Psychosomatics 45:366-368, August 2004
© 2004 The Academy of Psychosomatic Medicine
Wernicke-Korsakoff Syndrome and Galantamine
B. Kirk Phillips, M.D.,
M. Victoria Ingram, Psy.D., and
Geoffrey G. Grammer, M.D., Washington, D.C.
Key Words: other neuropsychiatric • other somatic therapy
TO THE EDITOR: Korsakoff's psychosis, a chronic amnestic disorder, is defined as a severe anterograde amnesia in which memory is not transferred from short- to long-term storage.1 It is believed to be a consequence of Wernicke's encephalopathy, a thiamine-deficient state resulting in encephalopathy, truncal ataxia, ophthalmoplegia, and mental confusion. Of those with Wernicke's encephalopathy who survive, about three-fourths will develop Korsakoff's psychosis.1,2 These two disorders are often described together as Wernicke-Korsakoff syndrome.
Prompt administration of thiamine to patients with Wernicke's encephalopathy can prevent or reduce the severity of Korsakoff's psychosis and prevent the progression of deficits, although it is unlikely to reverse existing deficits in patients who already have Korsakoff's psychosis.2 It should also be noted, however, that a study by Davis et al. found Wernicke-Korsakoff syndrome to be permanent in at least a partial form in about 80% of patients.3 Because of the lack of effective proven treatment for Wernicke-Korsakoff syndrome and recent case reports documenting promising responses to the anticholinesterase drugs donepezil and rivastigmine, the patient was given the anticholinesterase inhibitor galantamine for the treatment of Wernicke-Korsakoff syndrome.4,5 This case report documents that patient's clinical improvement while taking galantamine and illustrates the potential benefit of galantamine in the treatment of Wernicke-Korsakoff syndrome. This case report is also unique in that it is believed to document the first described case of Wernicke-Korsakoff syndrome resulting from malnutrition caused by the postsurgical dysphagia of uvulopalatopharyngoplasty.
Case Report
Mr. A was an obese 63-year-old married African American man with a history of chronic alcohol use and severe obstructive sleep apnea who underwent uvulopalatopharyngoplasty for removal of his upper palate. During his postoperative recovery from surgery, he experienced painful dysphagia, leading to near-absent oral intake for 9 weeks after his procedure. His reduced caloric and nutritional intake resulted in a weight loss of 95 lb (from 380 to 285 lb). Toward the latter part of the 9-week period, he began experiencing moderate to severe short-term memory difficulty, agitation, urinary incontinence, a wide-based unsteady gait, and combined horizontal-vertical nystagmus.
He came in for medical care for these symptoms and was treated with intravenous thiamine, vitamin B12, and a multivitamin. He was sent home after an initial improvement in his mental status. Unfortunately, 2 weeks later, his spouse brought him to medical attention secondary to a decline in his mental status and development of bilateral lower extremity edema. He was admitted for further evaluation, treatment, and coordination of medical care. On day 2 of this hospitalization, Mr. A developed aggressive behavior and paranoid delusions, requiring psychiatric consult, restraint, and sedation. He was noted to have dense anterograde amnesia and was diagnosed with progression of his Wernicke's encephalopathy to Wernicke-Korsakoff syndrome. He was again given intravenous thiamine, 100 mg/day. Because of continuing dense anterograde amnesia, Mr. A began a trial of oral galantamine (4 mg b.i.d.) on day 10. On day 31, his galantamine was increased to 8 mg b.i.d. Repeat bedside examination of Mr. A on day 44, 2 weeks after the increase in galantamine, was significant for improved short-term recall. He was able to identify the location, current treatment plan, and reason for hospitalization. He was also able to recall through conversation the cause of his illness and his provider's role in his care. His improvement in mental status was also noted by his spouse. On the day of his discharge (day 49), Mr. A continued to show improvement, although a significant anterograde memory deficit remained.
On subsequent outpatient follow-up appointments, Mr. A had continued severe anterograde amnesia with decreased attention. Of note, approximately 3 months after his hospital discharge, caregiver noncompliance resulted in a 3–4-week period in which Mr. A did not receive his galantamine.
A neuropsychological evaluation was conducted at 4 weeks after his initial diagnosis of Wernicke's encephalopathy (just before the initiation of galantamine) and subsequently at 40 weeks postdiagnosis. Upon his initial evaluation, Mr. A demonstrated mild confabulation and reported no cognitive difficulties, despite dramatic cognitive impairment. An assessment documented a score on the Mini-Mental State Examination (MMSE) of 18 of 30, with a full 11 points lost on orientation and recall tasks.6 The remaining objective test results indicated a profound impairment in new learning and memory. Mr. A made four errors on the Trail Making Test B as a result of forgetting the instruction set while actively completing the task. His learning curves were repeatedly poor and reflected strong recency effects. After distraction and delay, Mr. A was entirely incapable of free recall for any items, and his recognition memory performances were at chance levels, suggesting that he had been unable to encode the new information to which he had been exposed.
At the 40-week follow-up testing, Mr. A again reported no significant difficulties with cognitive functioning, remained living in a continuous supervision facility, and was described as continuing to demonstrate considerable anterograde amnesia. Anecdotally, however, employees of his residential facility reported that his memory seemed to be slightly better than when he arrived at the facility months earlier and that during a brief period when he was unable to take his "memory pill" (galantamine), they noticed a worsening in his memory. At the 40-week follow-up, Mr. A's MMSE score had improved to 21 of 30 but remained impaired because of poor performances on orientation and recall tasks. Unlike at the previous testing, he was able to provide correct responses on several orientation-to-location questions; however, behavioral observations during the testing noted that he used environmental cues to do so. Mr. A's remaining test results demonstrated improved attention and working memory abilities as evidenced by his increased total scores across three trial list learning tasks, decreased errors on the Trail Making Test B, a markedly improved logical memory I score on the Wechsler Memory Scale—Revised, and an increase of one standard deviation in his digit span score on the WAIS-R. Mr. A was also able to accurately report two pieces of information after a 30-minute delay on logical memory, and his recognition memory performance on the Hopkins Verbal Learning Test word list had improved from chance (46%) to somewhat better than chance (75%), suggesting the possibility that he was not as grossly amnestic at this evaluation as he was at first. The results clearly demonstrated persisting, severe impairment in Mr. A's ability to encode new information at the 40-week follow-up; however, the test results also provided subtle evidence for his caregivers' anecdotal reports that his cognitive functioning had improved.
Discussion
Damage to the corpus mamillare and the dorsomedial nucleus of the thalamus is seen as etiologically responsible for the severe anterograde amnesia of patients with Wernicke-Korsakoff syndrome because they are the basic relay stations in the two parallel pathways connecting the hippocampus and the amygdala with the other structures of the episodic memory's neural network.7 The rationale for pharmacological treatment by manipulation of different neurotransmitter systems in patients with Wernicke-Korsakoff syndrome is based on the observation of lesions in the ascending neurotransmitter nuclei (i.e., the noradrenergic locus ceruleus, the serotonergic dorsal raphe nucleus, and the cholinergic basal nucleus of Meynert).7 Cholinergic projections from the brainstem relay through the thalamus to reach the cerebral cortex, and one of the major effects of acetylcholine on the neurons of the cerebral cortex is to "make cortical neurons more receptive to other excitatory inputs."8 Given this and inconsistent results in the literature for cholinergic drugs in the treatment of patients with Wernicke-Korsakoff syndrome, the potential effectiveness of an acetylcholinesterase inhibitor in treating amnesia associated with damage to these structures or pathways merited further study in this individual.4,5,7
To our knowledge, this is the first described case of Wernicke-Korsakoff syndrome resulting from malnutrition caused by the postsurgical dysphagia of uvulopalatopharyngoplasty. This case demonstrates the necessity of monitoring patients for weight loss and nutritional deficiencies following complicated oral surgery. Especially vulnerable are those postsurgical patients who may have predisposed themselves to nutritional deficiencies from a prior history of chronic alcohol use or those that continue to use alcohol as an anesthetic to help alleviate postsurgical pain. It is also significant that treatment with galantamine, a competitive and reversible inhibitor of acetylcholinesterase, did not result in any harm to the patient and was noted to have resulted in at least mild clinical improvement in attention and memory. While significant subjective and objective improvements were observed in this patient's memory immediately after an increase of galantamine to 8 mg b.i.d., a subsequent 3–4 week period of medication noncompliance may have limited the effectiveness of the medication in this patient. Formal neuropsychological testing performed after the period of noncompliance compared to pregalantamine neuropsychological test results demonstrated clinical improvement, with only mild objective improvement in attention deficits. Although it is hypothesized that the improvements in attention noted in this case were likely a product of concurrent medical, nutritional, and psychiatric stabilization, a contribution from the acetylcholinesterase inhibitor to this process cannot be ruled out.
REFERENCES
- Hales RE, Yudofsky SC, Talbott JA: Textbook of Psychiatry, 3rd ed. Washington, DC, American Psychiatric Press, 1999, p 377
- Simon RP, Aminoff MJ, Greenberg DA: Clinical Neurology, 4th ed. Norwalk, Conn, Appleton & Lange, 1999, p 73
- Davis VM, Adams RD, Collins GH: The Wernicke-Korsakoff syndrome: a clinical and pathological study of 245 patients, 82 with post-mortem examinations. Contemp Neurol 1971; 7:1–206
- Angunawela I, Barker A: Anticholinesterase drugs for alcoholic Korsakoff syndrome. Int J Geriatr Psychiatry 2001; 16:338–339[CrossRef][Medline]
- Iga J, Araki M, Ishimoto Y, Ohmori T: A case of Korsakoff's syndrome improved by high doses of donepezil. Alcohol Alcohol 2001; 36:553–555[Abstract/Free Full Text]
- Folstein MF, Folstein SE, McHugh PR: "Mini-Mental State": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198[CrossRef][Medline]
- Sahin HA, Gurvit IH, Bilgic B, Hanagasi HA, Emre M: Therapeutic effects of an acetylcholinesterase inhibitor (donepezil) on memory in Wernicke-Korsakoff's disease. Clin Neuropharmacol 2002; 25:16–20[CrossRef][Medline]
- Mesulam M: Principles of Behavioral and Cognitive Neurology, 2nd ed. Oxford, UK, Oxford University Press, 2000, p 77
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