B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse.

Alcohol misuse and alcohol withdrawal are associated with a variety of neuropsychiatric syndromes, some of which are associated with significant morbidity and mortality. B vitamin deficiency is known to contribute to the aetiology of a number of these syndromes, and B vitamin supplementation thus plays a significant part in prophylaxis and treatment. In particular, the Wernicke Korsakoff syndrome (WKS). due to thiamine deficiency, is a common condition in association with alcohol misuse, and is associated with high morbidity and mortality. Nicotinamide deficiency may result in a rarer condition, alcoholic pellagra encephalopathy, which often has a similar clinical presentation to WKS. This review considers the role of B vitamins in the aetiology and treatment of neuropsychiatric syndromes associated with alcohol misuse, with particular emphasis on WKS.

Brain pyruvate oxidation in experimental thiamin-deficiency encephalopathy.

Pyrithiamine-induced thiamin deficiency has been used in rat as an experimental form of Wernicke-Korsakoff encephalopathy, a disease associated with chronic alcoholism. Although the main etiological factor is known to be the lack of thiamin, the biochemical mechanisms involved in the pathogenesis remain unclear. Thiamin-dependent enzymes were studied in brain mitochondria: alpha-ketoglutarate dehydrogenase activity exhibited 40% reduction, whereas pyruvate dehydrogenase did not change significantly. Polarographic recordings of mitochondrial respiration revealed a decreased State 3, when using pyruvate/malate, alpha-ketoglutarate or glutamine as a substrate, but the respiration rates remained unchanged with glutamate or succinate. This fall in pyruvate oxidation may be due to the impairment of alpha-ketoglutarate dehydrogenase, which follows pyruvate dehydrogenase in the metabolic pathway. A time course of lactate concentration showed dramatic increases in thalamus, mid brain, hypothalamus and colliculli, consistent with the anatomopathological findings. No increases were found before the onset of neurological symptoms.

The Korsakoff syndrome.

BACKGROUND: Investigations of the Korsakoff syndrome by researchers from different disciplines have proliferated in recent years, making it apposite to review the various findings. METHOD: This review is based on the author's knowledge of reports in the major clinical and neuropsychological journals, supplemented by Medline searches to update particular subtopics. RESULTS: The Korsakoff syndrome is defined as a disproportionate impairment in memory, relative to other aspects of cognitive function, resulting from a nutritional (thiamine) depletion. The initial manifestations of the disorder are variable, and a persistent memory impairment can result from a non-alcoholic aetiology, although this seems to happen much less commonly than in the past - presumably because of generally higher standards of nutrition. Although there is agreement on the underlying neuropathology, the critical lesion sites for memory disorder have been debated. Recent evidence suggests that the circuit involving the mammillary bodies, the mammillo-thalamic tract and the anterior thalamus, rather than the medial dorsal nucleus of the thalamus, is particularly critical in the formation of new memories. The relationship of these deficits to thiamine depletion remains a topic of current investigation, as does the purported role of neurotransmitter depletions in the cholinergic, glutamate/GABA and catecholamine and serotonergic systems. Neuro-imaging studies have confirmed autopsy findings of more widespread structural and metabolic abnormalities, particularly involving the frontal lobes. CONCLUSIONS: The relationship of these neuropathological, neurochemical, and metabolic abnormalities to cognitive functioning, with particular reference to specific aspects of memory processing, has been considered in some detail. Whereas structural and/or neurochemical abnormalities within the limbic/diencephalic circuits account for anterograde amnesia, some other factor, such as frontal lobe dysfunction, must underlie the severe retrograde memory loss which is characteristically found in this syndrome.

Random generation deficit in alcoholic Korsakoff patients.

Korsakoff's syndrome often affects "executive" functions [Baddeley, A. Human Memory, Theory and Practice, 1990], which in anatomical terms are associated with the frontal lobes. However, in a previous study, Wiegersma, S. and de Jong, E. [J. clin. exp. Neuropsychol. 13, 847-853, 1991] failed to observe a diminished performance on the random generation task, although this task is thought to be sensitive to "executive" deficits. In the present study, we sought to replicate and clarify these earlier findings of Wiegersma and de Jong with a group of Korsakoff patients in whom frontal lobe dysfunction was indicated by a reduced performance on fluency tasks. Patients and controls were presented with three tasks. Digit span was used as an index of short-term memory capacity; memory search and comparison processes were measured with the missing item scan; and the randomisation task was used to assess the ability to produce non-routine, random sequences. The results showed that the performance of Korsakoff patients declined on the randomisation task while short-term retention and scanning were intact. Analysis of the responses indicated that the Korsakoff patients are able to suppress the dominant response, but have problems in generating and carrying out alternative strategies in novel problem situations.

Wernicke's encephalopathy and Korsakoff's psychosis: to fortify or not to fortify?

The conventional wisdom suggests that Korsakoff's psychosis, an amnesic disorder associated with prolonged alcohol consumption, is the chronic outcome of a thiamin deficiency first exhibited as Wernicke's encephalopathy. The present paper describes the debate in Australia over whether flour and alcoholic beverages should be fortified with thiamin, in an attempt to prevent Wernicke's encephalopathy and thus Korsakoff's psychosis. We conclude that the scientific evidence linking Wernicke's encephalopathy and Korsakoff's psychosis is tenuous. Certainly, it is not sufficient to support what would amount to mass medication.

[Korsakoff's syndrome as a prominent feature of bilateral paramedian thalamic infarction--a case report].

We reported the first Japanese case of bilateral paramedian thalamic infarction associated with prominent Korsakoff's syndrome. 53-year-old man suffered from semicoma on the morning of September 16th, 1988. After recovery of consciousness disturbance, neurological examination revealed vertical eye gaze palsy, areflexia of lower extremities, apathy with hypersomnia and amnesia. Amnesia was accompanied with prominent confabulation, disorientation and lack of insight into his own disability. While X ray-CT revealed only ambiguous low density area in the bilateral thalamus, MRI of horizontal section by short spin echo revealed symmetrical low signal area restricted in the paramedian area of bilateral thalamus, and that of coronal section revealed characteristic butterfly-shaped lesion. Left BAG revealed that both posterior thalamoperforating arteries showed type 3 variation of Percheron's classification which arisen from artery arcade bridging between both side of interpeduncular segment of posterior cerebral artery. He showed gradual improvement in apathy with hypersomnia and disorientation but not in Korsakoff's syndrome nor ophthalmoplegia.

Memory impairments caused by experimental thalamic lesions in monkeys.

A series of experiments examined the effects of selective diencephalic lesions upon object recognition in the cynomolgus monkey (Macaca fascicularis). In the first experiment it was found that extensive lesions of the medial thalamus (MT) produced a severe deficit in both relearning the recognition task and subsequently performing with retention intervals longer than 10 sec. Additional experiments showed that more selective lesions in either the anterior medial thalamus (AMT), the posterior medial thalamus (PMT), or the medial mamillary nucleus (MB) only produced mild recognition memory impairments. It is argued that a combination of damage is required to produce the severe memory impairments observed in cases of global diencephalic amnesia.

[Neuropathology of amnesic syndromes in man]. / Neuropathologie des syndromes amnésiques chez l'homme.

Controversies exist about the type of lesions observed in Korsakoff's syndrome or amnestic syndromes. A review of clinicopathologic data in the literature and findings in a personal series of 31 patients with amnestic syndromes (14 with alcoholism and nutritional deficiency, 8 with tumors including 2 with craniopharyngiomas, 5 with Pick's disease and presbyophrenic manifestations, 2 with vascular affections and one each with anoxia and herpetic encephalitis) were used to determine most frequently responsible lesions. Although it is generally accepted that there must be bilateral lesions divergent opinions are found with regard to the significance of limbic-hippocampomammillary circuit lesions. Some authors refute any specific role for the limbic circuit, and particularly any part played by Ammon's horn, in favor of a role for the temporal isthmus while others reject the possible role of the mammillary bodies and implicate the dorsomedian nucleus of the thalamus. The present study confirmed the importance of the limbic-hippocampomammillocingulus circuit in the maintenance of long-term memory. Involvement of the hippocampus appears obvious, particularly in disorders due to lesions of the subiculum and sommer's field. Mammillary body lesions are a constant finding in amnestic syndromes due to alcoholic nutritional deficiency and may also be present in Korsakoff's syndromes of tumoral origin e.g. a compression due to a craniopharyngioma. The rarely mentioned lesions of the cingular convolution are a further possible cause. The role of a thalamic lesion has not been totally confirmed, findings indicating equally frequent involvement of laterodorsal and dorsomedian nuclei. Clinical evidence, however, points to correlations between fabulation, false recognition and a thalamic lesion. The role of the fornix is debatable, although it is difficult to understand how destruction of the hippocampic formation or of the mammillary bodies can provoke memory disorders while an interruption in the structure that links them would have no consequences, unless it is admitted that as in animals other pathways exist that pass little or not at all through the fornix. Clinical expression of bilateral lesions of these structures differs according to whether they affect the posterior Ammon's horn region or lie more anteriorly in the trigonomammillothalamo-cingular complex. Clinical features of hippocampic amnesia include continuous anterograde amnesia with successive periods of forgetfulness, retrograde deficit of variable duration, parallel alterations of verbal and visuospatial memory and absence of fabulation.(ABSTRACT TRUNCATED AT 400 WORDS)

The Wernicke-Korsakoff syndrome in Queensland, Australia: antecedents and prevention.

The Wernicke-Korsakoff (W-K) syndrome is commonplace in Queensland, Australia. In a population of mental hospital inpatients with the W-K syndrome, males, particularly single males and widowers, and subjects who had undergone partial gastrectomy were over-represented. Some possible antecedents of the W-K syndrome are examined by focusing, not on W-K patients, but on problem drinkers. The results of a cross-national comparison of drinkers from Queensland, Australia and Merseyside, in the United Kingdom, are presented. The data support the hypothesis that Queensland drinkers are comparatively less involved with their families than Merseyside drinkers. This parallels a social perspective which regards allegiance to a male drinking group as very important in confirming social solidarity and 'mateship' in Australia. Such groups attach no importance to eating, setting the stage for dietary neglect and thiamine deficiency of which the W-K syndrome may be the end result. The fortification of alcoholic beverages with thiamine in Queensland has been previously proposed and attracted much local publicity. It seems possible that this publicity may have contributed to an increased awareness by heavy drinkers in Queensland of the need for supplementary B vitamins. However, this awareness is not so complete as to rule out the need for further measures aimed at reducing the incidence of the W-K syndrome in that state.