of survival through the lean winter months. Fruit would be dried, and other foods fermented, but especially in the colder climates, people would rely on wild animals or fish for most of their food in the winter. Meat and fat do not induce a big insulin response. So, perhaps in the body's wisdom, it did not think it needed more than one method to lower blood sugar, as high carbohydrate (plant food) diets simply did not happen day in day out all year round except possibly in tropical climates.”
So what happens if there is not enough insulin? Quite simply, there is unopposed action of glucagon and other anti-insulin hormones (catecholamines, cortisol), and the following results:
DIABETES AETIOLOGY & PATHOGENESIS
But how is diabetes caused? The general consensus is that type 1 is an autoimmune condition triggered by environmental and genetic factors.
The autoimmune aspect is postulated because three reasons:
The association of type 1 diabetes with other autoimmune diseases such as vitiligo, pernicious anaemia, Grave’s disease, and Addison’s disease.
The presence of T-cell infiltrates within the islets of type 1 diabetics
Detection of antibodies to islet cell antibodies (ICA) and glutamic acid decarboxylase (GAD) in their serum.
Autoimmune diseases are a minefield, and we will discuss them in more detail in the immunology section, but just to overview, they chiefly result from what is known as loss of tolerance. The normal human body has mechanisms that ensure B-cells are unresponsive to self-components, and that T-cells are not mobilized by self-peptides expressed on the MHC of healthy cells. This tolerance may be central, achieved by clonal inactivation or deletion of autoreactive T-cells in the thymus and B-cells in the bone marrow, as well as peripheral.
Autoimmune diseases, although dreadful, highlight to the majority of mankind the presence of these mechanisms. Were they not present, would we have appreciated ‘tolerance’ and its very clever mechanisms? The answer is probably not. This is another argument for intelligent design – a normal human body cannot exist without a perfect immune system, which recognizes itself and only attacks others. Even with a normal heart, lung, joints, GI tract etc; if the immune system does not institute tolerance, disaster will follow, as all type 1 diabetics, and patients of other autoimmune disease know. Other examples of autoimmune disease are tabled below.
The autoimmune event may be triggered or propagated by environmental factors. This is suggested by epidemiological studies, which show that clinical onset of type 1 diabetes peaks in the spring and autumn months, coinciding with higher incidence of viral infections at these times.
Genetic factors are suggested by studies on its prevalence in twins – 50% in monozygotic twins, and 6% in dizygotic twins, and an increased risk of 6% of developing type 1 DM in first-degree relatives of patients with it. It is interesting to note that people at such increased risk may be monitored in the future by measuring the aforementioned ICA antibodies, which precede development of hyperglycaemia by many months, possibly years.
An interesting observation is that the body has a huge reserve of islet cells, and that hyperglycaemia only develops once 75% of beta cells are lost. Such is the kindness of the Creator. He has given us more than we need.
As for type 2 diabetes, there is no autoimmune component, but genetic, environmental and possibly also fetomaternal factors are important. Let us reflect on these aspects for a minute.
Genetic factors are suggested by a higher concordance in monozygotic than dizygotic twins, as for type 1 diabetes, and also a higher prevalence in certain full-blooded populations compared to mixed races (e.g. Naurans in the South Pacific). Indeed, certain genetic defects have been illustrated in some cases (MODY – maturity onset diabetes of the young). These are listed in the tables below, with a table of the classification of MODY disorders. It is important to have an intact enzymatic pathway for insulin action and beta cell function. In addition, there are a number of ‘insulinopathies’, very rare genetic conditions inherited also in an AD fashion where abnormal insulin is secreted. The amino acid changes are so subtle, yet end in disaster, highlighting the magnificent accuracy of the human body in the majority of us with normal insulin. Had we not known about these insulinopathies, would we have appreciated this aspect, one wonders? Very unlikely, and the synthesis of insulin would have been taken for granted.
GENE
% OF MODY
CASES
CLASSIFICATION
Glucokinase
20
MODY 2 – mild; complications are rare
HNF-1a
60
MODY 3 – diagnosed later (around 35 years of age)
HNF-4a
1
MODY 1
HNF-1b
1
MODY 5
IPF-1
1
MODY 4
Unknown
15
MODY X
SUR1
<1
Hyperinsulinism in infancy and beta cell failure in childhood
The main risk factor for type 2 diabetes is obesity, with the accumulation of visceral abdominal fat rather than subcutaneous fat being deleterious. About 80% of type 2 diabetics are obese. Fat is a highly active tissue, and not as inert as people think. It produces a variety of hormones and chemicals which modulate insulin action, including TNF-alpha. Why should the distribution of the fat be of any significance? The mechanism is still unclear.
Now we shall discuss obesity and its complications in due course, but it is worthwhile mentioning the verse, “Eat and drink but not to excess” (7:32). Umar, the second Caliph, is reported to have said: “Avoid getting a pot-belly, for it spoils the body, causes diseases, and makes doing the prayer tiring. And avoid all excess, for God hates a learned man who is fat.” Ali ibn al-Husayn ibn al-Wafid said. ‘God put all medicine into half of one verse [of the Qur’an] when He said: Eat and drink but not to excess.’ The Prophet (PBUH) also drew attention to obesity and over-eating. For example, as recorded by Al-Haythami, on seeing a fat man, he said: “If you did not have a paunch, it would be better for you”. He also is reported to have said, “Overeating does not go with good health”.
It is also felt that physical inactivity is a risk factor for type 2 DM independent of weight gain. Exercise possibly reduces the risk but increasing whole body insulin sensitivity. Hence, there is great wisdom in the Islamic advice regarding physical activity.
CONSEQUENCES OF DIABETES
KNIVES
· Kidneys - leading eventually to diabetic nephropathy and chronic renal failure
· Neuromuscular – causing peripheral neuropathy, autonomic neuropathy, mononeuritis, radiculopathy, and amyotrophy
· Infective – increased risk of urinary tract infections, skin and soft tissue infections, tuberculosis and moniliasis
· Vascular – affecting both large vessels (leading to ischaemic heart disease and peripheral vascular disease) and small vessels (microangiopathy producing renal failure, gangrene of skin and feet, with wedge-shaped infarcts.
· Eyes – an increased risk of cataracts, retinopathy, glaucoma, blurred vision, and retinal detachment.
· Skin – particularly affecting the feet (deformities, ulcers and gangrene, necrobiosis lipoidica, granuloma annulare, cellulitis, acanthosis nigricans)
Almost all organs and body processes are afflicted by diabetes. The main chronic ones are summarized by KNIVES. However, it is important to realize that diabetes affects virtually all body organs in one way or another, to the extent that I have heard consultants advise their students that, if asked about the causes of any illness (or risk factors) then saying diabetes and drugs is likely to be a successful choice! The reason for this is simple – all organs need metabolism to survive, and glucose is its chief currency. If glucose cannot be utilized, metabolism will eventually fail in one way or another. In addition, if it accumulates it can cause microvascular and macrovascular damage. The former is how the eyes and kidneys are damaged, and the latter is how the nerves and arteries are damaged.
How does this occur? Several mechanisms have been suggested. The most established one is that of nonenzymatic glycosylation of proteins in capillary basement membranes and other tissues, leading to damage through loss of function, turning on and off of signal pathways within cells, or alteration in gene expression. Very cleverly, this observation is used in the assessment of long term control of diabetic patients. One of the proteins which is glycated is haemoglobin. Because red blood cells survive in the blood for 90-120 days, the HbA1c provides a means to assess glycaemic control over this period. I have seen many patients who, in order to please their doctor, decide to optimize their glucose control in the days immediate to their next appointment with him, failing to realize that by HbA1C, we have the truest reflection of their control over the past three months. BMs can be easily manipulated, through an excess intake of medication, but glycated haemoglobins are not. The following table illustrates the average BMs of patients with relation to their glycated haemoglobin:
HbA1c(%)
Avg. Blood Sugar
(mmol/L)
(mg/dL)
4
3.3
60
5
5.0
90
6
6.7
135
7
8.3
170
8
10.0
205
9
11.7
240
10
13.3
275
11
15.0
310
12
16.7
345
13
18.3
380
14
20.0
415
Note therefore, that in patients with a shortened RBC lifespan, such as those with haemolytic anaemia or sickle cell disease, there is no point using HbA1C. In these patients, fructosamine is used; this is formed when the carbonyl group of glucose reacts with an amino group of a protein. This is usually albumin, and because the half life of albumin is about 3 weeks, fructosamine assays are only true measures of diabetic control for that time. Unfortunately, patients with thalassemia have an increased affinity to glucose anyway, as well as patients with uraemia – this may lead to falsely high HbA1C, and this possibility should be raised in such cases.
The other mechanism by which microvascular damage is caused is by hyperglycaemia increasing the activity of the enzyme aldose reductase, which converts glucose to sorbitol. This causes damage by the mechanisms outlined below, and indeed one of the exciting developments in the management of diabetic complications is the manufacture of specific aldose reductase inhibitors, which have been successful in many animal trials, but owing to their high toxicity profile, remain far from human application.
Macrovascular complications are due to atherosclerosis, which we explain in the section on ischaemic heart disease. One of the interesting suspected reasons for increased atherosclerosis in type 2 diabetics is hyperinsulinaemia; this occurs due to increased insulin resistance. This explains why drugs that increase peripheral insulin sensitivity such as biguanides (e.g. metformin) are preferred to insulin secretagogues such as the sulphonylureas.
A reflection point here is that, if hyperinsulinaemia were to cause disease, it is an absolute prerequisite that a system to counteract it, namely the hyperglycaemic hormones – glucagon, adrenaline and cortisol – should be present at the same time to ensure survival. This is another pointer in the direction of intelligent design.
KIDNEYS
Significant renal disease occurs in 40% of type 1 diabetics and 20% of type 2 diabetics. The reason for the higher incidence in type ones may be the earlier onset of the disease in their case.
So why is the kidney affected by diabetes? Partly, it is because of the fact that the kidney is an extremely vascular organ, and a huge proportion of the body’s cardiac output is delivered to it.
It is interesting to note that there appears to be a genetic link in diabetic nephropathy; a history of nephropathy in other members of the family with diabetes greatly increases the risk of nephropathy. Studies have shown the possibility of problems with the ACE gene; there may be increased secretion of ACE, leading to increased microvascular damage. This may explain why ACE-inhibitors are of prognostic value in diabetic patients, and, as put by the OHCM, every type II diabetic should be on one. There is another reason how ACE-I may help, which we shall explain later.
The kidneys of diabetics show an increase in the mesangial matrix, increased width of the glomerular basement membrane and arteriosclerosis of the afferent and efferent arterioles. The kidneys become malnourished and disfigured, so to speak, with what are called ‘Kimmelsteil-Wilson’ nodules, characteristic of diabetic nephropathy. This leads to an increase in transglomerular pressure, and eventually to a decrease on capillary filtering area. The GFR declines. The increased transglomerular pressure is followed by loss of the negative charge on the basement membrane and thus reduced repulsion between it and the polyanionic albumin molecule. This leads to microlalbuminuria initially, then macroalbuminuria when the pore size enlarges. Later on, the tubules start to fail to reabsorb filtered protein.
Microalbuminuria is the first manifestation of diabetic nephropathy. This can be assessed by timed urine collections (20-200 micrograms/minute, or 30-300 mg/day). To make life easier, and rather than get a patient to give a 24-hour sample, the urinary albumin:creatinine ratio in a random sample of urine can be used. An ACR of >2.5 defines microalbuminuria. Later on, grams of albumin may be lost in a day, at which point the patient may have what is called the nephrotic syndrome, defined as proteinuria of >3.5 g/day, hypoalbuminaemia and oedema.
Now, let us for a few moments discuss this concept of nephrotic syndrome, which has previously puzzled me. Why is this disease, defined by a clinical finding (oedema) and two biochemical tests (proteinuria and hypoalbuminaemia) discussed in textbooks as if it were a separate disease entity? Are they not all part of the same thing – in other words, isn’t proteinuria obviously going to cause hypoalbuminaemia and oedema? Why do we call it a syndrome?
The usefulness of the concept of the nephrotic syndrome is that, once its triad occurs, the patient is at a highly increased risk of hyperlipidaemia, infection, thromboembolism and iatrogenic acute renal failure (due to the diuretics used for the oedema), and the patient must be put on appropriate anticoagulants, antibiotics, and statins. The diagnosis simply guides more cautious treatment of the patient, and not new pathology. That is why some believe that syndromes should not be in the ICD, the list of human diseases as published by the World Health Organisation (WHO), because they are not diseases, but the disease and its sequelae.
NEUROPATHY
This is the most common chronic complication of diabetes. The pathogenesis of these neuropathies is mainly microvascular, although lack of neurotrophic factor support (important in maintenance of normal neural function) and laminin expression (involved in neurite extension and normal function) are also likely to be important. There are many different forms which it can take, summarized as follows:
There is a lot to learn from neuropathy, in particular the importance of pain. Anyone who denies the existence of God based on the fact that pain exists should attend a diabetic clinic, and observe the feet of a patient with poorly controlled diabetes. The most distal parts of the longest nerves are the first things to be affected, with feet first then hands. Perhaps it is because the longest nerves are the ones that need the most support. There is loss of pain sensation firstly, then numbness and tingling, and eventually unrecognized trauma, severe pain, ulcers and neuropathic joints. The ulcers may become infected, leading to osteomyelitis and possible amputation.
Here we have a clear illustration of the importance of pain. As one philosopher put it, “Despite its unpleasantness, pain is an important part of the existence of humans and other animals; in fact, it is vital to survival. Pain encourages an organism to disengage from the noxious stimulus associated with the pain. Preliminary pain can serve to indicate that an injury is imminent, such as the ache from a soon-to-be-broken bone. Pain may also promote the healing process, since most organisms will protect an injured region in order to avoid further pain. People born with congenital insensitivity to pain usually have short life spans, and suffer numerous ailments such as broken bones, bed sores, and chronic infection.” To argue that the presence of pain is inconsistent with the presence of a merciful deity is invalid. Pain is – if anything – a pointer towards the contrary.
Virtually any nerve can be affected by diabetes. The brain is affected chiefly through the increased risk of stroke, which is actually a macrovascular, not a microvascular complication.
The cranial nerves are also affected. Most commonly, the third, fourth and sixth cranial nerves are affected, causing diplopia. Why these nerves are most affected is unclear.
The autonomic nervous system has its origins in the brainstem. Neuropathy may manifest itself in cardiac arrhythmias, postural hypotension, vomiting (gastroparesis), diarrhoea, urinary retention (neuropathic bladder) and impotence.
INFECTION
The risk of infection is increased in diabetes because of impaired leukocyte, particularly neutrophil, function. Urinary tract and skin infections (e.g. cellulitis, boils, abscesses), as well as candida and tuberculosis, are increased. The destructive effects of the infection in diabetics are multiplied, because the infection leads to activation of the fight-and-flight (sympathetic) response, in an attempt to counteract the insult. This results in release of the hyperglycaemic hormones, cortisol and adrenaline, which further worsen the hyperglycaemia, and may lead to such severe consequences as DKA. Knowledge of this can only lead to gratefulness about the perfect metabolic state of the immune system in the 97% of human beings, who are not diabetic.
EYES
Several aspects of the eye are affected by diabetes. This includes the nervous control (discussed above due to neuropathy), the lens (cataracts), aqueous humour (glaucoma) and retina.
The mechanism for diabetic retinopathy is analogous to that of nephropathy. In both cases, there is thickening of the basement membrane as an early pathological feature. There is loss of vascular tone regulation (similar to that which occurs in the afferent and efferent renal arterioles), which is partly due to loss of pericytes (contractile cells which control vessel caliber and flow). There is loss of endothelial cells like in the kidneys. The capillaries become more fragile and leaky, and the first sign usually seen with an opthalmoscope is microaneurysm formation, which are blind outpouchings of the capillaries which appear as red dots. These aneurysms, like any aneurysm, can bleed, and these are the ‘blots’, and once they become more frequent and more severe, cotton-wool spots form. These are not areas of infarction as is commonly believed, but elevations of the nerve fibre layer due to intracellular accumulation of axoplasmic material at the areas of microvascular infarction. Whereas in the kidneys there is mainly leakage of albumin and other protein, in the eyes there is leakage of both protein and lipid, and these form hard exudates. All these changes form the non-proliferative phase.
Once the above becomes excessive, the preproliferative phase occurs. This is characterized by multiple haemorrhages in all four quadrants, five or more cotton wool spots, venous dilatation and beading, and intraretinal microvascular abnormalities (IRMAs) – abnormally branched vessels in the retina, representing attempts to revascularise the ischaemic retina.
Contrary to intuition, when one would expect ischaemia to mean reduction and loss of activity, the ischaemic areas of the retina actually secrete several growth factors, especially VEGF. This is the body’s attempt to compensate, and if they were normal vessels, then all would be well. However, these vessels are both histologically and anatomically defective. They are very fragile, and bleed easily, and grow forward towards the vitreous fluid and can overlie the optic disc. These are the most dangerous ones. Their bleeding can lead to vitreous haemorrhage and retinal detachment. Growth of new vessels can also occur over the iris, leading to ‘rubeosis iridis’. Obstruction of the drainage angle by new vessels may then cause a painful secondary glaucoma. All these things constitute proliferative retinopathy. Maculopathy occurs if any of the above takes place around the macula site. The following table summarises the pathophysiology of diabetic retinopathy.
SKIN
The skin is affected in diabetes through multiple mechanisms. In fact, one can use the surgical sieve to organize skin disease in diabetes.
Vascular disease can lead to arterial ulcers. Infections lead to cellulitis, boils, abscesses, candidiasis, and tinea (dermatophyte infections). Trauma, due to neuropathy, can also lead to ulcers and all sorts of skin damage. Autoimmune conditions such as vitiligo are associated with type 1 diabetes. The condition necrobiosis lipoidica diabeticorum is felt by some to be a metabolic condition, where there is hyaline degeneration of collagen (necrobiosis) surrounded by fibrosis. Lysyl oxidase levels have been found in some diabetic persons to be elevated and are responsible for increased collagen cross-linking. Increased collagen cross-linking could explain basement membrane thickening in this condition. (Why it occurs only in the legs is an interesting question).
Iatrogenic skin conditions in diabetes include lipoatrophy and lipohypertrophy. Neoplastic conditions (although not malignant) include Dupytren’s contracture and acanthosis nigricans, a hyperpigmented velvety outgrowth of the epidermis, usually in the flexural areas of the axilla, groin and neck. It also occurs in several malignancies. It is most likely caused by factors that stimulate keratinocyte, melanocyte and dermal fibroblast proliferation. The factor is probably insulin or an insulinlike growth factor. In malignant AN, the stimulating factor is believed to be a substance secreted either by the tumor or in response to the tumor.
OTHER ORGANS
The liver and most other organs are affected by diabetes. LFTs can be deranged.
HISTORY
Patient presents with symptoms of fatigue, thirst, polyuria, weight loss or weight gain, features of complications, or are completely asymptomatic and detected on assessment for other illnesses. The patient may present for the first time with diabetic ketoacidosis, i.e., smelling of ketones, hyperventilating, dehydrated, and even drowsy, confused, or comatose
PMH
Other HLA-DR3 associated disorders; rare causes of DM – chronic pancreatitis, cystic fibrosis, Cushing’s syndrome, acromegaly, phaechromocytoma, pregnancy, MJ THREADS.
DH
Steroids
Thiazides
Beta-blockers
FH/SH
Smoking
Determine if patient drives or not in ADL (need to notify DVLA if private vehicle license, and is banned permanently if HGV)
Alcohol (needs to stop)
May be a strong FH of DM
ROS
As appropriate; all systems are affected by DM.
PHYSICAL EXAMINATION
GENERAL
Unwell, obese or wasted patient – check BMI in all endocrine patients
Raised BP very common
Urine output increased
Other vital signs variable
JACCOL may or may not be relevant, e.g. jaundice in fatty liver, anaemia in pernicious disease. May be dehydrated
CVS
Blood pressure must be measured sitting & standing (to detect any postural drop)
Peripheral pulses may be absent
Signs of ischaemic heart disease or PVD
RS
Apart from the increased risk of tuberculosis, no marked consequences here
ABDOMEN
Hepatomegaly possible
Ensure urine is dipsticked, looking for PBL KNG
NEUROLOGICAL
Diabetic neuropathy may be somatic (including polyneuropathy which may be symmetrical, sensory and distal or asymmetrical motor and proximal); to remember which is which – remember pROximal is motOR (includes amyotrophy), therefore distal is sensory
Cranial nerves commonly affected include optic nerve, oculomotor and abducens nerves.
Examine eyes fully, including the red reflex (cataracts), acuity, colour vision, and fundoscopy.
Fundoscopy may reveal any of the four grades of diabetic retinopathy; spots (cotton wool spots which are ischaemic nerve fibres), dots (microaneurysms) and blots (haemorrhages due to rupture of microaneurysms)
1) Background à dots and blots and hard exudates
2) Preproliferative à add soft exudates
3) Proliferative à add new vessels
4) Maculopathy à if visual acuity is down and no cataract
- Hypertensive changes commonly co-exist; also note that venous dilatation is the earliest change, including central vein occlusion
Other commonly affected nerves include the femoral and sciatic nerves. Lateral polpliteal nerve palsy and carpal tunnel syndrome also may occur.
SKIN
The dermatological complications of diabetes are:
CENTURY
· Cellulitis / Candidiasis
· Eruptive xanthomas
· Necrobiosis lipoidica (the most specific; occur on shins mainlyl yellow plaques with red edges & may ulcerate)
· Tense bullae over lower legs
· Ulcers (neuropathic, arteriopathic)
· Rubeosis (chronic flushed appearance of face caused by decreased vascular tone and pooling of blood)
· Yellow skin (increased beta carotene levels)
INVESTIGATIONS
DIAGNOSTIC
Random blood glucose > 11 in a symptomatic patient (only one value needed); in asymptomatic patient blood glucose > 11 on two separate occasions
Fasting glucose > 7.0 (at least 8 hour fast) is diagnostic; if borderline .i.e. 6-7.0 then do an OGTT (75 g glucose, a lucozade bottle); if it shows 7.8-11.0 then it is diagnostic of impaired glucose tolerance; 20-50% of people with impaired glucose tolerance will progress to type 2 diabetes within 10 years of diagnosis. In addition, people with impaired glucose tolerance are known to be at significantly increased risk of cardiovascular disease, which may present before the onset of diabetes. Rates of cardiovascular risk factors are intermediate between those with normal glucose tolerance and those with diabetes. Impaired fasting glycaemia has not been shown to be a risk factor for cardiovascular disease. Baseline plasma glucose is the most consistent predictor of progression to diabetes. Impaired glucose tolerance has not been clearly associated with microvascular complications, e.g. nephropathy, retinopathy or neuropathy
CAUSE
BMI (obesity)
TFTs (thyroid disease so commonly associated)
US or CT (pancreatic disease)
Iron & TIBC (haemochromatosis)
CONSEQUENCES
HbA1C or fructosamine (long-term diabetic control)
U&Es & creatinine & urinalysis (kidneys)
ECG (IHD)
ABPI (PVD)
Blood cultures (infections)
Retinal photography (retinopathy)
LFTs (fatty liver, GGT)
Lipids
Ketones, blood glucose, ABG – diabetic ketoacidosis
DIABETIC KETOACIDOSIS
Its clinical features are DKA:
· Dehydrated / Drowsiness that can lead to coma
· Ketoacidosis/Kussmauls breathing / K+ imbalance
· Acidosis / Acetone breath / Abdominal pain
The treatment involves the following ABC, MOVE & FUCKING:
Fluids (crystalloids) (1 L over first 30 minutes, then over 1 hour, then 2 hours, then 4, then 6 – use normal saline, switching over to dextrose when glucose < 11 mmol)
Urea & Creatinine (check it)
CXR / Cultures (blood, urine) / Clexane
K+ (potassium)
Insulin sliding scale
Nasogastic tube (if patient comatose)
Glucose (once serum levels < 12)
*Soluble insulin mixed with normal saline should be given intravenously by syringe pump. The rate is usually 4-12 units per hour according to the blood glucose level. When the blood glucose level has normalized and the patient is rehydrated and eating, the patient may be returned to subcutaneous insulin.
*Under MOVE, monitor all vital signs, including GCS and urine output (often neglected)
*Example of sliding scale is as follows:
- The aim is to maintain the blood glucose between 4.0 and 7.0mmol/l.- Prescribe 50U soluble insulin (e.g. actrapid) in 50mls N Saline to run IV according to sliding scale below (a stat dose of insulin is not necessary).- Measure glucose hourly for the first 4 hours, then 2-4 hourly thereafter, and alter insulin infusion accordingly.
Capillary glucose (mmol/l)
Soluble insulin (units/hour) e.g. actrapid
0 - 4.0
If appropriate treat for hypoglycaemia
4.1 – 7.0
1
7.1 - 11.0
2
11.1 – 14.0
3
14.1 – 17.0
4
17.1 – 20.0
5
>20
6
This is one of the most common and important emergencies. Although it is commonly believed that it only occurs in type one diabetics, this is not true. Any patient with severe starvation of any sort can becoming ketotic, and severe type 2 diabetes (usually they would be on insulin too) can be regarded as a form of starvation – body cells are starved of glucose, so to speak, which they cannot use. They resort to ketones instead. Indeed, ketoacidosis is less common in type 2 diabetics, because they have some insulin which suppresses ketogenesis by the liver.
One of the clever aspects of starvation physiology is that the brain, normally glucose-exclusive in its fuel usage, can then switch over to ketone use. The ketones are acids, which lead to the acidosis.
The most important aspect of DKA is fluid replacement. Patients die first of hypovolaemia, not hyperglycaemia. Fluid losses of over 5 litres are not uncommon; this is a huge proportion of the cardiac output, with severe possible complications (see below). The fluid replacement not only rehydrates the dry patient but also lowers serum glucose levels even without the insulin, which we shall come to next. This is does by increasing urine flow (and hence glycosuria) and by decreasing the levels of catecholamines and cortisol, which were increased by the stimulus of hypovolaemia.
It is always said that fluids should be replaced in a specific order (see figure below). Why should fluids be replaced in that way? Well, it is important to realize that no randomized trials of fluid replacement have been conducted, and over the years, a variety of regimens have been proposed. This is simply the most common one used in England, and it appears pretty safe.
The next question is – should all DKA patients have a central line put in to monitor their fluid balance? This is a difficult question to answer. CVP lines are not without complications, and two of them in particular – infection and thrombosis – may even worsen the scenario.
Because insulin is important in shifting potassium into the intracellular compartment, DKA patients often have hyperkalaemia initially, which increases their cardiovascular morbidity. The insulin that is administered to control the hyperglycaemia will treat this, and infact may lower potassium to hypokalaemia levels, at which point replacement may be necessary.
The insulin is the second most important aspect of the treatment, and must be administered intravenously. This is because volume depletion and vascular collapse impair the absorption of IM or SC insulin.
Now, the logical explanation to a severe hyperglycaemia, as occurs in DKA, is to lower it as much as possible as quickly as possible. However, this should never be done. This is because of the risk of cerebral oedema. Brain cells take longer than other cells to adjust, and if plasma glucose is reduced too fast, water enters the brain cells by osmosis. The aim therefore is to reduce glucose by 3 mmol/litre/hour. Indeed, cerebral oedema is the main cause of death in children with DKA.
It is important to realize another point with regards to the sliding scale. It should not be stopped even if the BMs of the patient have normalized. This is because patients may still be acidotic and need insulin to metabolize their ketones.
Because of the severe hypovolaemia, the patient’s urea, electrolytes and creatinine are vastly deranged. Sodium may be high (due to dehydration) or low (pseudohyponatraemia or vomiting). The patient is an increased risk of DVT due to haemoconcentration of the clotting factors and the ‘stickiness’ if you like of the blood – it is hyperviscous. It is important to monitor U&Es regularly (initially two hourly) and put the patient on clexane.
Finally it is important to look for and treat the cause of DKA. This is frequently forgotten but crucial. Perhaps it is because the majority of cases have unknown triggers. The table below illustrates this. Causes can be recalled thus:
8 I
Initial presentation
Infection (UTI, pneumonia)
Insulin reduction or omission
Injury
Intercurrent illness (e.g. MI)
Ignorance (poor control)
Intoxication (alcohol)
Idiopathic
HONK is very similar in management; it occurs in type 2 diabetics. The onset of this is gradual over days. The patient is often elderly and may not be a known diabetic. Polyuria leads to dehydration. The blood glucose is very high and plasma osmolality is increased – this is calculated follows:
- Plasma osmolality = 2 (Na+K) + urea + glucose; normal = 285 – 295 mOsm/L
There is no acidosis or ketonuria as there is no change to ketone metabolism. Patients require small doses of intravenous insulin and hypotonic saline, although long-term insulin may not be required. Central venous pressure monitoring may be required. Patients are at a high risk of DVT and are given prophylactic subcutaneous heparin. The mortality rate is up to 50%.
What about hyperosmolar non-ketotic coma (HONK)? This is treated in the same way as DKA, with more aggressive attention to the fluid balance and osmolality; whereas in DKA the main aim is to reduce plasma glucose by 3 mmol/l/hr but in HONK plasma osmolality is the more important guide; aim to reduce plasma osmolality by 3 mOsmol/l/hr.
TREATMENT OF CHRONIC DIABETES
The management of diabetes is multidisciplinary and involves attention to SAFE WEIGHT & INFORM:
Salt reduced/Smoking stop
Alcohol stop
Fats reduce
Exercise increase
Weight loss
Information – diabetic nurses, leaflets, websites, exaplining DM, control, complications, consequences of disease & implications on life, pregnancy, breast feeding. Need to inform DVLA unless controlled by diet alone
Nutrition – optimising meal plan, diet comprising complex carbohydrates, SAFE WEIGHT, dietitian referral
Foot care – regular inspection and chiropody inpit
Organisations – local and national support groups, e.g. diabetes UK
Recognition of hypoglycaemia
Monitoring of glycaemic control
The oral types of drugs used in type II diabetes include SMART:
Sulphonylureas
Metformin
Acarbose
Repaglinide
Thiazolidinediones (e.g. rosiglitazone, proglitazone)
Very interestingly, intensive BP control is believed to be at least as important as intensive treatment of glucose levels in reduction of complications in diabetic patients.
REVIEW ASSESSMENT
All patients with type 2 diabetes should have glycaemic control reviewed at 2-6 monthly intervals. Other aspects of diabetes should be reviewed every 6-12 months and should include:
Glycaemic control and any perceived problems
Reinforce need for lifestyle measures
BMI
HbA1c (check every 2-6 months, aim for level of 6.5%-7.5%)
Full lipid profile
Level of urinary albumin/protein
+/- U+Es
BP measurement (Maintain below 130/80)
Examination of eyes for signs of retinopathy and cataracts
Examination of feet for ulceration /sensation/peripheral pulses
Examination of injection sites if appropriate
If male, ask about impotence
SPECIAL CIRCUMSTANCES
Surgery - diabetic patients should be first on the operating list, and fasted on the morning of surgery. Oral agents should be stopped 24 hours before surgery, and restarted postoperatively unless the patient is ill or the blood glucose is very high, necessitating a period on insulin.
For patients already on insulin, the usual insulin should be given the night before the operation. An intravenous infusion of 500 mL of 5% glucose with 10 mmol KCl should be started early on the day of the operation and run at a constant rate to the patient's fluid requirements. A 1 unit/mL solution of soluble insulin in 0.9% saline should also be infused intravenously using a syringe pump. The rate varies according to the patient's blood glucose concentration, which should be measured every 2 hours until stable and every 6 hours thereafter. When the patient starts to eat and drink, he or she may be restarted on the normal insulin regimen.
NOTES ON MEDICATION
Metformin is the first line oral antihyperglycaemic. This is because the vast majority of type 2 diabetics are obese, and metformin is an appetite suppressant. How it does this is by unclear; perhaps it is because it is derived from a bitter herb – Galega Officinalis, or French lilac. It is biguanide; and this name helps us remember ‘bi’ (two) actions of the drug – suppressing gluconeogenesis and increasing peripheral metabolism of glucose. Because it does not act on insulin, it cannot cause hypoglycaemia. Its most interesting side effect is lactic acidosis – caused by reducing pyruvate dehydrogenase activity and mitochondrial transport of reducing agents, thus enhancing anaerobic metabolism. Because of this risk, it is contraindicated in those with creatinine of >150 (where the excretion of lactate would be reduced), and other conditions where lactic acidosis is a risk, such as sepsis, severe heart failure, liver disease or any potentially nephrotoxic procedure.
The thiazolidinediones are a product of genetic studies. One of the current pocketbooks popular among medical students, Baby Kumar, describes them as follows: “Glitazones e.g. rosiglitazone bind to and activate a transcription factor called nuclear peroxisome proliferators-activated receptor gamma (PPAR-gamma), which is a nuclear receptor expressed predominantly in adipose tissue.” As you can see, this is a very poor and confused explanation, and should be revised. What the authors should have done is reverse the order – the glitazones bind to and activate PPAR-gamma, which is an intracellular receptor (as it says on the tin), which in turn shifts into the nucleus, acts as a transcription factor, and stimulates the transcription and synthesis of lipoprotein lipase, fatty acid transporter protein, insulin-sensitive glucose transporter (GLUT-4) and other proteins. In addition, they are believed to reduce the production of TNF-alpha, which is implicated in the pathogenesis of type 2 diabetes.
These two types are antihyperglycaemic, and need insulin to act, unlike the sulphonylureas, whose mechanism of action was explained earlier.
Many type 2 diabetic patients will eventually require insulin, and all type 1 diabetics need it. There are many peripheral issues which we can discuss with regards to this amazing hormone.
Its remarkable history is outlined in the endocrine drugs section in the Cannon. The genius of Banting, McLeod and Best (then a medical student), and the grace of God, is the reason why so many diabetics survive their difficult illness. It is truly fascinating that the patent for this life saving medication was sold for just one dollar.
Insulin was originally extracted from dogs, then cows and oxen, and eventually pigs and finally, we have the human version.
There are two questions that are raised here. Are Muslims allowed to use porcine insulin?
Unfortunately, there is a huge misunderstanding with regards to this issue. The Muslim position is believed by some to go along the following lines, "Muslims are strictly forbidden to drink alcohol. Eating pork is totally prohibited, so porcine insulin is unacceptable to Muslims" (Gwen Hall, 2007). Other authoritative textbook states, “Animal-derived insulins are unacceptable to devout followers of Islam and Judaism and to strict vegans” (Krentz & Bailey, 2005).
The truth of the matter is that – porcine insulin is not forbidden in Islam, and in essence, the refusal of Muslims to use it, is due to psychological, rather than religious issues. This is because the Islamic stance over pig products is clear. The verses are:
"Forbidden to you for (food) are: dead meat, blood and the flesh of the swine and that which hath been invoked the name other than Allah." (5:4)
"Allah has forbidden you only what dies of itself and blood and the flesh of swine and that over which any other name than that of Allah has been invoked; but whoever is driven to (it), not desiring nor exceeding the limit, then surely Allah is Forgiving, Merciful." (16:115).
So it is the ‘flesh’ of swine, not its products that are forbidden. Insulin is not flesh – it is a hormone. Even if it were flesh, the Qur’an does not forbid it if it were a medical necessity, as the second verse concludes.
This brings us to the broad topic of the use of ‘prohibited substances’ in the case of illness. The Islamic stance is discussed very comprehensively by Yusuf Al-Qaradawi, as follows:
“In case of a necessity a different rule applies, as was discussed earlier. Allah Ta'ala says: ...He has explained to you what He has made haram for you, except that to which you are compelled... (6:119)
And after mentioning the prohibitions concerning the flesh of dead animals, blood, and so, He says: ...but if one is compelled by necessity, neither craving (it) nor transgressing, there is no sin on him; indeed, Allah is Forgiving, Merciful. (2:172-173)
The consensus of the jurists is that necessity in this case signifies the need for food to alleviate hunger when no food other than the prohibited food is available, some jurists holding the opinion that at least one day and one night should pass without food. In such a situation a person may eat as much will satisfy his hunger and thus save himself from death. Said Imam Malik, "The amount of it is what will alleviate his hunger, and he should not eat more than what will keep him alive." This, perhaps, is the meaning of Allah's words, "neither craving (it) nor transgressing,"—that is, neither desiring it nor eating more than necessary. That hunger can be a compelling need is expressly mentioned in the Qur'anic ayah: ...but if one is compelled by hunger, without any inclination to sin, then indeed Allah is Forgiving, Merciful. (5:4 (3))
Concerning the question of whether some of the prohibited food substances can be used as medicine, there is a difference of opinion among jurists. Some do not consider medicine to belong in the category of a compelling necessity like food, and in support of their position they cite the hadith: "Assuredly Allah did not provide a cure for you in what He has prohibited to you." (Reported by al-Bukhari on the authority of Ibn Mas'ood.)
Others consider the need for medicine equal to that of food, as both are necessary for preserving life. In support of their position that prohibited food substances may be used as medicine, they argue that the Prophet (peace be on him) allowed 'Abd al-Rahman bin 'Awf and al-Zubair bin al-'Awwam to wear silk because they were suffering from scabies. (The text of this hadith is quoted in the subsection of this book entitled "Clothing and Ornaments.")
Perhaps this latter view is closer to the spirit of Islam which, in all its legislations and teachings, is concerned with the preservation of human life. However, taking medicine containing some of the haram substances is permissible only under the following conditions:
The patient's life is endangered if he does not take this medicine.
No alternative or substitute medication made from entirely halal sources is available.
The medication is prescribed by a Muslim physician who is knowledgeable as well as God-fearing.
We may, however, add that on the basis of our own observations and the opinions of expert physicians, we have arrived at the conclusion that there hardly exists any medical necessity which requires ingesting what is haram, as for example, taking medicine. Nevertheless, we have stated this principle in case a Muslim happens to be in a place where he cannot find medications other than those which contain haram substances.”
To this I may add that God created the entirety of the universe for the service of man. This is clear from the following verse, "Do you not see that Allah made available for you all what is in the skies and what is in the earth, flooded you with many blessings known and unknown." (31:20).
Now, the other interesting issue that arises with insulin is the topic of genetic engineering. The vast majority of insulin these days is genetically engineered, which is regarded by some as ‘playing God’ or changing the creation.
There is no changing the creation here – all that is done is an organism is modified to serve a function that it does not normally have, and since the entire universe was made for the service of humans, there can be no real objection to the use of the products of genetic engineering. Once again, it is valuable to quote Qaradawi on this issue, in an article published on his IslamOnline website:
“One of the blessings of Islam is that it never abstracts scientific programs or narrows the scope of the mind in the field of science and technology. Unlike other religions, there is no conflict between science and religion in Islam. Christian clergy opposed scientists, thinkers and pioneers of technology that we take for granted today. Many were punished, tortured and sentenced to death.
The Qur’an shows that Allah, Almighty, bestows many gifts on mankind enabling them to discover the mysterious nature around them and to recognize the laws that control the universe. Allah Almighty also submits the whole universe with its heavens, earth, sun and moon to mankind.
Allah Almighty says: (See ye not how Allah hath made serviceable unto you whatsoever is in the skies and whatsoever is in the earth and hath loaded you with His favors both without and within? Yet of mankind is he who disputeth concerning Allah, without knowledge or guidance or a Scripture giving light.) (Luqman 31: 20)
He Almighty also says, (And in the earth are portents for those whose faith is sure. And (also) in yourselves. Can ye then not see??w (Adh-dhariat 51: 20-21)
When man’s knowledge advances, it becomes compulsory for him to deepen his faith and moral virtues. One must not go alone, doing whatever one wants, ignoring religious morals or the welfare of people in general. The problem in Western civilization is that science is separated from religion and in some cases it fights religion. Allah Almighty says, (And when he turneth away (from thee) his effort in the land is to make mischief therein and to destroy the crops and the cattle; and Allah loveth not mischief.) (Al-Baqarah 2: 205)
We welcome the idea of genetic engineering. It is one of the greatest discoveries of our time and is shared by many countries. Whether it is considered more important than the discovery of penicillin or man landing on the moon, we hope it is used for the benefit of humanity and that its guidelines will be according to the views of qualified jurists.
There are many benefits we can derive from this, say, for instance, in treating genetic diseases by using the effective genes to prevent harm or disease. This is something commendable in Islam according to the legal rule "Prevention is better than cure"; the rule is taken from the hadith; “There should be neither harm nor reciprocating injury.” By this, through the assistance of such a scientific device, man will be able to prevent many diseases.”
The ultimate dream of the diabetic is to retrieve normal pancreatic function and/or peripheral sensitivity to insulin. They would like to stop taking these tablets, stop injecting themselves, and retrieve a normal metabolism. That is a gift many of us do not appreciate. By reflecting on their adversity, we must learn to be appreciative of normal glucose metabolism and the gift of not being a diabetic.
Tuesday, 16 September 2008
REFLECTIONS ON STROKES
ON STROKES
This disease is a serial killer, being the third commonest cause of death and the biggest cause of serious physical disability in the Western world. It is any focal CNS disturbance due to a vascular cause where the deficit persists.
The first question that can be raised regarded something so deadly, is why it carries such a gentle name, can mean ‘an inspired or effective idea or act’ or even to caress. The etymology of the term was explained by Dirckx (1986) as follows, “According to the Oxford English Dictionary, a sudden, inexplicable cerebrovascular accident was first likened to a "stroke of God's hand" in 1599. The relationship of a cerebral infarction to an act of God exists in other cultures as well: the Greek verb plesso means to "stroke, hit, or beat," and the derivative plegia gives us our term hemiplegia.”
The epidemiology of stroke, although certainly a subject of great importance has not really been studied in the depth it deserves. What is established however is that although from 1950 to 1980 the incidence of stroke was on the fall, an effect attributed to increasing awareness, detection and treatment of hypertension, the biggest risk factor for stroke other than ageing, there has been a gradual increase since 1980 (Robinson, 2007), attributed to “the adoption of less healthy lifestyles” (Davidsons, 2005). However, because of improving management of the condition, perhaps most importantly due to the development of the concept of the stroke unit, morbidity and mortality from the condition is falling.
Cerebrovascular accident is a sudden onset of a focal neurological deficit lasting >24 h= stroke; <24 h = TIA. It is the 3rd most common cause of death, and the biggest cause of serious physical disability. It costs the NHS £2.3 billion a year (2 x CAD). The epidemiology is:
Incidence is 2/1000/yr
Occurred in 8/1000 population
> 50 years mainly
Preceded by TIA in 15% pts
> 50% are physically dependent on others 6 mths after
The International Stroke Trial “highlighted that the UK centres had the poorest survival from stroke in the world” (Newson & Patel, 2002)
A HISTORY OF STROKE
There are great difficulties in understanding the history of stroke. This is because it is difficult to really ascertain whether many of the descriptions given are truly those of stroke, or other conditions causing focal neurological deficits like epilepsy. Apoplexy, the old term for stroke simply means ‘struck down with violence,’ and the word stroke was used as a synonym for apoplectic seizure as early as 1599. Nevertheless, we can probably share the view expressed by Thompson in his Willis Lectures in 1999, where he said that, “With the advent of Hippocrates (460 to 370 BC), ancient descriptive neurology was born. It was known that paralysis and convulsions followed injuries to the brain, with paralysis on the opposite side to the wound. Hippocrates described paralysis of the right arm with loss of speech in what is probably the first written description of aphasia. In one of his aphorisms Hippocrates stated, "Unaccustomed attacks of numbness and anesthesia are signs of impending apoplexy," a description of a TIA”.
Without a CT-scan, we would really be unable to identify if what historians regard as stroke is truly stroke or not. But if we are to go by tradition, which classifies stroke as a clinical diagnosis, then all acute neurological presentations of history, pre-CT must be regarded as stroke.
With regards to the famous victims of stroke, being such a common condition, it has claimed victims in every province of human enterprise. No one is spared – young or old, male or female, of all colours and races. But we shall focus on a few interesting cases which teach us something about this fascinating condition.
In an imaginary political graveyard, where the world leaders of the 20th century are laid to ‘rest’, would very interestingly, have a great proportion of victims of stroke. There are no formal reports or papers on the association of stroke and politics, but it would make for interesting reading.
POLITICIANS
RUSSIA
We have already looked at the fates of three of Russia’s former leaders in our reflections on hypertension, namely Lenin, Trotsky and Stalin. We only briefly mentioned Lenin there, stating that his hypertension diagnosis is rather uncertain. But we he certainly had, based on a detailed autopsy report, is a stroke, due to “haemorrhage over the corpora quadrigemina area of the brain, and it was stressed that most of the very severe brain damage must have been present for some time before death” (Leavesly, 1998).
Lenin’s case is interesting for three reasons. Firstly, the manner of his death. As everyone now knows, he was a very evil man, who is responsible for the deaths of nearly 4 million people, according to the ‘Black Book of Communism’, all in the name of communism. He was a faithless man, who believed that “the end justifies the means”, that “there are no morals in politics; there is only expedience. A scoundrel may be of use to us just because he is a scoundrel”, that, “We need the real, nation-wide terror which reinvigorates the country and through which the Great French Revolution achieved glory” and that the communist “program necessarily includes the propaganda of atheism”, and felt that “liberty is precious - so precious that it must be rationed”. Is it surprising that a man of such evil dies should die the humiliating death he did? Perhaps the best description anyone has made of him is Bertrand Russell, who met him personally in 1920, and described the encounter in his ‘Autobiography’ as follows:
“Lenin, with whom I had an hour’s conversation, rather disappointed me. I do not think that I should have guessed him to be a great man, but in the course of our conversation I was chiefly conscious of his intellectual limitations, and his rather narrow Marxian orthodoxy, as well as a distinct vein of impish cruelty”
Under the heading, ‘Lenin’s End is a Lesson for All’ in his book, ‘Communism in Ambush’, Harun Yahya put the above picture and the following caption, which says more than a thousand words, “Before he died, Lenin became mad. This photograph, taken shortly before his death, teaches an example of the torment God sends in this world upon leaders of irreligion. This end is announced in Verse 30:10 of the Qur'an: "Then the final fate of those who did evil will be the Worst because they denied God's Signs and mocked at them."…he suffered his first stroke in May 1922. On December 16, 1922, he suffered another major attack. Half paralyzed, he was confined to bed. In March of 1923, his illness worsened significantly and he lost the ability to speak. Afflicted by terrible headaches, he spent most of 1923 in a wheelchair. In the final months of his life, those who saw him were horrified at the frightful, half-mad expression on his face. He died of a brain hemorrhage on January 21, 1924.”
The second interesting lesson that Lenin’s stroke teaches us is that it highlights the difficulties inherent in the diagnosis of stroke in pre-CT days. Apparently, only eight out of the 27 physicians looking after Lenin believed that he died of a stroke. But the post-mortem is pretty conclusive. Our suggestion in the hypertension chapter that Lenin had a hypertension-induced stroke is based purely on epidemiological suspicions. However, it is possible that he had another cause – namely syphilis. Learning about Lenin’s case teaches us about this often forgotten cause of stroke, which is generally not mentioned in most medical books, but is always cited in the biggest books. We read in Adams and Victor’s ‘Principles of Neurology’ that, “Whereas in the past strokes accounted for only 10 percent of neurosyphilitic syndromes, their frequency is now estimated to be 35 percent. The most common time of occurrence of meningovascular syphilis is 6 to 7 years after the original infection, but it may be as early as 9 months or as late as 10 to 12 years”. The following table from Harrison’s also lists it among the causes of ischaemic stroke.
The possibility that Lenin had neurosyphillis was raised and extensively discussed in an article, ‘The Enigma of Lenin's Malady’ (Eur J Neurol. 2004 Jun;11(6):371-6) by Lerner, Finkelstein and Witztum. We will discuss this at greater length in our discussion of syphilis in our infectious diseases section. But it is a very interesting possibility.
Another interesting informative Russian stroke case is that of the wife of the last leader of the USSR, Mikhail Gorbachev, Mrs. Raisa Gorbachev. She suffered from leukaemia, but died following a stroke in 1999. Knowing this will help recall leukaemia, and indeed chemotherapy, as a risk factor for stroke; both lead to a hypercoagulable state which like we saw in the DVT section, leads to vascular thrombosis.
USA
As opposed to Russian leaders, who hide much of their health data, the American leaders are a lot more open, and conform much more to the contemporary requirement for accountability. Hence we have a lot more data regarding their illnesses.
Many American presidents sustained strokes – including John Adams, John Tyler, Woodrow Wilson, Eisenhower, Richard Nixon and Gerald Ford. We will only focus on what I feel are the more interesting cases here.
Woodrow Wilson was the man who led the USA during the First World War, and who is famous for setting up the ‘League of Nations’, the immediate precursor of the United Nations, and was awarded the Nobel Peace Prize in 1919 “in recognition of his Fourteen Points peace program and his work in achieving inclusion of the Covenant of the League of Nations in the 1919 Treaty of Versailles”. His fascinating medical history is recounted extensively by Edwin Weinstein in ‘Woodrow Wilson: A Medical and Psychological Biography’. John Sotos, a cardiologist and America's leading Presidential health historian and an expert in unusual signs of disease summarised many of the points made by Weinstein in his Doctorzebra website:
“Wilson's first stroke was in May 1896. It caused marked weakness of the right upper limb plus sensory disturbances in the fingers. The finger problems were mis-diagnosed as neuritis. Wilson was unable to write normally for almost a year afterwards.
In June 1904 Wilson developed weakness in the right upper limb that lasted for several months. On May 28, 1906, Wilson suddenly lost vision in his left eye. This persisted. Weakness of the right upper limb was present. In November 1907 he developed weakness and numbness of fingers or right upper limb that lasted several months; in July 1908 he had two attacks of "neuritis" affecting the right upper limb; in December 1910 he had transitory weakness of the right hand. Wilson's problems with blood circulation in his brain and eyes continued after he became President: April 1913 - Attack of "neuritis" involving right upper limb; May 1914 - Abnormal retinal arteries observed; May-Sept. 1915 - Episodes of transient weakness in his right hand. From 1915 to 1919 Wilson had episodic severe headaches, lasting for days. It is possible these were due to [uncontrolled] hypertension. In September 1919 Wilson was having severe headaches, double vision, and signs of a weakened heart. On Sept. 25 he developed a transitory weakness on the left side of his body. Wilson suffered a catastrophic, disabling stroke while President (Oct. 3, 1919), as recounted in multiple sources, including an entire book on the subject. (Any biography covering Wilson's presidential years should devote extensive coverage to this event.) This was the most serious illness suffered by any sitting President. Wilson had bad headaches before becoming president, but presidential physician Cary Grayson ascribed the stroke to a thrombosis, stating it was not hemorrhagic”.
Aside from his multiple strokes, I will take this occasion to go through one of Woodrow Wilson’s little known political contributions - The King-Crane Commission’s report. This is how Ron David, the Jewish author of ‘Arabs and Israel For Beginners’ summarised it in that absolutely splendid book:
“When WW-I ended, no one could reconcile the claims of Arabs, Zionists, British & French so, in 1919, Woodrow Wilson and his democracy-mad Americans "dispatched the King-Crane Commission to the former Arab provinces of the Ottoman Empire to ascertain the wishes of their inhabitants regarding the postwar settlement of their territories." [Britannica]
The King-Crane report stated:
90% of Palestine's inhabitants were non Jewish & did NOT want a Jewish state in Palestine;
If they are given Palestine, "Zionists looked forward to a practically complete dispossession of the present non-Jewish inhabitants."
The King-Crane Commission said that a Jewish state in Palestine would violate the Palestinian Arabs' right to self-determination. They recommended that Zionists respect the wishes of Palestine's inhabitants & find another place to plant the Jewish state.
The Zionists were furious! They didn’t want democracy; they didn’t give a damn about “the will of the people.” The Zionists wanted Palestine, no matter what they had to do to get it. So they simply “rewrote” the history of the conflict.
The usual versions of Israel's history either don't mention The King-Crane Commission Report or they minimize its importance. In my opinion, any lover of democracy must consider the King-Crane Commission’s report a major event. Anyone who believes in Democracy must consider the King-Crane Commission's official report—which even now can be documented by any interested partyment agency—irrefutable proof that:
In 1919, even after 30 years of iintensive Jewish emigration into Palestine (inspired by Theodore Herzl’s The Jewish State, published in 1898), 90% of Palestine’s inhabitants were non-Jewish and did not want a Jewish state in Palestine. The will of the people was clear
The Zionists knew they were acting against the will of the people.
The Zionists knowingly subverted Democracy.
The Government of the United States confirmed the legitimacy of the claim that Palestinians make today
Some Quotes from the Commission's Report
"a national home for the Jewish people is not equivalent to making Palestine into a Jewish State."
"nor can the erection of such a Jewish State be accomplished without the gravest trespass upon the civil and religious rights of existing non-Jewish communities in Palestine."
"In his address of July 4, 11918, President Wilson laid down the following principle as one of the four great 'ends for which the associated peoples of the world were fighting': 'The settlement of every question, whether of territory or of political relationship upon the basis of the free acceptance of that settlement by the people immediately concerned, and not upon the basis of the material interest or advantage of any other nation or people which may desire a different settlement for their own exterior influence or mastery."
"If that principle is to rule, and so the wishes of Palestine's population are to be decisive as to what is to be done to Palestine, then it is to be remembered that the non-Jewish population of Palestine—nearly nine-tenths of the whole—are emphatically against the entire Zionist program. To subject a people so minded to unlimited Jewish immigration, and to steady financial and social pressure to surrender the land, would be a gross violation of the principles just quoted, and of the peoples' rights, though it kept within the forms of the law."
"No British officer, consulted by the Commissioners, believed that the Zionist program could be carried out except by force of arms."
"That of itself is evidence of a strong sense of injustice of the Zionist program.”
"The fact came out repeatedly in the Commission's conference with Jewish representatives that the Zionists looked forward to a practically complete dispossession of the present non-Jewish inhabitants of Palestine.''
“The initial claim, often submitted by Zionist representatives, that they have a 'right' to Palestine, based on an occupation of two thousand years ago, can hardly be seriously considered."
The full report can be found on the internet, and makes for even more fascinating reading. I cannot agree more with Ron David, that the report is a major event that should be more widely known.
The other interesting case of stroke among the American presidents is that of Gerald Ford. His story reveals an interesting cause of stroke, a tongue abscess. This is how Tasos summarises things,
“During the 2000 Republican National Convention in Philadelphia, Ford appeared "sluggish and sick" on television during a tribute to him. A few hours later, shortly after midnight on Wednesday, August 2, Ford presented to the emergency room at Hahnemann University Hospital, complaining of facial pain. The physician diagnosis was "a sinus attack." Ford stayed only a half-hour, and declined the recommendation to have a CT scan. Upon awakening on Wednesday morning, Ford had new symptoms and returned to the hospital. He apparently had left arm weakness, balance difficulties, and slurred speech. A stroke was diagnosed and he was treated with "blood thinners". The slurred speech, however, was ascribed to a swollen, painful tongue, which proved to be abscessed with actinomycosis. (This is an exceedingly rare cause of a tongue abscess.) The abscess was drained under general anesthesia. (It is not clear when the anticoagulants were started, in relation to the abscess drainage.) Later, a Ford spokesman declared that Ford had developed tongue pain while in Colorado, before Ford departing for the convention. By August 5 Ford was "completely recovered from the stroke" (there were also questions about a possible other strokes). He left the hospital on August 9, still taking antibiotics and blood thinners. The Hahnemann University Hospital was obviously embarassed by missing the diagnosis on the first night, but refused to admit anything. A hospital spokesman said "We do not believe there was any misdiagnosis there." He then shamelessly shifted the blame to the patient, saying "The activities that evening were totally controlled by the President". The question is: how could the abscess have been missed on physical examination the first night, especially when Ford had noted tongue pain days earlier? How did the physician(s) arrive at the mistaken diagnosis of a sinus problem? A CT scan is usually not required to discover a tongue abscess. It is possible that missing the tongue abscess the first night played a role in causing the stroke, as there is a tight relationship between inflammation and acute vascular events. In simple terms, inflammation (the classic response to an infection) makes the blood more likely to clot (the actual event triggering a stroke). Older physicians, for example, will recall the classic association between pneumonia and acute myocardial infarction. In Ford's case, the missed diagnosis allowed the infection, hence the inflammation, to progress for the extra few hours leading to the stroke.” In any case, Ford was to die of stroke many years later, in 2006, at the age of 93, completely unrelated to his first far more interesting one.
ENGLAND
Although many British leaders suffered strokes, including most recently Princess Margaret, who died of a massive stroke on the 9th of February 2002, and Baroness Margaret Thatcher, which has affected the Iron Lady tremendously; apparently she has no short term memory now.
But of far more interest and importance are the strokes of Sir Winston Churchill. In an article entitled ‘Was Winston Churchill Fit to Rule?’, George Biro argues that Churchill failed miserably with regard to his duties as a prime minister by hiding away the fact that he had several major strokes while leading the nation. He argued that, “Should not have Moran (Churchill’s personal doctor) have balanced the duty to his patient against the interests of the country? Could he have induced Churchill to step down earlier? Could anyone else have done so? If we make pilots and bus drivers pass medical examinations, why don’t we do the same for politicians?” We all know, as doctors, confidentiality is important, is part of the basic right to autonomy. But if maintaining confidentiality will impinge on the health and safety of others, the principle can be broken.
Churchill was certainly not a sane man. He was renowned for his bouts of severe depression, his ‘black dog’, and many people have labelled him a cyclothyme. In ‘Encounters with Winston Churchill’, W Russell Brain, the great neurologist of the 20th century said, “I should think that from what Moran told me that Churchill is a cyclothyme. Apparently he was subject to depression in his earlier days. He has the drive and vitality and youthfulness of a cyclothyme.” (Medical History, 2000, 44: 3-20). A man no less than the great psychiatrist Anthony Storr devoted a whole book to the issue, entitled, ‘Churchill’s Black Dog’. He argued that, "Had he been a stable and equable man, he could never have inspired the nation. In 1940, when all the odds were against Britain, a leader of sober judgment might well have concluded that we were finished." He also said, "The kind of inspiration with which Churchill sustained the nation is not based on judgment, but on an irrational conviction independent of factual reality. Only a man convinced that he had a heroic mission, who believed that, in spite of all evidence to the contrary, he could yet triumph, and who could identify himself with a nation's destiny could have conveyed his inspiration to others." We will leave the discussion of whether people with chronic psychiatric illness should be allowed to lead nations to our psychiatry section.
But as for those with acute confusional states, the answer must be a definite no, until he or she recovers fully from it. In 1944, following several attacks of pneumonia, Allanbrooke, Chief of the Imperial General Staff stated, “He seems quite incapable of concentrating for a few minutes on end, and keeps wandering continuously”. In 1952, “Churchill had a more serious stroke affecting his speech. By now he insisted on even the most complex issues being condensed into one paragraph before he would consider them. Moreover, the Prime Minister often could not even follow a discussion. Moran wrote, “He was not doing his work. He did not want to be bothered by anything; he was living in the past””.
But rather than advise Churchill to resign, Moran did the opposite. He said, “Winston once asked me whether he ought to have retired earlier. I was, I think, alone in urging him to hang on, though I knew that he was hardly up to his job for at least a year before he resigned office. His family and friends pressed him to retire; they feared that he might do something which would injure his reputation. I held that this was none of my business. I knew that he would feel that life was over when he resigned. It was my job as his doctor to postpone that day as long as I could”.
Biro continues, “But somehow, the wilful, wily old man defied such opinions, and carried on the pretence: instead of dealing with matters of state, Churchill read novels and played cards…In 1954, he had to apologise after misleading the Commons (and jeopardising the government’s foreign policy) about a telegram he claimed to have sent to Field-Marshal Montgomery during the war. There was no such telegram; by now even the Conservatives had had enough. But it was April 1955 before the Prime Minister finally stepped down. By then, he was spending most of his days in bed.” Reflecting on this, I feel Russell Brain is deeply mistaken in his reflections on Churchill, that between in 1949 and 1964, Churchill was “fit enough to go to the House of Commons”. However, his description of his stroke has not been bettered:
“I found that Churchill had had a stroke. He had been feeling very tired lately on account of the Coronation and of having to do the work of the Foreign Secretary as well as his own on account of Eden's illness. The previous morning Moran had been to see him to pay a routine visit and thought his speech was somewhat slurred. In the evening, he had presided over a dinner for the Italian Premier, at the end of which he had made a speech, and again his speech was somewhat slurred, and he became unsteady on his legs, and had to be assisted out of the room. He had a good night and on the morning of June 24th, Moran saw him again, and found his speech still slurred. He presided over a Cabinet Meeting, however, which lasted two hours. He felt very tired, and his slurring speech was noticed by his colleagues. He slept in the afternoon and his secretary mentioned that she thought there was some drooping of the left side of his face. This was apparent when he spoke and also when he smiled, and his speech was at first somewhat slurred, but there was at no time any evidence of aphasia. There was slight weakness of the left lower face on voluntary and emotional movement, and his tongue deviated slightly to the left. There was no weakness of the limbs, and no change in sensation, but the left plantar reflex was extensor while the right was flexor. He walked about the room with only a slight trace of unsteadiness. He said he had no headache but felt as though there was something in his head. He was put on a dose of trinitrin night and morning.”
Winston Churchill illustrates several risk factors for stroke – he was overweight, probably obese, a heavy drinker ("Alcohol has been a very good friend to me…I like to take a fair proportion of my calories in the alcohol"), and famously a chain smoker. He smoked about ten cigars a day. One of his interesting stories regarding these two things was told in his memoirs, regarding a meeting he had in February 1945 in honour of King Ibn Sa'ud of Saudi Arabia, "A number of social problems arose. I had been told that neither smoking nor alcoholic beverages were allowed in the Royal Presence. As I was the host at the luncheon I raised the matter at once, and said to the interpreter that if it was the religion of His Majesty to deprive himself of smoking and alcohol I must point out that my rule of life prescribed as an absolutely sacred rite smoking cigars and also the drinking of alcohol before, after and if need be during all meals and in the intervals between them. The King graciously accepted the position." (One is immediately reminded here of the famous hadith, reported on the Prophet (PBUH), "Whoever believes in Allah and the Last Day must not sit at table at which khamr is consumed.") Surprisingly, Churchill, according to the website of his name, had “a normal blood pressure for his age”.
ISRAEL
Moving on swiftly from ‘The Last Romantic Zionist Gentile’, as Yoav Tenembaum described Churchill (he is clearly unaware of Churchill’s Jewish ancestry and his Jewish mother, Jenny Jacobson), let us look at some interesting cases from Israel.
We have already discussed the case of Ariel Sharon in our reflections on congenital heart disease. His is actually a fascinating one, because it illustrates a very rare risk factor for stroke – paradoxical embolism.
The case of David Ben-Gurion, the first Prime Minister of Israel, is a lot less interesting, but he endured the same fate. This is how his biographer Bar Zohar somewhat dramatically depicted it,
“In 1973 Ben-Gurion suffered a massive stroke. I hurried to the hospital where he was lying and was let into a quiet, white room. Ben-Gurion was lying quietly in his bed. He couldn't speak, he just looked at me with his deep, wise eyes. He communicated with me by tightening his grip on my hand. I was looking at the quiet, calm face of the father of my nation, the man who made me and so many homeless Jews a people again; and I thought of his moral testament to all of us. "The existence of Israel," he told me over and over again, "depends on her force - and on her righteousness. We must be a light into the nations." I had never met another statesman or political leader for whom moral values were so important, who believed that his nation will have the right to exist only if it sticks to those moral percepts, given to us all, Jews and Christians and Muslims, in the Bible. I don't know if we have succeeded to accomplish this moral commandment of Israel's Old Man. But I see it as a call to my generation and those who will come after me - to try to build a country worthy of the teachings of Israel's ancient prophets.”
The sheer deception and hypocrisy of this statement, highlights a high degree of confusion in Ben-Gurion’s mind, as it contradicts a lot of what he said and believed. But then again, Ben Gurion is a politician, and there are hardly any politicians out who have clarity and consistency of thought. Politicians are not mathematicians or scientists. They are not concerned with truth, but power and control, no matter by what means these are achieved. The classic recent example is that of the crimes of George W. Bush and Tony Blair in Iraq. Bertrand Russell brilliantly summed it all up, “I am persuaded that there is absolutely no limit in the absurdities that can, by government action, come to be generally believed. Give me an adequate army, with power to provide it with more pay and better food than falls to the lot of the average man, and I will undertake, within thirty years, to make the majority of the population believe that two and two are three, that water freezes when it gets hot and boils when it gets cold, or any other nonsense that might seem to serve the interest of the State…Politics is largely governed by sententious platitudes which are devoid of truth.”
Ben-Gurion was not the romantic that Bar-Zohar is trying to depict. He is not “part Washington, part Moses”, as Amos Oz was foolishly telling us in his article on Ben-Gurion in ‘Time Magazine's’ ‘100 Most Important People of the Century’. For one, both Moses and Washington believed in God, and Ben-Gurion, a Russian in origin, was an atheist, like so many other Zionist leaders, including the founding father of Zionism, Theodor Hertzl. As stated by Alfred Mendes, “The State of Israel was … set up in 1948 by the Zionists, under the leadership of the Russian-born David Ben-Gurion (another atheist) who had emigrated to Palestine in 1906. The very term ‘atheist’ means disbelief in any ‘God’ and/or ‘religion’. Hence, an atheist cannot consider him/herself a Jew in the strictly religious sense of the term. To quote Rabbi E. Weissfish: “The Zionist ideology has no connection whatsoever with Judaism, on the contrary Judaism is totally opposed to Zionism”. It is thus incontrovertible that the two terms ‘Judaism’ and ‘Atheism’ are antonymous, a fact that Ben Gurion would certainly have been aware of - but here we have Ben Gurion himself, in his address to a special session of the Knesset in 1971, saying “An Arab can be Muslim or Christian. A Jew, however, cannot be a member of another faith and still be a Jew. A Jew can be an atheist, but if he adopts the Christian or Muslim faith - he is no longer a Jew”. This was clearly a duplicitous statement on his part, and, as such, therefore designed to confuse and divert attention from some hidden agenda”.
Moses and Washington were not racists, while Ben Gurion was. He “never believed in the possibility of coexistence with the Arabs. The fewer Arabs there were within the borders of the future state of Israel, the better it would be. He did not say so explicitly, but the overall impression one gets from his speeches and his comments is clear: a major offensive against the Arabs would not only defeat their attacks but would also reduce as far as possible the percentage of the Arab population within the State. "He can be accused of racism, but then one will have to put on trial the entire Zionist movement, which is founded on the principle of a purely Jewish entity in Palestine."” He also, according to his official biographer Shabtai Tebeth, “advocated exclusively Jewish labor (Avodah Ivrit) in Jewish businesses. He explained why a Jewish laborer should earn a higher salary because "[he was] more intelligent and diligent" than the Arab.” His racism extended, of course to destruction of all Arabs, both within Palestine and outside.
Within Palestine, Israeli historian Simha Flapan exposed him, saying, “That Ben-Gurion’s ultimate aim was to evacuate as much of the Arab population as possible from the Jewish state can hardly be doubted, if only from the variety of means he employed to achieve his purpose...most decisively, the destruction of whole villages and the eviction of their inhabitants...even [if] they had not participated in the war and had stayed in Israel hoping to live in peace and equality, as promised in the Declaration of Independence.”
Outside of it, two examples suffice to expose Ben-Gurion, one from Egypt, the other from Lebanon. He was exposed in Egypt after the famous Lavon affair. Ron David summarised this beautifully, exposing him fully, “Around the time that Gamal Abdul Nasser became Egypt’s leader, David Ben Gurion had decided (partly out of spite) to step down as Prime Minister of Israel and let Moshe Sharett see if he could do a better job. Sharett was less of a ‘Hawk’ than Ben Gurion and, by 1954, had reached the point where he was on the verge of signing a peace treaty with Nasser of Egypt. Nasser is usually depicted as one of the bad guys. Recently declassified State Department documents indicate the exact opposite. Documentary evidence [1948-54] shows Nasser expressing tolerance and respect for Israel to CIA officials, members of British Parliament, and two American Ambassadors. In October 1954 Nasser became one of the only heads of state to refuse military aid from the U.S. He preferred economic aid. Then, in 1954, Israeli terrorists attacked American installations in Egypt! Then the Israelis rigged it so the attacks would be blamed on Egyptians! Then the Israelis got caught and put in Egyptian prisons....all of which convinced Egypt’s Nasser that the Israelis couldn’t be trusted, so he broke off the peace talks and took weapons from whomever offered them—including the Soviets. Ben Gurion blamed the blundering terrorists on his Defense Minister, Pinchas Lavon—but several years later, Lavon found documents that proved Ben Gurion was behind it! Ben Gurion’s motive was simple: he and Moshe Dayan wanted a war with Egypt and Sharett’s peace talks might deprive them of it. In June 1955, Moshe Sharett [in his Diaries] wrote: ‘Dayan said, “above all, let us hope for a new war with the Arab countries, so that we may finally get rid of our troubles and acquire space.”’ Another of Sharett’s Diary entries for June 1955: ‘Ben Gurion himself said it would be worthwhile to pay an Arab a million pounds to start a war. What a slip of the tongue!’”
His crimes in Lebanon are also summarised by Ron David in his aforementioned book, “In 1954, former Prime Minister Ben Gurion mentioned to Prime Minister Moshe Sharett that it would be in Israel's interest to provoke a Civil War in Lebanon between Christians and Muslims. On May 16, 1955, Ben Gurion got more specific: he said that Israel should provoke Lebanon's Muslims to attack Lebanon's Christians in the hope of igniting a Civil War in Lebanon. Prime Minister Sharett (whose published Diary details this) was shocked.”
Most fundamentally (apart from the obvious difference of theological beliefs), Moses (PBUH) was the saviour of the people of the People of Israel, the man who gave them a moral and religious foundation, while Ben-Gurion lacked morals, and at times was the anti-Saviour of the Jewish people. His only obsession was the creation of the state of Israel, at all costs, even if it meant the destruction of world Jewry. Did he not say, "The Zionist's task is not to save the "rest" of Israel which finds itself in Europe, but to save the land of Israel for the Jewish people"? Was he not involved, in the murder of many Jews throughout his life. To quote his official biographers yet again, “In 1940, to arouse indignation against the English, who had decided to save the Jews threatened by Hitler by taking them to Mauritius, the Zionist leaders of the "Hagannah" (led by Ben Gurion) did not hesitate to blow up the ship when it called at Haifa on December 25th 1940, causing the death of 252 Jews and English crew-members.” (Dr. Herzl Rosenblum, director of "Yediot Aahronot", revelation made in 1958 and justified in "Jewish Newsletter", N.Y.,November 1958). Did he not famously say, "If I knew it was possible to save all the children in Germany by taking them to England, and only half of the children by taking them to Eretz Israel, I would choose the second solution. For we must take into account not only the lives of these children but also the history of the people of Israel"? How could a man of any morals praise the actions of Adolf Hitler - "Jewish suffering is also a political factor, and whoever says that Hitler diminished our strength, is not telling the truth." In one of history's crueller ironies, those words proved prophetic. Millions of Jews did not storm the beaches of Palestine, for they could not rise from the ashes of the death camps. But the Holocaust--they zenith of Jewish agony-- became the same "political force" of which Ben-Gurion spoke before he even imagined the systematic destruction of European Jewry. After the war, the Holocaust was a powerfully influential factor in turning world public in Zionism's favor, and was the decisive factor in defeating the policy of the British 1939 White Paper (which called for a united bi-national Palestinian state no later than 1949 and the cessation of Jewish immigration). Guilt, sorrow, and remorse---what might be called the collective conscience of humanity--led many nations (referring to 1947 UN proposed partition plan) finally to grant survivors, that which might have saved the many victims: a "Jewish state."” (Shabtai Teveth, p. 196).
The Israeli historian, Tom Segev, in his book ‘The Seventh Million’ exposed Ben-Gurion too, saying that, “In the wake of the Kristallnacht pogroms, Ben-Gurion commented that ‘the human conscience’ might bring various countries to open their doors to Jewish refugees from Germany. He saw this as a threat and warned: ‘Zionism is in danger.’”. How could anyone regard this evil man as a Prophet, the highest accolade that can be bestowed on a man?
What puzzles me about Ben-Gurion is that, as evil as he is; he did say many truthful things throughout his political career. Perhaps it is one of the characteristics of the hypocritical mind that it often exposes itself under close scrutiny, where the power to withhold the truth is overwhelmed by the power of truth itself. It is one of the ironies of history that one could easily quote the creator of Israel to support the Palestinian cause, and oppose the falsities of other Zionist politicians!
For example, in response to Golda Meir’s famous statement, “It was not as though there was a Palestinian people in Palestine considering itself as a Palestinian people and we came and threw them out and took their country away from them. They did not exist”, Ben-Gurion defends us saying, “Palestine is not an empty country” and "The Arab community in Palestine is an organic, inseparable part of the landscape. It is embedded in the country.” In response to the eternal question – who is the true criminal, Ben Gurion has the true answer, "When we say that the Arabs are the aggressors and we defend ourselves - that is only half the truth. As regards our security and life we defend ourselves. . . . But the fighting is only one aspect of the conflict, which is in its essence a political one. And politically we are the aggressors and they defend themselves." He even went so far as to say, “Why should the Arabs make peace? If I was an Arab leader, I would never make terms with Israel. That is natural: we have taken their country. Sure, God promised it to us, but what does that matter to them? Our God is not theirs, We come from Israel, it’s true, but two thousand years ago, and what is that to them? There has been anti-Semitism, the Nazis, Hitler, Auschwitz, but was that their fault? They only see one thing: we came here and stole their country. Why should they accept that?”
Even Ben-Gurion’s exposures of his fellow colleagues are very telling. Take for instance what he says about Menachem Begin, the Prime Minister who signed the first Camp David accords with Anwar El-Sadat in 1979, "Begin undeniably belongs to the Hitlerian type. He is a racist, ready to destroy all the Arabs in his dream of unification of Israel, prepared to resort to any means to realize this sacred goal”.
It is probably time to move on to other figures whose strokes are of interest for medical history, apart from politicians.
NOVELISTS
Two of the most famous people to have died of stroke are among the greatest of English authors: Samuel Johnson, the most quoted English writer after Shakespeare, and author of ‘A Dictionary of the English Language’, the father of all dictionaries, and Charles Dickens, arguably the greatest English novelist. Their strokes are of interest as they teach us a few things.
Although he is often referred to as Dr. Johnson, Samuel Johnson was not a physician. He was a great friend of physicians, and was very interested in all matters medical, as is highlighted in his biographies (see for example, the article by T Jock Murray, ‘Samuel Johnson: his ills, his pills and his physician’ in ‘Clinical Medicine’ (Vol 3 No 4 July/August 2003)). He even gave medical advice to people on a regular basis – perhaps therein lies the confusion.
In any case, Samuel Johnson suffered a stroke in 1783, which he described in the following words, “Another time ... another place...[I] waked and sat up ... when I felt a confusion and indistinctness in my head ....I was alarmed and prayed God, that however he might afflict my body he would spare my understanding ... Soon after I perceived that
I had suffered a paralytick stroke and that my Speech was taken from me”. Johnson had many risk factors for stroke; he was obese (and therefore likely to be hyperlipidaemic in the pre-cholesterol age), had “suffered from oedematous legs, shortness of breath, a smothering sensation when lying down, and attacks of dyspnoea that awoke him from sleep – all signs of right heart failure” (Murray, 2003) (heart failure is a major cause of stroke), and most likely had the most important risk factor for stroke other than age, hypertension. Henry Rolleston argued that his right heart failure and other illnesses of late life were due to hypertension, a condition unknown in his time (Rolleston, 1929). Hypertension may have indirectly led to his right heart failure via causing ischaemic heart disease – he very likely suffered this, according to Murray (2003), “At age 71 he was having chest discomfort, ‘convulsions in my breast which had distressed me for more than 20 years’”. But only pulmonary, as opposed to systemic hypertension, can cause right heart failure directly. This is the stronger possibility, which is also suggested by his autopsy results which showed pulmonary fibrosis and cardiac failure (ibid). It is possible that he had polycythaemia too – this may be related to his chronic lung disease (which was incorrectly attributed to asthma – highlighting difficulties in diagnosis in pre-CXR and CT days). This polycythemia, an independent risk factor for stroke as we outline below is suggested by his frequent phlebotomies - he “even cut his own vein to do his own phlebotomy, bleeding so much that the stream of blood had to be stopped with the help of Robert Levet and Johnson’s black servant Francis Barber” (ibid). Johnson was also a heavy drinker, who “admitted that at times he drank a lot, and at other times abstained – it was moderation he found difficult. Although he mostly abstained, he lamented, ‘There is no doubt that not to drink wine is a great deduction from life’.” Excess alcohol is risk factor for stroke.
As for Charles Dickens, he too “had signs of heart disease, perhaps precipitated by renal disease, for several years, and in 1866 he was prescribed iron, quinine, and digitalis. Watson also noted signs of cardiac enlargement” (McManus, 2001). His stroke has even been localised – without an autopsy or CT-scan, highlighting some of the unique aspects to neurological diagnosis. As explained by McManus, “For the last 5 years of his life, Charles Dickens had a range of symptoms, mostly affecting his left side, including hemispatial neglect for words, paroxysmal pains, hyperpathia or allodynia and hypoalgesia in the left foot, and a feeling of the world falling to the left. He also seemed to be unaware of the seriousness of his symptoms, which suggests some form of anosognosia. Dickens was known to have had a definite attack of right-sided cerebral insufficiency, and he died of apoplexy affecting the right side of the brain. Dickens' left-sided symptoms thus could suggest damage to the right temporoparietal area.”
There is much of interest in Dickens’ life, but if I were to look at him from my two most personal perspectives, I find him most amusing.
As a doctor, Dickens views on the medical profession are peculiar and reveal to us a lot about how the medical profession was viewed in early Victorian times. He portrayed many doctors in his novels, 27 according to Dana (1898), and “out of these twenty-seven medical men, not one is characterized especially as having ability, as being a person of good sound sense having ability, as being a person of good sound sense; not one would seem to indicate by anything he is allowed to say in the pages in which he lives, that he is a man of brains, with the possible exception of Dr. Manette in the " Tale of Two Cities," and Joe Specks in the ' Uncommercial Traveller." Alfred Heathfield, Alexander Manette, Joe Specks and Allan Woodcourt are men whom one might be willing to associate with freely, though even they rather savor of the cheap comic paper. The remaining twenty-three are, as the notes indicate, either silly, idiotic, pretentious, weak, or are simply caricatures of men. As I went on with my examination I was at first inclined to draw some rather broad conclusions from this table. It seemed to indicate that in Dickens' time, say forty years ago, the medical profession in England received very little consideration at the hands of people of thought. The doctors generally, were looked upon as weak and r.,ther silly; and the lower middle class, even, considered them as little more than necessary evils or subjects for jokes.”
As a Palestinian, I find his views on the Jews very interesting. Even this great novelist was not spared the accusation of anti-Semitism by his Jewish readers. Why can’t Jews accept criticism? Why are they so pathetic? Why do we need to distort history so that we please them? Why can’t they accept that they committed the many crimes that they have committed throughout their history? Why do they want everyone to think that they are the angels of Earth, perfect, innocent, who have never done any evil, the ones who are hated ‘because they are so good’, because we are jealous of them? The Jews’ portrayal of themselves in current media as the most perfect of people is nonsense, pure fiction. The Jews are like every other people – there is both good and evil in them, although history, and the word of God, tells us that there is probably more evil in them than good.
The Quran indicates to us that there are good Jews, saying, “Not all of them are alike: of the People of the book are a portion that stand (for the right); they rehearse the signs of Allah all night long and then prostrate themselves in adoration. They believe in Allah and the Last Day; they enjoin what is right and forbid what is wrong; and they (hasten in emulation) in (all) good works; they are in the ranks of the righteous. Of the good that they do nothing will be rejected of them; for Allah knoweth well those that do right” (3:113-115). It even promises Paradise to some of them, “Verily! Those who believe and those who are Jews and Christians, and Sabians, whoever believes in Allah and the Last Day and do righteous good deeds shall have their reward with their Lord, on them shall be no fear, nor shall they grieve”.( 2:62). But in the main, it is critical of their actions; entire books have been dedicated to this topic, which I will not recount here.
God cannot be accused of the anti-Semitism that so many fair and just thinkers have been accused of because they spoke the truth about the Jews. Everyone knows that Shakespeare has been accused of anti-Semitism following his depiction of the character Shylock in the Merchant of Venice, the famous miserly money lending Jew. So was Dickens, following his depiction of the character Fagin, in his novel Oliver Twist, the Jewish leader of “a group of children, the Artful Dodger among them, whom he teaches to make their livings by pickpocketing and other criminal activities in exchange for a roof over their heads.” The great man was criticised by readers everywhere, and responded, "I know of no reason the Jews can have for regarding me as inimical to them...on the contrary, I believe I do my part toward the assertion of their civil and religious liberty, and in my Child's History of England, I have expressed a strong abhorrence of their persecution in old time"
To a criticism published in the Jewish Chronicle, Dickens wrote the following response:
"If there can be any general feeling on the part of the intelligent Jewish people that I have done them what you describe as a 'great wrong', they are a far less sensible, and far less just, and a far less good-tempered people than I have always supposed them to be be. Fagin, in Oliver Twist, is a Jew, because it unfortunately was true of the time to which that story refers, that that class of criminal almost invariably was a Jew. But surely no sensible man or woman of your persuasion can fail to observe...that all the rest of the wicked dramatis personae are Christians"
Dickens was being fair, and a true observer of history. We shall not feign history to portray the Jews as they wish were, rather than what they actually were. One can give statement by virtually all great non-Jewish thinkers of all ages to show what a terrible people they generally were. I find it an extremely useful exercise to list some of these statements.
1. François Marie Arouet Voltaire, the 18th century French philosopher and novelist:
“Why are the Jews hated? It is the inevitable result of their laws; they either have to conquer everybody or be hated by the whole human race. The Jewish nation dares to display an irreconcilable hatred toward all nations, and revolts against all masters; always superstitious, always greedy for the well-being enjoyed by others, always barbarous--cringing in misfortune and insolent in prosperity”. (Essai sur les moeurs)
“You seem to me to be the maddest of the lot. The Kaffirs, the Hottentots, and the Negroes of Guinea are much more reasonable and more honest people than your ancestors, the Jews. You have surpassed all nations in impertinent fables, in bad conduct and in barbarism. You deserve to be punished, for this is your destiny. (From a letter to a Jew who had written to him, complaining of his 'anti-Semitism.' Examen des quelques objections. . . dans l'Essai sur les moeurs.) You will only find in the Jews an ignorant and barbarous people, who for a long time have joined the most sordid avarice to the most detestabJe superstition and to the most invincible hatred of all peoples which tolerate and enrich them. ("Juif," Dictionnaire Philosophique)”
“I know that there are some Jews in the English colonies. These marranos go wherever there is money to be made But whether these circumcised who sell old clothes claim that they are of the tribe of Naphtali or Issachar is not of the slightest importance. They are, simply, the biggest scoundrels who have ever dirtied the face of the earth. (Letter to Jean-Baptiste Nicolas de Lisle de Sales, December 15, 1773. Correspondance. 86:166)”
“They are, all of them, born with raging fanaticism in their hearts, just as the Bretons and the Germans are born with blond hair. I would not be in the least bit surprised if these people would not some day become deadly to the human race. (Lettres de Memmjus a Ciceron, 1771)”
2. Benjamin Franklin – the great American thinker:
“I fully agree with General Washington, that we must protect this young nation from an insidious influence and impenetration. That menace, gentlemen, is the Jews. In whatever country Jews have settled in any great number, they have lowered its moral tone; depreciated its commercial integrity; have segregated themselves and have not been assimilated; have sneered at and tried to undermine the Christian religion upon which that nation is founded, by objecting to its restrictions; have built up a state within the state; and when opposed have tried to strangle that country to death financially, as in the case of Spain and Portugal. For over 1,700 years, the Jews have been bewailing their sad fate in that they have been exiled from their homeland, as they call Palestine. But, gentlemen, did the world give it to them in fee simple, they would at once find some reason for not returning. Why? Because they are vampires, and vampires do not live on vampires. They cannot live only among themselves. They must subsist on Christians and other peoples not of their race. If you do not exclude them from these United States, in this Constitution, in less than 200 years they will have swarmed here in such great numbers that they will dominate and devour the land and change our form of government, for which we Americans have shed our blood, given our lives, our substance and jeopardized our liberty. If you do not exclude them, in less than 200 years our descendants will be working in the fields to furnish them substance, while they will be in the counting houses rubbing their hands. I warn you, gentlemen, if you do not exclude Jews for all time, your children will curse you in your graves. Jews, gentlemen, are Asiatics, let them be born where they will or how many generations they are away from Asia, they will never be otherwise. Their ideas do not conform to an American's, and will not even though they live among us ten generations. A leopard cannot change its spots. Jews are Asiatics, are a menace to this country if permitted entrance, and should be excluded by this Constitutional Convention.”
3. Mark Twain – the great American writer:
“I feel convinced that the Crucifixion has not much to do with the world's attitude toward the Jew; that the reasons for it are much older than that event...I am convinced that the persecution of the Jew is not in any large degree due to religious prejudice. No, the Jew is a money-getter. He made it the end and aim of his life. He was at it in Rome. He has been at it ever since. His success has made the whole human race his enemy. You will say that the Jew is everywhere numerically feeble. When I read in the Cyclopedia Britannica that the Jewish population in the United States was 250,000 I wrote the editor and explained to him that I was personally acquainted with more Jews than that, and that his figures were without doubt a misprint for 25,000,000. People told me that they had reasons to suspect that for business reasons, many Jews did not report themselves as Jews. It looks plausible. I am strongly of the opinion that we have an immense Jewish population in America. I am assured by men competent to speak that the Jews are exceedingly active in politics... ("Concerning the Jews," Harper's Monthly Magazine, September 1899)”
4. George Bernard Shaw, the 20th century Irish dramatist:
“This is the real enemy, the invader from the East, the Druze, the riffian, the oriental parasite; in a word the Jew”. (London Morning Post, December 3, 1925)
“This craving for bouquets by Jews is a symptom of racial degeneration. The Jews are worse than my own people. Those Jews who still want to be the chosen race (chosen by the late Lord Balfour) can go to Palestine and stew in their own juice. The rest had better stop being Jews and start being human beings”. (Literary Digest, October 12, 1932)
5. H G Wells, English novelist and historian:
“Zionism is an expression of Jewish refusal to assimilate. If the Jews have suffered, it is because they have regarded themselves as a chosen people”. (The Anatomy of Frustration)
“A careful study of anti-Semitic prejudice and accusations might be of great value to many Jews, who do not adequately realize the irritations they inflict”. (Letter of November 11, 1933)
Can all these people be wrong, and the Jews right? I think not. I hasten to add however, that I am not against Judaism, but only against Zionist Jews, and believe historical accounts given by people whose judgement and veracity I cannot question.
MUSICIANS
There is much interest these days on the effect of music therapy on strokes, and the effect of strokes on the minds of musicians. As for famous musicians who endured them, the two most interesting cases are those of Johann Sebastian Bach, widely regarded as the third greatest composer of history, after Beethoven and Mozart, and Georg Handel, another great German composer.
As for Bach, his “cerebrovascular risk profile included age, obesity, possible hypertension and diabetes that led to his fatal stroke in 1750" (Breitenfeld et al, 2006). The stroke was complicated by pneumonia, presumably, as it usually is in those cases, due to aspiration.
Bach, as we say is thought to be the third of the greatest composers of history, though he preceded and influenced all of them. His ‘Mass In B Minor’ is widely regarded as only second to Beethoven’s ninth symphony as the greatest classical piece ever. His legacy was clear to all, non-musicians and musicians. For example, George Bernard Shaw remarked that, “Bach belongs not to the past, but to the future - perhaps the near future.”
Douglas Adams, author of the ‘Hitchhiker’s Guide To The Galaxy’ wrote, “I don't think a greater genius has walked the earth. Of the 3 great composers Mozart tells us what it's like to be human. Beethoven tells us what it's like to be Beethoven and Bach tells us what it's like to be the universe.” The great German poet Goethe suggested that listening to Bach was “as though eternal harmony were conversing with itself, as it may have happened in God's bosom shortly before He created the world.” The famous American physician and author, Lewis Thomas remarked somewhere about how he reckons the people of Earth should communicate with extraterrestrials, "I would vote for Bach, all of Bach, streamed out into space, over and over again. We would be bragging of course, but it is surely excusable to put the best possible face on at the beginning of such an acquaintance. We can tell the harder truths later." He was a true genius.
As for musicians, the contemporary American composer Michael Torke made the fantastic remark, “Why waste money on psychotherapy when you can listen to the B Minor Mass?” As for the more famous ones, their praise is even greater. Beethoven played a pun on Bach’s name in German, “Not brook but sea should be his name” (“nicht Bach, sondern Meer”). On a visit to Thomasschule, Mozart heard a performance of one of Bach’s pieces and exclaimed, "Now, here is something one can learn from!"; on being given the motets' parts, "Mozart sat down, the parts all around him, held in both hands, on his knees, on the nearest chairs. Forgetting everything else, he did not stand up again until he had looked through all the music of Sebastian Bach". The great French pianist Chopin described Bach as “like an astronomer who, with the help of ciphers, finds the most wonderful stars...Beethoven embraced the universe with the power of his spirit...I do not climb so high. A long time ago I decided that my universe will be the soul and heart of man.” Schumann stated that “music owes as much to Bach as religion to its founder”. Wagner made the greatest claim, that Bach is “the most stupendous miracle in all music”.
Bach was a remarkably religious man, who felt that “music's only purpose should be for the glory of God and the recreation of the human spirit." His music is to this day, heard in Churches all over the world. His religiosity is deeply expressed in his work, as the Wikipedia article on him explains:
“Bach's apparently devout, personal relationship with the Christian God in the Lutheran tradition and the high demand for religious music of his times inevitably placed sacred music at the centre of his repertory; more specifically, the Lutheran chorale hymn tune, the principal musical aspect of the Lutheran service, was the basis of much of his output. He invested the chorale prelude, already a standard set of Lutheran forms, with a more cogent, tightly integrated architecture, in which the intervallic patterns and melodic contours of the tune were typically treated in a dense, contrapuntal lattice against relatively slow-moving, overarching statements of the tune. Bach's theology also informed his compositional structures: Sei Gegrüsset is perhaps the finest example where there is a theme with 11 variations (making 12 movements) that, while still one work, becomes two sets of six—to match Lutheran preaching principles of repetition. At the same time the theological interpretation of 'master' and 11 disciples would not be lost on his contemporary audience. Further, the practical relationship of each variation to the next (in preparing registration and the expected textural changes) seems to show an incredible capacity to preach through the music using the musical forms available at the time.”
As for Handel, he too is regarded as one the top ten composers of all time, being ranked ninth in a recent poll, although the ‘Hallelujah Chorus’ of his masterpiece, ‘The Messiah’, is regarded as the most popular of all classical compositions (whether it is truly the most popular or simply the most well known or imposed (being always played in every Christmas) is a matter of debate. His legacy is celebrated in many places, such as this interesting piece that compares him with Bach:
“Throughout his life Handel avoided the rigorous contrapuntal techniques of his compatriot and exact contemporary Johann Sebastian Bach and achieved his effects through the simplest of means, trusting always his own innate musicianship. The music of both composers, however, sums up the age in which they lived. After them, opera took a different path; the favorite baroque genres of chamber and orchestral music, trio sonata and concerto grosso, were largely abandoned; and the development of the symphony orchestra and the pianoforte led into realms uncharted by the baroque masters. Thus, their influence cannot be found in specific examples. Rather, Handel's legacy lies in the dramatic power and lyrical beauty inherent in all his music. His operas move from the rigid use of conventional schemes toward a more flexible and dramatic treatment of recitative, arioso, aria, and chorus. His ability to build large scenes around a single character was further extended in the dramatic scenas of composers such as Wolfgang Amadeus Mozart and the Italian Gioacchino Rossini. Handel's greatest gift to posterity was undoubtedly the creation of the dramatic oratorio genre, partly out of existing operatic traditions and partly by force of his own musical imagination; without question, the oratorios of both the Austrian composer Joseph Haydn and the German composer Felix Mendelssohn owe a large debt to those of Handel”
In an article, ‘Georg Friedrich Händel’s Strokes’ by Bazner and Hennerici (2005), it was concluded, “that Händel, a man with a probable wide profile of risk factors including systemic hypertension, smoking and most probably hyperlipidemia, had recurrent palsies of his right side (following the available sources involving uniformly his upper extremity), partly with simultaneous speech impairment, either dysarthia as a component of the dysarthria-clumsy-hand-syndrome or dysphasia as a result of embolic middle cerebral artery stroke, which may have been interpreted as confusion. He may well have had a severe stenosis of his left carotid artery with recurrent embolism to the left hemisphere. Since for a certain period of time only his left eye was affected by visual loss, the suspected left carotid artery stenosis may also have been the source for embolic events within the left retina.”
OTHER ARTISTS
In addition to musicians and novelists, the impact of strokes on the creative output of artists is demonstrated in many other types of artist. For example, it was only “when a stroke rendered painting impossible” that the great Italian painter of the Mona Lisa, Leonardo da Vinci stopped and focused on his other artistic passion of designing, until his death on May 2, 1519. Strokes robbed the Arab world of some of its biggest comedian actors, stripping it of a great element of laughter – actors like George Sidhom, Sayyid Zayyan and Younis Shalabi.
SCIENTISTS
I cannot recall reading about any great scientist’s stroke as vividly as I recall that of Louis Pasteur, the great Frenchman, whose life teaches us so much wisdom, and indeed teaches us some interesting aspects about stroke.
Pasteur is arguably the only scientist in history to find his way into every single home in the Western world, into every Western refrigerator – with his invention of the procedure of Pasteurisation – a procedure that must have saved millions of lives. It is this, plus many dozens of other contributions that led David Wood to justifiably state that, “If one were to choose among the greatest benefactors of humanity, Louis Pasteur would certainly rank at the top. He solved the mysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed to the development of the first vaccines. He debunked the widely accepted myth of spontaneous generation... He described the scientific basis for fermentation, wine-making, and the brewing of beer. Pasteur's work gave birth to many branches of science, and he was singlehandedly responsible for some of the most important theoretical concepts and practical applications of modern science...All of these achievements point to singular brilliance and perseverance in Pasteur's nature. His work served as the springboard for branches of science and medicine such as stereochemistry, microbiology, bacteriology, virology, immunology, and molecular biology.”
Pasteur was immortalised in the Oscar winning movie ‘The Story of Louis Pasteur’, and was regarded by Michael Hart as the eleventh most influential person in history. He was a remarkable genius, and there are many excellent biographies describing this genius. What I would like to pay attention to here is two aspects of his life which are highly educational from the perspective of this book.
The first aspect is his great religious zeal, and his great faith in God. Pasteur famously remarked that, "A bit of science distances one from God, but much science nears one to Him; the more I study nature, the more I stand amazed at the work of the Creator." His grandson and first biographer, Vallery-Radot commented that, “Absolute faith in God and in Eternity, and a conviction that the power for good given to us in this world will be continued beyond it, were feelings which pervaded his whole life; the virtues of the gospel had ever been present to him. Full of respect for the form of religion which had been that of his forefathers, he came simply to it and naturally for spiritual help in these last weeks of his life”. To see such a great scientist believe in God, and showing great gratitude to Him, is a sign that He is the truth.
Louis Pasteur suffered his first stroke on October the 19th 1868, at the age of forty-five. He described it saying, “There is a time in every man's life when he looks to his God, when he looks at his life, when he wonders how he will be remembered. It can happen with age or with tragedy or closeness of death. I am lying here at age 45, not able to feel my left side. Not knowing if this stroke that has befallen me will end my life before the mysteries that I have unlocked can be resolved”. His suffering teaches us two main things about stroke. Firstly, that it can happen to every one of all ages – stroke is not just a disease of the elderly, although it is true that age is its biggest risk factor.
Secondly, it teaches us that stroke need not be the end of the contributions of a human being. Some of his greatest work was produced after his stroke, with his election to the Academy of Medicine in 1873, publishing his studies on beer in 1876, and his studies on anthrax in 1877. In 1879, during his studies on chicken cholera, Pasteur discovered how to immunize against disease using weakened bacteria, and in 1880 he began his legendary studies of rabies. In 1885, Joseph Meister, bitten by a rabid dog, was brought to Pasteur who decided to vaccinate him, the first person ever to be vaccinated. After his survival, patients flocked from all over the world to see Pasteur. In 1894, The Pasteur Institute succeeded in producing a vaccine for diphtheria. All this life-saving work was done after Pasteur’s stroke. It all shows that stroke does not necessarily mean the end, and rehabilitation from stroke should always be hoped for and considered.
TYPES OF STROKE
Strokes are divided into two main types – ischaemic and haemorrhagic. There is a division of strokes into TIAs and completed strokes, the difference being duration; TIA – as it says on the tin – are transient attacks, lasting less than 24 hours. The importance of their diagnosis is that by detecting them and treating them, you can avoid their escalation into completed strokes; about 15% of patients who have had a TIA develop a completed stroke at a later stage.
Strokes develop when the blood supply to the part of the brain involved in the stroke is reduced to levels at which the neurons do not meet their minimum blood supply. As usual, the human body has been endowed with protective mechanisms that help in these circumstances, one physiological – the CNS ischaemic response, and one anatomical - the Circle of Willis.
The CNS ischaemic response is explained clearly here by Guyton:
“Most nervous control of blood pressure is achieved by reflexes that originate in the baroreceptors, the chemoreceptors, and the low-pressure receptors, all of which are located in the peripheral circulation outside the brain. However, when blood flow to the vasomotor center in the lower brain stem becomes decreased severely enough to cause nutritional deficiency—that is, to cause cerebral ischemia—the vasoconstrictor and cardioaccelerator neurons in the vasomotor center respond directly to the ischemia and become strongly excited. When this occurs, the systemic arterial pressure often rises to a level as high as the heart can possibly pump. This effect is believed to be caused by failure ofthe slowly flowing blood to carry carbon dioxide away from the brain stem vasomotor center: at low levels of blood flow to the vasomotor center, the local concentration of carbon dioxide increases greatly and has an extremely potent effect in stimulating the sympathetic vasomotor nervous control areas in the brain’s medulla.
It is possible that other factors, such as build up of lactic acid and other acidic substances in the vasomotor center, also contribute to the marked stimulation and elevation in arterial pressure. This arterial pressure elevation in response to cerebral ischemia is known as the central nervous system ischemic response, or simply CNS ischemic response.
The magnitude of the ischemic effect on vasomotor activity is tremendous: it can elevate the mean arterial pressure for as long as 10 minutes sometimes to as high as 250 mm Hg. The degree of sympathetic vasoconstriction caused by intense cerebral ischemia is often so great that some of the peripheral vessels become totally or almost totally occluded. The kidneys, for instance, often entirely cease their production of urine because of renal arteriolar constriction in response to the sympathetic discharge. Therefore, the CNS ischemic response is one of the most powerful of all the activators of the sympathetic vasoconstrictor system.”
This explains why it is advised not to treat hypertension in the case of an ischaemic stroke. It is actually a protective response in the acute scenario.
Without the amazing spider-like structure called the Circle of Willis, the like of which is not present in any other part of the human body, the incidence of strokes will be multiplied manifold. Somehow, the human body knew that neurons are very fragile structures, and they need a persistent blood supply. So it devised this incredible system, which unfortunately been a cause of headache in the vast majority of medical students who are always asked to recall its many branches during their exams! It is a great example of Divine Providence.
So how do strokes occur? The risk factors for stroke are the same as those of ischaemic heart disease (SHIFTMAID) in the case of ischaemic strokes, which account for the majority:
§ Smoking
§ Hypertension / Heart disease (esp. heart failure & atrial fibrillation)/ Hypercoagulability (including polycythemia)/ Hypocoagulability conditions
§ IDDM/NIDDM
§ Family history
§ Triglycerides (cholesterol)
§ Male
§ Age
§ Inactivity
§ Drinking (alcohol)
In addition, heart disease itself, prothrombotic (including polycythaemia) conditions, and a previous CVA predispose to them. In addition, haemorrhagic stroke is predisposed to by any bleeding diathesis (including iatrogenic due to warfarin) and weakening of the blood vessels by the SHIFTMAID. The rupture may be caused by sudden rise in blood pressure. These risk factors take time to cause disease, and hence stroke is usually a disease of the elderly (generally over 50s).
However, if confronted with a young patient with stroke, one must think of the 7Cs, which are:
Cocaine
Cytological (mitochondrial diseases - MELAS)
Consanguinity [familial such as neurofibromatosis and von Hippel-Lindau]
Cardiogenic emboli (e.g. infective endocarditis)
Coagulopathy (e.g. ALASCA, antiphospholipid syndrome, contraceptive)
Congenital heart disease
Cerebral vasculitis (e.g. Moya Moya, carotid/vertebral dissection, vasculitis)
So what does knowledge of SHIFTMAID and stroke teach us? Well, it teaches us that there are multiple factors in the prevention of stroke. You need normal vasculature, blood and blood supply.
The supply of blood is provided by the heart – and hence a normal heart is a prerequisite to the prevention of strokes. If the heart is not working properly, it would naturally fail to pump arterial blood up to the brain. In addition, a failing pump leads to blood stasis in the chambers of the heart, leading to emboli, which can be pumped eventually into the brain, blocking off the arterial supply. This is the same way through which atrial fibrillation can lead to strokes, and why anticoagulation is such an important aspect of its management.
Normal blood is the other precondition to the prevention of stroke. As we all know, blood contains red blood cells, white blood cells, and platelets, clotting factors, other blood proteins and plasma. Defects in any of these will lead to stroke. Defects can be divided into excess, deficiency and function defects.
Excessive red blood cells – namely polycythaemia can cause stroke. This is because of hyperviscosity of blood. This reduces its flow rate, and predisposes to clot formation.
Low levels of red blood cells – namely anaemia can also lead to stroke. This is a logical, although not a commonly mentioned textbook cause of stroke – a typical list goes along the following lines:
If there is not enough blood, highlighted by a low haemoglobin, then clearly the brain is not going to receive the oxygen it needs to function, and therefore it will infarct. A very interesting recent study by Maguire et al (2008) showed that, “More than half of the stroke cases among children without underlying medical illness consisted of children with IDA, suggesting that IDA is a significant risk factor for stroke in otherwise healthy children.” (Association between iron-deficiency anemia and stroke in young children. Maguire J, deVeber G, Parkin PC. Pediatrics 120(5): 1053-7. )
However, one type of anaemia is nearly always mentioned as a cause – namely sickle cell anaemia. The mechanism is due to occlusion of brain vasculature by long-jams of sickled red cells.
A chronic severe excess of leukocytes can lead to stroke by the same hyperviscosity mechanism as polycythemia. (Inoue, 2006). Leukopenia does not lead to stroke.
An excess of platelets (thrombocytosis) can lead to strokes by predisposing to emboli formation. It is important to realise too that any infarction or bleed can cause secondary thrombocytosis. So if you find a high platelet count in a patient who has had a stroke – it may be a cause or consequence. A low level of platelets can lead to all sorts of bleeds, haemorrhagic brain strokes included. This is the same mechanism by which low clotting factors can lead to stroke. The most common reason for this is warfarin use, but other reasons are failure to synthesise clotting factors (e.g. cirrhosis) or to keep them in the circulation (nephrotic syndrome).
An excess of clotting factors (thombophilia) or deficiency of endogenous anticoagulants can lead to stroke by increasing the risk of emboli formation. The prothrombotic conditions are ALASCA:
· Acquired (e.g. smoking, surgery, HRT, OCP, dehydration, malignancy, cancer chemotherapy)
· Leyden (factor V Leyden)
· Antithrombin-III deficiency
· S- and C- protein deficiency
· Antiphospholipid syndrome
The final risk factor for stroke is abnormal vasculature. This is how the majority of strokes occur. The main disease affecting the vessels is atherosclerosis, whose main risk factors are SHIFTMAID. In addition we have the vasculitides, which include Moya Moya disease and carotid arterial dissection.
Knowledge of the above highlights the importance of the normality of the above in most human beings, who are spared the torment of strokes. To that we should be grateful.
Now that we have discussed the causes of stroke, we can discuss its presentation.
THE PRESENTATION OF STROKES
Strokes can present in virtually any mixture of neurological symptoms – weakness, altered sensation, tremor, convulsions, headache, visual, auditory, and speech problems.
To reflect on the presentation of strokes is to reflect on the magnificence of the normal brain. Indeed, our knowledge of the normal brain is based mostly on knowledge of the aftermath of strokes and traumatic head injury, being the most common neurological presentations, if I may call head injury a neurological, rather than surgical condition. Correlating autopsy and more recently, MRI findings to presentations of patients during their life, we have learnt much about the role of different areas of the brain. What such studies have revealed is the specific role of each part of the brain. Although, macroscopically at least, brain tissue appears pretty much homogenous, there are huge differences between different parts. The functions of the different lobes are as follows:
Frontal - associated with reasoning, planning, parts of speech, movement, emotions, and problem solving
Parietal - associated with movement, orientation, recognition, perception of stimuli
Occipital - associated with visual processing
Temporal - associated with perception and recognition of auditory stimuli, memory, and speech
When one reflects on the symptoms that patients present with in stroke, it is hard to not think of the brain as yet another example of intelligent design and part of an outstanding irreducibly complex system.
Stroke is the most common neurological emergency, and, because effective treatment is available that must be started within minutes, most acute neurological presentations should be assumed to be a stroke until proven otherwise by history, exam, or radiographic testing. The diagnosis is often clear from the history and examination, but the following pathologies can also produce a clinical picture that is identical to stroke and should be considered in atypical presentations – namely MICES:
Multiple sclerosis / Migraine (hemiplegic) (typical features of migraine also present, resolving within 24 hours).
Intracranial mass e.g. tumour (history of cancer) or abscess (consider if patient has bronchiectasis or murmur (infective endocarditis)).
Chronic subdural haematoma – consider in elderly and alcoholics
Encephalitis / Epilepsy - Todd's paralysis following a Jacksonian seizure.
Sugar – hypoglycemia mainly
Any patient with a suspected stroke should be assessed with ABCDEFG and MOVE first as large strokes and reduced GCS, or with strokes affecting the tongue and pharynx, can lead to severe airway problems. If hypertensive, do not treat HT (Cushing’s reflex); take a full history, enquiring carefully into all neurological symptoms, and PMH of CV illness. This should be enough to differentiate CVA from other focal lesions (e.g. migraine, fits, and tumour). Consider an urgent CT if suspect intracranial bleeding (headache, on warfarin, history of trauma or falls). Otherwise get CT within 24 hrs.
A basic understanding of brain vascular anatomy is important to understand strokes, as follows:
CLASSIFICATION OF STROKE
Oxfordshire Stroke Subtype Classification uses clinical history and physical exam findings to classify stroke patients into 5 subtypes
675 cases of first-ever stroke encountered over 5 years
Interobserver reliability for classification employing the Oxfordshire system is good
Subtypes are associated with different incidences of medical complications and dependency at discharge:
1. Primary intracerebral hemorrhage (PICH)
2. Total anterior circulation infarct (TACI): 17%, high mortality and poor chance of good functional outcome
3. Partial anterior circulation infarct (PACI): 24%, more likely to have an early recurrent stroke
4. Lacunar infarct (LACI: )25%.
5. Posterior circulation infarct (POCI): 24%, more likely to have a late recurrent stroke but an overall good functional outcome
TACI FEATURES - 3H
· Hemiplegia (contralateral to lesion)
· Homonymous hemianopia
· Higher cortical dysfunction (e.g. dysphasia, dyspraxia, neglect)
- PACI is 2/3 of the above
- LACI is a pure hemimotor or hemisensory loss.
With posterior circulation strokes the main features are of homonymous hemianopia, with macular sparing and brainstem disturbance - 4D:
· Dizziness
· Diplopia
· Dysarthria
· Dysphagia
The presence of dysphasia or Gerstmann’s syndrome suggests dominant parietal lobe involvement
SITES & MANIFESTATIONS OF STROKE
1.Cerebral hemisphere infarcts may be classified by vascular territory:
Anterior cerebral artery infarcts: proximal to the medial striate branch, they cause contralateral hemiplegia; distal to the medial striate branch, they cause contralateral paralysis with sparing of the arm and face.
Middle cerebral artery infarcts: causes contralateral hemiplegia, often sparing the leg, and hemianopia. Aphasia is present if the dominant hemisphere is affected.
Posterior cerebral artery infarcts: causes contralateral hemianopia.
Motor signs are upper motor neuron.
2. Lacunar strokes
Lacunar strokes are due to small areas of infarction usually occurring around the basal ganglia, thalamus, and pons.
Clinical features include pure motor or sensory signs, a mixed motor and sensory picture, ataxia, and dysarthria.
They may also be asymptomatic and found at post-mortem examination.
3. Brainstem infarcts
Clinical features include hemi- or quadriplegia, sensory loss, diplopia, facial weakness and numbness, nystagmus, dysphasia, and coma due to damage to the reticular formation.
The locked-in syndrome results from upper brain-stem infarction. The patient is conscious but unable to respond.
The most common brainstem vascular syndrome is lateral medullary syndrome (Wallenberg's syndrome), which is due to thromboembolism of the posterior inferior cerebellar artery. The patient presents with sudden vertigo and vomiting. Ipsilateral signs include 9th and 10th nerve lesions, Horner's syndrome, spinothalamic sensory loss in the face, diplopia, and cerebellar signs in the limbs. Contralateral signs include spinothalamic sensory loss in the body.
HISTORY
HPC
Either sudden onset or a step-wise progression of symptoms and signs over hours (or even days) is typical. TIA <> 24 hours. The features depend on the vascular territory involved (as above). Note risk factors for stroke. The neurological symptoms that stroke victims may present with include:
1. Weakness
· Determine if in lower face, arms and legs.
· Pure weakness à internal capsule
· A leg weakness à anterior cerebral
· A face, leg AND arm weak à middle cerebral
· Both legs weak à vertobrobasilar (but hemiparesis more common) (Posterior cerebral vasculopathy not associated with weakness)
2. Walking (gait) abnormalities
Patient primarily complain of this because of weakness, but it may also be due to basal ganglia disease, or multi lacunar infarcts (marche a petits pas)
Hemiplegic gait shows the pyramidal pattern of weakness.
Ataxic gait may occur in VB CVA
3. Altered sensation:
Middle cerebral artery supplies the somatosensory cortex; therefore sensory loss occurs only in MCA disease
If pure sensory loss however with no other features, internal capsule (medial lemniscus) infarct likely.
Thalamic infarcts cause hemisensory deficit (PCA supply), but so rare & associated excruciating pain is almost pathognomonic
4. Tremor and involuntary movements
Suggest basal ganglia stroke (i.e. lacunar infarct)
5. Confusion & convulsions
Patient is confused and disorientated in most cases
Rare in ischaemic stroke; more common is haemorrhagic stroke
6. Headache
Common; but if of severe intensity then suggests a haemorrhagic stroke
7. Eye & Ear problems
Visual problems are common, and can only truly be distinguished by physical examination
Amaurosis fugax points to carotid disease
‘like a curtain descending over my field of view’ (OHCM, p.350)
Deafness and/or tinnitus occur in vertebrobasilar strokes (OHCM, p.350).
8. Other
Dysphagia
Incontinence in anterior cerebral occlusion
Consciousness; coma does not occur in early stroke unless severe haemorrhagic; need to differentiate ‘locked-in-syndrome’ (‘pseudocoma’). Reticular strokes do not occur!
Speech (especially articulation and language production) - any dysphasia may occur
PMH
· Previous CVA, IHD or MI
· RF
· DM
· HT
· Congenital heart disease
· Arrhythmias
· Hyperlipidaemia
· Vasculitis
· Connective tissue disease
· Coagulopathies & other blood disease
· Virchow’s triad applies here as it does for DVT (so OCP equally as important)
DH
· Warfarin suggests haemorrhagic stroke
· Cocaine abuse in young patients
· OCP
FH/SH
· Note any FH of stroke or risk factors for stroke
· Smoking
· Alcohol
· Determine occupation and if patient drives; a one month ban applies if normal driver, if HGV and persistent deficit then banned for good.
ROS
· Note particularly the presence of any cardiorespiratory or arteriopathy symptoms
PHYSICAL EXAMINATION
GENERAL
· Acutely unwell patient
· GCS (falls if extensive hemispheric involvement due to cerebral oedema or severe bleed)
· BP may be high as a cause or consequence; a low BP may occur in haemorrhagic stroke
· Tachycardia (stress response, AF)
· Tachypnea (stress, anxiety, aspiration pneumonia, PE)
· Saturations (ensure saturations are above 95% [Witham 2005])
· Pyrexia (if aspiration pneumonia or UTI - common)
· Urine output (catheterise)
OTHER
· Neuro à full higher function, CN, sensory and motor testing
· CVS à JVP raised, xanthelasma, arcus, murmurs, carotids, peripheral pulses, check for DVT (may be difficult). (Fundoscopy done)
· RS à pneumonia
· Abdo à urinary retention
NEUROLOGICAL EXAMINATION IN STROKE
Posture is flexed upper limbs and extended lower limbs (pyramidal weakness); may have clear involuntary movements in lacunar infarcts.
CRANIAL NERVES
I à rarely involved
II à contralateral homonymous hemianopia in anterior circulation; with macular sparing in posterior circulation . Fundoscopy.
III, IV, VI à diplopia, ipsilateral Horner’s in lateral medullary syndrome. Nystagmus.
V à facial sensory loss; brisk jaw jerk in pseudobulbar palsy
VII à facial weakness (differentiate from Bell’s palsy)
VIII à rarely useful
IX & X à lateral medullary infarcts; PBP
XI à not useful
XII à PBP – this is bilateral IX, X, XII lesions
MOTOR
Wasting is not a feature of UMN lesions
Involuntary movements may be seen in basal ganglia infarcts
Initially flaccid hemiplegia; within days becomes spastic
Spastic weakness of pyramidal distribution (weakness greater in extensors than flexors in UL, and vice versa) – reason unclear; myometry has cast doubt on this pattern (Ginsberg, 1999), but remains clinically useful
Incoordination and other cerebellar signs common in posterior circulation CVAs
Reflexes decreased initially, then exaggerated.
Clonus present (>4 beats)
Check pts gait
SENSORY IMPAIRMENT
More for proprioception and light touch, than for pain and temperature
Loss of two-point discrimination
Astereognosis
Extinction
INVESTIGATIONS
4Ps
Plasma – FBC, U&E, ESR, glucose, lipids
Pump – i.e. heart (ECG, echocardiogram)
Pipes – carotid Doppler US
Picture of brain – CT or MRI
DIAGNOSTIC
Stroke is a clinical diagnosis
CT scan done urgently or within 24 hrs to establish mechanism
CAUSE
FBC (e.g. polycythemia. Raised WCC. If HB low and African, consider SCD)
ESR (e.g. IE, vasculitis)
Glucose
Lipids
Blood film in Afrocarribean of unknown sickle status
Blood cultures
Cholesterol
Glucose
VDRL
Coagulation screen
ECG
CXR
Echocardiography (to detect cardiac abnormalities and lung tumours)
Doppler carotids
MRA – this delineates extracranial arterial disease (internal carotid artery dissection must be considered in young patients) and proximal intracranial arteries, and detects thrombosis of major cerebral veins, venous sinuses and aneurysms
CONSEQUENCES
FBC, CXR (pneumonia), blood cultures (e.g. pneumonia, UTI)
Doppler US (legs – for DVT)
Note that large strokes, especially bleeds, can cause ST elevation on ECG and result in a rise in cardiac enzymes. This is often secondary to sympathetic activation, not necessarily to a primary myocardial event.
TREATMENT OF STROKE
Acutely, once ABCDEF & MOVE, and keep patient NBM if swallowing impaired until assessed by speech therapist.
Patients should be admitted to hospital (ideally a stroke unit for initial care and treatment, unless the diagnosis will make no difference to management, e.g. where optimal management is palliative care).
Aspirin (300 mg) should be given as soon as possible after the onset of stroke symptoms once a diagnosis of primary haemorrhage has been excluded. Antiplatelet therapy should then be continued indefinitely. Aspirin should be delayed for 24 hours following thrombolysis.
Anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke.
Unless there are contraindications, thrombolytic treatment appears to be effective in improving prognosis after an acute stroke. Treatment with alteplase should only be given provided that it is administered within three hours of onset of stroke symptoms (unless as part of a clinical trial) and haemorrhage has been definitively excluded.
Bleeds require an urgent neurosurgical opinion
Drugs depressing the function of the central nervous system (e.g. anxiolytics and tranquillisers) and new prescriptions for sedatives should be avoided.
Patients with TIA, or patients with a stroke who have made a good recovery when seen, should be assessed and investigated in a specialist service (e.g. neurovascular clinic) as soon as possible within seven days of the incident.
Conservative and supportive management is the mainstay of treatment subssequently
Treat underlying cause and RF, e.g. AF, hyperlipidaemia, HT, DM, smoking
All blood pressure medications should be held in order to ensure proper brain perfusion. Increases in the ICP sometimes force the systemic blood pressure higher than normal. In the presence of an acute bleed, the ICP should be measured. For ischemic stroke, blood pressure should not be treated unless it is severe (>220 systolic or >120 diastolic). This is often true for up to 2 weeks following acute presentation as well.
If there is a severe internal carotid artery stenosis (of more than 70%) and the patient has had TIAs within the past 6 months, endarterectomy should be considered.
Medical therapy includes aspirin 75 mg od for life. Clopidogrel or dypiridamole if intolerant.
Surgical options are carotid endarterctomy and STA-MCA anastamoses
Multidisciplinary care
Recovery and rehabilitation require an integrated approach between physicians (neurologists or geriatricians), nurses, dieticians (nasogastric feeding in 24-48 hours if bulbar function compromised), physiotherapists, OTs, and social workers
Stroke units improve outcome relative to general ward
PSYCHOLOGICAL ISSUES IN STROKE
Reaction to illness (depression in >30%)
Financial status and occupation assessment
Disability insurance (pt may be worried about how family will cope financially)
Emotional lability explanation to family so that they do not feel responsible for pts reactions
SPEECH THERAPIST ROLE
Need to distinguish from depression
Facial muscle exercises
Communication, repetition, patience and positive reinforcement
Communication board if Broca’s aphasia
Speech pathologist may be involved if very severe (?)
OCCUPATIONAL THERAPY ROLE
Assesses requirement for and arranging provision of various aids and modifications in the home
Done before discharge from hospital
Stair rails, hoists, wheelchairs, antiskid patches in bathtub
Free home of scatter rugs or other obstacles in walking pathways
PHYSIOTHERAPIST ROLE
Especially useful in first few months
Reduce spasticity
Relieve contractures
Walking aids
STROKE UNIT NURSE
Ties everything together
Intermittent catheterisation
Bladder training program – patient offered urinal, or put on commode every 2 hrs
Bowel training program
Encourage dietary fibre and fluid intake of >2L/day to avoid constipation
Apple or prune juice may help
DISCHARGE PLAN
To home, rehabilitation centre, long-term care facility (e.g. nursing home)
Ensure OT recommendations in place and pt understands them
Educate patient about drugs and schedule
Ensure pt confident in safely climbing stairs, transfer from chair to bed, etc
Family education
Provide information leaflets and details of support groups (e.g. NSF)
Ø Adaptive devices in place & understood
Ø Bowel and Bladder control
Ø Communication possible
Ø Dietary advice
Ø Eats without choking or aspiration
Ø Family support
PROGNOSIS IN STROKE
10% dead in 1 month
50 % survivors disabled
10 % recurrence in 1 yr
This disease is a serial killer, being the third commonest cause of death and the biggest cause of serious physical disability in the Western world. It is any focal CNS disturbance due to a vascular cause where the deficit persists.
The first question that can be raised regarded something so deadly, is why it carries such a gentle name, can mean ‘an inspired or effective idea or act’ or even to caress. The etymology of the term was explained by Dirckx (1986) as follows, “According to the Oxford English Dictionary, a sudden, inexplicable cerebrovascular accident was first likened to a "stroke of God's hand" in 1599. The relationship of a cerebral infarction to an act of God exists in other cultures as well: the Greek verb plesso means to "stroke, hit, or beat," and the derivative plegia gives us our term hemiplegia.”
The epidemiology of stroke, although certainly a subject of great importance has not really been studied in the depth it deserves. What is established however is that although from 1950 to 1980 the incidence of stroke was on the fall, an effect attributed to increasing awareness, detection and treatment of hypertension, the biggest risk factor for stroke other than ageing, there has been a gradual increase since 1980 (Robinson, 2007), attributed to “the adoption of less healthy lifestyles” (Davidsons, 2005). However, because of improving management of the condition, perhaps most importantly due to the development of the concept of the stroke unit, morbidity and mortality from the condition is falling.
Cerebrovascular accident is a sudden onset of a focal neurological deficit lasting >24 h= stroke; <24 h = TIA. It is the 3rd most common cause of death, and the biggest cause of serious physical disability. It costs the NHS £2.3 billion a year (2 x CAD). The epidemiology is:
Incidence is 2/1000/yr
Occurred in 8/1000 population
> 50 years mainly
Preceded by TIA in 15% pts
> 50% are physically dependent on others 6 mths after
The International Stroke Trial “highlighted that the UK centres had the poorest survival from stroke in the world” (Newson & Patel, 2002)
A HISTORY OF STROKE
There are great difficulties in understanding the history of stroke. This is because it is difficult to really ascertain whether many of the descriptions given are truly those of stroke, or other conditions causing focal neurological deficits like epilepsy. Apoplexy, the old term for stroke simply means ‘struck down with violence,’ and the word stroke was used as a synonym for apoplectic seizure as early as 1599. Nevertheless, we can probably share the view expressed by Thompson in his Willis Lectures in 1999, where he said that, “With the advent of Hippocrates (460 to 370 BC), ancient descriptive neurology was born. It was known that paralysis and convulsions followed injuries to the brain, with paralysis on the opposite side to the wound. Hippocrates described paralysis of the right arm with loss of speech in what is probably the first written description of aphasia. In one of his aphorisms Hippocrates stated, "Unaccustomed attacks of numbness and anesthesia are signs of impending apoplexy," a description of a TIA”.
Without a CT-scan, we would really be unable to identify if what historians regard as stroke is truly stroke or not. But if we are to go by tradition, which classifies stroke as a clinical diagnosis, then all acute neurological presentations of history, pre-CT must be regarded as stroke.
With regards to the famous victims of stroke, being such a common condition, it has claimed victims in every province of human enterprise. No one is spared – young or old, male or female, of all colours and races. But we shall focus on a few interesting cases which teach us something about this fascinating condition.
In an imaginary political graveyard, where the world leaders of the 20th century are laid to ‘rest’, would very interestingly, have a great proportion of victims of stroke. There are no formal reports or papers on the association of stroke and politics, but it would make for interesting reading.
POLITICIANS
RUSSIA
We have already looked at the fates of three of Russia’s former leaders in our reflections on hypertension, namely Lenin, Trotsky and Stalin. We only briefly mentioned Lenin there, stating that his hypertension diagnosis is rather uncertain. But we he certainly had, based on a detailed autopsy report, is a stroke, due to “haemorrhage over the corpora quadrigemina area of the brain, and it was stressed that most of the very severe brain damage must have been present for some time before death” (Leavesly, 1998).
Lenin’s case is interesting for three reasons. Firstly, the manner of his death. As everyone now knows, he was a very evil man, who is responsible for the deaths of nearly 4 million people, according to the ‘Black Book of Communism’, all in the name of communism. He was a faithless man, who believed that “the end justifies the means”, that “there are no morals in politics; there is only expedience. A scoundrel may be of use to us just because he is a scoundrel”, that, “We need the real, nation-wide terror which reinvigorates the country and through which the Great French Revolution achieved glory” and that the communist “program necessarily includes the propaganda of atheism”, and felt that “liberty is precious - so precious that it must be rationed”. Is it surprising that a man of such evil dies should die the humiliating death he did? Perhaps the best description anyone has made of him is Bertrand Russell, who met him personally in 1920, and described the encounter in his ‘Autobiography’ as follows:
“Lenin, with whom I had an hour’s conversation, rather disappointed me. I do not think that I should have guessed him to be a great man, but in the course of our conversation I was chiefly conscious of his intellectual limitations, and his rather narrow Marxian orthodoxy, as well as a distinct vein of impish cruelty”
Under the heading, ‘Lenin’s End is a Lesson for All’ in his book, ‘Communism in Ambush’, Harun Yahya put the above picture and the following caption, which says more than a thousand words, “Before he died, Lenin became mad. This photograph, taken shortly before his death, teaches an example of the torment God sends in this world upon leaders of irreligion. This end is announced in Verse 30:10 of the Qur'an: "Then the final fate of those who did evil will be the Worst because they denied God's Signs and mocked at them."…he suffered his first stroke in May 1922. On December 16, 1922, he suffered another major attack. Half paralyzed, he was confined to bed. In March of 1923, his illness worsened significantly and he lost the ability to speak. Afflicted by terrible headaches, he spent most of 1923 in a wheelchair. In the final months of his life, those who saw him were horrified at the frightful, half-mad expression on his face. He died of a brain hemorrhage on January 21, 1924.”
The second interesting lesson that Lenin’s stroke teaches us is that it highlights the difficulties inherent in the diagnosis of stroke in pre-CT days. Apparently, only eight out of the 27 physicians looking after Lenin believed that he died of a stroke. But the post-mortem is pretty conclusive. Our suggestion in the hypertension chapter that Lenin had a hypertension-induced stroke is based purely on epidemiological suspicions. However, it is possible that he had another cause – namely syphilis. Learning about Lenin’s case teaches us about this often forgotten cause of stroke, which is generally not mentioned in most medical books, but is always cited in the biggest books. We read in Adams and Victor’s ‘Principles of Neurology’ that, “Whereas in the past strokes accounted for only 10 percent of neurosyphilitic syndromes, their frequency is now estimated to be 35 percent. The most common time of occurrence of meningovascular syphilis is 6 to 7 years after the original infection, but it may be as early as 9 months or as late as 10 to 12 years”. The following table from Harrison’s also lists it among the causes of ischaemic stroke.
The possibility that Lenin had neurosyphillis was raised and extensively discussed in an article, ‘The Enigma of Lenin's Malady’ (Eur J Neurol. 2004 Jun;11(6):371-6) by Lerner, Finkelstein and Witztum. We will discuss this at greater length in our discussion of syphilis in our infectious diseases section. But it is a very interesting possibility.
Another interesting informative Russian stroke case is that of the wife of the last leader of the USSR, Mikhail Gorbachev, Mrs. Raisa Gorbachev. She suffered from leukaemia, but died following a stroke in 1999. Knowing this will help recall leukaemia, and indeed chemotherapy, as a risk factor for stroke; both lead to a hypercoagulable state which like we saw in the DVT section, leads to vascular thrombosis.
USA
As opposed to Russian leaders, who hide much of their health data, the American leaders are a lot more open, and conform much more to the contemporary requirement for accountability. Hence we have a lot more data regarding their illnesses.
Many American presidents sustained strokes – including John Adams, John Tyler, Woodrow Wilson, Eisenhower, Richard Nixon and Gerald Ford. We will only focus on what I feel are the more interesting cases here.
Woodrow Wilson was the man who led the USA during the First World War, and who is famous for setting up the ‘League of Nations’, the immediate precursor of the United Nations, and was awarded the Nobel Peace Prize in 1919 “in recognition of his Fourteen Points peace program and his work in achieving inclusion of the Covenant of the League of Nations in the 1919 Treaty of Versailles”. His fascinating medical history is recounted extensively by Edwin Weinstein in ‘Woodrow Wilson: A Medical and Psychological Biography’. John Sotos, a cardiologist and America's leading Presidential health historian and an expert in unusual signs of disease summarised many of the points made by Weinstein in his Doctorzebra website:
“Wilson's first stroke was in May 1896. It caused marked weakness of the right upper limb plus sensory disturbances in the fingers. The finger problems were mis-diagnosed as neuritis. Wilson was unable to write normally for almost a year afterwards.
In June 1904 Wilson developed weakness in the right upper limb that lasted for several months. On May 28, 1906, Wilson suddenly lost vision in his left eye. This persisted. Weakness of the right upper limb was present. In November 1907 he developed weakness and numbness of fingers or right upper limb that lasted several months; in July 1908 he had two attacks of "neuritis" affecting the right upper limb; in December 1910 he had transitory weakness of the right hand. Wilson's problems with blood circulation in his brain and eyes continued after he became President: April 1913 - Attack of "neuritis" involving right upper limb; May 1914 - Abnormal retinal arteries observed; May-Sept. 1915 - Episodes of transient weakness in his right hand. From 1915 to 1919 Wilson had episodic severe headaches, lasting for days. It is possible these were due to [uncontrolled] hypertension. In September 1919 Wilson was having severe headaches, double vision, and signs of a weakened heart. On Sept. 25 he developed a transitory weakness on the left side of his body. Wilson suffered a catastrophic, disabling stroke while President (Oct. 3, 1919), as recounted in multiple sources, including an entire book on the subject. (Any biography covering Wilson's presidential years should devote extensive coverage to this event.) This was the most serious illness suffered by any sitting President. Wilson had bad headaches before becoming president, but presidential physician Cary Grayson ascribed the stroke to a thrombosis, stating it was not hemorrhagic”.
Aside from his multiple strokes, I will take this occasion to go through one of Woodrow Wilson’s little known political contributions - The King-Crane Commission’s report. This is how Ron David, the Jewish author of ‘Arabs and Israel For Beginners’ summarised it in that absolutely splendid book:
“When WW-I ended, no one could reconcile the claims of Arabs, Zionists, British & French so, in 1919, Woodrow Wilson and his democracy-mad Americans "dispatched the King-Crane Commission to the former Arab provinces of the Ottoman Empire to ascertain the wishes of their inhabitants regarding the postwar settlement of their territories." [Britannica]
The King-Crane report stated:
90% of Palestine's inhabitants were non Jewish & did NOT want a Jewish state in Palestine;
If they are given Palestine, "Zionists looked forward to a practically complete dispossession of the present non-Jewish inhabitants."
The King-Crane Commission said that a Jewish state in Palestine would violate the Palestinian Arabs' right to self-determination. They recommended that Zionists respect the wishes of Palestine's inhabitants & find another place to plant the Jewish state.
The Zionists were furious! They didn’t want democracy; they didn’t give a damn about “the will of the people.” The Zionists wanted Palestine, no matter what they had to do to get it. So they simply “rewrote” the history of the conflict.
The usual versions of Israel's history either don't mention The King-Crane Commission Report or they minimize its importance. In my opinion, any lover of democracy must consider the King-Crane Commission’s report a major event. Anyone who believes in Democracy must consider the King-Crane Commission's official report—which even now can be documented by any interested partyment agency—irrefutable proof that:
In 1919, even after 30 years of iintensive Jewish emigration into Palestine (inspired by Theodore Herzl’s The Jewish State, published in 1898), 90% of Palestine’s inhabitants were non-Jewish and did not want a Jewish state in Palestine. The will of the people was clear
The Zionists knew they were acting against the will of the people.
The Zionists knowingly subverted Democracy.
The Government of the United States confirmed the legitimacy of the claim that Palestinians make today
Some Quotes from the Commission's Report
"a national home for the Jewish people is not equivalent to making Palestine into a Jewish State."
"nor can the erection of such a Jewish State be accomplished without the gravest trespass upon the civil and religious rights of existing non-Jewish communities in Palestine."
"In his address of July 4, 11918, President Wilson laid down the following principle as one of the four great 'ends for which the associated peoples of the world were fighting': 'The settlement of every question, whether of territory or of political relationship upon the basis of the free acceptance of that settlement by the people immediately concerned, and not upon the basis of the material interest or advantage of any other nation or people which may desire a different settlement for their own exterior influence or mastery."
"If that principle is to rule, and so the wishes of Palestine's population are to be decisive as to what is to be done to Palestine, then it is to be remembered that the non-Jewish population of Palestine—nearly nine-tenths of the whole—are emphatically against the entire Zionist program. To subject a people so minded to unlimited Jewish immigration, and to steady financial and social pressure to surrender the land, would be a gross violation of the principles just quoted, and of the peoples' rights, though it kept within the forms of the law."
"No British officer, consulted by the Commissioners, believed that the Zionist program could be carried out except by force of arms."
"That of itself is evidence of a strong sense of injustice of the Zionist program.”
"The fact came out repeatedly in the Commission's conference with Jewish representatives that the Zionists looked forward to a practically complete dispossession of the present non-Jewish inhabitants of Palestine.''
“The initial claim, often submitted by Zionist representatives, that they have a 'right' to Palestine, based on an occupation of two thousand years ago, can hardly be seriously considered."
The full report can be found on the internet, and makes for even more fascinating reading. I cannot agree more with Ron David, that the report is a major event that should be more widely known.
The other interesting case of stroke among the American presidents is that of Gerald Ford. His story reveals an interesting cause of stroke, a tongue abscess. This is how Tasos summarises things,
“During the 2000 Republican National Convention in Philadelphia, Ford appeared "sluggish and sick" on television during a tribute to him. A few hours later, shortly after midnight on Wednesday, August 2, Ford presented to the emergency room at Hahnemann University Hospital, complaining of facial pain. The physician diagnosis was "a sinus attack." Ford stayed only a half-hour, and declined the recommendation to have a CT scan. Upon awakening on Wednesday morning, Ford had new symptoms and returned to the hospital. He apparently had left arm weakness, balance difficulties, and slurred speech. A stroke was diagnosed and he was treated with "blood thinners". The slurred speech, however, was ascribed to a swollen, painful tongue, which proved to be abscessed with actinomycosis. (This is an exceedingly rare cause of a tongue abscess.) The abscess was drained under general anesthesia. (It is not clear when the anticoagulants were started, in relation to the abscess drainage.) Later, a Ford spokesman declared that Ford had developed tongue pain while in Colorado, before Ford departing for the convention. By August 5 Ford was "completely recovered from the stroke" (there were also questions about a possible other strokes). He left the hospital on August 9, still taking antibiotics and blood thinners. The Hahnemann University Hospital was obviously embarassed by missing the diagnosis on the first night, but refused to admit anything. A hospital spokesman said "We do not believe there was any misdiagnosis there." He then shamelessly shifted the blame to the patient, saying "The activities that evening were totally controlled by the President". The question is: how could the abscess have been missed on physical examination the first night, especially when Ford had noted tongue pain days earlier? How did the physician(s) arrive at the mistaken diagnosis of a sinus problem? A CT scan is usually not required to discover a tongue abscess. It is possible that missing the tongue abscess the first night played a role in causing the stroke, as there is a tight relationship between inflammation and acute vascular events. In simple terms, inflammation (the classic response to an infection) makes the blood more likely to clot (the actual event triggering a stroke). Older physicians, for example, will recall the classic association between pneumonia and acute myocardial infarction. In Ford's case, the missed diagnosis allowed the infection, hence the inflammation, to progress for the extra few hours leading to the stroke.” In any case, Ford was to die of stroke many years later, in 2006, at the age of 93, completely unrelated to his first far more interesting one.
ENGLAND
Although many British leaders suffered strokes, including most recently Princess Margaret, who died of a massive stroke on the 9th of February 2002, and Baroness Margaret Thatcher, which has affected the Iron Lady tremendously; apparently she has no short term memory now.
But of far more interest and importance are the strokes of Sir Winston Churchill. In an article entitled ‘Was Winston Churchill Fit to Rule?’, George Biro argues that Churchill failed miserably with regard to his duties as a prime minister by hiding away the fact that he had several major strokes while leading the nation. He argued that, “Should not have Moran (Churchill’s personal doctor) have balanced the duty to his patient against the interests of the country? Could he have induced Churchill to step down earlier? Could anyone else have done so? If we make pilots and bus drivers pass medical examinations, why don’t we do the same for politicians?” We all know, as doctors, confidentiality is important, is part of the basic right to autonomy. But if maintaining confidentiality will impinge on the health and safety of others, the principle can be broken.
Churchill was certainly not a sane man. He was renowned for his bouts of severe depression, his ‘black dog’, and many people have labelled him a cyclothyme. In ‘Encounters with Winston Churchill’, W Russell Brain, the great neurologist of the 20th century said, “I should think that from what Moran told me that Churchill is a cyclothyme. Apparently he was subject to depression in his earlier days. He has the drive and vitality and youthfulness of a cyclothyme.” (Medical History, 2000, 44: 3-20). A man no less than the great psychiatrist Anthony Storr devoted a whole book to the issue, entitled, ‘Churchill’s Black Dog’. He argued that, "Had he been a stable and equable man, he could never have inspired the nation. In 1940, when all the odds were against Britain, a leader of sober judgment might well have concluded that we were finished." He also said, "The kind of inspiration with which Churchill sustained the nation is not based on judgment, but on an irrational conviction independent of factual reality. Only a man convinced that he had a heroic mission, who believed that, in spite of all evidence to the contrary, he could yet triumph, and who could identify himself with a nation's destiny could have conveyed his inspiration to others." We will leave the discussion of whether people with chronic psychiatric illness should be allowed to lead nations to our psychiatry section.
But as for those with acute confusional states, the answer must be a definite no, until he or she recovers fully from it. In 1944, following several attacks of pneumonia, Allanbrooke, Chief of the Imperial General Staff stated, “He seems quite incapable of concentrating for a few minutes on end, and keeps wandering continuously”. In 1952, “Churchill had a more serious stroke affecting his speech. By now he insisted on even the most complex issues being condensed into one paragraph before he would consider them. Moreover, the Prime Minister often could not even follow a discussion. Moran wrote, “He was not doing his work. He did not want to be bothered by anything; he was living in the past””.
But rather than advise Churchill to resign, Moran did the opposite. He said, “Winston once asked me whether he ought to have retired earlier. I was, I think, alone in urging him to hang on, though I knew that he was hardly up to his job for at least a year before he resigned office. His family and friends pressed him to retire; they feared that he might do something which would injure his reputation. I held that this was none of my business. I knew that he would feel that life was over when he resigned. It was my job as his doctor to postpone that day as long as I could”.
Biro continues, “But somehow, the wilful, wily old man defied such opinions, and carried on the pretence: instead of dealing with matters of state, Churchill read novels and played cards…In 1954, he had to apologise after misleading the Commons (and jeopardising the government’s foreign policy) about a telegram he claimed to have sent to Field-Marshal Montgomery during the war. There was no such telegram; by now even the Conservatives had had enough. But it was April 1955 before the Prime Minister finally stepped down. By then, he was spending most of his days in bed.” Reflecting on this, I feel Russell Brain is deeply mistaken in his reflections on Churchill, that between in 1949 and 1964, Churchill was “fit enough to go to the House of Commons”. However, his description of his stroke has not been bettered:
“I found that Churchill had had a stroke. He had been feeling very tired lately on account of the Coronation and of having to do the work of the Foreign Secretary as well as his own on account of Eden's illness. The previous morning Moran had been to see him to pay a routine visit and thought his speech was somewhat slurred. In the evening, he had presided over a dinner for the Italian Premier, at the end of which he had made a speech, and again his speech was somewhat slurred, and he became unsteady on his legs, and had to be assisted out of the room. He had a good night and on the morning of June 24th, Moran saw him again, and found his speech still slurred. He presided over a Cabinet Meeting, however, which lasted two hours. He felt very tired, and his slurring speech was noticed by his colleagues. He slept in the afternoon and his secretary mentioned that she thought there was some drooping of the left side of his face. This was apparent when he spoke and also when he smiled, and his speech was at first somewhat slurred, but there was at no time any evidence of aphasia. There was slight weakness of the left lower face on voluntary and emotional movement, and his tongue deviated slightly to the left. There was no weakness of the limbs, and no change in sensation, but the left plantar reflex was extensor while the right was flexor. He walked about the room with only a slight trace of unsteadiness. He said he had no headache but felt as though there was something in his head. He was put on a dose of trinitrin night and morning.”
Winston Churchill illustrates several risk factors for stroke – he was overweight, probably obese, a heavy drinker ("Alcohol has been a very good friend to me…I like to take a fair proportion of my calories in the alcohol"), and famously a chain smoker. He smoked about ten cigars a day. One of his interesting stories regarding these two things was told in his memoirs, regarding a meeting he had in February 1945 in honour of King Ibn Sa'ud of Saudi Arabia, "A number of social problems arose. I had been told that neither smoking nor alcoholic beverages were allowed in the Royal Presence. As I was the host at the luncheon I raised the matter at once, and said to the interpreter that if it was the religion of His Majesty to deprive himself of smoking and alcohol I must point out that my rule of life prescribed as an absolutely sacred rite smoking cigars and also the drinking of alcohol before, after and if need be during all meals and in the intervals between them. The King graciously accepted the position." (One is immediately reminded here of the famous hadith, reported on the Prophet (PBUH), "Whoever believes in Allah and the Last Day must not sit at table at which khamr is consumed.") Surprisingly, Churchill, according to the website of his name, had “a normal blood pressure for his age”.
ISRAEL
Moving on swiftly from ‘The Last Romantic Zionist Gentile’, as Yoav Tenembaum described Churchill (he is clearly unaware of Churchill’s Jewish ancestry and his Jewish mother, Jenny Jacobson), let us look at some interesting cases from Israel.
We have already discussed the case of Ariel Sharon in our reflections on congenital heart disease. His is actually a fascinating one, because it illustrates a very rare risk factor for stroke – paradoxical embolism.
The case of David Ben-Gurion, the first Prime Minister of Israel, is a lot less interesting, but he endured the same fate. This is how his biographer Bar Zohar somewhat dramatically depicted it,
“In 1973 Ben-Gurion suffered a massive stroke. I hurried to the hospital where he was lying and was let into a quiet, white room. Ben-Gurion was lying quietly in his bed. He couldn't speak, he just looked at me with his deep, wise eyes. He communicated with me by tightening his grip on my hand. I was looking at the quiet, calm face of the father of my nation, the man who made me and so many homeless Jews a people again; and I thought of his moral testament to all of us. "The existence of Israel," he told me over and over again, "depends on her force - and on her righteousness. We must be a light into the nations." I had never met another statesman or political leader for whom moral values were so important, who believed that his nation will have the right to exist only if it sticks to those moral percepts, given to us all, Jews and Christians and Muslims, in the Bible. I don't know if we have succeeded to accomplish this moral commandment of Israel's Old Man. But I see it as a call to my generation and those who will come after me - to try to build a country worthy of the teachings of Israel's ancient prophets.”
The sheer deception and hypocrisy of this statement, highlights a high degree of confusion in Ben-Gurion’s mind, as it contradicts a lot of what he said and believed. But then again, Ben Gurion is a politician, and there are hardly any politicians out who have clarity and consistency of thought. Politicians are not mathematicians or scientists. They are not concerned with truth, but power and control, no matter by what means these are achieved. The classic recent example is that of the crimes of George W. Bush and Tony Blair in Iraq. Bertrand Russell brilliantly summed it all up, “I am persuaded that there is absolutely no limit in the absurdities that can, by government action, come to be generally believed. Give me an adequate army, with power to provide it with more pay and better food than falls to the lot of the average man, and I will undertake, within thirty years, to make the majority of the population believe that two and two are three, that water freezes when it gets hot and boils when it gets cold, or any other nonsense that might seem to serve the interest of the State…Politics is largely governed by sententious platitudes which are devoid of truth.”
Ben-Gurion was not the romantic that Bar-Zohar is trying to depict. He is not “part Washington, part Moses”, as Amos Oz was foolishly telling us in his article on Ben-Gurion in ‘Time Magazine's’ ‘100 Most Important People of the Century’. For one, both Moses and Washington believed in God, and Ben-Gurion, a Russian in origin, was an atheist, like so many other Zionist leaders, including the founding father of Zionism, Theodor Hertzl. As stated by Alfred Mendes, “The State of Israel was … set up in 1948 by the Zionists, under the leadership of the Russian-born David Ben-Gurion (another atheist) who had emigrated to Palestine in 1906. The very term ‘atheist’ means disbelief in any ‘God’ and/or ‘religion’. Hence, an atheist cannot consider him/herself a Jew in the strictly religious sense of the term. To quote Rabbi E. Weissfish: “The Zionist ideology has no connection whatsoever with Judaism, on the contrary Judaism is totally opposed to Zionism”. It is thus incontrovertible that the two terms ‘Judaism’ and ‘Atheism’ are antonymous, a fact that Ben Gurion would certainly have been aware of - but here we have Ben Gurion himself, in his address to a special session of the Knesset in 1971, saying “An Arab can be Muslim or Christian. A Jew, however, cannot be a member of another faith and still be a Jew. A Jew can be an atheist, but if he adopts the Christian or Muslim faith - he is no longer a Jew”. This was clearly a duplicitous statement on his part, and, as such, therefore designed to confuse and divert attention from some hidden agenda”.
Moses and Washington were not racists, while Ben Gurion was. He “never believed in the possibility of coexistence with the Arabs. The fewer Arabs there were within the borders of the future state of Israel, the better it would be. He did not say so explicitly, but the overall impression one gets from his speeches and his comments is clear: a major offensive against the Arabs would not only defeat their attacks but would also reduce as far as possible the percentage of the Arab population within the State. "He can be accused of racism, but then one will have to put on trial the entire Zionist movement, which is founded on the principle of a purely Jewish entity in Palestine."” He also, according to his official biographer Shabtai Tebeth, “advocated exclusively Jewish labor (Avodah Ivrit) in Jewish businesses. He explained why a Jewish laborer should earn a higher salary because "[he was] more intelligent and diligent" than the Arab.” His racism extended, of course to destruction of all Arabs, both within Palestine and outside.
Within Palestine, Israeli historian Simha Flapan exposed him, saying, “That Ben-Gurion’s ultimate aim was to evacuate as much of the Arab population as possible from the Jewish state can hardly be doubted, if only from the variety of means he employed to achieve his purpose...most decisively, the destruction of whole villages and the eviction of their inhabitants...even [if] they had not participated in the war and had stayed in Israel hoping to live in peace and equality, as promised in the Declaration of Independence.”
Outside of it, two examples suffice to expose Ben-Gurion, one from Egypt, the other from Lebanon. He was exposed in Egypt after the famous Lavon affair. Ron David summarised this beautifully, exposing him fully, “Around the time that Gamal Abdul Nasser became Egypt’s leader, David Ben Gurion had decided (partly out of spite) to step down as Prime Minister of Israel and let Moshe Sharett see if he could do a better job. Sharett was less of a ‘Hawk’ than Ben Gurion and, by 1954, had reached the point where he was on the verge of signing a peace treaty with Nasser of Egypt. Nasser is usually depicted as one of the bad guys. Recently declassified State Department documents indicate the exact opposite. Documentary evidence [1948-54] shows Nasser expressing tolerance and respect for Israel to CIA officials, members of British Parliament, and two American Ambassadors. In October 1954 Nasser became one of the only heads of state to refuse military aid from the U.S. He preferred economic aid. Then, in 1954, Israeli terrorists attacked American installations in Egypt! Then the Israelis rigged it so the attacks would be blamed on Egyptians! Then the Israelis got caught and put in Egyptian prisons....all of which convinced Egypt’s Nasser that the Israelis couldn’t be trusted, so he broke off the peace talks and took weapons from whomever offered them—including the Soviets. Ben Gurion blamed the blundering terrorists on his Defense Minister, Pinchas Lavon—but several years later, Lavon found documents that proved Ben Gurion was behind it! Ben Gurion’s motive was simple: he and Moshe Dayan wanted a war with Egypt and Sharett’s peace talks might deprive them of it. In June 1955, Moshe Sharett [in his Diaries] wrote: ‘Dayan said, “above all, let us hope for a new war with the Arab countries, so that we may finally get rid of our troubles and acquire space.”’ Another of Sharett’s Diary entries for June 1955: ‘Ben Gurion himself said it would be worthwhile to pay an Arab a million pounds to start a war. What a slip of the tongue!’”
His crimes in Lebanon are also summarised by Ron David in his aforementioned book, “In 1954, former Prime Minister Ben Gurion mentioned to Prime Minister Moshe Sharett that it would be in Israel's interest to provoke a Civil War in Lebanon between Christians and Muslims. On May 16, 1955, Ben Gurion got more specific: he said that Israel should provoke Lebanon's Muslims to attack Lebanon's Christians in the hope of igniting a Civil War in Lebanon. Prime Minister Sharett (whose published Diary details this) was shocked.”
Most fundamentally (apart from the obvious difference of theological beliefs), Moses (PBUH) was the saviour of the people of the People of Israel, the man who gave them a moral and religious foundation, while Ben-Gurion lacked morals, and at times was the anti-Saviour of the Jewish people. His only obsession was the creation of the state of Israel, at all costs, even if it meant the destruction of world Jewry. Did he not say, "The Zionist's task is not to save the "rest" of Israel which finds itself in Europe, but to save the land of Israel for the Jewish people"? Was he not involved, in the murder of many Jews throughout his life. To quote his official biographers yet again, “In 1940, to arouse indignation against the English, who had decided to save the Jews threatened by Hitler by taking them to Mauritius, the Zionist leaders of the "Hagannah" (led by Ben Gurion) did not hesitate to blow up the ship when it called at Haifa on December 25th 1940, causing the death of 252 Jews and English crew-members.” (Dr. Herzl Rosenblum, director of "Yediot Aahronot", revelation made in 1958 and justified in "Jewish Newsletter", N.Y.,November 1958). Did he not famously say, "If I knew it was possible to save all the children in Germany by taking them to England, and only half of the children by taking them to Eretz Israel, I would choose the second solution. For we must take into account not only the lives of these children but also the history of the people of Israel"? How could a man of any morals praise the actions of Adolf Hitler - "Jewish suffering is also a political factor, and whoever says that Hitler diminished our strength, is not telling the truth." In one of history's crueller ironies, those words proved prophetic. Millions of Jews did not storm the beaches of Palestine, for they could not rise from the ashes of the death camps. But the Holocaust--they zenith of Jewish agony-- became the same "political force" of which Ben-Gurion spoke before he even imagined the systematic destruction of European Jewry. After the war, the Holocaust was a powerfully influential factor in turning world public in Zionism's favor, and was the decisive factor in defeating the policy of the British 1939 White Paper (which called for a united bi-national Palestinian state no later than 1949 and the cessation of Jewish immigration). Guilt, sorrow, and remorse---what might be called the collective conscience of humanity--led many nations (referring to 1947 UN proposed partition plan) finally to grant survivors, that which might have saved the many victims: a "Jewish state."” (Shabtai Teveth, p. 196).
The Israeli historian, Tom Segev, in his book ‘The Seventh Million’ exposed Ben-Gurion too, saying that, “In the wake of the Kristallnacht pogroms, Ben-Gurion commented that ‘the human conscience’ might bring various countries to open their doors to Jewish refugees from Germany. He saw this as a threat and warned: ‘Zionism is in danger.’”. How could anyone regard this evil man as a Prophet, the highest accolade that can be bestowed on a man?
What puzzles me about Ben-Gurion is that, as evil as he is; he did say many truthful things throughout his political career. Perhaps it is one of the characteristics of the hypocritical mind that it often exposes itself under close scrutiny, where the power to withhold the truth is overwhelmed by the power of truth itself. It is one of the ironies of history that one could easily quote the creator of Israel to support the Palestinian cause, and oppose the falsities of other Zionist politicians!
For example, in response to Golda Meir’s famous statement, “It was not as though there was a Palestinian people in Palestine considering itself as a Palestinian people and we came and threw them out and took their country away from them. They did not exist”, Ben-Gurion defends us saying, “Palestine is not an empty country” and "The Arab community in Palestine is an organic, inseparable part of the landscape. It is embedded in the country.” In response to the eternal question – who is the true criminal, Ben Gurion has the true answer, "When we say that the Arabs are the aggressors and we defend ourselves - that is only half the truth. As regards our security and life we defend ourselves. . . . But the fighting is only one aspect of the conflict, which is in its essence a political one. And politically we are the aggressors and they defend themselves." He even went so far as to say, “Why should the Arabs make peace? If I was an Arab leader, I would never make terms with Israel. That is natural: we have taken their country. Sure, God promised it to us, but what does that matter to them? Our God is not theirs, We come from Israel, it’s true, but two thousand years ago, and what is that to them? There has been anti-Semitism, the Nazis, Hitler, Auschwitz, but was that their fault? They only see one thing: we came here and stole their country. Why should they accept that?”
Even Ben-Gurion’s exposures of his fellow colleagues are very telling. Take for instance what he says about Menachem Begin, the Prime Minister who signed the first Camp David accords with Anwar El-Sadat in 1979, "Begin undeniably belongs to the Hitlerian type. He is a racist, ready to destroy all the Arabs in his dream of unification of Israel, prepared to resort to any means to realize this sacred goal”.
It is probably time to move on to other figures whose strokes are of interest for medical history, apart from politicians.
NOVELISTS
Two of the most famous people to have died of stroke are among the greatest of English authors: Samuel Johnson, the most quoted English writer after Shakespeare, and author of ‘A Dictionary of the English Language’, the father of all dictionaries, and Charles Dickens, arguably the greatest English novelist. Their strokes are of interest as they teach us a few things.
Although he is often referred to as Dr. Johnson, Samuel Johnson was not a physician. He was a great friend of physicians, and was very interested in all matters medical, as is highlighted in his biographies (see for example, the article by T Jock Murray, ‘Samuel Johnson: his ills, his pills and his physician’ in ‘Clinical Medicine’ (Vol 3 No 4 July/August 2003)). He even gave medical advice to people on a regular basis – perhaps therein lies the confusion.
In any case, Samuel Johnson suffered a stroke in 1783, which he described in the following words, “Another time ... another place...[I] waked and sat up ... when I felt a confusion and indistinctness in my head ....I was alarmed and prayed God, that however he might afflict my body he would spare my understanding ... Soon after I perceived that
I had suffered a paralytick stroke and that my Speech was taken from me”. Johnson had many risk factors for stroke; he was obese (and therefore likely to be hyperlipidaemic in the pre-cholesterol age), had “suffered from oedematous legs, shortness of breath, a smothering sensation when lying down, and attacks of dyspnoea that awoke him from sleep – all signs of right heart failure” (Murray, 2003) (heart failure is a major cause of stroke), and most likely had the most important risk factor for stroke other than age, hypertension. Henry Rolleston argued that his right heart failure and other illnesses of late life were due to hypertension, a condition unknown in his time (Rolleston, 1929). Hypertension may have indirectly led to his right heart failure via causing ischaemic heart disease – he very likely suffered this, according to Murray (2003), “At age 71 he was having chest discomfort, ‘convulsions in my breast which had distressed me for more than 20 years’”. But only pulmonary, as opposed to systemic hypertension, can cause right heart failure directly. This is the stronger possibility, which is also suggested by his autopsy results which showed pulmonary fibrosis and cardiac failure (ibid). It is possible that he had polycythaemia too – this may be related to his chronic lung disease (which was incorrectly attributed to asthma – highlighting difficulties in diagnosis in pre-CXR and CT days). This polycythemia, an independent risk factor for stroke as we outline below is suggested by his frequent phlebotomies - he “even cut his own vein to do his own phlebotomy, bleeding so much that the stream of blood had to be stopped with the help of Robert Levet and Johnson’s black servant Francis Barber” (ibid). Johnson was also a heavy drinker, who “admitted that at times he drank a lot, and at other times abstained – it was moderation he found difficult. Although he mostly abstained, he lamented, ‘There is no doubt that not to drink wine is a great deduction from life’.” Excess alcohol is risk factor for stroke.
As for Charles Dickens, he too “had signs of heart disease, perhaps precipitated by renal disease, for several years, and in 1866 he was prescribed iron, quinine, and digitalis. Watson also noted signs of cardiac enlargement” (McManus, 2001). His stroke has even been localised – without an autopsy or CT-scan, highlighting some of the unique aspects to neurological diagnosis. As explained by McManus, “For the last 5 years of his life, Charles Dickens had a range of symptoms, mostly affecting his left side, including hemispatial neglect for words, paroxysmal pains, hyperpathia or allodynia and hypoalgesia in the left foot, and a feeling of the world falling to the left. He also seemed to be unaware of the seriousness of his symptoms, which suggests some form of anosognosia. Dickens was known to have had a definite attack of right-sided cerebral insufficiency, and he died of apoplexy affecting the right side of the brain. Dickens' left-sided symptoms thus could suggest damage to the right temporoparietal area.”
There is much of interest in Dickens’ life, but if I were to look at him from my two most personal perspectives, I find him most amusing.
As a doctor, Dickens views on the medical profession are peculiar and reveal to us a lot about how the medical profession was viewed in early Victorian times. He portrayed many doctors in his novels, 27 according to Dana (1898), and “out of these twenty-seven medical men, not one is characterized especially as having ability, as being a person of good sound sense having ability, as being a person of good sound sense; not one would seem to indicate by anything he is allowed to say in the pages in which he lives, that he is a man of brains, with the possible exception of Dr. Manette in the " Tale of Two Cities," and Joe Specks in the ' Uncommercial Traveller." Alfred Heathfield, Alexander Manette, Joe Specks and Allan Woodcourt are men whom one might be willing to associate with freely, though even they rather savor of the cheap comic paper. The remaining twenty-three are, as the notes indicate, either silly, idiotic, pretentious, weak, or are simply caricatures of men. As I went on with my examination I was at first inclined to draw some rather broad conclusions from this table. It seemed to indicate that in Dickens' time, say forty years ago, the medical profession in England received very little consideration at the hands of people of thought. The doctors generally, were looked upon as weak and r.,ther silly; and the lower middle class, even, considered them as little more than necessary evils or subjects for jokes.”
As a Palestinian, I find his views on the Jews very interesting. Even this great novelist was not spared the accusation of anti-Semitism by his Jewish readers. Why can’t Jews accept criticism? Why are they so pathetic? Why do we need to distort history so that we please them? Why can’t they accept that they committed the many crimes that they have committed throughout their history? Why do they want everyone to think that they are the angels of Earth, perfect, innocent, who have never done any evil, the ones who are hated ‘because they are so good’, because we are jealous of them? The Jews’ portrayal of themselves in current media as the most perfect of people is nonsense, pure fiction. The Jews are like every other people – there is both good and evil in them, although history, and the word of God, tells us that there is probably more evil in them than good.
The Quran indicates to us that there are good Jews, saying, “Not all of them are alike: of the People of the book are a portion that stand (for the right); they rehearse the signs of Allah all night long and then prostrate themselves in adoration. They believe in Allah and the Last Day; they enjoin what is right and forbid what is wrong; and they (hasten in emulation) in (all) good works; they are in the ranks of the righteous. Of the good that they do nothing will be rejected of them; for Allah knoweth well those that do right” (3:113-115). It even promises Paradise to some of them, “Verily! Those who believe and those who are Jews and Christians, and Sabians, whoever believes in Allah and the Last Day and do righteous good deeds shall have their reward with their Lord, on them shall be no fear, nor shall they grieve”.( 2:62). But in the main, it is critical of their actions; entire books have been dedicated to this topic, which I will not recount here.
God cannot be accused of the anti-Semitism that so many fair and just thinkers have been accused of because they spoke the truth about the Jews. Everyone knows that Shakespeare has been accused of anti-Semitism following his depiction of the character Shylock in the Merchant of Venice, the famous miserly money lending Jew. So was Dickens, following his depiction of the character Fagin, in his novel Oliver Twist, the Jewish leader of “a group of children, the Artful Dodger among them, whom he teaches to make their livings by pickpocketing and other criminal activities in exchange for a roof over their heads.” The great man was criticised by readers everywhere, and responded, "I know of no reason the Jews can have for regarding me as inimical to them...on the contrary, I believe I do my part toward the assertion of their civil and religious liberty, and in my Child's History of England, I have expressed a strong abhorrence of their persecution in old time"
To a criticism published in the Jewish Chronicle, Dickens wrote the following response:
"If there can be any general feeling on the part of the intelligent Jewish people that I have done them what you describe as a 'great wrong', they are a far less sensible, and far less just, and a far less good-tempered people than I have always supposed them to be be. Fagin, in Oliver Twist, is a Jew, because it unfortunately was true of the time to which that story refers, that that class of criminal almost invariably was a Jew. But surely no sensible man or woman of your persuasion can fail to observe...that all the rest of the wicked dramatis personae are Christians"
Dickens was being fair, and a true observer of history. We shall not feign history to portray the Jews as they wish were, rather than what they actually were. One can give statement by virtually all great non-Jewish thinkers of all ages to show what a terrible people they generally were. I find it an extremely useful exercise to list some of these statements.
1. François Marie Arouet Voltaire, the 18th century French philosopher and novelist:
“Why are the Jews hated? It is the inevitable result of their laws; they either have to conquer everybody or be hated by the whole human race. The Jewish nation dares to display an irreconcilable hatred toward all nations, and revolts against all masters; always superstitious, always greedy for the well-being enjoyed by others, always barbarous--cringing in misfortune and insolent in prosperity”. (Essai sur les moeurs)
“You seem to me to be the maddest of the lot. The Kaffirs, the Hottentots, and the Negroes of Guinea are much more reasonable and more honest people than your ancestors, the Jews. You have surpassed all nations in impertinent fables, in bad conduct and in barbarism. You deserve to be punished, for this is your destiny. (From a letter to a Jew who had written to him, complaining of his 'anti-Semitism.' Examen des quelques objections. . . dans l'Essai sur les moeurs.) You will only find in the Jews an ignorant and barbarous people, who for a long time have joined the most sordid avarice to the most detestabJe superstition and to the most invincible hatred of all peoples which tolerate and enrich them. ("Juif," Dictionnaire Philosophique)”
“I know that there are some Jews in the English colonies. These marranos go wherever there is money to be made But whether these circumcised who sell old clothes claim that they are of the tribe of Naphtali or Issachar is not of the slightest importance. They are, simply, the biggest scoundrels who have ever dirtied the face of the earth. (Letter to Jean-Baptiste Nicolas de Lisle de Sales, December 15, 1773. Correspondance. 86:166)”
“They are, all of them, born with raging fanaticism in their hearts, just as the Bretons and the Germans are born with blond hair. I would not be in the least bit surprised if these people would not some day become deadly to the human race. (Lettres de Memmjus a Ciceron, 1771)”
2. Benjamin Franklin – the great American thinker:
“I fully agree with General Washington, that we must protect this young nation from an insidious influence and impenetration. That menace, gentlemen, is the Jews. In whatever country Jews have settled in any great number, they have lowered its moral tone; depreciated its commercial integrity; have segregated themselves and have not been assimilated; have sneered at and tried to undermine the Christian religion upon which that nation is founded, by objecting to its restrictions; have built up a state within the state; and when opposed have tried to strangle that country to death financially, as in the case of Spain and Portugal. For over 1,700 years, the Jews have been bewailing their sad fate in that they have been exiled from their homeland, as they call Palestine. But, gentlemen, did the world give it to them in fee simple, they would at once find some reason for not returning. Why? Because they are vampires, and vampires do not live on vampires. They cannot live only among themselves. They must subsist on Christians and other peoples not of their race. If you do not exclude them from these United States, in this Constitution, in less than 200 years they will have swarmed here in such great numbers that they will dominate and devour the land and change our form of government, for which we Americans have shed our blood, given our lives, our substance and jeopardized our liberty. If you do not exclude them, in less than 200 years our descendants will be working in the fields to furnish them substance, while they will be in the counting houses rubbing their hands. I warn you, gentlemen, if you do not exclude Jews for all time, your children will curse you in your graves. Jews, gentlemen, are Asiatics, let them be born where they will or how many generations they are away from Asia, they will never be otherwise. Their ideas do not conform to an American's, and will not even though they live among us ten generations. A leopard cannot change its spots. Jews are Asiatics, are a menace to this country if permitted entrance, and should be excluded by this Constitutional Convention.”
3. Mark Twain – the great American writer:
“I feel convinced that the Crucifixion has not much to do with the world's attitude toward the Jew; that the reasons for it are much older than that event...I am convinced that the persecution of the Jew is not in any large degree due to religious prejudice. No, the Jew is a money-getter. He made it the end and aim of his life. He was at it in Rome. He has been at it ever since. His success has made the whole human race his enemy. You will say that the Jew is everywhere numerically feeble. When I read in the Cyclopedia Britannica that the Jewish population in the United States was 250,000 I wrote the editor and explained to him that I was personally acquainted with more Jews than that, and that his figures were without doubt a misprint for 25,000,000. People told me that they had reasons to suspect that for business reasons, many Jews did not report themselves as Jews. It looks plausible. I am strongly of the opinion that we have an immense Jewish population in America. I am assured by men competent to speak that the Jews are exceedingly active in politics... ("Concerning the Jews," Harper's Monthly Magazine, September 1899)”
4. George Bernard Shaw, the 20th century Irish dramatist:
“This is the real enemy, the invader from the East, the Druze, the riffian, the oriental parasite; in a word the Jew”. (London Morning Post, December 3, 1925)
“This craving for bouquets by Jews is a symptom of racial degeneration. The Jews are worse than my own people. Those Jews who still want to be the chosen race (chosen by the late Lord Balfour) can go to Palestine and stew in their own juice. The rest had better stop being Jews and start being human beings”. (Literary Digest, October 12, 1932)
5. H G Wells, English novelist and historian:
“Zionism is an expression of Jewish refusal to assimilate. If the Jews have suffered, it is because they have regarded themselves as a chosen people”. (The Anatomy of Frustration)
“A careful study of anti-Semitic prejudice and accusations might be of great value to many Jews, who do not adequately realize the irritations they inflict”. (Letter of November 11, 1933)
Can all these people be wrong, and the Jews right? I think not. I hasten to add however, that I am not against Judaism, but only against Zionist Jews, and believe historical accounts given by people whose judgement and veracity I cannot question.
MUSICIANS
There is much interest these days on the effect of music therapy on strokes, and the effect of strokes on the minds of musicians. As for famous musicians who endured them, the two most interesting cases are those of Johann Sebastian Bach, widely regarded as the third greatest composer of history, after Beethoven and Mozart, and Georg Handel, another great German composer.
As for Bach, his “cerebrovascular risk profile included age, obesity, possible hypertension and diabetes that led to his fatal stroke in 1750" (Breitenfeld et al, 2006). The stroke was complicated by pneumonia, presumably, as it usually is in those cases, due to aspiration.
Bach, as we say is thought to be the third of the greatest composers of history, though he preceded and influenced all of them. His ‘Mass In B Minor’ is widely regarded as only second to Beethoven’s ninth symphony as the greatest classical piece ever. His legacy was clear to all, non-musicians and musicians. For example, George Bernard Shaw remarked that, “Bach belongs not to the past, but to the future - perhaps the near future.”
Douglas Adams, author of the ‘Hitchhiker’s Guide To The Galaxy’ wrote, “I don't think a greater genius has walked the earth. Of the 3 great composers Mozart tells us what it's like to be human. Beethoven tells us what it's like to be Beethoven and Bach tells us what it's like to be the universe.” The great German poet Goethe suggested that listening to Bach was “as though eternal harmony were conversing with itself, as it may have happened in God's bosom shortly before He created the world.” The famous American physician and author, Lewis Thomas remarked somewhere about how he reckons the people of Earth should communicate with extraterrestrials, "I would vote for Bach, all of Bach, streamed out into space, over and over again. We would be bragging of course, but it is surely excusable to put the best possible face on at the beginning of such an acquaintance. We can tell the harder truths later." He was a true genius.
As for musicians, the contemporary American composer Michael Torke made the fantastic remark, “Why waste money on psychotherapy when you can listen to the B Minor Mass?” As for the more famous ones, their praise is even greater. Beethoven played a pun on Bach’s name in German, “Not brook but sea should be his name” (“nicht Bach, sondern Meer”). On a visit to Thomasschule, Mozart heard a performance of one of Bach’s pieces and exclaimed, "Now, here is something one can learn from!"; on being given the motets' parts, "Mozart sat down, the parts all around him, held in both hands, on his knees, on the nearest chairs. Forgetting everything else, he did not stand up again until he had looked through all the music of Sebastian Bach". The great French pianist Chopin described Bach as “like an astronomer who, with the help of ciphers, finds the most wonderful stars...Beethoven embraced the universe with the power of his spirit...I do not climb so high. A long time ago I decided that my universe will be the soul and heart of man.” Schumann stated that “music owes as much to Bach as religion to its founder”. Wagner made the greatest claim, that Bach is “the most stupendous miracle in all music”.
Bach was a remarkably religious man, who felt that “music's only purpose should be for the glory of God and the recreation of the human spirit." His music is to this day, heard in Churches all over the world. His religiosity is deeply expressed in his work, as the Wikipedia article on him explains:
“Bach's apparently devout, personal relationship with the Christian God in the Lutheran tradition and the high demand for religious music of his times inevitably placed sacred music at the centre of his repertory; more specifically, the Lutheran chorale hymn tune, the principal musical aspect of the Lutheran service, was the basis of much of his output. He invested the chorale prelude, already a standard set of Lutheran forms, with a more cogent, tightly integrated architecture, in which the intervallic patterns and melodic contours of the tune were typically treated in a dense, contrapuntal lattice against relatively slow-moving, overarching statements of the tune. Bach's theology also informed his compositional structures: Sei Gegrüsset is perhaps the finest example where there is a theme with 11 variations (making 12 movements) that, while still one work, becomes two sets of six—to match Lutheran preaching principles of repetition. At the same time the theological interpretation of 'master' and 11 disciples would not be lost on his contemporary audience. Further, the practical relationship of each variation to the next (in preparing registration and the expected textural changes) seems to show an incredible capacity to preach through the music using the musical forms available at the time.”
As for Handel, he too is regarded as one the top ten composers of all time, being ranked ninth in a recent poll, although the ‘Hallelujah Chorus’ of his masterpiece, ‘The Messiah’, is regarded as the most popular of all classical compositions (whether it is truly the most popular or simply the most well known or imposed (being always played in every Christmas) is a matter of debate. His legacy is celebrated in many places, such as this interesting piece that compares him with Bach:
“Throughout his life Handel avoided the rigorous contrapuntal techniques of his compatriot and exact contemporary Johann Sebastian Bach and achieved his effects through the simplest of means, trusting always his own innate musicianship. The music of both composers, however, sums up the age in which they lived. After them, opera took a different path; the favorite baroque genres of chamber and orchestral music, trio sonata and concerto grosso, were largely abandoned; and the development of the symphony orchestra and the pianoforte led into realms uncharted by the baroque masters. Thus, their influence cannot be found in specific examples. Rather, Handel's legacy lies in the dramatic power and lyrical beauty inherent in all his music. His operas move from the rigid use of conventional schemes toward a more flexible and dramatic treatment of recitative, arioso, aria, and chorus. His ability to build large scenes around a single character was further extended in the dramatic scenas of composers such as Wolfgang Amadeus Mozart and the Italian Gioacchino Rossini. Handel's greatest gift to posterity was undoubtedly the creation of the dramatic oratorio genre, partly out of existing operatic traditions and partly by force of his own musical imagination; without question, the oratorios of both the Austrian composer Joseph Haydn and the German composer Felix Mendelssohn owe a large debt to those of Handel”
In an article, ‘Georg Friedrich Händel’s Strokes’ by Bazner and Hennerici (2005), it was concluded, “that Händel, a man with a probable wide profile of risk factors including systemic hypertension, smoking and most probably hyperlipidemia, had recurrent palsies of his right side (following the available sources involving uniformly his upper extremity), partly with simultaneous speech impairment, either dysarthia as a component of the dysarthria-clumsy-hand-syndrome or dysphasia as a result of embolic middle cerebral artery stroke, which may have been interpreted as confusion. He may well have had a severe stenosis of his left carotid artery with recurrent embolism to the left hemisphere. Since for a certain period of time only his left eye was affected by visual loss, the suspected left carotid artery stenosis may also have been the source for embolic events within the left retina.”
OTHER ARTISTS
In addition to musicians and novelists, the impact of strokes on the creative output of artists is demonstrated in many other types of artist. For example, it was only “when a stroke rendered painting impossible” that the great Italian painter of the Mona Lisa, Leonardo da Vinci stopped and focused on his other artistic passion of designing, until his death on May 2, 1519. Strokes robbed the Arab world of some of its biggest comedian actors, stripping it of a great element of laughter – actors like George Sidhom, Sayyid Zayyan and Younis Shalabi.
SCIENTISTS
I cannot recall reading about any great scientist’s stroke as vividly as I recall that of Louis Pasteur, the great Frenchman, whose life teaches us so much wisdom, and indeed teaches us some interesting aspects about stroke.
Pasteur is arguably the only scientist in history to find his way into every single home in the Western world, into every Western refrigerator – with his invention of the procedure of Pasteurisation – a procedure that must have saved millions of lives. It is this, plus many dozens of other contributions that led David Wood to justifiably state that, “If one were to choose among the greatest benefactors of humanity, Louis Pasteur would certainly rank at the top. He solved the mysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed to the development of the first vaccines. He debunked the widely accepted myth of spontaneous generation... He described the scientific basis for fermentation, wine-making, and the brewing of beer. Pasteur's work gave birth to many branches of science, and he was singlehandedly responsible for some of the most important theoretical concepts and practical applications of modern science...All of these achievements point to singular brilliance and perseverance in Pasteur's nature. His work served as the springboard for branches of science and medicine such as stereochemistry, microbiology, bacteriology, virology, immunology, and molecular biology.”
Pasteur was immortalised in the Oscar winning movie ‘The Story of Louis Pasteur’, and was regarded by Michael Hart as the eleventh most influential person in history. He was a remarkable genius, and there are many excellent biographies describing this genius. What I would like to pay attention to here is two aspects of his life which are highly educational from the perspective of this book.
The first aspect is his great religious zeal, and his great faith in God. Pasteur famously remarked that, "A bit of science distances one from God, but much science nears one to Him; the more I study nature, the more I stand amazed at the work of the Creator." His grandson and first biographer, Vallery-Radot commented that, “Absolute faith in God and in Eternity, and a conviction that the power for good given to us in this world will be continued beyond it, were feelings which pervaded his whole life; the virtues of the gospel had ever been present to him. Full of respect for the form of religion which had been that of his forefathers, he came simply to it and naturally for spiritual help in these last weeks of his life”. To see such a great scientist believe in God, and showing great gratitude to Him, is a sign that He is the truth.
Louis Pasteur suffered his first stroke on October the 19th 1868, at the age of forty-five. He described it saying, “There is a time in every man's life when he looks to his God, when he looks at his life, when he wonders how he will be remembered. It can happen with age or with tragedy or closeness of death. I am lying here at age 45, not able to feel my left side. Not knowing if this stroke that has befallen me will end my life before the mysteries that I have unlocked can be resolved”. His suffering teaches us two main things about stroke. Firstly, that it can happen to every one of all ages – stroke is not just a disease of the elderly, although it is true that age is its biggest risk factor.
Secondly, it teaches us that stroke need not be the end of the contributions of a human being. Some of his greatest work was produced after his stroke, with his election to the Academy of Medicine in 1873, publishing his studies on beer in 1876, and his studies on anthrax in 1877. In 1879, during his studies on chicken cholera, Pasteur discovered how to immunize against disease using weakened bacteria, and in 1880 he began his legendary studies of rabies. In 1885, Joseph Meister, bitten by a rabid dog, was brought to Pasteur who decided to vaccinate him, the first person ever to be vaccinated. After his survival, patients flocked from all over the world to see Pasteur. In 1894, The Pasteur Institute succeeded in producing a vaccine for diphtheria. All this life-saving work was done after Pasteur’s stroke. It all shows that stroke does not necessarily mean the end, and rehabilitation from stroke should always be hoped for and considered.
TYPES OF STROKE
Strokes are divided into two main types – ischaemic and haemorrhagic. There is a division of strokes into TIAs and completed strokes, the difference being duration; TIA – as it says on the tin – are transient attacks, lasting less than 24 hours. The importance of their diagnosis is that by detecting them and treating them, you can avoid their escalation into completed strokes; about 15% of patients who have had a TIA develop a completed stroke at a later stage.
Strokes develop when the blood supply to the part of the brain involved in the stroke is reduced to levels at which the neurons do not meet their minimum blood supply. As usual, the human body has been endowed with protective mechanisms that help in these circumstances, one physiological – the CNS ischaemic response, and one anatomical - the Circle of Willis.
The CNS ischaemic response is explained clearly here by Guyton:
“Most nervous control of blood pressure is achieved by reflexes that originate in the baroreceptors, the chemoreceptors, and the low-pressure receptors, all of which are located in the peripheral circulation outside the brain. However, when blood flow to the vasomotor center in the lower brain stem becomes decreased severely enough to cause nutritional deficiency—that is, to cause cerebral ischemia—the vasoconstrictor and cardioaccelerator neurons in the vasomotor center respond directly to the ischemia and become strongly excited. When this occurs, the systemic arterial pressure often rises to a level as high as the heart can possibly pump. This effect is believed to be caused by failure ofthe slowly flowing blood to carry carbon dioxide away from the brain stem vasomotor center: at low levels of blood flow to the vasomotor center, the local concentration of carbon dioxide increases greatly and has an extremely potent effect in stimulating the sympathetic vasomotor nervous control areas in the brain’s medulla.
It is possible that other factors, such as build up of lactic acid and other acidic substances in the vasomotor center, also contribute to the marked stimulation and elevation in arterial pressure. This arterial pressure elevation in response to cerebral ischemia is known as the central nervous system ischemic response, or simply CNS ischemic response.
The magnitude of the ischemic effect on vasomotor activity is tremendous: it can elevate the mean arterial pressure for as long as 10 minutes sometimes to as high as 250 mm Hg. The degree of sympathetic vasoconstriction caused by intense cerebral ischemia is often so great that some of the peripheral vessels become totally or almost totally occluded. The kidneys, for instance, often entirely cease their production of urine because of renal arteriolar constriction in response to the sympathetic discharge. Therefore, the CNS ischemic response is one of the most powerful of all the activators of the sympathetic vasoconstrictor system.”
This explains why it is advised not to treat hypertension in the case of an ischaemic stroke. It is actually a protective response in the acute scenario.
Without the amazing spider-like structure called the Circle of Willis, the like of which is not present in any other part of the human body, the incidence of strokes will be multiplied manifold. Somehow, the human body knew that neurons are very fragile structures, and they need a persistent blood supply. So it devised this incredible system, which unfortunately been a cause of headache in the vast majority of medical students who are always asked to recall its many branches during their exams! It is a great example of Divine Providence.
So how do strokes occur? The risk factors for stroke are the same as those of ischaemic heart disease (SHIFTMAID) in the case of ischaemic strokes, which account for the majority:
§ Smoking
§ Hypertension / Heart disease (esp. heart failure & atrial fibrillation)/ Hypercoagulability (including polycythemia)/ Hypocoagulability conditions
§ IDDM/NIDDM
§ Family history
§ Triglycerides (cholesterol)
§ Male
§ Age
§ Inactivity
§ Drinking (alcohol)
In addition, heart disease itself, prothrombotic (including polycythaemia) conditions, and a previous CVA predispose to them. In addition, haemorrhagic stroke is predisposed to by any bleeding diathesis (including iatrogenic due to warfarin) and weakening of the blood vessels by the SHIFTMAID. The rupture may be caused by sudden rise in blood pressure. These risk factors take time to cause disease, and hence stroke is usually a disease of the elderly (generally over 50s).
However, if confronted with a young patient with stroke, one must think of the 7Cs, which are:
Cocaine
Cytological (mitochondrial diseases - MELAS)
Consanguinity [familial such as neurofibromatosis and von Hippel-Lindau]
Cardiogenic emboli (e.g. infective endocarditis)
Coagulopathy (e.g. ALASCA, antiphospholipid syndrome, contraceptive)
Congenital heart disease
Cerebral vasculitis (e.g. Moya Moya, carotid/vertebral dissection, vasculitis)
So what does knowledge of SHIFTMAID and stroke teach us? Well, it teaches us that there are multiple factors in the prevention of stroke. You need normal vasculature, blood and blood supply.
The supply of blood is provided by the heart – and hence a normal heart is a prerequisite to the prevention of strokes. If the heart is not working properly, it would naturally fail to pump arterial blood up to the brain. In addition, a failing pump leads to blood stasis in the chambers of the heart, leading to emboli, which can be pumped eventually into the brain, blocking off the arterial supply. This is the same way through which atrial fibrillation can lead to strokes, and why anticoagulation is such an important aspect of its management.
Normal blood is the other precondition to the prevention of stroke. As we all know, blood contains red blood cells, white blood cells, and platelets, clotting factors, other blood proteins and plasma. Defects in any of these will lead to stroke. Defects can be divided into excess, deficiency and function defects.
Excessive red blood cells – namely polycythaemia can cause stroke. This is because of hyperviscosity of blood. This reduces its flow rate, and predisposes to clot formation.
Low levels of red blood cells – namely anaemia can also lead to stroke. This is a logical, although not a commonly mentioned textbook cause of stroke – a typical list goes along the following lines:
If there is not enough blood, highlighted by a low haemoglobin, then clearly the brain is not going to receive the oxygen it needs to function, and therefore it will infarct. A very interesting recent study by Maguire et al (2008) showed that, “More than half of the stroke cases among children without underlying medical illness consisted of children with IDA, suggesting that IDA is a significant risk factor for stroke in otherwise healthy children.” (Association between iron-deficiency anemia and stroke in young children. Maguire J, deVeber G, Parkin PC. Pediatrics 120(5): 1053-7. )
However, one type of anaemia is nearly always mentioned as a cause – namely sickle cell anaemia. The mechanism is due to occlusion of brain vasculature by long-jams of sickled red cells.
A chronic severe excess of leukocytes can lead to stroke by the same hyperviscosity mechanism as polycythemia. (Inoue, 2006). Leukopenia does not lead to stroke.
An excess of platelets (thrombocytosis) can lead to strokes by predisposing to emboli formation. It is important to realise too that any infarction or bleed can cause secondary thrombocytosis. So if you find a high platelet count in a patient who has had a stroke – it may be a cause or consequence. A low level of platelets can lead to all sorts of bleeds, haemorrhagic brain strokes included. This is the same mechanism by which low clotting factors can lead to stroke. The most common reason for this is warfarin use, but other reasons are failure to synthesise clotting factors (e.g. cirrhosis) or to keep them in the circulation (nephrotic syndrome).
An excess of clotting factors (thombophilia) or deficiency of endogenous anticoagulants can lead to stroke by increasing the risk of emboli formation. The prothrombotic conditions are ALASCA:
· Acquired (e.g. smoking, surgery, HRT, OCP, dehydration, malignancy, cancer chemotherapy)
· Leyden (factor V Leyden)
· Antithrombin-III deficiency
· S- and C- protein deficiency
· Antiphospholipid syndrome
The final risk factor for stroke is abnormal vasculature. This is how the majority of strokes occur. The main disease affecting the vessels is atherosclerosis, whose main risk factors are SHIFTMAID. In addition we have the vasculitides, which include Moya Moya disease and carotid arterial dissection.
Knowledge of the above highlights the importance of the normality of the above in most human beings, who are spared the torment of strokes. To that we should be grateful.
Now that we have discussed the causes of stroke, we can discuss its presentation.
THE PRESENTATION OF STROKES
Strokes can present in virtually any mixture of neurological symptoms – weakness, altered sensation, tremor, convulsions, headache, visual, auditory, and speech problems.
To reflect on the presentation of strokes is to reflect on the magnificence of the normal brain. Indeed, our knowledge of the normal brain is based mostly on knowledge of the aftermath of strokes and traumatic head injury, being the most common neurological presentations, if I may call head injury a neurological, rather than surgical condition. Correlating autopsy and more recently, MRI findings to presentations of patients during their life, we have learnt much about the role of different areas of the brain. What such studies have revealed is the specific role of each part of the brain. Although, macroscopically at least, brain tissue appears pretty much homogenous, there are huge differences between different parts. The functions of the different lobes are as follows:
Frontal - associated with reasoning, planning, parts of speech, movement, emotions, and problem solving
Parietal - associated with movement, orientation, recognition, perception of stimuli
Occipital - associated with visual processing
Temporal - associated with perception and recognition of auditory stimuli, memory, and speech
When one reflects on the symptoms that patients present with in stroke, it is hard to not think of the brain as yet another example of intelligent design and part of an outstanding irreducibly complex system.
Stroke is the most common neurological emergency, and, because effective treatment is available that must be started within minutes, most acute neurological presentations should be assumed to be a stroke until proven otherwise by history, exam, or radiographic testing. The diagnosis is often clear from the history and examination, but the following pathologies can also produce a clinical picture that is identical to stroke and should be considered in atypical presentations – namely MICES:
Multiple sclerosis / Migraine (hemiplegic) (typical features of migraine also present, resolving within 24 hours).
Intracranial mass e.g. tumour (history of cancer) or abscess (consider if patient has bronchiectasis or murmur (infective endocarditis)).
Chronic subdural haematoma – consider in elderly and alcoholics
Encephalitis / Epilepsy - Todd's paralysis following a Jacksonian seizure.
Sugar – hypoglycemia mainly
Any patient with a suspected stroke should be assessed with ABCDEFG and MOVE first as large strokes and reduced GCS, or with strokes affecting the tongue and pharynx, can lead to severe airway problems. If hypertensive, do not treat HT (Cushing’s reflex); take a full history, enquiring carefully into all neurological symptoms, and PMH of CV illness. This should be enough to differentiate CVA from other focal lesions (e.g. migraine, fits, and tumour). Consider an urgent CT if suspect intracranial bleeding (headache, on warfarin, history of trauma or falls). Otherwise get CT within 24 hrs.
A basic understanding of brain vascular anatomy is important to understand strokes, as follows:
CLASSIFICATION OF STROKE
Oxfordshire Stroke Subtype Classification uses clinical history and physical exam findings to classify stroke patients into 5 subtypes
675 cases of first-ever stroke encountered over 5 years
Interobserver reliability for classification employing the Oxfordshire system is good
Subtypes are associated with different incidences of medical complications and dependency at discharge:
1. Primary intracerebral hemorrhage (PICH)
2. Total anterior circulation infarct (TACI): 17%, high mortality and poor chance of good functional outcome
3. Partial anterior circulation infarct (PACI): 24%, more likely to have an early recurrent stroke
4. Lacunar infarct (LACI: )25%.
5. Posterior circulation infarct (POCI): 24%, more likely to have a late recurrent stroke but an overall good functional outcome
TACI FEATURES - 3H
· Hemiplegia (contralateral to lesion)
· Homonymous hemianopia
· Higher cortical dysfunction (e.g. dysphasia, dyspraxia, neglect)
- PACI is 2/3 of the above
- LACI is a pure hemimotor or hemisensory loss.
With posterior circulation strokes the main features are of homonymous hemianopia, with macular sparing and brainstem disturbance - 4D:
· Dizziness
· Diplopia
· Dysarthria
· Dysphagia
The presence of dysphasia or Gerstmann’s syndrome suggests dominant parietal lobe involvement
SITES & MANIFESTATIONS OF STROKE
1.Cerebral hemisphere infarcts may be classified by vascular territory:
Anterior cerebral artery infarcts: proximal to the medial striate branch, they cause contralateral hemiplegia; distal to the medial striate branch, they cause contralateral paralysis with sparing of the arm and face.
Middle cerebral artery infarcts: causes contralateral hemiplegia, often sparing the leg, and hemianopia. Aphasia is present if the dominant hemisphere is affected.
Posterior cerebral artery infarcts: causes contralateral hemianopia.
Motor signs are upper motor neuron.
2. Lacunar strokes
Lacunar strokes are due to small areas of infarction usually occurring around the basal ganglia, thalamus, and pons.
Clinical features include pure motor or sensory signs, a mixed motor and sensory picture, ataxia, and dysarthria.
They may also be asymptomatic and found at post-mortem examination.
3. Brainstem infarcts
Clinical features include hemi- or quadriplegia, sensory loss, diplopia, facial weakness and numbness, nystagmus, dysphasia, and coma due to damage to the reticular formation.
The locked-in syndrome results from upper brain-stem infarction. The patient is conscious but unable to respond.
The most common brainstem vascular syndrome is lateral medullary syndrome (Wallenberg's syndrome), which is due to thromboembolism of the posterior inferior cerebellar artery. The patient presents with sudden vertigo and vomiting. Ipsilateral signs include 9th and 10th nerve lesions, Horner's syndrome, spinothalamic sensory loss in the face, diplopia, and cerebellar signs in the limbs. Contralateral signs include spinothalamic sensory loss in the body.
HISTORY
HPC
Either sudden onset or a step-wise progression of symptoms and signs over hours (or even days) is typical. TIA <> 24 hours. The features depend on the vascular territory involved (as above). Note risk factors for stroke. The neurological symptoms that stroke victims may present with include:
1. Weakness
· Determine if in lower face, arms and legs.
· Pure weakness à internal capsule
· A leg weakness à anterior cerebral
· A face, leg AND arm weak à middle cerebral
· Both legs weak à vertobrobasilar (but hemiparesis more common) (Posterior cerebral vasculopathy not associated with weakness)
2. Walking (gait) abnormalities
Patient primarily complain of this because of weakness, but it may also be due to basal ganglia disease, or multi lacunar infarcts (marche a petits pas)
Hemiplegic gait shows the pyramidal pattern of weakness.
Ataxic gait may occur in VB CVA
3. Altered sensation:
Middle cerebral artery supplies the somatosensory cortex; therefore sensory loss occurs only in MCA disease
If pure sensory loss however with no other features, internal capsule (medial lemniscus) infarct likely.
Thalamic infarcts cause hemisensory deficit (PCA supply), but so rare & associated excruciating pain is almost pathognomonic
4. Tremor and involuntary movements
Suggest basal ganglia stroke (i.e. lacunar infarct)
5. Confusion & convulsions
Patient is confused and disorientated in most cases
Rare in ischaemic stroke; more common is haemorrhagic stroke
6. Headache
Common; but if of severe intensity then suggests a haemorrhagic stroke
7. Eye & Ear problems
Visual problems are common, and can only truly be distinguished by physical examination
Amaurosis fugax points to carotid disease
‘like a curtain descending over my field of view’ (OHCM, p.350)
Deafness and/or tinnitus occur in vertebrobasilar strokes (OHCM, p.350).
8. Other
Dysphagia
Incontinence in anterior cerebral occlusion
Consciousness; coma does not occur in early stroke unless severe haemorrhagic; need to differentiate ‘locked-in-syndrome’ (‘pseudocoma’). Reticular strokes do not occur!
Speech (especially articulation and language production) - any dysphasia may occur
PMH
· Previous CVA, IHD or MI
· RF
· DM
· HT
· Congenital heart disease
· Arrhythmias
· Hyperlipidaemia
· Vasculitis
· Connective tissue disease
· Coagulopathies & other blood disease
· Virchow’s triad applies here as it does for DVT (so OCP equally as important)
DH
· Warfarin suggests haemorrhagic stroke
· Cocaine abuse in young patients
· OCP
FH/SH
· Note any FH of stroke or risk factors for stroke
· Smoking
· Alcohol
· Determine occupation and if patient drives; a one month ban applies if normal driver, if HGV and persistent deficit then banned for good.
ROS
· Note particularly the presence of any cardiorespiratory or arteriopathy symptoms
PHYSICAL EXAMINATION
GENERAL
· Acutely unwell patient
· GCS (falls if extensive hemispheric involvement due to cerebral oedema or severe bleed)
· BP may be high as a cause or consequence; a low BP may occur in haemorrhagic stroke
· Tachycardia (stress response, AF)
· Tachypnea (stress, anxiety, aspiration pneumonia, PE)
· Saturations (ensure saturations are above 95% [Witham 2005])
· Pyrexia (if aspiration pneumonia or UTI - common)
· Urine output (catheterise)
OTHER
· Neuro à full higher function, CN, sensory and motor testing
· CVS à JVP raised, xanthelasma, arcus, murmurs, carotids, peripheral pulses, check for DVT (may be difficult). (Fundoscopy done)
· RS à pneumonia
· Abdo à urinary retention
NEUROLOGICAL EXAMINATION IN STROKE
Posture is flexed upper limbs and extended lower limbs (pyramidal weakness); may have clear involuntary movements in lacunar infarcts.
CRANIAL NERVES
I à rarely involved
II à contralateral homonymous hemianopia in anterior circulation; with macular sparing in posterior circulation . Fundoscopy.
III, IV, VI à diplopia, ipsilateral Horner’s in lateral medullary syndrome. Nystagmus.
V à facial sensory loss; brisk jaw jerk in pseudobulbar palsy
VII à facial weakness (differentiate from Bell’s palsy)
VIII à rarely useful
IX & X à lateral medullary infarcts; PBP
XI à not useful
XII à PBP – this is bilateral IX, X, XII lesions
MOTOR
Wasting is not a feature of UMN lesions
Involuntary movements may be seen in basal ganglia infarcts
Initially flaccid hemiplegia; within days becomes spastic
Spastic weakness of pyramidal distribution (weakness greater in extensors than flexors in UL, and vice versa) – reason unclear; myometry has cast doubt on this pattern (Ginsberg, 1999), but remains clinically useful
Incoordination and other cerebellar signs common in posterior circulation CVAs
Reflexes decreased initially, then exaggerated.
Clonus present (>4 beats)
Check pts gait
SENSORY IMPAIRMENT
More for proprioception and light touch, than for pain and temperature
Loss of two-point discrimination
Astereognosis
Extinction
INVESTIGATIONS
4Ps
Plasma – FBC, U&E, ESR, glucose, lipids
Pump – i.e. heart (ECG, echocardiogram)
Pipes – carotid Doppler US
Picture of brain – CT or MRI
DIAGNOSTIC
Stroke is a clinical diagnosis
CT scan done urgently or within 24 hrs to establish mechanism
CAUSE
FBC (e.g. polycythemia. Raised WCC. If HB low and African, consider SCD)
ESR (e.g. IE, vasculitis)
Glucose
Lipids
Blood film in Afrocarribean of unknown sickle status
Blood cultures
Cholesterol
Glucose
VDRL
Coagulation screen
ECG
CXR
Echocardiography (to detect cardiac abnormalities and lung tumours)
Doppler carotids
MRA – this delineates extracranial arterial disease (internal carotid artery dissection must be considered in young patients) and proximal intracranial arteries, and detects thrombosis of major cerebral veins, venous sinuses and aneurysms
CONSEQUENCES
FBC, CXR (pneumonia), blood cultures (e.g. pneumonia, UTI)
Doppler US (legs – for DVT)
Note that large strokes, especially bleeds, can cause ST elevation on ECG and result in a rise in cardiac enzymes. This is often secondary to sympathetic activation, not necessarily to a primary myocardial event.
TREATMENT OF STROKE
Acutely, once ABCDEF & MOVE, and keep patient NBM if swallowing impaired until assessed by speech therapist.
Patients should be admitted to hospital (ideally a stroke unit for initial care and treatment, unless the diagnosis will make no difference to management, e.g. where optimal management is palliative care).
Aspirin (300 mg) should be given as soon as possible after the onset of stroke symptoms once a diagnosis of primary haemorrhage has been excluded. Antiplatelet therapy should then be continued indefinitely. Aspirin should be delayed for 24 hours following thrombolysis.
Anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke.
Unless there are contraindications, thrombolytic treatment appears to be effective in improving prognosis after an acute stroke. Treatment with alteplase should only be given provided that it is administered within three hours of onset of stroke symptoms (unless as part of a clinical trial) and haemorrhage has been definitively excluded.
Bleeds require an urgent neurosurgical opinion
Drugs depressing the function of the central nervous system (e.g. anxiolytics and tranquillisers) and new prescriptions for sedatives should be avoided.
Patients with TIA, or patients with a stroke who have made a good recovery when seen, should be assessed and investigated in a specialist service (e.g. neurovascular clinic) as soon as possible within seven days of the incident.
Conservative and supportive management is the mainstay of treatment subssequently
Treat underlying cause and RF, e.g. AF, hyperlipidaemia, HT, DM, smoking
All blood pressure medications should be held in order to ensure proper brain perfusion. Increases in the ICP sometimes force the systemic blood pressure higher than normal. In the presence of an acute bleed, the ICP should be measured. For ischemic stroke, blood pressure should not be treated unless it is severe (>220 systolic or >120 diastolic). This is often true for up to 2 weeks following acute presentation as well.
If there is a severe internal carotid artery stenosis (of more than 70%) and the patient has had TIAs within the past 6 months, endarterectomy should be considered.
Medical therapy includes aspirin 75 mg od for life. Clopidogrel or dypiridamole if intolerant.
Surgical options are carotid endarterctomy and STA-MCA anastamoses
Multidisciplinary care
Recovery and rehabilitation require an integrated approach between physicians (neurologists or geriatricians), nurses, dieticians (nasogastric feeding in 24-48 hours if bulbar function compromised), physiotherapists, OTs, and social workers
Stroke units improve outcome relative to general ward
PSYCHOLOGICAL ISSUES IN STROKE
Reaction to illness (depression in >30%)
Financial status and occupation assessment
Disability insurance (pt may be worried about how family will cope financially)
Emotional lability explanation to family so that they do not feel responsible for pts reactions
SPEECH THERAPIST ROLE
Need to distinguish from depression
Facial muscle exercises
Communication, repetition, patience and positive reinforcement
Communication board if Broca’s aphasia
Speech pathologist may be involved if very severe (?)
OCCUPATIONAL THERAPY ROLE
Assesses requirement for and arranging provision of various aids and modifications in the home
Done before discharge from hospital
Stair rails, hoists, wheelchairs, antiskid patches in bathtub
Free home of scatter rugs or other obstacles in walking pathways
PHYSIOTHERAPIST ROLE
Especially useful in first few months
Reduce spasticity
Relieve contractures
Walking aids
STROKE UNIT NURSE
Ties everything together
Intermittent catheterisation
Bladder training program – patient offered urinal, or put on commode every 2 hrs
Bowel training program
Encourage dietary fibre and fluid intake of >2L/day to avoid constipation
Apple or prune juice may help
DISCHARGE PLAN
To home, rehabilitation centre, long-term care facility (e.g. nursing home)
Ensure OT recommendations in place and pt understands them
Educate patient about drugs and schedule
Ensure pt confident in safely climbing stairs, transfer from chair to bed, etc
Family education
Provide information leaflets and details of support groups (e.g. NSF)
Ø Adaptive devices in place & understood
Ø Bowel and Bladder control
Ø Communication possible
Ø Dietary advice
Ø Eats without choking or aspiration
Ø Family support
PROGNOSIS IN STROKE
10% dead in 1 month
50 % survivors disabled
10 % recurrence in 1 yr
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