Randomized clinical trial of melatonin after night-shift work: efficacy and neuropsychologic effects.

OBJECTIVE: Melatonin has received considerable publicity for its sleep-promoting properties; however, there is little scientific evidence of its efficacy. The objective of this study is to determine whether there are measurable beneficial effects from exogenous melatonin in emergency physicians after intermittent night-shift duty. METHODS: This randomized, placebo-controlled, double-blind, crossover trial was conducted in the emergency department of an urban tertiary care hospital. Fifteen emergency physicians were given melatonin 5 mg or placebo for 3 consecutive nights after night-shift duty with crossover to the opposite agent after a subsequent block of night shifts. The primary outcome measure was the global assessment of recovery measured by a visual analog scale. Secondary outcome measures included sleep quality, duration, and tiredness. In addition, the Profile of Mood States questionnaire and neuropsychologic testing were performed. RESULTS: There was no difference between melatonin and placebo in the global assessment of recovery (60.4+/-16.9 and 58.9+/-14.5, respectively; P=.29). There were no differences in sleep quality, duration or tiredness scores, sleep latency, hours of sleep obtained per night, and night or early awakening at any measurement point. Profile of Mood States and neuropsychologic test performances were similar. CONCLUSION: We found no beneficial effect of melatonin on sleep quality, tiredness, or cognitive function in emergency physicians after night-shift duty. Our results suggest that exogenous melatonin is of limited value in recovery from night-shift work in emergency physicians.

"Wineglass" confabulations among brain-damaged alcoholics on the Wechsler Memory Scale-Revised visual reproduction subtest.

Confabulation is a clinically well-documented accompaniment of selective types of memory impairment, especially in brain-damaged alcoholics. This study reports specific occurrences of visual confabulation consisting of spontaneous alterations of Card D of the Visual Reproduction subtest of the Wechsler Memory Scale-Revised. The resemblance of a wineglass was fashioned by a 90-degree rotation into a "bowl and stem", observed in six of 30 brain-damaged alcoholics. There were no such instances in 132 other patients, including alcoholic controls, those with Parkinson's Disease, temporal lobe epileptics (pre- or post-surgery), and those with neurotoxic exposure. When asked, the subjects who identified the figure as a wineglass or similar drinking instrument reported that they had drawn it as originally shown to them. "Wineglass" confabulators had shorter periods of abstinence, longer drinking histories and lower intellectual functioning than their brain-damaged peers or an alcoholic control group. These findings lend support for the association of alcohol-related confabulation with visual, as well as previously-documented verbal material among brain-damaged alcoholics.

Fine motor speed deficits in alcoholic Korsakoff's syndrome.

Forty-two alcoholic Korsakoff's syndrome (KS) patients (12 in study 1, 30 in study II) averaged slower tapping speeds than 35 alcoholic controls on the Halstead-Reitan manual finger tapping task. KS subjects also tapped slower than 26 normal volunteers in study II. Inverse relationships were found between finger-tapping speed dominant hand and verbal word fluency in one sample, and tapping speed and time to completion on Trail Making Part B and Tactual Performance Test in the other. The most powerful demographic predictors of tapping speed among age, education, length of abstinence, and affective state were age and education. Tapping speed was associated with cognitive tasks measuring frontal systems function (i.e., verbal fluency and Trail Making Part B) in KS subjects. There was no relationship between fine motor performance and general memory scores in the KS subjects. Decreased tapping speed for KS patients was postulated to result from compromised fine motor task initiation and persistence rather than mere slowing, as in Parkinson's disease. These findings suggest disruption of frontocerebellar systems that influence motor generation and set maintenance not previously explored in KS.

Educational and gender normative data for the Boston Naming Test in a group of older adults.

The 60-item version of the Boston Naming Test (BNT) was administered to a group of 176 normal older adults in Middle Tennessee ranging in age from 60 to 93 years. Results are reported in five age groupings by gender and education. Although a few studies have previously examined the performance of the elderly on the BNT, the current study attempted to recruit individuals in proportion to the demographics of the regional population including gender, race, and, as much as possible, education and occupation. The results indicate that while age significantly affected confrontational naming ability, the interaction of age and education appeared to be a better predictor of performance. As with previous studies, more variability was found in higher age groups and in those with less education. Naming ability remained stable in the higher education group (> or = 12th grade) until 80 years, whereas those patients with less than a high school education demonstrated a decrement in naming ability at 70 years. Current results also revealed a gender bias for this population, with males scoring higher on 17 of 19 items where a significant difference existed.

Severe global amnesia presenting as Wernicke-Korsakoff syndrome but resulting from atypical lesions.

A female alcoholic presented with Wernicke's encephalopathy subsequent to administration of diazepam and glucose (without thiamine) for treatment of withdrawal seizures. Nystagmus and cerebellar ataxia quickly resolved when administered thiamine, although severe global amnesia consistent with Korsakoff's syndrome persisted. Magnetic resonance imaging (MRI) revealed infarction of the right temporal lobe with hippocampal atrophy, but no lesions of thalamus or atrophy of mammillary bodies. Positron emission tomography (PET) confirmed decreased cerebral metabolic rates for glucose (CMRglu) in the right temporal lobe corresponding to MRI findings, but also significant metabolic asymmetry of dorsal thalamus, i.e. reduced CMRglu in left versus right. This patient is unique in that neuroradiological findings revealed intact mammillary bodies and suggest asymmetrical dysfunctions (structural right temporal and functional left diencephalic) to produce her profound amnesia.

Brain proton magnetic resonance spectroscopy studies in recently abstinent alcoholics.

Chronic alcohol-dependent patients have reduced brain volumes and concomitant neurobehavioral deficits that may recover during abstinence. In 10 chronic alcoholic patients, using localized proton magnetic resonance spectroscopy, we found reliable increases during the first 3-4 weeks of abstinence in the concentrations within the superior cerebellar vermis of choline (Cho)-containing compounds relative to the neuronal marker, N-acetylaspartate (NAA). Lesser changes were observed following 1 month of abstinence, and in one of the patients studied longitudinally over 3 months, a marked reduction in the Cho/NAA ratio was associated with relapse. After detoxification, the Cho/NAA ratio correlated with a composite clinical impression of brain functions. The lowest Cho/NAA was observed in a patient with persisting alcoholic dementia, in striking contrast to reduced relative concentrations of NAA reported in dementia of the Alzheimer's type. Possible molecular explanations for these brain metabolic changes are discussed.

Elemental mercury vapour toxicity, treatment, and prognosis after acute, intensive exposure in chloralkali plant workers. Part II: Hyperchloraemia and genitourinary symptoms.

Exposure to elemental mercury vapour is known to influence renal function; however, severe renal disease has not been consistently identified. Eleven men were evaluated for renal disease after acute, massive mercury poisoning. Significant hyperchloraemia was identified in this group of patient and a reversible renal tubular defect was suggested by low normal serum bicarbonate, a normal serum anion gap and a positive urinary anion gap. The only other evidence of renal dysfunction was transient, mild proteinuria in one of the 11 patients. During this same time period, neuropsychological impairment was identified on a test of cognitive and visual-motor function, 'Trailmaking B', in seven of the 11 patients. Additionally, dysuria and ejaculatory pain occurred without evidence of urological disease. These complaints were more frequent in those patients with impairment on 'Trailmaking B' suggesting a neurological basis for these symptoms. The findings of this study support earlier observations that the brain rather than the kidney is the critical target organ after elemental mercury vapour exposure.

Elemental mercury vapour toxicity, treatment, and prognosis after acute, intensive exposure in chloralkali plant workers. Part I: History, neuropsychological findings and chelator effects.

Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the 'Symptom Check List 90-Revised' (SCL-90R) and tests of visual-motor function such as 'Trailmaking Parts A and B', 'Finger Tapping', 'Stroop Colour Word Test' and 'Grooved Pegboard.' On day 85 +/- 11 (mean +/- s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents. Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes long-term, probably irreversible, neurological sequelae.

Organic disorders of personality.

Organic illnesses may produce alterations in behavior that closely resemble personality disorders. Careful differential diagnosis is necessary in formulating appropriate treatment.