Contribution of the daily melatonin profile to diagnosis of tumors of the pineal region.

Tumors of the pineal region (TPR) include different entities: germ cell tumors (GCT), pineal parenchymal tumors (PPT), meningiomas, and glial tumors. Except for GCT, there are no peripheral markers and histopathological diagnosis needs biopsy or surgery. We studied daily melatonin variations in twenty-nine patients with TPR and five with tectal plate glioma (TPG), used as controls, before and/or after surgery. Before surgery, a melatonin nycthemeral rhythm was observed in patients with TPG and TPR (one cyst, three PPT, one papillary tumor of the pineal region, two meningiomas, six gliomas). Melatonin rhythm was dramatically reduced for undifferentiated or invasive tumors. After surgery, the absence of melatonin variation in some cases could be the consequence of pineal damage by surgery. The contribution of determination of melatonin profiles to the diagnosis of TPR remains limited but of interest. The evidence for melatonin deficiency could justify melatonin administration to prevent the postpinealectomy syndrome.

Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings.

OBJECTIVE: To determine Red Blood Cell (RBC) antioxidant enzyme activities and plasma Thiobarbituric Acid Reactive Substances (TBARS) in clinically stable patients with schizophrenia and their unaffected siblings. METHODS: A case-control study carried out on three groups: 60 schizophrenic patients treated with neuroleptics, 33 of their unaffected siblings and 30 healthy controls with no family psychiatric history. Biological markers were measured on fasting patients after a period of tobacco abstinence: RBC antioxidant enzyme activities - superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) - by spectrophotometry and plasma levels of TBARS by spectrofluorimetry. RESULTS: RBC SOD and CAT activities were significantly lower in schizophrenic patients and their unaffected siblings compared to the control group (P<0.001). Schizophrenic patients also had significantly lower RBC GSH-Px activity than controls (P=0.03), whereas their unaffected siblings had significantly higher RBC GSH-Px activity than controls (P=0.04). Plasma TBARS were higher in schizophrenic patients than their unaffected siblings: 2.1+/-0.8 micromol/l vs. 1.7+/-0.6 micromol/l (P=0.06). CONCLUSIONS: Our results showed a decrease in antioxidant enzyme activities and an increase in lipid peroxidation confirming the existence of oxidative stress in schizophrenic patients treated with neuroleptics. Additionally, this suggests that the increase in GSH-Px activity in unaffected siblings would be a protective mechanism against oxidative stress and damage. Other studies are necessary to confirm these findings.

The basic physiology and pathophysiology of melatonin.

Melatonin is a methoxyindole synthesized and secreted principally by the pineal gland at night under normal environmental conditions. The endogenous rhythm of secretion is generated by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production according to the light schedule. The nycthohemeral rhythm of this hormone can be determined by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body physiology. This information is used for the organisation of functions, which respond to changes in the photoperiod such as the seasonal rhythms. Seasonal rhythmicity of physiological functions in humans related to possible alteration of the melatonin message remains, however, of limited evidence in temperate areas in field conditions. Also, the daily melatonin secretion, which is a very robust biochemical signal of night, can be used for the organisation of circadian rhythms. Although functions of this hormone in humans are mainly based on correlative observations, there is some evidence that melatonin stabilises and strengthens coupling of circadian rhythms, especially of core temperature and sleep-wake rhythms. The circadian organisation of other physiological functions could depend on the melatonin signal, for instance immune, antioxidative defences, hemostasis and glucose regulation. Since the regulating system of melatonin secretion is complex, following central and autonomic pathways, there are many pathophysiological situations where the melatonin secretion can be disturbed. The resulting alteration could increase predisposition to disease, add to the severity of symptoms or modify the course and outcome of the disorder.

Prevalence and description of chronic daily headache in the general population in France.

The objective of this study was to describe the epidemiology, clinical presentation and consequences of chronic daily headache (CDH) in France. A representative nation-wide sample of the general population was identified using a stratified sampling method. Ten thousand five hundred and eight-five subjects were screened in face-to-face interviews, and data collected using a standard questionnaire. An overall point prevalence of CDH in the general population of 2.98% was observed. Two-thirds of these subjects presented migraine-like features. Severity, functional impact and healthcare consumption were higher than in subjects reporting episodic migraine in the same sample. Of the subjects, 28.2% reported the most severe migraine disability assessment scores (Grades 3 and 4), compared to 12% of episodic migraineurs. A qualité de vie et migraine score of 68.4 was observed, indicating severely attenuated quality of life. Only 6.6% of subjects were taking prophylactic treatment, whilst 88% were using non-specific acute headache treatments. The frequency of physician consultations and laboratory examinations was significantly higher than in individuals with episodic headache. CDH is thus a relatively prevalent condition in the general French population, associated with an important burden of suffering and with considerable expenditure in the health service. Management of this condition is generally inappropriate.

Economic impact of migraine and other episodic headaches in France: data from the GRIM2000 study.

BACKGROUND: Migraine is a prevalent and incapacitating condition that affects individuals in the prime of their productive life, thus generating an economic burden for both society and healthcare systems. The direct annual healthcare costs of migraine in France were assessed over 10 years ago, and the current study updates these figures. OBJECTIVE: The objective of this study was to determine the economic cost (primarily direct costs) of migraine and other episodic headache in France based on a general population survey of headache, the GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). DESIGN: From a representative general population sample of 10,585 individuals aged > or = 15 years in France in 1999, 1486 individuals experiencing headaches were identified and interviewed regarding healthcare resource consumption in the previous 6 months. By applying unit costs to the resource data, costings (in 1999 values) were determined for physician consultations, hospitalisation, medication use and diagnostic/laboratory tests, and evaluated from a healthcare system perspective. Information on absenteeism and lost productivity was derived from the Migraine Disability Assessment Score (MIDAS) questionnaire. RESULTS: The prevalence of migraine (including migrainous disorder) was determined to be 17%. Total annual direct healthcare costs were estimated to be Euros 128 per individual with migraine in 1999, corresponding to Euros 1044 million when extrapolated to all individuals experiencing migraine and aged > or = 15 years. Around two-thirds of this cost accrued to the social security system (Euros 698 million; Euros 85 per individual). The total annual direct cost of other forms of episodic headache was much lower at Euros 28 per individual (social security cost Euros 18); with a prevalence of 9.2%, the annual national direct cost for other forms of episodic headache totalled Euros 124 million. The principal cost element was physician consultations. However, it was found that many individuals had never consulted a physician for their headaches, and self-medication contributed substantially to the medication costs (the second greatest cost factor for migraine). The cost per individual rose steeply with increasing severity of headache. CONCLUSIONS: The direct healthcare costs of migraine do not seem to have risen significantly over the past decade. A small minority of individuals with more severe headaches consume most of the healthcare resources devoted to migraine, while most individuals generate relatively low direct costs. The total annual direct costs in France for migraine are almost 10-fold higher than those of other episodic headache.

Involvement of neuroleptic drugs in selenium deficiency and sudden death of cardiac origin: study and human post-mortem examination.

The involvement of psychotropic drugs in sudden deaths has been highlighted. The objective of this work was to establish a link between selenium levels in heart tissue, psychotropic treatment and sudden death. Selenium levels were measured by electrothermal atomic absorption spectroscopy post-mortem in heart, brain and liver. Histological examination evidenced dilated cardiomyopathy in 45% of cases, left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%. A significant reduction of myocardial selenium levels compared to controls was seen in patients treated with neuroleptic drugs or meprobamate. No changes in brain or liver selenium levels were seen. These results suggest that selenium deficiency can facilitate sudden death in patients on psychotropic drugs. The reduced activity of glutathione peroxidase due to selenium deficiency can result in augmented oxidative stress in myocardial cells and myocardiopathy leading to sudden death.

Increased detection of 14-3-3 protein in cerebrospinal fluid in Sporadic Creutzfeldt-Jakob Disease during the disease course.

Diagnosis of Creutzfeldt-Jakob Disease (CJD) is based on neurological signs associated with characteristic electroencephalographic activity or detection of 14-3-3 protein in cerebrospinal fluid. However, the time course of 14-3-3 protein release during sporadic CJD is unknown. We report two observations in which the level of the detected 14-3-3 protein increased significantly with time. These preliminary cases suggest that there may be an increased release of 14-3-3 protein during the course of CJD as already proven for iatrogenic CJD.

Impact of headache on quality of life in a general population survey in France (GRIM2000 Study).

OBJECTIVES: The objectives of this study were to determine the impact of headache on health-related quality of life in a nationwide sample of the French general population using a disease-specific measure, the Qualité de Vie et Migraine (QVM), to compare quality of life in subjects reporting different headache to types, and to evaluate the relationship between quality of life and severity, frequency, associated disability, and treatment responsiveness of headaches. METHODS: The QVM questionnaire was included within a large epidemiological survey of 1486 headache sufferers. Diagnosis was assigned retrospectively using an algorithm based on the International Headache Society classification. Headache severity was assessed with the MIGSEV scale and disability with the MIDAS scale. RESULTS: The mean global QVM score in the sample was 80.2. Quality of life was poorer in subjects with chronic daily headache (QVM score: 66.2) than in those with migraine (QVM score: 76.7), while those with other forms of episodic headache had the best quality of life (QVM score: 91.7). Quality-of-life scores were correlated with frequency, severity, disability, and treatment resistance of headaches (P <.001). CONCLUSION: The QVM scale is a sensitive tool to measure health-related quality of life in headache sufferers in the general population.