Undetectable CSF hypocretin-1 levels are highly specific to narcolepsy and rare cases of GBS. Measuring hypocretin-1 levels in the CSF of patients suspected of narcolepsy is a useful diagnostic procedure. Low hypocretin levels are also observed in a large range of neurologic conditions, most strikingly in subjects with head trauma. These alterations may reflect focal lesions in the hypothalamus, destruction of the blood brain barrier, or transient or chronic hypofunction of the hypothalamus. Future research in this area is needed to establish functional significance.

We treated 149 patients meeting criteria for age-associated memory impairment (AAMI) for 12 weeks with a formulation of phosphatidylserine (100 mg BC-PS tid) or placebo. Patients treated with the drug improved relative to those treated with placebo on performance tests related to learning and memory tasks of daily life. Analysis of clinical subgroups suggested that persons within the sample who performed at a relatively low level prior to treatment were most likely to respond to BC-PS. Within this subgroup, there was improvement on both computerized and standard neuropsychological performance tests, and also on clinical global ratings of improvement. The results suggest that the compound may be a promising candidate for treating memory loss in later life.

The authors examined the charts of 22 outpatients who had received intramuscular fluphenazine decanoate and oral fluphenazine hydrochloride to assess the incidence of tardive dyskinesia. The severity of tardive dyskinesia was assessed with the Abnormal Involuntary Movement Scale (AIMS). Both the total dose and average daily dose of fluphenazine decanoate correlated significantly with high AIMS scores. There were also significant correlations of AIMS scores with total dose of antiparkinsonian medication and total dose of other neuroleptics. Total dose of antiparkinsonian medication correlated with total dose of fluphenazine decanoate. The authors discuss the clinical and physiological implications of these correlations.

No abstract

To the Editor: Valproic acid was approved in the US for use as an antiepileptic in 1978. Pharmacologically it has antiepileptic activity against a variety of seizure types while causing minimal central nervous system side effects.' Although the mechanism of action of valproic acid is unknown, evidence suggests that valproic acid selectively increases concentrations of gamma-aminobutyric acid in synaptic regions.' Valproic acid's psychopharmacological indications have expanded to include use for mood stabilization: a n~i e t y ,~ behavioral dyscontrol? and as an adjunctive modality in the treatment of psychosis.' The most common side effects are gastrointestinal symptoms, including anorexia, nausea, and vomiting. Elevation of hepatic enzymes has been observed in 15 to 30% of patients, often occurring asymptomatically early in the treatment. Heretofore, we were unaware of pancytopenia occurring in adults treated with valproic acid; here we present a case of myelotoxicity associated with valproic acid. Case ReportMr. M is a 66-year-old male, with a confirmed history of bipolar-manic type, hypothyroidism, alcohol abuse, and degenerative joint disease. A decompensation following medication noncompliance led to hospitalization. He was started on haloperidol 2 mg PO bid and 5 mg q hs, valproic acid 500 mg q hs, levothyroxine sodium 0.075 PO qd, and mvt/ thiamine. Valproic acid was increased to 500 mg bid, with serum levels remaining below 60 ng/mL. Admission labs revealed WBC of 4.2, HGB of 10.5, and HCT of 31.3. The hematologic indices fell inversely with increases in valproic acid, reaching WBC of 2.5, HGB of 9.0, and HCT of 27.1. Physical examination found fatigue and weakness without petechiae hemorrhages, ecchymosis, or edema. Hematology consult concluded a pancytopenia secondary to valproic acid, which was immediately discontinued. Within days, all hematologic indices normalized, and symptoms resolved without consequence. DiscussionHematological abnormalities have been reported with valproate use,6 but most studies have been conducted on children and adolescents.' In one hematological study of longterm side effects in 60 patients, 33% developed at least one prominent abnormality. Thrombocytopenia and macrocytosis were the most common findings. None of the patients demonstrated hepatic dysfunction, nor were the hematologic toxicity's severe enough to discontinue therapy.6Aplastic anemia, is attributable to a failure or suppression of pluripotential stem cells, leading to cytopenia of cell lineages. Primary aplastic anemia is without an identifiable cause. Secondary causes of reduction in functional marrow mass may include toxic, radiant, or immunologic injury to stem cells.8 Myelotoxicity is a particular concern for the geriatric population because bone marrow cellular density decreases with advancing age. There is a reduction to approximately 50% cellular density at age 65, with a further reduction in cellularity to about 30% occurring over the next decade.' Age, illness, and medications may create a synergistic v...