Department of Neuropsychiatry, University of Tokushima School of Medicine, 3-18-15 Kuramoto-Cho, Tokushima-Shi-770 8503, Japan
Received 14 February 2001; in revised form 9 April 2001; accepted 21 May 2001
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ABSTRACT |
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INTRODUCTION |
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CASE REPORT |
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In March 2000, her husband noticed that she was not eating at all. She was hospitalized because of dehydration and weakness. The patient's physical condition improved following rehydration, but her craving for alcohol, her inappropriate behaviour, as well as her severe memory disturbance were noted. She was transferred to the Department of Psychiatry at the University Hospital of Tokushima 12 days later.
On admission to the University Hospital, a marked retrograde memory loss of about 10 years was observed. The patient claimed to be younger than she really was and denied giving birth to, and caring for, her child, insisting that the child belonged to her elder sister. There was also a marked disturbance of recent memory, disorientation, confabulation, and an indifferent attitude. Neurological examination revealed nystagmus in the right and left gaze, difficulty in standing on one foot bilaterally but no disturbance of co-ordination. Physical examination showed peri-oral erythemas, slight abdominal distention and bilateral pretibial oedema. There was no abnormality of electrocardiogram, electroencephalogram, brain computed tomography or magnetic resonance imaging scans. There was a slight rise of aspartate aminotransferase, alanine aminotransferase, pancytopenia, and low serum albumin levels. The physicians diagnosed compensated cirrhosis and oesophageal varices.
The patient was treated with peroral vitamins (thiamine 200 mg, pyridoxine 200 mg and cyanocobalamin 2 mg/day) from admission and until day 210. Her nystagmus and gait disturbance improved within a week, but the amnesia, disorientation and confabulation did not improve. She complained that her money had been stolen and her belongings were broken and she sometimes quarrelled with other patients. The patient could not take care of her own needs adequately and required constant nursing care.
The patient was given 25 mg/day of fluvoxamine in addition to the vitamin preparation, starting 21 days after admission to the University Hospital (day 21). Fluvoxamine was gradually increased up to 200 mg/day over the next 3 weeks and continued until day 56 without any improvement and was therefore discontinued. A 3 mg/day dose of donepezil was started 7 days later (day 63) and the dosage of donepezil was gradually increased to 15 mg/day. The patient's clinical symptoms were evaluated using the revised Hasegawa dementia scale (HDS-R) (Hasegawa, 1983) and a mini-mental state examination (MMSE) (Folstein et al., 1975
) was carried out every week (Fig. 1
). The patient did not remember the last examination at all. Thirty-five days later (day 97), she developed insight into her memory disturbance and began to cry when she realized her inability to remember. Her memory gradually improved and she remembered her child. She was often seen reading newspapers and magazines. The changes of scores of HDS-R and MMSE are shown in Fig. 1
. The nurses' rating scores (KOMI chart) (Hitoe, 1996
) for cognitive and behavioural aspects of daily life were 12/75 and 16/75 respectively on admission. The score of cognition and behaviour improved to 56/75 and 47/75 respectively by the end of November 2000 (i.e. on day 231).
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DISCUSSION |
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Cholinergic involvement in Korsakoff's syndrome has been suggested. Mayes et al. (1988) made morphometric measurements of cholinergic nuclei in the basal forebrains of two cases of Korsakoff's syndrome, the patients having been psychometrically tested while alive and their diagnoses confirmed at post-mortem. In both cases, the post-mortem study showed a decrease in the number or nucleolar volume of magnocellular neurons in the nucleus basalis of Meynert, the major source of cortical acetylcholine. It has also been reported that thiamine deficiency may damage the cholinergic system as a result of a complex interaction between cellular, neurochemical and metabolic properties (Witt, 1985). Moreover, it is reported that cholinergic-rich brain transplants or cholinergic drugs reverse alcohol-induced memory deficits in animals (Arendt et al., 1988
; Hodges et al., 1991
). Donepezil may improve the amnestic symptoms by activating the cholinergic transmission from the basal forebrain to the cortex. Larger trials are needed to substantiate the safety and efficacy of donepezil for treatment of memory impairment of Korsakoff syndrome.
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FOOTNOTES |
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