Box 1 | Korsakoff's syndrome and amnesia

From the following article:

The mammillary bodies: two memory systems in one?

Seralynne D. Vann & John P. Aggleton

Nature Reviews Neuroscience 5, 35-44 (January 2004)

doi:10.1038/nrn1299

The Russian clinician Sergei Sergeievich Korsakov first described the confusion and amnesia (both retrograde and anterograde) that are associated with nutritional (thiamine) deficiency (1887). This syndrome is most frequent in alcoholics but can have other causes119, 120. Wernicke's syndrome (1881) has a similar aetiology but relates to the nystagmus, confusion and ataxia that are sometimes associated with Korsakoff's syndrome. In this review, 'Korsakoff's syndrome' relates only to amnesias that result from nutritional deficiencies.

The pathology in Korsakoff's syndrome always involves the medial mammillary nucleus119, 121 and sometimes the lateral mammillary nucleus121. There is almost invariably other pathology in periventricular regions, including the thalamus121, 122, 123, 124. The cerebral cortex can also show atrophy125, and cortical functional imaging abnormalities might be the norm111, 126. Although in rare cases the pathology seems to be restricted to the mammillary bodies127, 128, these cases lack a detailed description of other susceptible areas. Mammillary body damage is not sufficient to account for all of the memory deficits that are associated with Korsakoff's syndrome. Severe retrograde amnesia is not seen in patients with mammillary body damage from other causes5, 106, 107, and the confabulation that is seen in patients probably results from frontal-lobe dysfunction129. Further evidence that mammillary body degeneration is not sufficient to induce the anterograde amnesia in Korsakoff's syndrome comes from studies of alcoholics with or without Wernicke's syndrome, in which mammillary body degeneration is sometimes found in the absence of amnesia121, 130, 131. Such examples have led to differing claims that the best predictor of memory loss is pathology in the anterior thalamic nuclei131, the medial dorsal thalamic nucleus111 or the midline thalamic nuclei123, 132. Given the variability in degree and sites of pathology, a careful quantitative analysis of cell loss in Korsakoff's syndrome is required. Using unbiased stereological techniques, Harding et al.131 compared patients with Korsakoff's syndrome, Wernicke's syndrome and alcoholism. They found that anterior thalamic nucleus pathology was the best predictor of memory loss131. Medial mammillary pathology was found in both Wernicke and Korsakoff cases, and was not specifically linked with amnesia.

This finding121 does not rule out a contribution from the mammillary bodies to amnesia, but indicates a primary role for the anterior thalamic nuclei. The most plausible account (see main text) is a threshold model in which partial medial mammillary body degeneration can accentuate the amnesic effects of anterior thalamic degeneration. There is some redundancy because the mammillary bodies project through the anterior thalamic nuclei. Medial dorsal thalamic damage could account for the executive deficits9, 39 that are found in some cases. It is also assumed that extensive mammillary pathology is sufficient to induce a demonstrable memory loss, which accounts for possible cases with no anterior thalamic pathology121, 127, 133. A related assumption is that the mammillary body damage in alcoholics and in Wernicke's syndrome (when there is no apparent memory loss) is incomplete134. This combined mammillary body–anterior thalamic account might also explain why it has proved difficult to find a consistent relationship between mammillary body volume and memory loss130, 131, 134, 135 — the presence of concurrent anterior thalamic pathology will outweigh the mammillary body effects.