Journal of the Neurological Sciences, 110 (1992) 62-67 © 1992 Elsevier Science Publishers B.V. All rights reserved 0022-510X/92/$05.00
62
JNS 03796
Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction Monroe Cole a, M.D. Winkelman a, J.C. Morris a.t, J.E. Simon b and T.A. Boyd c Departments of a Neuroiogy, b Radiology and c Psychiatry of the MetroHealth Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA (Received 25 September, 1991) (Revised, received 3 February, 1992) (Accepted 12 February, 1992)
Key words: Thalamus; Amnesia; Amnestic syndromes; Memory disorders; Korsakoff syndrome
Summary 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.
Introduction
Case reports
The role of the thalamus in m e m o r y was strongly emphasized in the 1971 seminal studies of Victor et al. concerning the alcoholic-nutritional Wernicke-Korsakoff syndrome. They pointed out that a persistent amnestic state ( K o r s a k o f f s y n d r o m e ) occurred only when there was a lesion in the dorsal-medial nucleus of thalamus. They defined the syndrome as " a n abnormal mental state in which m e m o r y a n d learning are affected out of all proportion to o t h e r cognititve functions in an otherwise alert and responsive p a t i e n t " , a definition which we employ in this report. We report 5 f u r t h e r cases resulting f r o m left thalamic infarction in o r d e r to a u g m e n t the m e a g e r literature supporting the thesis that a unilateral dominant thalamic lesion can cause Korsakoff syndrome.
Left thalamic infarction and permanent K o r s a k o f f syndrome Case 1 G.D., a 51-year.old right-handed woman, was referred for neurological evaluation for loss of memory. Because of a 6-month history of nocturnal chest pain unrelated to exertion, she had had a cardiac catheterization 3½ weeks prior to neurological evaluation. Electrocardiogram, stress tests, and catheterization were all normal. Her husband reported that she was in her usual health on arrival to hospital for cardiac catheterization. One hour post-procedure her husband noted that she was confused. She was discharged home 5 hours later (6.00 p.m.) and was observed to have diminished speech and to act 'as if in a fog'. She retired at 7.00 p.m. The next morning she was 'quiet and subdued' but went to work. Later in the day her husband spoke to her on the telephone, and she said that she had tried to call him but did not remember his telephone number, although she had called him daily for years. At the time of the initial neurological evaluation her condition was unimproved. Past history was noncontributory except for treated hypertension. Examination revealed her to be alert. She did not know the capitals of Ohio, New York, or Pennsylvania but did know the capital of the United States. The date was missed by 1, then 2 days. She achieved a score of 26 on the Mini-Mental Status Test of Folstein, Folstein and McHugh (1975). Given a 30-word s~.ory to remember she could recall no details after 2 repetitions and an interval of 10 minutes. Blood pressure was 140/80. The neurological examination was otherwise normal. MRI of the brain revealed a small infarct in the left dorsal-medial nucleus of the thalamus (Fig. 1). Psychometric evaluation re-
'Present address: Departments of Neurology and Pathology (Neuropathology), Washington University School of Medicine, St. Louis, MO 63110, USA. Correspondence to: Monroe Cole, M.D., Department of Neurology, MetroHealth Medical Center, 3995 Scranton Road, Cleveland, OIi 45109, USA. Tel.: (216) 459-3990; Fax: (216) 459-3119.
63 vealed a deficit of higher cognitive functions, but memory, and more particularly verbal memory, was impaired out of proportion to the other cognitive functions, as depicted in Table 1. Case 2 L.B., a 73-year-old right-handed white woman, was admitted to hospital in October 1979 because of a change in mentation. After a 2-day period of emesis, she was noted by her family to be 'confused' and speaking in a bizarre m a n n e r She ha J T~,~e II diabetes mellitus and hypertension. Examination revealed h~c to be lethargic and uncooperative. Blood pressure was 180/90 mmHg. She was oriented to person, place, and date but could not remember her children's names or ages, her address, phone number, or daughter's phone number. She could name the President, but no previous presidents. She could not name the mayor of Cleveland or the lake upon which the city is located. She could recall 1 / 3 objects in I minute and 0 / 3 in 5 minutes. Cranial nerves were normal except for punctate retinal hemorrhages. Strength was normal and there was no ataxia of limbs, hut the gait was slow and wide-based. There was evidence of a peripheral neuropathy. The cranial CT scan (Fig. 2) showed an infarct in the left thalamus. She was re-examined by one of us OCM) 2 years later. History given by her neighbor revealed that the patient spent most of her days l~,ing on the couch, occasionally watching television, and rarely going outside. She was pleasant, cooperative, and well-groomed, as well as alert and oriented to person, place and time. She knew her birthdate, birthplace and phone number, but not her street address. She did not remember the dates of either of her two weddings; nor did she remember the dates of either of her husbands' deaths. She was able to give the names but not the ages of 4 of her children. She did not recall what she had eaten for dinner on the night before the examination. She could not remember even 1 / 3 objects in 5 minutes.
She was unable to subtract 7 from 93 serially, but was able to do simple calculations correctly (8+4, 12+13, 100-7, $1.75 equals 7 quarters). She could correctly repeat 5 digits forward but only 2 in reverse. Language function was normal. No other significant neurological abnormalities were noted. We have seen 3 other patients with the sudden onset of an amnestic syndrome, either permanent or temporary, in whom the pathogenetic role of the infarct in the left thalamus for the memory loss is less clear.
Korsakoff syndrome with thalamic plus other infarcts Case 3 S.T., a 67-year-old white woman, suddenly fell, without loss of consciousness. For the remainder of the day she noted intermittent right-sided numbness ('tingling') and unsteadiness of gait. She was brought to hospital the next day. Examination revealed a blood pressure of 174/100 mm Hg and regular pulse of 120. She appeared bewildered and anxious but oriented to person and place, yet not to time. Language function was normal. She was unable to recall her birthplace, the ages of her children, or any recent Presidents of the United States. She could not remember 3 objects for 1 minute, nor recall what she had eaten for her last meal. She could not name the color of any object shown to her but could correctly name the color related to certain words, e.g. 'grass', 'sky'. Object naming was normal. There was a right homonymous inferior quadrantanopsia and right visual inattention. There was a mild right hemiparesis, including face, mild right hemihypesthesia, and pseudoathetosis of the right hand. Tendon reflexes were exalted on the right, and the right plantar response was extensor. CSF was unrevealing, serum and CSF serologies for syphilis non-reactive, and the
Fig. I. Case I. Infarct in left dorsal-medial thalamus (arrow). (A) horizontal, (B) coronal views.
64 TABLE 1 NEUROPSYCHOMETRIC EVALUATION OF CASE 1 WAIS-R Full Scale IQ 84 Verbal IQ 83 Performance IQ 88 PPVT-R 76 BNT Raw score 39 TONI 92 WRAT-R Reading 101 Spelling 103 Arithmetic 115 WMS-R General Memory Index 59 Verbal Index 56 Visual Index 92 Attention/Concentration 74 Delayed Recall Index 73 Sensory Perceptual Examination (27) Speech-Sounds Perception (27) Trails Test, A and B (27) Seashore Rhythm Test (27)
(14th percentile) (13th percentile) (21st percentile) (6th percentile) (mean 55.7 SD -- 3.3) (30th percentile) (53rd percentile) (58th percentile) (84th percentile) (lst perecentile) (lst percentile) (30th percentile) (4th percentile) (4th percentile) normal 0 errors (normal) normal 2 errors (normal)
Abbreriations: WAIS-R--Wechsler Adult Intelligence Scale - Revised (28); PPVT-R--Peabody Picture Vocabulary Test - Revised (29); BNT = Boston Naming Test (30); TON! = Test of Nonverbal Intelligence (31); WRAT-R =Wide Range Achievement Test Revised (32); WMS-R = Wechsler Memory Scale - Revised (33).
Fig. 3. Case 3, Left thalamic (arrow) and posterior temporal infarction. hospital course unchanged. Cranial CT (Fig. 3) showed development of a left occipital-posterior temporal infarct, as well as a left posterior thalamic infarct. One year later she continued to have a prominent Korsakoff psychosis, persistent color agnosia and a mild right hemiparesis and hemihypesthesia. Specifically, she could repeat 5 digits forwards and backwards but could not recall her wedding day, the cause of her husband's death or her children's ages. She did not know her current address or phone number and remembered 0/3 objects after 5 minutes. While she was described by her family as extremely hardworking prior to her illness, after hospitalization she spent most of her time sitting and watching television. She was fully oriented, displayed normal language function and performed simple calculations without error. Visual fields were normal to confrontational examination and the hemiparesis was improved. Case 4 S.N., a 72-year-old white man, was hospitalized on the Neurological Service of the Cleveland Metropolitan General Hospital with a severe right spastic hemiparesis, left 'oculomotor dysfunction' (not further defined), fluent aphasia and a Korsakoff syndrome. Cranial CT revealed a left thalamic infarct. The patient was re-examined by one of us (JCM) 1 year after ~lischarge. His family reported that he usually mistook his daughter for his deceased wife, or his granddaughter for his daughter. On examination he responded readily to queries, followed 3-step commands slowly but without error, was mildly dysarthric but not dysphasic. He could not repeat more than 4 digits forward. He could not subtract 7 from 100, but could correctly add 8+ 12 and 12+ 13. He knew his name but not the year. He did not know what part of tb,e city he was in, where he was born, his birthdate, or his age. He was able to repeat the names of 3 objects immediately, but not after 4 min, and did not remember his meals of the day. While he responded readily to questions, impulsion to thought or action was decreased.
65
Localization of lesions
Fig. 4. Case 5. Large left thalamic infarct. Note small right thalamic infarct (arrow).
Utilizing the method and atlas of Talairach and Tournoux (1988), we concluded that the lesion in Case 1 is in the nucleus dorsalis medialis and nucleus anterior thalami, and possibly the mamillothalamic tract (Fig. 1). The lesion in Case 2, which is larger than the lesion in Case 1, is in the nucleus centrum medianum, the inferior tip of the nucleus dorsalis medialis and probably the nucleus ventralis lateralis. The lesion in Case 3 appears to be in the nucleus puivinaris and probably the nucleus ventralis posterolateralis. In Case 4 we have only the report of a thalamic infarct without further localization. In Case 5 the infarct is in the lateral third of the nucleus dorsalis medialis and also involves the centrum medianum, ventralis lateralis, and probably the nucleus lateralis posterior and the mamillothalamic tract. In addition, a small infarct is present in the lateral part of the right nucleus dorsalis medialis. The localization in Cases 2 and 3 is tentative at best because of the quality of the CT, made over 10 years ago. We are more confident of our localization in Cases 1 and 5, for whom MRI is available. In Case 3, it may be argued that the infarction of the postero-inferior left temporal lobe is as likely to be the cause of the Korsakoff syndrome as is the infarction in the posterior lateral thalamus.
Discussion The patient had a right spastic hemiplegia involving face, arm and leg. There was a mild left hemihypesthesia and a mild paresis of adduction of the right eye without nystagmus of the abducting eye, ptosis or pupillary abnormality.
Large left and small right thalamic infarcts with temporary Korskaoff syndrome Case 5 V.S., an 80-year-old black woman, was admitted to hospital for confusion and decreased memory noted over the course of 1 week. When first evaluated she was uncooperative, lethargic, and oriented only to place. Language functions were intact. There was right-left confusion. She was able to remember I out of 3 objects in 3 rain. Attention and concentration were poor. No definite paresis, sensory deficit, or ataxia were noted. She gradually improved, but the ability to record new memories was severely enough impaired (compared to other cognitive functions) that 4 days after admission one of us (MW) considered her to have a Korsakoff syndrome. However, improvement continued. Nine days after admission she was alert, cheerful and humorous. She knew the month but not the day or year, nor the year of her birth. She gave her age as '69, no 70, no 79'. She knew that she had been tranferred to the Neurology Service one day previously, which floor her new room was on, and where in the hospital she had been previously. Language function was normal. She was able to remember most of a 30-word story for 5 and 10 min and knew the names and races of the present and previous mayors. There was a very slight right hemiparesis and no visual field defect to confrontational testing; there was no sensory deficit or ataxia. Cranial CT and MRI showed a large infarct in the left thalamus, as well as a small infarct in the right thalamus (Fig. 4).
Victor et al. (1971, 1989) emphasize that the persistent amnestic state (Korsakoff syndrome) was related to the presence of pathology in the medial-dorsal nucleus of the thalamus and the medial part of the pulvinar. In their analysis, data concerning thalamic nuclei were used only if the nucleus could be identified with certainty. Histopathological lesions consisted of neuronal loss, loss of myelinated fibers, and astrogliosis. The lesions were bilateral and reasonably symmetrical. Mair et al. (1979) argue against a crucial role for the medial-dorsal nucleus of the thalamus in the genesis of the amnestic syndrome, stressing instead the gliosis medial to the nucleus in the paratenial nucleus. Their figures 15 and 18 suggest to us, however, neuronal loss and gliosis within the dorsal-medial nucleus itself. Brion et al. (1985) conclude from their review of the literature that the role of a thalamic lesion has not been totally confirmed ('beaucoup d'incertitudes persistent...'). There is little question that localized lesions in the thalamus, usually vascular, occasionally traumatic, may cause Korsakoff syndrome. Von Cramon et al. (1985) describe 4 patients with chronic amnesia and ventral thalamic infarcts. Three had bilateral lesions and 1 a
66 left thalamic lesion. They comment that only a minor ventrobasal portion of the dorsal medial-nucleus was involved. In two other cases with large dorsal mediallesions memory was spared. They ascribe the amnestic syndrome to the lesion of the mamillothalamic tract. Nichelli et al. (1988) describe alterations in memory functions after bilateral infarction of the dorsal-medial and midline nuclei of the thalamus, as well as the internal medullary lamina, the mamillothalamic tract, and the lameUa medialis oralis. GraffoRadford et aL (1990) also describe a significant amnestic state in patients with bilateral anterior thalamic infarcts involving the mamillothalamic tracts. Anterograde amnesia due to bilateral infarcts of the dorsal medial and internal medullary nuclei and the mamillothalamic tracts was described in 1 case by Schott et al. (1980). Squire and Moore (1979) have provided CT evidence of a fencing foil lesion of the left dorsal-medial nucleus of the thalamus resulting in a well-studied case of Korsakoff syndrome. As pointed out in a later MRI study of the same patient (Squire et al., 1989), there was also damage to the hypothalamus, including the mamillary nuclei, by the passage of the foil, which pierced the right nostril. Patients 1, 2 and 3 of Graff-Radford et al. (1984) each showed deficits of verbal and visual memory after infarction in the distribution of the left tuberothalamic artery. The location of their lesions (of. Figs. 1-3) are virtually identical to the location of the lesion in our Case 1. Speedie and Heilman (1982) reported a case of sudden amnestic psychosis due to a presumed embolic infarct in the left dorsal-medial nucleus of the thalamus. The location of the lesion is similar to our Case 1. Michel et al. (1982) descr;be a persistent mild anterograde verbal amnesia with preservation of retrograde memory in a patient sustaining a large left thalamic infarct. Goldenberg et al. (1983) describe what they term 'transient global amnesia', which was maximal for 2 days but present for more than 5 days. The infarct of the left anterior thalamus involved nuclei ventralis anterior, ventralis lateral is, anterior, the anterior part of dorsalis medialis and the mamillothalamic tract. The amnesia partially resolved, leaving only a reduction in verbal memory capacity. The authors postulated that the partial recovery of memory function was due to the unilaterality of the lesion. Mori et al. (1986) carefully studied a patient with an anterograde verbal amnesia after left anterior thalamic infarction. The infarct was in the distribution of the polar (tuberothalamic artery (Graff-Radford et al. 1984) and paramedian arteries (Percheron 1973). The dorsal medial nucleus was considered to be largely spared. Akiguchi et al. (1987) reported 7 patients with left thalamic infarcts with recent memory loss and impaired learning of verbal information. One patient with
a right thalamic infarct was unable to learn visuospatial as well as verbal information. The authors localized the lesions to the dorsal-medial and anterior nuclei of the thalamus. Castaigne et al. (1980) describe 3 of their 28 patients with paramedian thalamic infarcts who could be adequately tested. These patients showed a marked deficit of anterograde memory 'confirming the clinical and experimental findings of Victor et al. (1971)'. In their patient 5, the mamiilothalamic tract was spared. They state, 'Involvement of the median nucleus does not appear to explain the memory deficit'. These authors imply that the lesion was unilateral but do not indicate which side was involved. They continue, 'Only bilateral and complete lesions of the median nucleus have been shown to cause disturbance of memory'. In their table 3 they indicate that the lesion in the median nucleus is in fact bilateral; table 4 is less clear. Wallesch et al. (1983) felt that laterality of a unilateral thalamic lesion was not the determining factor in amnesia but that rostral lesions of either side were more likely to cause memory loss than were posterior thalamic lesions. Finally, Case 3 of Gaffan et al. (1991) showed anterograde amnesia after a left dorsal-medial thalamic hemorrhage, and Case 4 of the same authors showed an anterograde verbal amnesia after left dorsal-medial thalamic infarction. Our cases, in addition to those previously published, allow us to arrive at some conclusions regarding the relation of thalamic lesions to an amnestic syndrome, i.e. Korsakoff syndrome. Unquestionably, bilateral thalamic lesions alone may cause Korsakoff syndrome. Unilateral (dominant) thalamic lesions may also cause Korsakoff syndrome without the presence of other lesions in the brain. Our Case 1 is a particularly good example but certainly not the first reported. Information as to the exact thalamic structures involved is less certain. There is very little good pathological data regarding Korsakoff syndrome with a vascular lesion limited to the dorsal-medial nucleus, or nuclei. In a few instances imaging data seem to be reasonably, but not irrefutably, certain. In Case 1, our best observed case, the lesion, although discrete, extends beyond the borders of the dorsal-medial nucleus. At this time we would agree with Mori et al. (1986) that 'it remains unproved whether combinations of lesions are required for amnesia, and if so, which combinations are necessary'. Furthermore, as pointed out in the excellent review by Stuss et al. (1988), not only are the 2 aliencephalic systems of the dorsal-medial and anterior nuclei intimately linked structurally, but it appears extremely difficult to damage one without damaging the other. As other investigators have pointed out (Kritchevsy et al., 1987) unilateral or bilateral thalamic lesions do not necessarily cause a permanent Korsakoff syn-
67
drome. This is illustrated by our Case 5, who is similar to the patients reported by Goldenberg et al. (1983), Muller et al. (1990) and Swanson and Schmidley (1985).
References Akiguchi, I., T. Ino, H. Nabatame, F. Udaka, K. Matsubayashi, H. Fukuyama and M. Kameyama (1987) Acute onset amnestic syndrome with localized infarct on the dominant side. Comparison between anteromedial thalamic lesion and posterior cerebral artery territory lesion. Jpn. J. Med. 26: 15-20. Brion, S., J. Mikol and J. Plas (1985) Neuropathologie des syndromes amn~siques chez l'homme. Rev. Neurol. (Paris) I0: 627-643. Brown, L., R.J. Sherbenou and S.K. Johnsen (1982) The Test of Nonverbal Intelligence Manual, Pro-Ed, Austin, TX. Castaigne, P., F. Lhermitte, A. Buge, R. Escourolle, J.J. Hauw and O. Lyon-Caen (1980) Paramedian thalamic and midbrain infarcts: clinical and neuropathological study. Ann. Neurol., I0: 127-148. Dunn, L.M. and L.M. Dunn (1981) Peabody Picture Vocabulary Test - Revised: Manual for Forms L and M, American Guidance Service, Circle Pines, MN. Folstcin, M.F., S.E. Folstein and P.R. McHugh (1975) "Mini-Mental State'. A practical method for grading the cognitive state of patients for the clinician. J. Psychiat. Res, 12: 189-198. Gaffan, E.A., D. Gaffan and J.R. Hodges (1991) Amnesia following damage to the left fornix and to other sites. A comparative study. Brain, 114: 1297-1313. Goldenberg, G., A. Wimmer and J. Maly (1983) Amnesic syndrome with a unilateral thalamic lesion: a case report. J. Neurol., 229: 79-86. Graff-Radford, N.R., P.J. Eslinger, A.R. Damasio and T. Yamada (1984) Nonhemorrhagic infarction of the thalamus: behavioral, anatomic, and physiologic correlates. Neurology, 34: 14-23. Graff-Radford, N.R., D. Tranel, G.W. Van Hoesen and J.P. Brandt (1990) Diencephalic amnesia. Brain, 113: 1-25. Jastak, S. and G. Wilkinson (1984) Wide Range Achievement Test Revised: Administration Manual, Jastak Associates, Wilmington, DE. Kaplan, E.F., H. Goodglass and S. Weintraub (1983) The Boston Naming Test, 2nd edn., Lea and Febiger, Philadelphia, PA. Kritchevsky, M., N.R. Graff-Redford and A.R. Damasio (1987) Normal memory after damage to medial thalamus. Arch. Neurol., 44: 959-962. Mair, W.G.P., E.K. Warrington and L. Weiskrantz (1979) Memory disorder in KorsakoWs psychosis. A neuropathological and neuropsychological investigation of two cases. Brain, 102: 749-783. Michel, D., B. Laurent, N. Foyatier, A. Blanc and M. Portafaix (1982) lnfarctus thalamique param~dian gauche. Rev. Neurol. (Paris), 138: 533-550. Mori, E., A. Yamadori and Y. Mitani (1986) Left thalamic infarction
and disturbance of verbal memory: a clinicoanatomical study with a new method of computed tomographic stereotaxic localization. Ann. Neurol., 20: 671-676. Muller, J. Ph., A. Destee, M. Steinling, J.P. Pruvo and P. Warot (1990) Infarctus bithalamique param~dian: 1 cas avec IRM et tomographie de ~mission gamma. Rev. Neurol. (Paris), 146: 732734. Nicheili, P., G. Bahmanian-Behbahani, M. Gentilini and A. Vecchi (1988) Preserved memory abilities in thalamic amnesia. Brain, 1! 1: 1337-1353. Percheron, G. (1973) The anatomy of the arterial supply of the human thalamus and its use for the interpretation of the thalamic vascular pathology. Z. Neurol., 205: 1-13. Reitan, R.M. and D. Wolfson (1985) The Halstead-Reitan New ropsychological Battery: Theory and Clinical Interpretation, New ropsychology Press, Tucson, AZ. Schott, B., F. Mauguiere, B. Laurent, O. Serclerat and C. Fischer (1980) L'amn~sie thalamique. Rev. Neurol. (Paris), 136: 117-130. Speedie, L.J. and K.M. l-leilman (1982) Amnestic disturbance following infarction of the left dorsomedial nucleus of the thalamus. Neuropsychologia, 20: 597-604. Squire, L.R.and R.Y. Moore (1979) Dorsal thalamic lesion in a noted case of human memory dysfunction. Ann. Neurol., 6: 503-506. Squire, L.R., D.G. Amaral, S. Zola-Morgan, M.P. Kritchevs~ and G. Press (1989) Description of brain injury in the amnesic patient N.A. based on magnetic resonance imaging. Exp. Neurol., 105: 23-35.. Stuss, D.T., R. Guberman, R. Nelson and S. Larochelle (1988) The neuropsychology of paramedian thalamic infarction. Brain and Cognition, 8: 348-378. Swanson, R.A. and J.W. Schmidley (1985) Amnestic syndrome and vertical gaze palsy: early detection of bilateral thalamic infarction by CT and NMR. Stroke, 16: 823-827. Talairach, J. and P. Tournoux (1988) Co-planar Stereotaxic Atlas of the Human Brain. Translated by M. Rayport, Thieme, New York and Stuttgart. Victor, M., R.D. Adams and G.H. Collins (1971) The WernickeKorsakoff Syndrome. A Clinical and Pathological Study of 245 Patients, 82 with Post-mortem Examinations, F.A. Davis, Philadelphia, PA. Victor, M., R.D. Adams and G.H. Collins (1989) The WernickeKorsakoff Syndrome and Related Neurologic Disorders due to Alcoholism and Malnutrition, 2nd edn., F.A. Davis, Philadelphia, PA, pp. 183-185. Von Cramon, D.Y., N. Hebel and I3. Schuri (1985) A contribution to the anatomical basis of thalamic amnesia. Brain, 108: 993-1008. Wallesch, C.W., H.H. Kornhuber, T. gunz and R.J. Brunner (1983) Neuropsychological deficits associated with small thalamic lesions. Brain, 106: 14-152. Wechsler, D. (1981) Wechsler Adult Intelligence Scale - Revised: Manual Psychological Corporation, New York, NY. Wechsler, D. (1987) Wechsler Memory Scale - Revised: Manual, Psychological Corporation, New York, NY.
62
JNS 03796
Thalamic amnesia: Korsakoff syndrome due to left thalamic infarction Monroe Cole a, M.D. Winkelman a, J.C. Morris a.t, J.E. Simon b and T.A. Boyd c Departments of a Neuroiogy, b Radiology and c Psychiatry of the MetroHealth Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA (Received 25 September, 1991) (Revised, received 3 February, 1992) (Accepted 12 February, 1992)
Key words: Thalamus; Amnesia; Amnestic syndromes; Memory disorders; Korsakoff syndrome
Summary 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.
Introduction
Case reports
The role of the thalamus in m e m o r y was strongly emphasized in the 1971 seminal studies of Victor et al. concerning the alcoholic-nutritional Wernicke-Korsakoff syndrome. They pointed out that a persistent amnestic state ( K o r s a k o f f s y n d r o m e ) occurred only when there was a lesion in the dorsal-medial nucleus of thalamus. They defined the syndrome as " a n abnormal mental state in which m e m o r y a n d learning are affected out of all proportion to o t h e r cognititve functions in an otherwise alert and responsive p a t i e n t " , a definition which we employ in this report. We report 5 f u r t h e r cases resulting f r o m left thalamic infarction in o r d e r to a u g m e n t the m e a g e r literature supporting the thesis that a unilateral dominant thalamic lesion can cause Korsakoff syndrome.
Left thalamic infarction and permanent K o r s a k o f f syndrome Case 1 G.D., a 51-year.old right-handed woman, was referred for neurological evaluation for loss of memory. Because of a 6-month history of nocturnal chest pain unrelated to exertion, she had had a cardiac catheterization 3½ weeks prior to neurological evaluation. Electrocardiogram, stress tests, and catheterization were all normal. Her husband reported that she was in her usual health on arrival to hospital for cardiac catheterization. One hour post-procedure her husband noted that she was confused. She was discharged home 5 hours later (6.00 p.m.) and was observed to have diminished speech and to act 'as if in a fog'. She retired at 7.00 p.m. The next morning she was 'quiet and subdued' but went to work. Later in the day her husband spoke to her on the telephone, and she said that she had tried to call him but did not remember his telephone number, although she had called him daily for years. At the time of the initial neurological evaluation her condition was unimproved. Past history was noncontributory except for treated hypertension. Examination revealed her to be alert. She did not know the capitals of Ohio, New York, or Pennsylvania but did know the capital of the United States. The date was missed by 1, then 2 days. She achieved a score of 26 on the Mini-Mental Status Test of Folstein, Folstein and McHugh (1975). Given a 30-word s~.ory to remember she could recall no details after 2 repetitions and an interval of 10 minutes. Blood pressure was 140/80. The neurological examination was otherwise normal. MRI of the brain revealed a small infarct in the left dorsal-medial nucleus of the thalamus (Fig. 1). Psychometric evaluation re-
'Present address: Departments of Neurology and Pathology (Neuropathology), Washington University School of Medicine, St. Louis, MO 63110, USA. Correspondence to: Monroe Cole, M.D., Department of Neurology, MetroHealth Medical Center, 3995 Scranton Road, Cleveland, OIi 45109, USA. Tel.: (216) 459-3990; Fax: (216) 459-3119.
63 vealed a deficit of higher cognitive functions, but memory, and more particularly verbal memory, was impaired out of proportion to the other cognitive functions, as depicted in Table 1. Case 2 L.B., a 73-year-old right-handed white woman, was admitted to hospital in October 1979 because of a change in mentation. After a 2-day period of emesis, she was noted by her family to be 'confused' and speaking in a bizarre m a n n e r She ha J T~,~e II diabetes mellitus and hypertension. Examination revealed h~c to be lethargic and uncooperative. Blood pressure was 180/90 mmHg. She was oriented to person, place, and date but could not remember her children's names or ages, her address, phone number, or daughter's phone number. She could name the President, but no previous presidents. She could not name the mayor of Cleveland or the lake upon which the city is located. She could recall 1 / 3 objects in I minute and 0 / 3 in 5 minutes. Cranial nerves were normal except for punctate retinal hemorrhages. Strength was normal and there was no ataxia of limbs, hut the gait was slow and wide-based. There was evidence of a peripheral neuropathy. The cranial CT scan (Fig. 2) showed an infarct in the left thalamus. She was re-examined by one of us OCM) 2 years later. History given by her neighbor revealed that the patient spent most of her days l~,ing on the couch, occasionally watching television, and rarely going outside. She was pleasant, cooperative, and well-groomed, as well as alert and oriented to person, place and time. She knew her birthdate, birthplace and phone number, but not her street address. She did not remember the dates of either of her two weddings; nor did she remember the dates of either of her husbands' deaths. She was able to give the names but not the ages of 4 of her children. She did not recall what she had eaten for dinner on the night before the examination. She could not remember even 1 / 3 objects in 5 minutes.
She was unable to subtract 7 from 93 serially, but was able to do simple calculations correctly (8+4, 12+13, 100-7, $1.75 equals 7 quarters). She could correctly repeat 5 digits forward but only 2 in reverse. Language function was normal. No other significant neurological abnormalities were noted. We have seen 3 other patients with the sudden onset of an amnestic syndrome, either permanent or temporary, in whom the pathogenetic role of the infarct in the left thalamus for the memory loss is less clear.
Korsakoff syndrome with thalamic plus other infarcts Case 3 S.T., a 67-year-old white woman, suddenly fell, without loss of consciousness. For the remainder of the day she noted intermittent right-sided numbness ('tingling') and unsteadiness of gait. She was brought to hospital the next day. Examination revealed a blood pressure of 174/100 mm Hg and regular pulse of 120. She appeared bewildered and anxious but oriented to person and place, yet not to time. Language function was normal. She was unable to recall her birthplace, the ages of her children, or any recent Presidents of the United States. She could not remember 3 objects for 1 minute, nor recall what she had eaten for her last meal. She could not name the color of any object shown to her but could correctly name the color related to certain words, e.g. 'grass', 'sky'. Object naming was normal. There was a right homonymous inferior quadrantanopsia and right visual inattention. There was a mild right hemiparesis, including face, mild right hemihypesthesia, and pseudoathetosis of the right hand. Tendon reflexes were exalted on the right, and the right plantar response was extensor. CSF was unrevealing, serum and CSF serologies for syphilis non-reactive, and the
Fig. I. Case I. Infarct in left dorsal-medial thalamus (arrow). (A) horizontal, (B) coronal views.
64 TABLE 1 NEUROPSYCHOMETRIC EVALUATION OF CASE 1 WAIS-R Full Scale IQ 84 Verbal IQ 83 Performance IQ 88 PPVT-R 76 BNT Raw score 39 TONI 92 WRAT-R Reading 101 Spelling 103 Arithmetic 115 WMS-R General Memory Index 59 Verbal Index 56 Visual Index 92 Attention/Concentration 74 Delayed Recall Index 73 Sensory Perceptual Examination (27) Speech-Sounds Perception (27) Trails Test, A and B (27) Seashore Rhythm Test (27)
(14th percentile) (13th percentile) (21st percentile) (6th percentile) (mean 55.7 SD -- 3.3) (30th percentile) (53rd percentile) (58th percentile) (84th percentile) (lst perecentile) (lst percentile) (30th percentile) (4th percentile) (4th percentile) normal 0 errors (normal) normal 2 errors (normal)
Abbreriations: WAIS-R--Wechsler Adult Intelligence Scale - Revised (28); PPVT-R--Peabody Picture Vocabulary Test - Revised (29); BNT = Boston Naming Test (30); TON! = Test of Nonverbal Intelligence (31); WRAT-R =Wide Range Achievement Test Revised (32); WMS-R = Wechsler Memory Scale - Revised (33).
Fig. 3. Case 3, Left thalamic (arrow) and posterior temporal infarction. hospital course unchanged. Cranial CT (Fig. 3) showed development of a left occipital-posterior temporal infarct, as well as a left posterior thalamic infarct. One year later she continued to have a prominent Korsakoff psychosis, persistent color agnosia and a mild right hemiparesis and hemihypesthesia. Specifically, she could repeat 5 digits forwards and backwards but could not recall her wedding day, the cause of her husband's death or her children's ages. She did not know her current address or phone number and remembered 0/3 objects after 5 minutes. While she was described by her family as extremely hardworking prior to her illness, after hospitalization she spent most of her time sitting and watching television. She was fully oriented, displayed normal language function and performed simple calculations without error. Visual fields were normal to confrontational examination and the hemiparesis was improved. Case 4 S.N., a 72-year-old white man, was hospitalized on the Neurological Service of the Cleveland Metropolitan General Hospital with a severe right spastic hemiparesis, left 'oculomotor dysfunction' (not further defined), fluent aphasia and a Korsakoff syndrome. Cranial CT revealed a left thalamic infarct. The patient was re-examined by one of us (JCM) 1 year after ~lischarge. His family reported that he usually mistook his daughter for his deceased wife, or his granddaughter for his daughter. On examination he responded readily to queries, followed 3-step commands slowly but without error, was mildly dysarthric but not dysphasic. He could not repeat more than 4 digits forward. He could not subtract 7 from 100, but could correctly add 8+ 12 and 12+ 13. He knew his name but not the year. He did not know what part of tb,e city he was in, where he was born, his birthdate, or his age. He was able to repeat the names of 3 objects immediately, but not after 4 min, and did not remember his meals of the day. While he responded readily to questions, impulsion to thought or action was decreased.
65
Localization of lesions
Fig. 4. Case 5. Large left thalamic infarct. Note small right thalamic infarct (arrow).
Utilizing the method and atlas of Talairach and Tournoux (1988), we concluded that the lesion in Case 1 is in the nucleus dorsalis medialis and nucleus anterior thalami, and possibly the mamillothalamic tract (Fig. 1). The lesion in Case 2, which is larger than the lesion in Case 1, is in the nucleus centrum medianum, the inferior tip of the nucleus dorsalis medialis and probably the nucleus ventralis lateralis. The lesion in Case 3 appears to be in the nucleus puivinaris and probably the nucleus ventralis posterolateralis. In Case 4 we have only the report of a thalamic infarct without further localization. In Case 5 the infarct is in the lateral third of the nucleus dorsalis medialis and also involves the centrum medianum, ventralis lateralis, and probably the nucleus lateralis posterior and the mamillothalamic tract. In addition, a small infarct is present in the lateral part of the right nucleus dorsalis medialis. The localization in Cases 2 and 3 is tentative at best because of the quality of the CT, made over 10 years ago. We are more confident of our localization in Cases 1 and 5, for whom MRI is available. In Case 3, it may be argued that the infarction of the postero-inferior left temporal lobe is as likely to be the cause of the Korsakoff syndrome as is the infarction in the posterior lateral thalamus.
Discussion The patient had a right spastic hemiplegia involving face, arm and leg. There was a mild left hemihypesthesia and a mild paresis of adduction of the right eye without nystagmus of the abducting eye, ptosis or pupillary abnormality.
Large left and small right thalamic infarcts with temporary Korskaoff syndrome Case 5 V.S., an 80-year-old black woman, was admitted to hospital for confusion and decreased memory noted over the course of 1 week. When first evaluated she was uncooperative, lethargic, and oriented only to place. Language functions were intact. There was right-left confusion. She was able to remember I out of 3 objects in 3 rain. Attention and concentration were poor. No definite paresis, sensory deficit, or ataxia were noted. She gradually improved, but the ability to record new memories was severely enough impaired (compared to other cognitive functions) that 4 days after admission one of us (MW) considered her to have a Korsakoff syndrome. However, improvement continued. Nine days after admission she was alert, cheerful and humorous. She knew the month but not the day or year, nor the year of her birth. She gave her age as '69, no 70, no 79'. She knew that she had been tranferred to the Neurology Service one day previously, which floor her new room was on, and where in the hospital she had been previously. Language function was normal. She was able to remember most of a 30-word story for 5 and 10 min and knew the names and races of the present and previous mayors. There was a very slight right hemiparesis and no visual field defect to confrontational testing; there was no sensory deficit or ataxia. Cranial CT and MRI showed a large infarct in the left thalamus, as well as a small infarct in the right thalamus (Fig. 4).
Victor et al. (1971, 1989) emphasize that the persistent amnestic state (Korsakoff syndrome) was related to the presence of pathology in the medial-dorsal nucleus of the thalamus and the medial part of the pulvinar. In their analysis, data concerning thalamic nuclei were used only if the nucleus could be identified with certainty. Histopathological lesions consisted of neuronal loss, loss of myelinated fibers, and astrogliosis. The lesions were bilateral and reasonably symmetrical. Mair et al. (1979) argue against a crucial role for the medial-dorsal nucleus of the thalamus in the genesis of the amnestic syndrome, stressing instead the gliosis medial to the nucleus in the paratenial nucleus. Their figures 15 and 18 suggest to us, however, neuronal loss and gliosis within the dorsal-medial nucleus itself. Brion et al. (1985) conclude from their review of the literature that the role of a thalamic lesion has not been totally confirmed ('beaucoup d'incertitudes persistent...'). There is little question that localized lesions in the thalamus, usually vascular, occasionally traumatic, may cause Korsakoff syndrome. Von Cramon et al. (1985) describe 4 patients with chronic amnesia and ventral thalamic infarcts. Three had bilateral lesions and 1 a
66 left thalamic lesion. They comment that only a minor ventrobasal portion of the dorsal medial-nucleus was involved. In two other cases with large dorsal mediallesions memory was spared. They ascribe the amnestic syndrome to the lesion of the mamillothalamic tract. Nichelli et al. (1988) describe alterations in memory functions after bilateral infarction of the dorsal-medial and midline nuclei of the thalamus, as well as the internal medullary lamina, the mamillothalamic tract, and the lameUa medialis oralis. GraffoRadford et aL (1990) also describe a significant amnestic state in patients with bilateral anterior thalamic infarcts involving the mamillothalamic tracts. Anterograde amnesia due to bilateral infarcts of the dorsal medial and internal medullary nuclei and the mamillothalamic tracts was described in 1 case by Schott et al. (1980). Squire and Moore (1979) have provided CT evidence of a fencing foil lesion of the left dorsal-medial nucleus of the thalamus resulting in a well-studied case of Korsakoff syndrome. As pointed out in a later MRI study of the same patient (Squire et al., 1989), there was also damage to the hypothalamus, including the mamillary nuclei, by the passage of the foil, which pierced the right nostril. Patients 1, 2 and 3 of Graff-Radford et al. (1984) each showed deficits of verbal and visual memory after infarction in the distribution of the left tuberothalamic artery. The location of their lesions (of. Figs. 1-3) are virtually identical to the location of the lesion in our Case 1. Speedie and Heilman (1982) reported a case of sudden amnestic psychosis due to a presumed embolic infarct in the left dorsal-medial nucleus of the thalamus. The location of the lesion is similar to our Case 1. Michel et al. (1982) descr;be a persistent mild anterograde verbal amnesia with preservation of retrograde memory in a patient sustaining a large left thalamic infarct. Goldenberg et al. (1983) describe what they term 'transient global amnesia', which was maximal for 2 days but present for more than 5 days. The infarct of the left anterior thalamus involved nuclei ventralis anterior, ventralis lateral is, anterior, the anterior part of dorsalis medialis and the mamillothalamic tract. The amnesia partially resolved, leaving only a reduction in verbal memory capacity. The authors postulated that the partial recovery of memory function was due to the unilaterality of the lesion. Mori et al. (1986) carefully studied a patient with an anterograde verbal amnesia after left anterior thalamic infarction. The infarct was in the distribution of the polar (tuberothalamic artery (Graff-Radford et al. 1984) and paramedian arteries (Percheron 1973). The dorsal medial nucleus was considered to be largely spared. Akiguchi et al. (1987) reported 7 patients with left thalamic infarcts with recent memory loss and impaired learning of verbal information. One patient with
a right thalamic infarct was unable to learn visuospatial as well as verbal information. The authors localized the lesions to the dorsal-medial and anterior nuclei of the thalamus. Castaigne et al. (1980) describe 3 of their 28 patients with paramedian thalamic infarcts who could be adequately tested. These patients showed a marked deficit of anterograde memory 'confirming the clinical and experimental findings of Victor et al. (1971)'. In their patient 5, the mamiilothalamic tract was spared. They state, 'Involvement of the median nucleus does not appear to explain the memory deficit'. These authors imply that the lesion was unilateral but do not indicate which side was involved. They continue, 'Only bilateral and complete lesions of the median nucleus have been shown to cause disturbance of memory'. In their table 3 they indicate that the lesion in the median nucleus is in fact bilateral; table 4 is less clear. Wallesch et al. (1983) felt that laterality of a unilateral thalamic lesion was not the determining factor in amnesia but that rostral lesions of either side were more likely to cause memory loss than were posterior thalamic lesions. Finally, Case 3 of Gaffan et al. (1991) showed anterograde amnesia after a left dorsal-medial thalamic hemorrhage, and Case 4 of the same authors showed an anterograde verbal amnesia after left dorsal-medial thalamic infarction. Our cases, in addition to those previously published, allow us to arrive at some conclusions regarding the relation of thalamic lesions to an amnestic syndrome, i.e. Korsakoff syndrome. Unquestionably, bilateral thalamic lesions alone may cause Korsakoff syndrome. Unilateral (dominant) thalamic lesions may also cause Korsakoff syndrome without the presence of other lesions in the brain. Our Case 1 is a particularly good example but certainly not the first reported. Information as to the exact thalamic structures involved is less certain. There is very little good pathological data regarding Korsakoff syndrome with a vascular lesion limited to the dorsal-medial nucleus, or nuclei. In a few instances imaging data seem to be reasonably, but not irrefutably, certain. In Case 1, our best observed case, the lesion, although discrete, extends beyond the borders of the dorsal-medial nucleus. At this time we would agree with Mori et al. (1986) that 'it remains unproved whether combinations of lesions are required for amnesia, and if so, which combinations are necessary'. Furthermore, as pointed out in the excellent review by Stuss et al. (1988), not only are the 2 aliencephalic systems of the dorsal-medial and anterior nuclei intimately linked structurally, but it appears extremely difficult to damage one without damaging the other. As other investigators have pointed out (Kritchevsy et al., 1987) unilateral or bilateral thalamic lesions do not necessarily cause a permanent Korsakoff syn-
67
drome. This is illustrated by our Case 5, who is similar to the patients reported by Goldenberg et al. (1983), Muller et al. (1990) and Swanson and Schmidley (1985).
References Akiguchi, I., T. Ino, H. Nabatame, F. Udaka, K. Matsubayashi, H. Fukuyama and M. Kameyama (1987) Acute onset amnestic syndrome with localized infarct on the dominant side. Comparison between anteromedial thalamic lesion and posterior cerebral artery territory lesion. Jpn. J. Med. 26: 15-20. Brion, S., J. Mikol and J. Plas (1985) Neuropathologie des syndromes amn~siques chez l'homme. Rev. Neurol. (Paris) I0: 627-643. Brown, L., R.J. Sherbenou and S.K. Johnsen (1982) The Test of Nonverbal Intelligence Manual, Pro-Ed, Austin, TX. Castaigne, P., F. Lhermitte, A. Buge, R. Escourolle, J.J. Hauw and O. Lyon-Caen (1980) Paramedian thalamic and midbrain infarcts: clinical and neuropathological study. Ann. Neurol., I0: 127-148. Dunn, L.M. and L.M. Dunn (1981) Peabody Picture Vocabulary Test - Revised: Manual for Forms L and M, American Guidance Service, Circle Pines, MN. Folstcin, M.F., S.E. Folstein and P.R. McHugh (1975) "Mini-Mental State'. A practical method for grading the cognitive state of patients for the clinician. J. Psychiat. Res, 12: 189-198. Gaffan, E.A., D. Gaffan and J.R. Hodges (1991) Amnesia following damage to the left fornix and to other sites. A comparative study. Brain, 114: 1297-1313. Goldenberg, G., A. Wimmer and J. Maly (1983) Amnesic syndrome with a unilateral thalamic lesion: a case report. J. Neurol., 229: 79-86. Graff-Radford, N.R., P.J. Eslinger, A.R. Damasio and T. Yamada (1984) Nonhemorrhagic infarction of the thalamus: behavioral, anatomic, and physiologic correlates. Neurology, 34: 14-23. Graff-Radford, N.R., D. Tranel, G.W. Van Hoesen and J.P. Brandt (1990) Diencephalic amnesia. Brain, 113: 1-25. Jastak, S. and G. Wilkinson (1984) Wide Range Achievement Test Revised: Administration Manual, Jastak Associates, Wilmington, DE. Kaplan, E.F., H. Goodglass and S. Weintraub (1983) The Boston Naming Test, 2nd edn., Lea and Febiger, Philadelphia, PA. Kritchevsky, M., N.R. Graff-Redford and A.R. Damasio (1987) Normal memory after damage to medial thalamus. Arch. Neurol., 44: 959-962. Mair, W.G.P., E.K. Warrington and L. Weiskrantz (1979) Memory disorder in KorsakoWs psychosis. A neuropathological and neuropsychological investigation of two cases. Brain, 102: 749-783. Michel, D., B. Laurent, N. Foyatier, A. Blanc and M. Portafaix (1982) lnfarctus thalamique param~dian gauche. Rev. Neurol. (Paris), 138: 533-550. Mori, E., A. Yamadori and Y. Mitani (1986) Left thalamic infarction
and disturbance of verbal memory: a clinicoanatomical study with a new method of computed tomographic stereotaxic localization. Ann. Neurol., 20: 671-676. Muller, J. Ph., A. Destee, M. Steinling, J.P. Pruvo and P. Warot (1990) Infarctus bithalamique param~dian: 1 cas avec IRM et tomographie de ~mission gamma. Rev. Neurol. (Paris), 146: 732734. Nicheili, P., G. Bahmanian-Behbahani, M. Gentilini and A. Vecchi (1988) Preserved memory abilities in thalamic amnesia. Brain, 1! 1: 1337-1353. Percheron, G. (1973) The anatomy of the arterial supply of the human thalamus and its use for the interpretation of the thalamic vascular pathology. Z. Neurol., 205: 1-13. Reitan, R.M. and D. Wolfson (1985) The Halstead-Reitan New ropsychological Battery: Theory and Clinical Interpretation, New ropsychology Press, Tucson, AZ. Schott, B., F. Mauguiere, B. Laurent, O. Serclerat and C. Fischer (1980) L'amn~sie thalamique. Rev. Neurol. (Paris), 136: 117-130. Speedie, L.J. and K.M. l-leilman (1982) Amnestic disturbance following infarction of the left dorsomedial nucleus of the thalamus. Neuropsychologia, 20: 597-604. Squire, L.R.and R.Y. Moore (1979) Dorsal thalamic lesion in a noted case of human memory dysfunction. Ann. Neurol., 6: 503-506. Squire, L.R., D.G. Amaral, S. Zola-Morgan, M.P. Kritchevs~ and G. Press (1989) Description of brain injury in the amnesic patient N.A. based on magnetic resonance imaging. Exp. Neurol., 105: 23-35.. Stuss, D.T., R. Guberman, R. Nelson and S. Larochelle (1988) The neuropsychology of paramedian thalamic infarction. Brain and Cognition, 8: 348-378. Swanson, R.A. and J.W. Schmidley (1985) Amnestic syndrome and vertical gaze palsy: early detection of bilateral thalamic infarction by CT and NMR. Stroke, 16: 823-827. Talairach, J. and P. Tournoux (1988) Co-planar Stereotaxic Atlas of the Human Brain. Translated by M. Rayport, Thieme, New York and Stuttgart. Victor, M., R.D. Adams and G.H. Collins (1971) The WernickeKorsakoff Syndrome. A Clinical and Pathological Study of 245 Patients, 82 with Post-mortem Examinations, F.A. Davis, Philadelphia, PA. Victor, M., R.D. Adams and G.H. Collins (1989) The WernickeKorsakoff Syndrome and Related Neurologic Disorders due to Alcoholism and Malnutrition, 2nd edn., F.A. Davis, Philadelphia, PA, pp. 183-185. Von Cramon, D.Y., N. Hebel and I3. Schuri (1985) A contribution to the anatomical basis of thalamic amnesia. Brain, 108: 993-1008. Wallesch, C.W., H.H. Kornhuber, T. gunz and R.J. Brunner (1983) Neuropsychological deficits associated with small thalamic lesions. Brain, 106: 14-152. Wechsler, D. (1981) Wechsler Adult Intelligence Scale - Revised: Manual Psychological Corporation, New York, NY. Wechsler, D. (1987) Wechsler Memory Scale - Revised: Manual, Psychological Corporation, New York, NY.
