Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks.

What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia?

In this review, the clinical, neuropsychological, and neuroimaging findings in the alcoholic Korsakoff syndrome and in thalamic amnesia, resulting from focal infarction, are compared. In both disorders, there is controversy over what is the critical site for anterograde amnesia to occur-damage to the anterior thalamus/mammillo-thalamic tract has most commonly been cited, but damage to the medio-dorsal nuclei has also been advocated. Both syndromes show 'core' features of an anterograde amnesic syndrome; but retrograde amnesia is generally much more extensive (going back many years or decades) in the Korsakoff syndrome. Likewise, spontaneous confabulation occurs more commonly in the Korsakoff syndrome, although seen in only a minority of chronic cases. These differences are attributed to the greater prevalence of frontal atrophy and frontal damage in Korsakoff cases.

An international perspective on the prevalence of the Wernicke-Korsakoff syndrome.

In the Western world previous studies have shown that the majority of cases of the Wernicke-Korsakoff syndrome (WKS), which is caused by thiamine deficiency, occur in alcoholics. However, in France, a country with one of the highest per capita consumptions of alcohol, the prevalence of the WKS was found to be only 0.4% in a small retrospective autopsy study. This figure is compared with data sent to the authors by a number of neuropathologists from the U.S.A., Europe, Scandinavia and Australia. There was no obvious correlation between the prevalence rates of the WKS, which were highest in Australia (2.8%-previously published), and per capita consumption of alcohol. Other issues such as diet, National programs for supplementation of foods with thiamine, and drinking habits are considered. The pathological diagnosis of the WKS can often be made on macroscopic examination of the brain after fixation in formalin. The mammillary bodies are smaller than normal in most cases of chronic WKS. However in this study it was found that the most common causes of small mammillary bodies were Alzheimer's disease and atrophy due to transneuronal degeneration secondary to lesions in the hippocampus.

Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction.

In order to support the concept that a lesion of the thalamus is sufficient to cause a Korsakoff syndrome, we are presenting 5 patients, all of whom developed the syndrome after sustaining a left (dominant) thalamic infarction. Two patients had pure thalamic strokes followed by a permanent Korsakoff syndrome. One of these patients was studied with neuropsychometric testing, as well as with a modern MRI scan. In 2 other patients, clinical and imaging data indicate that infarction was not limited to the thalamus. Another patient had bilateral thalamic infarcts but only a temporary Korsakoff syndrome. Neuropathological data are needed to elucidate the exact anatomical substrate of dominant thalamic Korsakoff syndrome.

The prevalence of the Wernicke-Korsakoff syndrome in Sydney, Australia: a prospective necropsy study.

In a prospective necropsy study, the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Sydney, Australia was 2.1% of adults over the age of 15 years. The population studied encompassed a wide spectrum of socio-economic and cultural backgrounds. Abuse of alcohol appeared to be the major predisposing factor to the development of the WKS in cases which were adequately documented. This high prevalence rate is in line with other clinical and pathological Australian studies and provides additional support for the idea of prevention of the WKS by the use of thiamin supplements in the Australian diet in flour, bread and perhaps alcoholic beverages.

Neuroanatomical consequences of thiamine deficiency: a comparative analysis.

In this paper, the neuroanatomical locus of lesions produced by thiamine deficiency was examined. An attempt was made to analyse the relationship between the pattern of development of neuropathological lesions and such experimental variables as length of deficiency, species, and method of deprivation. There is evidence in all species studied that certain structures are selectively vulnerable to thiamine deficiency. Current theories concerning the pathogenesis of lesions, including metabolic, neurophysiological, and genetic mechanisms were also discussed. It was concluded that the selective vulnerability of certain structures to thiamine deficiency is the result of a complex interaction between cellular, neurochemical, and metabolic properties of various brain regions which make them more susceptible to a breakdown in thiamine-dependent systems.

[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)

Memory impairments following restricted medial thalamic lesions in monkeys.

Thalamic contributions to memory were assessed in monkeys with lesions placed in the medial portions of either the anterior or posterior thalamus (AMT and PMT, respectively). Both lesions produced a moderate impairment in a test of object recognition memory. Furthermore, all three animals in the PMT group and two out of the three in the AMT group were moderately impaired on a test of object-reward associative memory. Comparison of these results with those of a previous study in which the AMT and PMT regions were removed jointly (Aggleton and Mishkin 1983) suggests that damage in either region can induce a memory loss but that combined damage to both is required to produce a full-blown amnesia.

System degeneration of the thalamus. A clinico-neuropathological study.

A case of essential degeneration of the thalamus is reported. The patient was a 43-year-old Japanese male, who, a few weeks after mild head trauma, suffered from forgetfulness, psychomotor slowing, and Korsakoff's syndrome. Four to five months later, there were optical hallucinations and delirium and he died 19 months after the onset of symptoms. Neuropathological examination revealed symmetrical thalamic degeneration, whose distribution corresponded to phylogenetically younger subunits of the thalamus. In addition, there was olivovermian degeneration. These findings are identical to those of eleven cases hitherto reported. Five of these were Japanese, including the present one. The syndrome thalamic degeneration may now be classified as a special type of "system degeneration".

"Thalamic" dementia in herpes encephalitis: clinico-pathological report.

Herpes zoster (HZ) primary affections of the CNS are rare and, in most of the reported patients, are representing variously extended forms of ascending myelitis. Our examination concerns a man who at the age of 37 developed apathy after a feverish episode with iridocyclitis. Six months later an ophthalmic HZ was diagnosed and thenceforth the patient showed a dementia with Korsakow's syndrome, apathy and a right hemipalsy, and diplopia appeared; the later symptoms remitted after steroid therapy. Post-mortem examination revealed a slowly progressive encephalitis with symmetrical impairment of the anterior ventral, medial, and centrum medianum of the thalamus. The HZ origin of the lesions and the relation between their site and the peculiar form of dementia, to be ascribed to the "thalamic" ones, are discussed. A vasculitis process can be hypothesized considering both the symmetrical localisation and the microscopical aspects of the lesions.

Memory disorder in Korsakoff's psychosis: a neuropathological and neuropsychological investigation of two cases.

Neuropathological findings in the brains of two alcoholic patients with Korsakoff's psychosis are reported. Their memory defects had been studied in detail quantitatively over a period of nine years in one case and three years in the other, relevant details of which are presented. Both patients had had a relatively pure long-term memory impairment in the absence of other cognitive deficits and in the absence of a short-term memory impairment. Their retrograde amnesia for public events and famous faces had been measured and found to have extended backwards over at least twenty-five years. There was severe impairment in anterograde recognition memory for both verbal and non-verbal material. On a newly prepared memory quotient battery both patients had scored well below the bottom of the normal scale (less than 60, where 100 is the mean with a standard deviation of +/- 15). Both patients had also shown the characteristic differential improvement in retention when tested by cued recall and also the characteristic 'prior learning effect', i.e. normal retention of one list of words when tested by cued recall but impaired retention of a second list sharing the same cues as the first list. There had been a slight but significant deterioration in intelligence in one of the patients in the two years prior to his death, although his IQ still fell within the normal range. The other patient remained undeteriorated until his death, and his IQ also was close to an estimated measure of his premorbid IQ. In the brains of both patients there was marked gliosis, shrinkage and discolouration bilaterally in the medial nuclei of the mammillary bodies. In addition there was a thin band of gliosis bilaterally between the wall of the third ventricle and the medial dorsal nucleus, the rostral limit lying anterior to the medial dorsal nucleus. In the patient with no intellectual deterioration these were the only pathological changes that were seen. In neither patient was there evident local loss of nerve cells, gliosis or any other qualitative evidence of abnormality in the hippocampi, the white matter of the temporal lobes or the greater part of the medial dorsal nuclei, although it is difficult to be certain whether there was any overlap between the band of gliosis and the most medial region of the medial dorsal nueleus and other adjacent thalamic nuclei. In the other patient there was also a small zone of softening in the cerebellum and an increase in astrocytes in other regions of the cerebral hemispheres, including the basal ganglia, amygdala, and brain-stem, but without noticeable loss of cells. The question of the minimal lesion for the alcoholic Korsakoff amnesic state, and some aspects of the related anatomy, is discussed in the context of other reports in the literature which are, however, difficult to assess in the absence of details of the specificity, severity and character of the memory disorders.