The influence of psychotropic drugs on cerebral cell death: female neurovulnerability to antipsychotics.

Tissue transglutaminase (tTG) is a marker for apoptosis, and its protein level is known to be increased in post-mortem Alzheimer's and Huntington's disease brains. tTG is increased in the cerebrospinal fluid of patients with Alzheimer's disease. However, the influence of psychotropic medication on acute cell death has not been studied so far in vivo, although some experiments performed in vitro suggest that antipsychotic drugs are neurotoxic. The protein level of tTG was examined in the cerebrospinal fluid obtained from 29 patients under neuroleptic medication in the last 24 h before lumbar puncture (eight patients diagnosed with Alzheimer's disease and 21 patients with other neurological diseases), and compared with those from 55 patients without antipsychotic medication (25 Alzheimer's patients and 30 others). In addition, the influence of several other psychotropic drugs on apoptosis was analysed. A significant influence (P<0.01) of antipsychotic drugs for both the Alzheimer's and the non-Alzheimer's group was found with respect to tTG protein levels in cerebrospinal fluid. By contrast to the male subgroups, the female groups showed a strong influence of neuroleptics on cerebral cell death. Surprisingly, atypical antipsychotics did not differ from typical neuroleptics in neurotoxicity. By contrast, no influence of antidepressants, cholinesterase-inhibitors, nootropics, tranquilizers and tramadol on cerebral cell death was found. The results suggest that typical and atypical antipsychotic drugs may induce cerebral cell death, especially in female patients. Subjects with Alzheimer's disease might be even more vulnerable to any antipsychotic. Therefore, subsequent research should aim to identify atypical neuroleptics without neurotoxicity. A limit on the use of first- and second-generation antipsychotics in elderly patients is proposed. Finally, the possible connection between the observed increased cerebral cell death and tardive dyskinesia, the most threatening side-effect in antipsychotic therapy, is discussed.

Transient hypoglycemic abducens palsy.

Since 1928, among the thousands of patients treated for insulinoma, only 32 cases with peripheral neuropathy have been reported. None of these described an affection of the cranial nerves. We present a 56 old woman, who suffered from chronic hyperinsulinism due to an insulinoma. For ten years, the patient has developed progressively marked hypoglycemic attacks of up to 20 mg/dl. Recently we have observed the development of a paresis of the right abducens nerve lasting for 6 weeks.

Prevalence of autoimmune thyroiditis and non-immune thyroid disease in multiple sclerosis.

Since multiple sclerosis (MS) and autoimmune thyroiditis (AIT) are presumed to be of autoimmune origin the correlation of these two diseases is of special interest. The aim of this study was to determine whether there are differences in the prevalence of thyroid disease with special emphasis on AIT compared with MS and normal subjects and whether the presence of thyroid disease correlates with disability, disease course, age, and disease duration. 353 consecutive patients with clinically definite MS, without interferon-beta treatment and 308 patients with low back pain or headache were extensively examined for the presence of non-immune or autoimmune thyroid disease. We found a significantly higher prevalence of AIT in male MS patients (9.4 %) than in male controls (1.9 %; p = 0.03). The prevalence of AIT in female MS patients (8.7 %) did not differ from female controls (9.2 %). Hypothyroidism, caused by AIT in almost all cases, showed a tendency to be more severe and more often present in patients with MS. There was no association between relapsing-remitting and secondary progressive disease course of MS and the prevalence of AIT. MS patients with AIT were significantly older but did not differ in disease duration and expanded disability status scale (EDSS). Further studies are warranted, to see if there is a difference in sex-hormone levels between MS patients with and without AIT and healthy controls. Longitudinal studies comparing MS patients with or without AIT could show whether there is an influence of AIT on the disease course or progression.

Zotepine in Huntington's disease.

The authors report a patient with Huntington's disease (HD) presenting with severe chorea. The motor scale of the unified HD rating scale (UHDRS-I) revealed 81 points. Motor function clearly improved with zotepine, until she reached an UHDRS-I of 34 points on day 7 of treatment. The patient was stable for at least 12 weeks. The improvement includes all seven categories of the UHDRS-I, especially chorea, gait and oral function. This is the first description of zotepine in HD. Our findings suggest that zotepine is useful in the treatment of HD chorea. Controlled trials of its use in HD would be welcome.

Ziprasidone in Huntington's disease: the first case reports.

Huntington's disease (HD) is a relentlessly progressive neuropsychiatric disorder with an underlying autosomal dominantly inherited genetic defect. Classical antipsychotics (i.e. phenothiazines or butyrophenones) are the most used medication to reduce the (probably dopamine-born) choreiform hyperkinesias. Ziprasidone is the latest of a new class of atypical antipsychotics; it has not been studied so far in this indication. We report three genetically confirmed HD patients who improved significantly in several categories of the motor scale of the Unified HD Rating Scale.

Cerebrospinal fluid tissue transglutaminase as a biochemical marker for Alzheimer's disease.

Tissue transglutaminase (tTG) is an indicator of acute cell death in vitro. An increase in tTG protein level is found in postmortem Alzheimer's disease (AD) brains as well as in Huntington's disease. No study revealed tTG in vivo so far. We investigated the concentrations of tTG in the cerebrospinal fluid (CSF) obtained from 84 patients using ELISA assays. We compared 33 patients with probable AD to 18 patients with probable vascular dementia (VaD) and 33 control patients without neuropsychological deficit. Diagnosis was supported by CSF parameter and neuroimaging. We found a highly significant difference (P = 0.001) between the concentration of tTG in the AD groups (7.58 pg/ml) and controls (2.99 pg/ml). There was no statistical difference between controls and VaD (2.93 pg/ml). Interestingly, tTG did not show an association with tau protein, Abeta42, apoE4, neuropsychological items, or age. Males showed lower tTG values than females; however, this difference did not reach statistical significance. To our knowledge, this is the first demonstration that tTG is increased in AD in vivo. Our results suggest that tTG may be a powerful biochemical marker of the acute degenerating process in vivo. It may serve as completion of CSF analysis in the diagnosis of dementing disorders and may be a simple way of assessing the efficacy of possible new antiapoptotic drugs.

Olanzapine for Huntington's disease: an open label study.

The aim of this prospective open label study was to assess the efficacy of olanzapine for motor symptoms in Huntington's disease (HD). Olanzapine was administrated to nine patients with genetically confirmed HD in increasing doses until satisfactory clinical effect or the appearance of side effects. The patients were evaluated at baseline and after 14 days of treatment using the motor scale of the Unified HD Rating Scale (UHDRS). The patients improved significantly in most subscores of the UHDRS, including fine motor tasks, although some patients needed a rather high dose (30 mg per day). No adverse effects were reported by the patents spontaneously or were observed directly by the investigator. High-dose olanzapine seems to be useful in choreatic HD patients. A double blind, placebo-controlled trial appears warranted to definitively establish the symptomatic value of olanzapine in HD.

Pramipexole ameliorates neurologic and psychiatric symptoms in a Westphal variant of Huntington's disease.

Levodopa is recommended as a therapeutic approach for patients with the hypokinetic-rigid, Westphal variant of Huntington's disease, but no guidelines are available for the case of nonrespondence to levodopa. In this study, however, we report a 34-year-old woman with this rare variant who showed a clear-cut improvement in motor function and depressive symptoms after treatment with pramipexole, a new dopamine agonist.