Does the name Korsakoff ring any bells for you? How about Wernicke? And what about Wernicke-Korsakoff? Ok, it may not mean much to you right now (except as a hyphenated name guaranteed to give some poor kid fits when they have to fill in the bubbles on the SAT), but after today, I hope it does. Because if you’re an alcoholic, Wernicke-Korsakoff Syndrome is something that could happen to you.
First of all, what IS Wernicke-Korsakoff Syndrome (and I’d better come up with a good abbreviation for this, because writing that over and over is going to kill my poor fingers. We’re going to call it W-K Syndrome, m’kay)?
Korsakoff, S.S. (1889) Psychic Disorder in Conjunction with Multiple Neuritis. (English translation with commentary). Neurology, 1955, 5: 394-406.
Well, it’s a little hard to explain, and even more difficult to spot. Only 20{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of cases are diagnosed while the patient is actually alive, the rest are usually diagnosed once you can get down and dirty with the autopsy. It doesn’t help that the main clinical features often coincide with other diseases, and that often, by the time you’re ready to get diagnosed with it, you’re so sick with something else that any of these less detectable symptoms are not really the first thing on a doctor’s mind.
Anyway, the main clinical features:
Ophthalmoplegia: paralysis or weakness of muscles that control eye movement.
Nystagmus: involuntary shaking or wobbly eyes.
Ataxia: not a lack of movement, but a lack of coordinated muscle movements.
Confused state
Amnestic disorder: this can include both anterograde amnesia (the inability to remember anything new presented to you), as well as retrograde amnesia (forgetting things from the past).
Peripheral neuropathy: usually described as pain or numbness in the limbs, particularly the hands and feet.
What causes W-K Syndrome? The direct cause is severe thiamine deficiency, but in practical terms, W-K syndrome is most often caused by alcoholism, and less often caused by severe malnutrition. Thiamine, aslso known as vitamin B1, is one of only a few nutrients associated with a human defiency disease. It is essential for normal neurological function and for the digestion of carbohydrates. The other word for thiamine deficiency that you may have heard is Beriberi, but that refers to thismine deficiency seen as a result of malnutrition (usually in populations that eat a lot of polished white rice, which is deficient in thiamine). W-K Syndrome refers (nowadays) pretty specifically to thiamine deficiency resulting from chronic alcoholism, though it can also refer to thiamine deficiency resulting from other causes not directly related to dietary malnutrition.
Thiamine deficiency results in chronic alcoholics because chronic exposure to alcohol will affect the intestine, reducing its ability to absord thiamine. Since thiamine is essential to glucose metabolism (several enzymes are dependent of thiamine diphosphate), anything that encourages the breakdown of glucose (such as the presence of glucose, and glucose is a basic sugar that is in literally EVERYTHING) will bring out a thiamine deficiency.
The practical upshot of a thiamine deficiency are the physical symptoms of things like paralysis, but also psychological symptoms such as memory loss, confusion, and hallucinations. When you look at the brains of people with W-K Syndrome, patients show a degeneration of an area of the brain known as the mammillary bodies. Right now it’s thought that degeneration of the mammillary bodies may play a role in the memory loss associated with W-K Syndrome. The mammillary bodies are in the Papez circuit, which is known to play a role in memory, so it’s possible that the connection is there.
You mammillary bodies, courtesy of NIAAA.
Wernicke-Korsakoff Syndrome actually refers to two stages of the same disease. The Wernicke part is the acute part, and the Korsakoff part is the chronic syndrome that occurs when Wernicke’s syndrome goes untreated. W-K Syndrome is found generally in less than 2{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} of the population, but numbers can be as high as 15{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} in psychiatric populations, and as high as 24{9f43b4361d9a125bc126dd2a2d1949be02545ec69880430bc4fed2272fd72da3} in the homeless (which often overlap with psychiatric problems, including drug and alcohol abuse). Though Wernicke described his section of he disorder in 1881, the paper that I’m looking at today is actually the Korsakoff portion, published for the first time in 1889, and found now courtesy of the section of classical neuroscience papers from the Society for Neuroscience.
Korsakoff was one of the giants of Russian medicine in the 19th century. Though now he’s known mostly for his syndrome, he also did a lot of work on paranoia, and the psychiatry textbook he wrote was used by Russian medical students until 25 years after his death. The paper I’m looking at today is actually the third of a three part series that Korsakoff wrote on psychiatric disturbances in alcoholic paralysis. The first one, written in 1887, was the first the charcterize the syndrome. He looked at 20 alcoholic patients, all of which began to suffer neuropathy. Usually these patients were documented as having only physical symptoms, usually pain in the limbs, paralysis, and muscle weakness. Korsakoff was not only the first person to recognize that psychiatric symptoms also accompanied the physical symptoms, but he was the first person to recognize that the physical and psychiatric symptoms were “two facets of the same disease”.
I’m very impressed that he did link the two sets of symptoms. Given the medical knowledge of the time, muscle weakness wasn’t really linked with neural problems, and psychiatric problems were usually considered something else entirely, and almost never considered to result from a disease or syndrome. But Korsakoff realized that memory disturbances in particular were characteristic of all the patients, even though they differed vastly in physical symptoms and other psychiatric symptoms. The patients also suffered from anxiety, paranoia, depression, and delirium. Interestingly, Korsakoff realized that the psychiatric symptoms could be present even in the absence of physical symptoms.
“The symptoms of multiple neuritis may be so slight that the whole disease manifests itself exclusively by psychiatric symptoms”
Nowadays, Korsakoff’s Syndrome is known primarily as a disorder of memory with resulting confabulation (lies), resulting from alcoholism. Of course, at the time, Korsakoff did not associate the symptoms with thiamine deficiency. He thought the issues was “toxemic”. He thought that alcoholism, as well as other types of gradual poisoning, such as that of lead, arsenic, mercury, and carbon monoxide, resulted in an “incorrect constitution of the blood”, which resulted in accumulation of toxic substances and poisoning of the brain and body. Of course he was wrong, but it would be years before people realized that a deficiency of any kind of nutrient could cause a disease.
In modern parlance, Korsakoff’s syndrome is thought of primarily as a disease of alcoholism (though thismine deficiency can result from several other malnutrition causes, such as severe prolonger vomiting from chemotherapy). But in this paper, his third, published in 1889, Korsokoff looked particularly at case studies of people who were NOT alcoholics, but who exhibited symptoms of his syndrome. Most of them were relatively young women (though a few were older men), and none of them were known for their alcohol intake. He only had 14 of these patients, though he had 30 people show the same symptoms comorbid with alcoholism. But the main symptoms of all of the patients were psychiatric and physical. They all showed partial paralysis, usually of the lower limbs, and all showed memory loss. Interestingly, many of the patients showed urine that was “the color of strong tea”.
Some of the memory loss was incredibly apparent, with patients unable to remember even the nurses who had been treating them for the better part of a year. Others had symptoms that were much less pronounced. Korsakoff was able to speak to them for a while, and some could even play a game of chess, without a problem. But soon the signs of memory loss would start to come out. Patients would say they had gone for a drive two days ago, when in fact they had been bedridden for months, and would tell the same stories over and over again, not realizing that they had told them before. In one case, a woman with psychiatric symptoms that came on after she had a baby actually forgot she’s given birth. These “confabulations” were not deliberate lies, instead the patients were repeating the story to themselves because they couldn’t remember what had really happened, and were just telling themselves a story until they believed it. Often the patients showed a lot of confusion as to where they were, what they had just said, and who was around them.
Another thing that stands out about all of the case studies is the existence of malnourishment. In several of the cases, the patients had been throwing up for days, or even weeks. In others, the patients had been suffering from typhoid or pneumonia, and in several of the female cases, the women who post-partum (just had a baby), and had already become infected (a common cause of death among women in the era before antibiotics was postpartum infection). But all of them had suffered from prolonged illness or other situations that could leave them severely malnourished and in a situation that might exacerbate or result in thiamine deficiency.
Luckily, most of the patients recovered. Four died soon after onset, and many of them never fully recovered psychiatric health, though in most cases the paralysis did get somewhat better. Now that we know about thiamine deficiency, doctors know to supplement thiamine as soon as symptoms occur, though the acute stage is known as Wernicke Syndrome. Thiamine supplements sometimes have to continue as long as three or four months after symptoms have resolved. But even then, if it’s caught too late, physical and psychiatric symptoms may never entirely go away.
There are other complications to treatment of W-K Syndrome. Because it’s now known as a disease resulting from alcoholism, you’re often stuck treating the alcoholism as well as the W-K. This can be especially difficult, as many alcoholics refuse treatment or have difficulty staying in treatment programs, and if you’re already suffering from W-K Syndrome, any more drinking is only going to exacerbate what’s already going on. And brain damage may be permanent even if W-K is treated immediately. So don’t give in to the alcohol. And if you do, watch your thiamine.
Bibliography:
1) Korsakoff, S.S. (1889) Psychic Disorder in Conjunction with Multiple Neuritis. (English translation with commentary). Neurology, 1955, 5: 394-406.
2) Zubaran et al. (1997) Wernicke-Korsakoff syndrom. Postgrad Med. J, 1997, 73: 27-31.
3) McKeon et al. (2008) The alcohol withdrawal syndrome. J. Nuerol. Neurosurg. Psychiatry, 2008, 79: 854-862.
Korsakoff, S.S (1955). Psychic Disorder in Conjunction with Multiple Neuritis. (English translation with commentary). Neurology, 5, 394-406
