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.
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Aggleton, J. P., & Brown, M. W. (1999). Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. The Behavioral and Brain Sciences, 22, 425–444. discussion 44–89.
Allsop, J., & Turner, B. (1966). Cerebellar degeneration associated with chronic alcoholism. Journal of the Neurological Sciences, 3, 238–258.
Arendt, T., Bigl, V., Arendt, A., & Tennstedt, A. (1983). Loss of neurons in the nucleus basalis of Meynert in Alzheimer’s disease, paralysis agitans and Korsakoff’s psychosis. Acta Neuropathologica, 61, 101–108.
Baker, K. G., Halliday, G. M., Harding, A. J., Kril, J. J., & Harper, C. G. (1999). Neuronal loss in functional zones of the cerebellum of chronic alcoholics with and without Wernicke’s encephalopathy. Neuroscience, 91, 429–438.
Brion, S., Plas, J., Mikol, J., Jeanneau, A., & Brion, F. (2001). Post-traumatic Korsakoff’s syndrome: clinical and anatomical report. Encephale, 27, 513–526.
Butterworth, R. F. (1989). Effects of thiamine deficiency on brain metabolism: implications for the pathogenesis of the Wernicke-Korsakoff syndrome. Alcohol and Alcoholism, 24, 271–279.
Caulo, M., Van Hecke, J., Toma, L., Ferretti, A., Tartaro, A., Colosimo, C., et al. (2005). Functional MRI study of diencephalic amnesia in Wernicke-Korsakoff syndrome. Brain, 128, 1584–1594.
Ciccia, R. M., & Langlais, P. J. (2000). An examination of the synergistic interaction of ethanol and thiamine deficiency in the development of neurological signs and long-term cognitive and memory impairments. Alcoholism, Clinical and Experimental Research, 24, 622–634.
Cole, M., Winkelman, M. D., Morris, J. C., Simon, J. E., & Boyd, T. A. (1992). Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction. Journal of the Neurological Sciences, 110, 62–67.
Cook, C. C., Hallwood, P. M., & Thomson, A. D. (1998). B-vitamin deficiency and neuro-psychiatric syndromes in alcohol misuse. Alcohol and Alcoholism, 33, 317–336.
Crowe, S. F., & El-Hadj, D. (2002). Phenytoin ameliorates the memory deficit induced in the young chick by ethanol toxicity in association with thiamine deficiency. Pharmacology Biochemistry and Behavior, 71, 215–221.
Cullen, K. M., Halliday, G. M., Caine, D., & Kril, J. J. (1997). The nucleus basalis (Ch4) in the alcoholic Wernicke-Korsakoff syndrome: Reduced cell number in both amnesic and non-amnesic patients. Journal of Neurology, Neurosurgery, and Psychiatry, 63, 315–320.
De Wardener, H. E., & Lennox, B. (1947). Cerebral beriberi. Lancet Jan, 4, 11–17.
Dusoir, H., Kapur, N., Byrnes, D. P., McKinstry, S., & Hoare, R. D. (1990). The role of diencephalic pathology in human memory disorder. Evidence from a penetrating paranasal brain injury. Brain, 113(Pt 6), 1695–1706.
Harding, A., Halliday, G., Caine, D., & Kril, J. (2000). Degeneration of anterior thalamic nuclei differentiates alcoholics with amnesia. Brain, 123(Pt 1), 141–154.
Harding, A. J., Wong, A., Svoboda, M., Kril, J. J., & Halliday, G. M. (1997). Chronic alcohol consumption does not cause hippocampal neuron loss in humans. Hippocampus, 7, 78–87.
Harper, C., & Kril, J. (1994). An introduction to alcohol-induced brain damage and its causes. Alcohol and Alcoholism. Supplement, 2, 237–243.
Harris J, Chimelli L, Kril JJ, Ray D (2008). Nutritional deficiencies, metabolic disorders and toxins affecting the nervous system. Greenfield’s Neuropathology Love S, Louis DN, Ellison DW. London, Edward Arnold Ltd. 8th Edition: 675–73.
He, X., Sullivan, E. V., Stankovic, R. K., Harper, C. G., & Pfefferbaum, A. (2007). Interaction of thiamine deficiency and voluntary alcohol consumption disrupts rat corpus callosum ultrastructure. Neuropsychopharmacology, 32, 2207–2216.
Homewood, J., & Bond, N. W. (1999). Thiamin deficiency and Korsakoff’s syndrome: failure to find memory impairments following nonalcoholic Wernicke’s encephalopathy. Alcohol, 19, 75–84.
Jarho, L. (1973). Korsakoff-like amnesic syndrome in penetrating brain injury. A study of Finnish war veterans. Acta Neurologica Scandinavica. Supplementum, 54, 3–156.
Karaiskos, I., Katsarolis, I., & Stefanis, L. (2008). Severe dysphagia as the presenting symptom of Wernicke-Korsakoff syndrome in a non-alcoholic man. Neurological sciences: official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 29, 45–46.
Konovalov, A. N., Dobrokhotova, T. A., Voronina, I. A., & Urakov, S. V. (1998). Case of Korsakoff syndrome and colloid cyst of the 3rd ventricle. Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova, 98, 49–51.
Kopelman, M. D. (1995). The Korsakoff syndrome. The British Journal of Psychiatry: The Journal of Mental Science, 166, 154–173.
Kopelman, M. D. (2002). Disorders of memory. Brain, 125, 2152–2190.
Kril, J. J., Halliday, G. M., Svoboda, M. D., & Cartwright, H. (1997). The cerebral cortex is damaged in chronic alcoholics. Neuroscience, 79, 983–998.
Kril, J. J., & Harper, C. G. (1989). Neuronal counts from four cortical regions of alcoholic brains. Acta Neuropathologica, 79, 200–204.
Langlais, P. J., & Savage, L. M. (1995). Thiamine deficiency in rats produces cognitive and memory deficits on spatial tasks that correlate with tissue loss in diencephalon, cortex and white matter. Behavioural Brain Research, 68, 75–89.
Mair, W. G. P., Warrington, E. K., & Weiskrantz, L. (1979). Memory disorder in Korsakoff’s psychosis. A neuropathological and neuropsychological investigation of two cases. Brain, 102, 749–783.
Malamud, N., & Skillicorn, S. A. (1956). Relationship between the Wernicke and the Korsakoff syndrome. Archives of Neurology and Psychiatry, 76, 585–596.
Mayes, A. R., Meudell, P. R., Mann, D., & Pickering, A. (1988). Location of lesions in Korsakoff’s syndrome: neuropsychological and neuropathological data on two patients. Cortex; a journal devoted to the study of the nervous system and behavior, 24, 367–388.
McEntee, W. J., Biber, M. P., Perl, D. P., & Benson, D. F. (1976). Diencephalic amnesia: a reappraisal. Journal of Neurology, Neurosurgery, and Psychiatry, 39, 436–441.
Parkin, A. J., Blunden, J., Rees, J. E., & Hunkin, N. M. (1991). Wernicke-Korsakoff syndrome of nonalcoholic origin. Brain and Cognition, 15, 69–82.
Pfefferbaum, A., Adalsteinsson, E., Bell, R. L., & Sullivan, E. V. (2007). Development and resolution of brain lesions caused by pyrithiamine- and dietary-induced thiamine deficiency and alcohol exposure in the alcohol-preferring rat: a longitudinal magnetic resonance imaging and spectroscopy study. Neuropsychopharmacology, 32, 1159–1177.
Phillips, S. C., Harper, C. G., & Kril, J. (1987). A quantitative histological study of the cerebellar vermis in alcoholic patients. Brain, 110, 301–314.
Phillips, S. C., Harper, C. G., & Kril, J. J. (1990). The contribution of Wernicke’s encephalopathy to alcohol-related cerebellar damage. Drug and Alcohol Review, 9, 53–60.
Pitkin, S. R., & Savage, L. M. (2001). Aging potentiates the acute and chronic neurological symptoms of pyrithiamine-induced thiamine deficiency in the rodent. Behavioural Brain Research, 119, 167–177.
Renou, P., Ducreux, D., Batouche, F., & Denier, C. (2008). Pure and acute Korsakoff syndrome due to a bilateral anterior fornix infarction: a diffusion tensor tractography study. Archives of Neurology, 65, 1252–1253.
Richardson, M. P., Strange, B. A., & Dolan, R. J. (2004). Encoding of emotional memories depends on amygdala and hippocampus and their interactions. Nature Neuroscience, 7, 278–285.
Squire, L. R., Amaral, D. G., Zola-Morgan, S., Kritchevsky, M., & Press, G. (1989). Description of brain injury in the amnesic patient N.A. based on magnetic resonance imaging. Experimental Neurology, 105, 23–35.
Squire, L. R., & Moore, R. Y. (1979). Dorsal thalamic lesion in a noted case of human memory dysfunction. Annals of Neurology, 6, 503–506.
Sullivan, E. V., Deshmukh, A., Desmond, J. E., Lim, K. O., & Pfefferbaum, A. (2000). Cerebellar volume decline in normal aging, alcoholism, and Korsakoff’s syndrome: relation to ataxia. Neuropsychology, 14, 341–352.
Sullivan, E. V., Rose, J., & Pfefferbaum, A. (2006). Effect of vision, touch and stance on cerebellar vermian-related sway and tremor: a quantitative physiological and MRI study. Cerebral Cortex, 16, 1077–1086.
Teuber, H. L., Milner, B., & Vaughan, H. G. (1968). Persistent anterograde amnesia after stab wound of the basal brain. Neuropsychologia, 6, 267–282.
Thomson, A. D., & Marshall, E. J. (2006). The natural history and pathophysiology of Wernicke’s Encephalopathy and Korsakoff’s Psychosis. Alcohol and Alcoholism, 41, 151–158.
Toth, C., Voll, C., & Macaulay, R. (2002). Primary CNS lymphoma as a cause of Korsakoff syndrome. Surgical Neurology, 57, 41–45.
Tsivilis, D., Vann, S. D., Denby, C., Roberts, N., Mayes, A. R., Montaldi, D., et al. (2008). A disproportionate role for the fornix and mammillary bodies in recall versus recognition memory. Nature Neuroscience, 11, 834–842.
Vetreno, R. P., Hall, J. M., & Savage, L. M. (2011). Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment. Neurobiology of Learning and Memory, 96, 596–608.
Victor, M., Adams, R. D., & Collins, G. H. (1989). The Wernicke-Korsakoff Syndrome and related Neurological Disorders of Alcoholism and Malnutrition. Philadelphia: FA Davis Co.
Wijnia, J. W., & Goossensen, A. (2010). Cerebellar neurocognition and Korsakoff’s syndrome: an hypothesis. Medical hypotheses, 75, 266–268.
Yarde, W. L., Kepes, J. J., & O’Boynick, P. (1995). Craniopharyngioma presenting as Korsakoff psychosis. Kansas Medicine, 96, 22–23.
Yoneoka, Y., Takeda, N., Inoue, A., Ibuchi, Y., Kumagai, T., Sugai, T., et al. (2004). Acute Korsakoff syndrome following mammillothalamic tract infarction. AJNR. American Journal of Neuroradiology, 25, 964–968.
Zahr, N. M., Pitel, A. L., Chanraud, S., & Sullivan, E. V. (2010). Contributions of studies on alcohol use disorders to understanding cerebellar function. Neuropsychology Review, 20, 280–289.
Zhang, S. X., Weilersbacher, G. S., Henderson, S. W., Corso, T., Olney, J. W., & Langlais, P. J. (1995). Excitotoxic cytopathology, progression, and reversibility of thiamine deficiency-induced diencephalic lesions. Journal of Neuropathology and Experimental Neurology, 54, 255–267.
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The research described in this article was facilitated by the NSW Tissue Resource Centre at the University of Sydney which is supported by the National Health and Medical Research Council of Australia, Schizophrenia Research Institute and the National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725).
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Kril, J.J., Harper, C.G. Neuroanatomy and Neuropathology Associated with Korsakoff’s Syndrome. Neuropsychol Rev 22, 72–80 (2012). https://doi.org/10.1007/s11065-012-9195-0
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DOI: https://doi.org/10.1007/s11065-012-9195-0