Ben Zimmer

EEG sleep in elderly depressed, demented, and healthy subjects

In a prospective study of EEG sleep patterns in 25 elderly depressives, 25 elderly demented patients, and 25 healthy, elderly control subjects, the sleep of depressives was characterized by reduced REM sleep latency, increased REM percent and first REM period density, and altered temporal distribution of REM sleep, as well as by diminished sleep maintenance (correlated significantly with Hamilton ratings of depression: multiple R = -0.42, p less than 0.05). In contrast, the sleep of demented patients showed reduced REM sleep percent, but normal REM temporal distribution, increased loss of spindles and K-complexes (the latter correlating significantly with severity of cognitive impairment as measured by the Folstein score: multiple R = -0.59, p less than 0.01), and less severe sleep maintenance difficulty than for depressives. An examination of REM latency demonstrated a skewed distribution in depression (i.e., 42% of nights with sleep-onset REM periods), but a normal distribution in the controls and demented subjects. A REM latency cut-off score of 30 min correctly classified 68% of all patients (kappa = 0.36; p less than 0.005), compared with 78% correctly identified in our retrospective study (Reynolds et al. 1983).

Open-trial response to antidepressant treatment in elderly patients with mixed depression and cognitive impairment

We report open-trial antidepressant response in 16 inpatients with mixed symptoms of depression and cognitive impairment, compared to 16 elderly depressives without cognitive impairment. Criteria for adequate treatment specified a steady-state plasma nortriptyline level of 50-150 ng/ml for 4 consecutive weeks or a minimum of six treatments with electroconvulsive therapy. Ten of 16 mixed-symptom patients showed a drop in Hamilton depression ratings greater than or equal to 50% during treatment. Similarly, Blessed dementia ratings declined significantly; the % change in Blessed dementia ratings was significantly correlated with improvement in Hamilton depression ratings. By contrast, Folstein mini-mental state scores did not change significantly during treatment. Six of 16 (37.5%) patients showed resolution of cognitive impairment with adequate treatment of depression. Mixed-symptom patients diagnosed as suffering from major depression (with cognitive impairment) showed more robust pre-post treatment differences, particularly in Hamilton, Folstein, and Blessed dementia scores, than did mixed patients diagnosed as having primary degenerative dementia (with depression). In cognitively intact elderly depressives, the mean % change in Hamilton ratings was 72% (4.3), not significantly different from mean % change in mixed-symptom patients (57.4 +/- 29.9). The proportion of intact depressives showing a reduction greater than or equal to 50% in Hamilton depression ratings was significantly greater (93.8%) than in the mixed group (62.5%). In both groups, 81.3% of patients (13 of 16 in each cell) had a final Hamilton rating less than or equal to 10. These data suggest that elderly patients with mixed depression and cognitive impairment respond to treatment similar to that used in cognitively intact elderly depressives. A controlled study of antidepressant treatment in mixed-symptom patients is warranted.

Serotonin Syndrome: A Case Report

J Clin Pharmacol 1986;26:77-78 77 study of a new dopamine derivative (diisobutyric ester of N. methyl-dopamine) orally active in chronic congestive heart failure. C Ital Cardiol 1977;40:900-905. 5. Ren H). Unverferth DV, Leier CV: The dopamine congener, ibopamine, in congestive heart failure. Cardiovasc Pharmacol 1984;6:748-755. 6. Melloni GF, Minoja GM, Sarazzati G, et al: Clinical tolerability of ibopamine hydrocloride (SB 7505). Fur CIin Pharmacol 4. Mengeot Ph, Piette F, Mirgaux M: Double-blind hemodynarnic 1981;19:409-411.

Elevated red blood cell/plasma choline ratio in dimentia of the Alzheimer type: Clinical and polysomnographic correlates

In a prospective study we have observed a shift in distribution of red blood cell (RBC)/plasma choline ratios among patients with probable dementia of the Alzheimer type (DAT), compared with healthy controls and depressed patients. Fifteen of 22 DAT patients (68%) showed RBC/plasma choline ratios greater than 1.9, in contrast to 9 of 26 healthy controls (35%) and 7 of 20 depressives (35%). These significant differences confirm and expand earlier observations. The subgroup of DAT patients with elevated RBC/plasma choline ratios is older and more cognitively impaired, shows later onset of dementia, and has less rapid eye movement (REM) sleep than the DAT subgroup with normal RBC/plasma choline ratios. Within the entire group of DAT patients, moreover, the RBC/plasma choline ratio shows a significant inverse correlation with REM sleep latency. These findings are discussed in relation to abnormalities in other nonneural Alzheimer tissues and within the context of cholinergic involvement in both DAT and the timing of REM sleep.

The role of lumbar puncture in the evaluation of dementia: the University of Pittsburgh Study.

In a retrospective study of 80 patients over 55 years old, the efficacy of lumbar puncture in evaluating elderly demented patients was examined. Despite a cost of

Lithium-Carbamazepine Neurotoxicity in the Elderly

381 per procedure, in addition to cerebrospinal fluid (CSF) evaluation, no diagnosis was made on the basis of the information obtained in any of the patients (53 per cent) who underwent lumbar puncture. The only abnormalities found were 11 cases of nonspecific elevations in CSF protein and one case of abnormal cellularity not related to bacterial infection. An additional 422 cases of dementia from other series were reviewed, and only four patients were found whose diagnosis could have been made by lumbar puncture—one patient had neurosyphilis, and the other three were postencephalitic. In addition, the literature on complications of lumbar puncture was reviewed. There were no serious complications of lumbar puncture in the present study. The authors concluded that although it is low‐risk, lumbar puncture cannot currently be recommended for routine use in the evaluation of elderly demented patients, but should be used in evaluating demented patients under 55 years of age, patients with rapid onset or progression of dementia, patients with syphilis serology in suspected cases of viral encephalitis, and patients with signs and symptoms of fungal meningitis. J Am Geriatr Soc 33:397, 1985

Insulin-induced factitious hypoglycemic coma

To the Editor:-Several repor.ts on the neurotoxic side effects associated with lithium-carbamazepine combinations have appeared in the literature. l v 2 Recently Sliukla and co-workers’ suggested that those at an increased risk for developing this reaction are those with a history of neurotoxicity during lithium therapies and those with the presence of concurrent compromised medical or neurologic functioning. These risk factors take on much meaning when one is dealing with a geriatric population. We recently had the opportunity to treat an elderly white woman with a rapid cycling, refractory, bipolar disorder who became toxic on this combination. This case clearly demonstrates the risk factors reported by Sliulka et al.,l and serves to further highlight other aspects of the patient’s illness that may be important in the pathogenesis of this adverse reaction. The patient, a 71-year-old white woman with a long history of bipolar affective disorder with frequent exacerbations, presented with a two-week history of manic behavior that included pressured speech, intrusiveness, and lack of sleep. Medications prescribed at admission included lithium carbonate 150 mg twice a day, haloperidol 0.5 mg twice a day, nortriptyline 20 mg twice a day, quinidine 324 mg twice a day, digoxin 0.125 mg daily, and levothyroxine 0.1 mg a day. She had been taking all her medications as prescribed. Her medical history is remarkable for congestive heart failure, atrial fibrillation, partial thyroidectomy, and mild hypertension. Routine laboratory examinations including complete blood count with differential, serum electrolytes, glucose, liver and thyroid hnctions, rapid plasma reagin test, and urinalysis all were normal except for the urinalysis, which revealed numerous white cells and bacteria. Urine culture and sensitivity revealed Eschericlzia coli sensitive to ampicillin, which was started at this time. Her urinary tract infection promptly resolved. Electrocardiogram and electroencephalogram were both within normal limits. Lithium carbonate level on admission was 0.41 mEq/L. Quinidine and digoxin levels were within the therapeutic range. Physical examination was unremarkable except for some mild buccal-lingual dyskinesia. Shortly after admission the haloperidol was discontinued and perphenazine was started and gradually increased to 8 mg at bedtime for its sedating effects. Nortriptyline also was discontinued. Sev-

Cultural Phenomenology and Residency Training Revisited A Personal Account

Hypoglycemia due to the ingestion of oral hypoglycemic agents or injection of insulin is a common way for chronic factitious disorder to present to physicians. Despite this fact, factitious hypoglycemic coma is rare. Because hypoglycemia is potentially fatal, with numerous sequelae, physicians need to be aware of its occurrence and method of detection. A case of chronic factitious disorder presenting as hypoglycemic coma is presented and its implications discussed.

“It Ain't Over til ….”: ECT, Depression, Competency, and Ethical Dilemmas

A field experience in the Northern Galilee area of Israel is described by a Senior American Resident in Psychiatry, with emphasis on the cultural aspects of the experience as well as the benefits related to professional maturation. The author discusses the field experience as part of a residency education, invites other such experiences, and compares his own experiences with others described in the literature.

A More Exclusive Club—The Future Geriatric Mental Health Practitioner

To the Editor:-Dr. James Kvale’ has described a highly suspicious relationship between an episode with some of the characteristics of untreated organophosphate poisoning and onset, 12 months later, of Alzheimer’s disease (or a very similar dementia) simultaneously in a married couple. Autopsy findings were consistent with a diagnosis of Alzheimer’s disease. Donald Hunter, in his classic textbook, Diseuses of Occupations,’ has meticulously described the case of a 28-year-old research chemist, one of three workers who became acutely ill in 1951 following exposure to mipafox (at that time an experimental organophosphate). The worker presented with vomiting and involuntary defecation, cramps in the legs, and generalized muscle weakness. She also had pinpoint pupils, muscle twitching, general muscle hypotonia, and diminished tendon reflexes. Both red cell and serum cholinesterase activity were severely diminished. The gastro-intestinal symptoms were controlled with frequent administration of atropine, of which she received a total of 54 mgm. After the onset of delirium and hallucinations, the atropine was discontinued, with total correction of her mental state. No cholinesterase reactivator was given by her primary care physician. Pralidoxime, newly discovered at that time by IB Wil~on,~ is now routinely given, usually together with atropine. This treats the neuromuscular debility which, as in this patient, increases after 3 weeks. The patient’s subsequent history under the care of Dr. Hunter was of slow progressive improvement of severe muscle symptoms over a period of 10 years. Her plasma cholinesterase took 3 months to return to normal. This patient is thus an example of treatment of the muscarinic features but not the nicotinic effects of the toxic agent. In spite of this, she had absolutely no loss of mental function except for delirium and hallucinations believed to be a result of heavy atropine dosage and resolving with its discontinuation. Indeed she went on to a PhD degree, and had two promotions, the second to Senior Lecturer in Biochemistry. However, as Dr. Kvale points out, there is now a suspicion that anticholinesterase poisoning may be an etiological factor in some patients with Parkinson’s disease or Alzheimer’s disease. The age-adjusted annual death rate for Alzheimer’s disease in the United States rose from 0.4 per 100,000 in 1979 to 4.2 per 100,000 in 1987.4 The contamination of ground-water is an increasing problem which should concern us all. Pesticides are significant contaminants. It now seems that even where pollution is identified, efforts at correction are inadequate.’ Therefore, a high index of suspicion is necessary whenever the clinical circumstances are consistent with acute organophosphate poisoning and (of historical and etiological value) whenever a patient with apparent Alzheimer’s disease is encountered who may have had subacute poisoning in the past.