Neuroanatomy and neuropathology associated with Korsakoff's syndrome

Abstract

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

Figure 1

A schematic diagram of the brain regions and connections involved in memory. The major hippocampus-anterior thalamus axis (shaded) involves the hippocampus, anterior thalamus, mammillary bodies and cingulate cortex and is connected by the fornix, mamillothalamic tract (MTT) and cingulum. The extended connections involving the amygdala, mediodorsal thalamus, and temporal and frontal cortices have a modulatory role (for description see (Aggleton and Brown, 1999)).

Figure 2

(A) A photograph of a coronal section through the diencephalon of a normal brain showing the nuclei involved in memory circuits. Nuclei labelled are AP= anterior principal nucleus of the thalamus; MD = mediodorsal nucleus of the thalamus; MB = mammillary body (medial mammillary nucleus of the hypothalamus). The tracts connecting these nuclei are the mamillothalamic tract (mtt) and fornix (f). The caudate nucleus (CN) and amygdala (Am) are also labelled. Photomicrographs of the anterior principal nucleus of the thalamus in a control subject (B, D) and KS patient (C, E). The volume of the nucleus is smaller in KS (C) compared with the control (B). A decreased density of neurons and increased density of glia can be seen in KS (E). Bar in A = 1cm. Bar in B = 1mm (equivalent for C). Bar in D = 50μm (equivalent for E).