Neuroanatomy and Neuropathology Associated with Korsakoff’s Syndrome

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.