Australian Drug and Alcohol Review 1988; 7:57-60

The Wernicke-Korsakoff Syndrome: Clinical Correlates and Dilemmas

John Price and Ray Kerr Department of Psychiatry, University of Queensland

Abstract: The Wernicke-Korsakoff syndrome remains common in Queensland despite a sharp fall in psychiatric hospital unit admissions with this diagnosis. The clinical features of the syndrome are discussed from neuropsychological and anatomical viewpoints. The so-called continuum hypothesis of memory impairment in problem drinkers has not been supported by recent neuropsychoIogical evidence. Alcoholic and non-alcoholic Wernicke's encephalopathy are compared. It is concluded that these two conditions differ in several respects and that thiamin deficiency might predispose certain areas of the brain to damage from alcohol.

Keywords: Alcoholism; brain damage, chronic; Wernicke's encephalopathy; alcohol amnestic disorder; thiamine deficiency; Queensland.

Introduction In 1979 Price and Theodoros ~ reported that

there were 170 cases of Korsakoff's psychosis in a Queensland mental hospital having at that time an inpatient population of 1,100. This was associated with a very high admission rate: 59 new admis- sions from January to June 1978. ~ However, the number of new admissions with this diagnosis has dropped markedly since this time) A good deal of the fall might simply be explained by changes in admission policy. Since 1978 this mental hospital has reduced its number of beds to about 600 and it has become very difficult to secure the admission there of patients with alcohol related brain damage.

The present situation in Queensland Two public hospitals perform most of the tests

of thiamin status carried out in Brisbane. Over the twelve month period beginning March 1986 we obtained from these laboratories details on 246 patients who had been found to be thiamin deficient (i.e. low red cell transketolase activity and/or raised thiamin pyrophosphate effect). Seventy-six per cent had documented heavy recent alcohol consumption. Of these 246, forty-four had alcohol related Wernicke's encephalopathy (WE). Our criteria required the presence of at

least two of the triad of confusional state, ophthalmoplegia and ataxia. Only 15 of these 44 patients had been referred for psychiatric opinion during the index admission and none was trans- ferred to psychiatric care. The first 19 WE patients have now been tested using the relevant sub-tests on the Wechsler Memory Scale and the majority have memory impairment of the Korsakoff type, that is, poor scores on logical memory, visual reproduction and associate learning. Our data are likely to underestimate the problem as many cases are almost certainly being missed? In addition, a number of cases may have been treated with thiamin without diagnostic tests being carried out. To summarise we believe that in Brisbane thiamin deficiency remains substantial.

In previous work we established several not- eworthy characteristics of Queensland Korsakoff patients.: Single males and widowers were sub- stantially over-represented. Generally the heavy drinking single males' social life pivoted around the use of alcohol from adolescence. Losing one's wife was one of a number of life events leading to increased drinking and subsequent WE after a relatively short period. Partial gastrectomy was a more common finding in Korsakoff patients than in an aged-matched population from alcohol rehabilitation units. Studies of thiamin absorption

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have not on the whole revealed that thiamin malabsorption is a feature in these patients?

Neuropsychological considerations One very important issue, the subject of much

debate, relates to what has come to be called the continuum hypothesis of Ryback. RybacD sug- gested that there is a continuum of cognitive impairment with the alcoholic Korsakoff patient occupying one end of this spectrum and the heavy social drinker the other end. According to this hypothesis, cognitive impairment is a function of the quantity and frequency of alcohol consump- tion as well as its duration. Ryan and Butters' originally supported Ryback's hypothesis. More recently Butters '~ has provided a summary of evidence tending to refute that hypothesis at least as far as memory is concerned. Firstly, long-term alcoholics with drinking histories similar to those of Korsakoff patients have much less severe learning impairments. Secondly, there is little evidence that similar processes underly the memory disorders of Korsakoff and alcoholic patients. Although the Korsakoff patients' in- ability to acquire new information involves an increasing sensitivity to interference, no evidence has been provided that the moderate learning deficits of alcoholics reflect this process. Thirdly, the alcoholics' memory deficits are most pronoun- ced and reliable when visual patterned materials serve as the to-be-remembered stimuli. In con- trast, Korsakoff patients are severely impaired in acquiring both verbal and non-verbal material2 ': There is very little evidence that the "typical" long~term alcoholic has a consistent problem in learning and remembering verbal information.

It has been suggested that the Korsakoff patients' inability to retrieve remote memories may be due to a primary defect in establishing new memories during the postulated years of failing memory prior to the diagnosis of Korsakoff's psychosis.

A convincing piece of evidence that does not support this hypothesis derives from a single case study2 The patient was an eminent scientist who developed alcoholic Korsakoff's psychosis at the age of 65, by which time he had written several hundred research papers and an extensive autobiography. On testing it became evident that he had a very severe retrograde amnesia for autobiographical events, with some sparing of information only from the very remote past. The critical point here is that this could not have been secondary to deficiency in original learning. Clearly his illness marked the acute onset of an

inability to access information once readily availa- ble to him and the hypothesis of an ongoing defect in establishing new memories was not supported. However, this does not exclude this occurrence in other individuals. In addition, the scientist in question also showed an impaired memory for scientific terms once known to him, showing that this form of memory can be impaired in Korsakoff patients.

Classification of alcohol related brain damage Cutting '' has tentatively proposed the following

classification for the more chronic organic syn- dromes which occur in problem drinkers:- 1. Subclinical psychological deterioration 2. Korsakoff's syndrome 3. Alcohol dementia or "accelerated psy-

chological deterioration" 4. Combined Korsakoff's syndrome and alco-

holic dementia 5. Subacute confusional state

Occasionally a patient may present, as one of our female patients does periodically, with de- lirium tremens following a prolonged binge. For some days after the sensorium clears she remains perplexed with inconsistent orientation and im- pairment of short-term memory. She has never shown biochemical evidence of thiamin de- ficiency. This pattern of disturbance recurs after a binge about every 2-8 months. During this period, it may appear that she has Korsakoff's psychosis and yet her rapid and total recovery and the pattern and precipitant of this state make this diagnosis untenable. She clearly belongs to category 5.

One problem with Cutting's classification lies in his conclusion that alcoholic dementia and "gradual-onset Korsakoff's psychosis" are one and the same. However, the incidence of eye signs in the series of cases he reviewed is given as 15% for alcoholic dementia and 41% for "gradual onset Korsakoff's psychosis". It seems reasonable to accept that the eye signs nystagmus and ophthal- moplegia relate to the Wernicke syndrome unless another explanation is evident, for example dilan- tin toxicity or acute alcoholic intoxication. Such patients should, perhaps, be included in category 4. The absence of eye signs, as Harper et al. have pointed out, '-~ does not exclude Wernicke's path- ology at necropsy but if they are present then it would seem reasonable to have a strong suspicion of Wernicke's pathology and thiamin deficiency. However, it does not follow that subsequent neuropsychological deficits relate to Wernicke's pathology: for, as Victor, Adams and Collins"

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point out, 16% of patients survive a full-blown Wernicke's encephalopathy with all the compon- ents of the Wernicke's triad but without develop- ing Korsakoff's psychosis. Complete recovery is not simply a function of a mild Wernicke's attack since in the majority of those who recovered the initial illness was severe. Perhaps in those patients the balance between the causative factors, thiamin deficiency and alcohol misuse, was weighted towards thiamin deficiency (see below).

From the clinical point of view there is nothing improbable in the notion that an established Korsakoff's psychosis may have evolved from a series of minor episodes of subclinical ence- phalopathy in each of which classical features of WE were absent or overlooked or misinterpreted. This would be comparable with multi-infarct dementia which runs an episodic course with some recovery of function between episodes while leading to a stepwise decline in function over time.

Anatomical considerations Wernicke's encephalopathy and Korsakoff's

psychosis are probably due to discrete midbrain and diencephalic (particularly medial thalamic) lesions secondary to thiamin deficiency. The cognitive impairment often seen in heavy drinkers may be due to changes in cerebral white matter,'* Torvik et al.~s reported on autopsies over a 5 year period where 29% of all deaths in Oslo were examined. They found no case of alcohol related brain damage without histological lesions of Wernicke's encephalopathy and suggested this was the main underlying lesion both in Korsak- off's psychosis and alcoholic dementia. Many of Torvik's cases presented the picture of global dementia,

Arendt et al. '~ have reported damage to the nucleus basalis of Meynert in "Korsakoff's dis- ease" but not in chronic alcoholics or Huntington chorea patients. This nucleus is the principal source of input of cholinergic fibres to the hippocampus and neocortex. Lesions here have been incriminated in the cholinergic depletion seen in Alzheimer's dementia. Lishman r has suggested that damage to this nucleus from thiamin deficiency might produce a global demen- tia. If so the subclinical psychological deficits in chronic alcoholics are not on a continuum with this severe form of alcoholic dementia and Cut- ring's term "accelerated psychological deteriora- tion" may need to be abandoned.

Non-alcoholic Wernicke's encephalopathy It is sometimes informative to compare what

one knows well with something that is closely

related to see what the similarities and differences encountered might mean - - this in accordance with the notion that "he knows not England who only England knows".

Let us compare non-alcoholic Wernicke's ence- phalopathy with the alcoholic variety. The former was well described in a 1947 paper *~ where 52 cases were encountered in a Singapore prisoner of war hospital during World War II. Polished rice was the principal dietary constituent and diarrhoeal diseases complicated practically every case. Alco- hol was not available and may be completely excluded from consideration.

The following observations warrant examina- tion and comment: 1. Anorexia and vomiting were prominent early

symptoms of the encephalopathy. Vomiting and nystagmus often developed together so that vomiting was best regarded as part of the encephalopathy not the cause of it. Victor, Adams and Collins ~ do not mention anorexia and vomiting as presenting features. Perhaps the gastro-intestinal disorders from which the POWs suffered predisposed them to these symptoms.

2. Nystagmus was always present in the POWs but all other eye signs were less frequent than in the alcoholic population described by Vic- tor, Adams and Collins.

3. Ataxia in the POWs was, except in 2 patients, related to peripheral nerve damage and appears not to have been a prominent feature. In the problem drinkers the ataxia was frequently cerebellar in type and the presenting feature in a third of all cases.

4. Hallucinations occurred in 25% of POWs. When hallucinations occur in patients with alcoholic Wernicke's encephalopathy they do not necessarily arise from alcohol withdrawal.

5. Cardiac beri-beri occurred in 20% of POWs. In the alcoholic Wernicke's patients the figure is less than 2%.

6. Acute memory loss was equally a feature in both series. Structures subserving memory function are therefore implicated in thiamin deficiency whether or not alcohol has been consumed.

7. All severe cases except one eventually re- covered completely from mental changes but after "prolonged administration of the whole vitamin-B complex". This strongly suggests that the permanent brain damage characterized by Korsakoff's psychosis has something to do directly with alcohol or with its metabolites. Thiamin deficiency and the accompanying tissue changes may allow alcohol in some way

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to damage the brain in a manner which otherwise would not occur.

8. During recovery large rice meals often brought about a temporary relapse in symptoms. This suggests an ongoing disturbance in cellular metabolism not immediately correctable by thiamin therapy.

In summary there are sufficient differences in these two forms of Wernicke's encephalopathy to indicate that they are not identical. Most striking is the entirely different prognosis in the two disorders. In conclusion, the arguments about the relative roles of thiamin deficiency and alcohol itself in the genesis of the alcoholic form of the Wernicke-Korsakoff syndrome seem likely to be resolved in favour of an interaction. What seems most likely on clinical evidence is that thiamin deficiency may predispose certain parts of the brain to damage from alcohol.

Correspondence and requests for reprints to: Dr. J. Price, Department of Psychiatry, Clinical Sciences Building, Royal Brisbane Hospital, Herston, Queensland, 4029.

References 1. Price J, Theodoros MT. The supplementation of

alcoholic beverages with thiamin - - a necessary preventive measure in Queensland. Aust NZ J Psychiatry 1979; 13: 315-320.

2. Price J, Kerr RA. Some observations on the Wernicke-Korsakoff syndrome in Australia. Br J Addict 1985; 80: 69- 76.

3. Price J, Kerr RA, Hicks M, Nixon PF. The Wernicke-Korsakoff syndrome in Queensland: a reappraisal with special reference to prevention. Med J Aust (in press)

4. Harper CG. Wernicke's encephalopathy: a more common disease than realised. J Neurol Neurosurg Psychiatry 1979; 42: 226- 231.

5. Kerr RA, Price J, Shanley BC. Partial gastrectomy and the Wernicke-Korsakoff syndrome. Aust Alco- hol Drug Rev 1983; 2: 65-67.

6. Ryback R. The continuity and specificity of the effects of alcohol on memory. Q J Stud Alcohol 1971; 32: 995-1016.

7. Ryan C, Butters N. Further evidence for a contin- uum of impairment encompassing male alcoholic Korsakoff patients and chronic alcoholic men. Alcoholism (NY) 1980; 4: 190-198.

8. Butters N. Alcoholic Korsakoff's syndrome: some unresolved issues concerning etiology, neuropath- ology and cognitive defects. J Clin Exp Neuropsych 1985; 7: 181-210.

9. Butters N, Cermak LS. Alcoholic Korsakoff's syndrome: an information processing approach to amnesia. New York: Academic Press, 1980.

10. Talland GA. Deranged memory. New York: Academic Press, 1965.

11. Cutting J. The relationship between Korsakoff's syndrome and ~Alcoholic Dementia". Br J Psy- chiatry 1978; 132: 240- 251.

12. Harper C, Giles M, Finlay-Jones R. Clinical signs in the Wernicke-Korsakoff complex: a retrospective analysis of 131 cases diagnosed by necropsy. J Neurol Neurosurg Psychiatry 1986; 49: 341-345.

13. Victor M, Adams RD, Collins GH. The Wernicke- Korsakoff syndrome. Philadelphia: FA Davis, 1971.

14. Harper CG, Kril IJ, Holloway RL. Brain shrinkage in alcoholics: a pathological study. Br Med J 1985; 290: 501- 4.

15. Torvik A, Linboe CF, Rogde S. Forebrain lesions in alcoholics. J Neurol Sci 1982; 56: 233-248.

16. Arendt T, Bigl V, Arendt A, Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsak- off's disease. Acta Neuropathol 1983; 61: 101-108.

17. Lishman LA. Alcoholic dementia: a hypothesis. Lancet 1986; 1: 1184-1186.

18. de Wardener HE, Lennox B. Cerebral beri beri (Wernicke's encephalopathy). Lancet 1947; 1: 11- 17.

19. Cragg B, Phillips S. Toxic effect of alcohol on brain cells and alternative mechanisms of brain damage in alcoholism. Aust Alcohol Drug Rev 1983; 2: 64-70.