Serum copper, zinc and selenium levels in Tunisian patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder. The etiology of this disease is still not fully clear, but free radicals have been proposed to cause neuronal injury. Metals play a key role in the intracellular oxidative balance. However their implication in the degeneration process remains unknown. AIM: To assess Cu, Zn and Se concentrations in serum of a group of PD patients in order to determinate, in comparison with age-matched controls, whether alteration in their levels could be involved in PD. METHODS: A serum level of 3 trace elements (Cu, Zn and Se) was investigated in 48 patients with PD and 36 matched controls using plasma atomic absorption spectrometry. We compared these parameters in PD patients with controls, and we also compared the variations within the PD group according to age, illness duration, stage of the disease and levodopa intake. RESULTS: Patients with PD had significantly lower Cu levels compared to controls. The mean Zn and Se levels in PD patients did not differ significantly from those of controls. Levodopa therapy, age, stage, and illness duration did not significantly influence the measured parameters. CONCLUSION: These results suggest that a disturbance of the plasmatic rate of Cu could be a marker of PD or at least, a risk factor for the development of this disease. Although zinc participates to the reduction of oxidative stress and the antioxidant role of the selenium, their implication in the onset of PD is not clearly established. Perspectives for the future could include antioxidant therapy. For this reason, other prospective studies should be conducted on this subject to elucidate the implication of trace elements in PD.

[Conclusions and recommendations of a WHO expert consultation meeting on iron supplementation for infants and young children in malaria endemic areas]. / Conclusions et recommandations à l'issue de la consultation de l'OMS sur la lutte contre la carence martiale chez le nourrisson et le jeune enfant dans les pays d'endémie palustre.

This article presents the results of an expert consultation meeting aimed at evaluating the safety and public health implications of administering supplemental iron to infants and young children in malaria-endemic areas. Participants at this meeting that took place in Lyon, France on June 12-14, 2006 reached consensus on several important issues related to iron supplementation for infants and young children in malaria-endemic areas. The conclusions in this report apply specifically to regions where malaria is endemic.

[Neurobiology of lithium].

In addition to well-documented mood-stabilizing effects, lithium can be used in the treatment of acute brain injuries (ischemia) and chronic (neurodegenerative) diseases. Recent in vitro and in vivo studies reveal that the long-term treatment with lithium up-regulates cell survival molecules (Bcl-2, cAMP-responsive element binding protein, GRP 78, brain-derived neurotrophic factor, Hsp70) and down-regulates pro-apoptotic activities (e.g., excitotoxicity, p53, Bax, caspase, cytochrome C release, beta-amyloid peptide production and tau hyperphosphorylation) thus preventing or even reversing the neuronal cell death and neurogenesis retardation.

Peripheral blood markers of oxidative stress in Parkinson's disease.

Oxidative stress and generation of reactive oxygen species are believed to be implicated in Parkinson's disease (PD). Erythrocyte activity of superoxide dismutase (SOD) and catalase, the blood glutathione system, and plasma levels of thiobarbituric-acid-reactive substances (TBARS) were measured in 80 PD patients. These biochemical parameters were also measured in 29 age-matched controls. Patients with PD had significantly higher red blood corpuscle (RBC) activity of SOD. The mean RBC activity of catalase in PD patients did not differ significantly from those of controls. RBC catalase activity was significantly lower in advanced cases of PD compared to early cases. Oxidized glutathione was significantly higher in RBCs of PD patients, although there were no changes in total glutathione and reduced glutathione compared to controls. TBARS content was increased in patients with PD. Levodopa therapy, age and duration of illness did not significantly influence the measured parameters. Our study supports the previous hypothesis that oxidative stress is implicated in the pathogenesis of PD. Perspectives for treatment of PD in the future could include antioxidant therapy.

Rating of olfactory judgements in migraine patients.

The aim of this study was to evaluate olfactory hypersensitivity (OHS) between attacks in migraine patients. Seventy-four migraine patients and 30 controls were enrolled. The presence of OHS was evaluated using an oral questionnaire and a chemical odour intolerance index. Subjects had to rate the intensity and hedonicity of 12 odourants using a linear rating scale. Twenty-six patients (35.2%) but no control subjects reported an interictal OHS (P<0.001). Logistic regression analysis showed that patients with OHS presented a greater attack frequency, a higher number of odour-induced migraines and visual hypersensitivity when compared with other patients. Disease duration, age, gender and auditory hypersensitivity were not associated with OHS. OHS patients judged odours less pleasant than did other patients and controls, whereas the intensity scores were identical in both groups. OHS between attacks was significantly associated with odour-triggered migraine and an alteration of hedonic judgement.

[Intra-cavernous aneurysm of the internal carotid artery complicating sphenoid sinusitis]. / Anévrysme de la carotide interne intra-caverneuse compliquant une sinusite sphénoïdale.

INTRODUCTION: Mycotic or post-infectious aneurysm of the intra-cavernous portion of the internal carotid artery is uncommon. CASE REPORT: We report here the case of a patient who developed progressive left ophthalmoplegia, with left hemi-crania three weeks after a tooth extraction. The patient was febrile. Neuroradiological and microbiological analysis led to the diagnosis of sphenoidal and ethmoidal sinus infection with extension to the left cavernous sinus. An aneurysm of the intra-cavernous portion of the left internal carotid artery was also found. CONCLUSIONS: The risk of rupture for this kind of aneurysm is difficult to assess. Treatment always consists in prolonged and adapted antibiotic therapy. For certain patients neurosurgical or endovascular repair is necessary. We followed our patient for four Years without surgical intervention. The diameter of the aneurysm has remained stable.

Use and misuse of triptans in France: data from the GRIM2000 population survey.

The extent and nature of triptan use for headache relief has been evaluated in a large epidemiological survey in the French general population. Over 25 000 individuals were screened for headache and for triptan use. Of this sample, 290 triptan users were identified from whom extensive data on headache characteristics and healthcare resource consumption were obtained. The use of triptans is relatively infrequent, 0.2% in the general population, with only 7.5% of migraine sufferers using these drugs. The majority of triptan users were female (80%) and presented headache characteristics typical of migraine (80%). The remaining 20% of subjects were thus using triptans for headache types in which the utility of these drugs has not been demonstrated. Among migraineurs, triptan consumers reported more frequent and severe headaches than non-consumers, and reported a higher incidence of nausea and vomiting. The principal determinant of triptan prescription was consultation with a general practitioner (GP), which may itself have been triggered by the severity of the headaches. GPs, rather than specialists, are the primary prescribers of triptans in France.

Melatonin secretion is supersensitive to light in migraine.

The present study examined the sensitivity to light of melatonin (MLT) secretion in familial migraine during a headache-free interval. Twelve female patients and 12 healthy controls were included in the trial. All subjects were studied twice. In each session, light exposure (300 lx) or placebo was randomly administered for 30 min between 00.30 and 01.00 h. Blood was sampled hourly between 20.00 and 24.00 h, and 02.00 and 04.00 h and every 15 min between 00.30 and 01.30 h. Plasma MLT levels were determined by radioimmunoassay. MLT suppression was more marked in the migraine group than in the control group [difference of area under curve (DeltaAUC)=-53.8 +/- 16.2 vs. 18.5 +/- 12.7 pg/h/ml, P<0.005; maximum of MLT suppression (Delta)=-35.7 +/- 10.2 vs. - 6.7 +/- 5.8 pg/ml, P<0.05]. These findings show a clear hypersensitivity to light in young female migraineurs during the headache-free period.

The timing of antiparkinsonian treatment reduction after subthalamic nucleus stimulation.

The objective of this work was to precisely analyse the reduction of the antiparkinsonian treatment in 18 consecutive patients with Parkinson's disease (PD) operated on for bilateral subthalamic nucleus (STN) stimulation, first after 1 month of follow-up, then at 1 year postoperatively. Trihexyphenidyle, selegiline, entacapone, apomorphine and lisuride could be withdrawn shortly after starting STN electrical stimulation. The levodopa mean daily dose was reduced by 57% at 1 month after surgery and remained stable at 1 year. The mean ropinirole and bromocriptine daily dose decrements after surgery corresponded to 54 and 63%, respectively, at 1 month and to 77 and 40% at 1 year. At 12 months postoperatively, one third of the patients no longer received any antiparkinsonian drugs and the others were on monotherapy of either levodopa or dopamine agonists or received a combined treatment of a dopaminergic agonist and levodopa. In conclusion, STN stimulation allows a major reduction and simplification of antiparkinsonian treatment which can usually be achieved during the early postoperative period.

[Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (Melas) associated with a Fahr disease and cerebellar calcifications]. / Encéphalomyopathie mitochondriale de type Melas associée à un syndrome de Fahr avec calcifications cérébelleuses.

INTRODUCTION: Melas syndrome is a mitochondrial disease which corresponds to the association of mitochondrial encephalopathy, lactic acidosis and stroke-like espisodes. CASE REPORT: The authors report the case of a 39 year-old woman presenting with hearing loss, seizures, visual field deficit, three stroke-like episodes and calcifications of the basal ganglia and cerebellar dentate nuclei. Melas syndrome was suspected and confirmed by muscle biopsy, showing ragged red fibers and the presence of an A3243G mutation of mitochondrial DNA. CONCLUSION: This clinical, pathological and radiological observation shows that intracerebral calcifications may involve the dentate nuclei of the cerebellum in the Melas syndrome.

Prevalence and clinical characteristics of migraine in France.

OBJECTIVE: To determine the prevalence and clinical features of migraine and related headache types in France. METHODS: The authors recruited a population of subjects with headache representative of the national population using a stratified sampling method. They screened 10,585 subjects aged 15 and older who were representative of the general population. They identified 1,486 of these as having headaches, and these subjects were subsequently interviewed for information on clinical features, natural history, and functional impact of headache. The authors categorized subjects based on the International Headache Society (IHS) classification and assessed disability using the MIDAS questionnaire. RESULTS: The authors found a standardized prevalence for migraine (IHS categories 1.1 and 1.2) of 7.9% (11.2% for women and 4.0% for men) and 9.1% for migrainous disorder (IHS category 1.7). Migraine attacks were associated with a considerable degree of handicap in activities of daily living, with a MIDAS grade distribution of 74.7% (grade 1), 13.3% (grade 2), 7.7% (grade 3), and 4.3% (grade 4). The prevalence of migraine with MIDAS grade 3 or 4 was 1.6%. CONCLUSIONS: The prevalence of migraine (IHS categories 1.1 and 1.2) in France is 7.9%, and that of total migraine is 17.0%; this does not seem to have evolved over the past 10 years.

Subthalamic nucleus stimulation in Parkinson's disease: clinical evaluation of 18 patients.

The aim of the present study was to assess the efficacy and safety of chronic subthalamic nucleus deep-brain stimulation (STN-DBS) in patients with Parkinson's disease (PD). 18 consecutive severely affected PD patients were included (mean age, SD: 56.9+/-6 years; mean disease duration: 13.5+/-4.4 years). All the patients were evaluated clinically before and 6 months after the surgical procedure using the Unified Parkinson's Disease Rating Scale (UPDRS). Additionally, a 12 months follow-up was available in 14 patients. The target coordinates were determined by ventriculography under stereotactic conditions, followed by electrophysiology and intraoperative stimulation. After surgery, continuous monopolar stimulation was applied bilaterally in 17 patients at 2.9+/-0.4 V through 1 (n = 31) or 2 contacts (n = 3). One patient had bilateral bipolar stimulation. The mean frequency of stimulation was 140+/-16 Hz and pulse width 68+/-13 micros. Off medication, the UPDRS part III score (max = 108) was reduced by 55 % during on stimulation (score before surgery: 44.9+/-13.4 vs at 6 months: 20.2+/-10; p < 0.001). In the on medication state, no difference was noted between the preoperative and the postoperative off stimulation conditions (scores were respectively: 17.9+/-9.2 and 23+/-12.6). The severity of motor fluctuations and dyskinesias assessed by UPDRS IV was reduced by 76 % at 6 months (scores were respectively: 10.3+/-3 and 2.5+/-3; p < 0.001). Off medication, the UPDRS II or ADL score was reduced by 52.8 % during on stimulation (26.9+/-6.5 preop versus 12.7+/-7 at 6 months). The daily dose of antiparkinsonian treatment was diminished by 65.5 % (levodopa equivalent dose -- mg/D -- was 1045 +/- 435 before surgery and 360 +/- 377 at 6 months; p < 0.01). These results remained stable at 12 months for the 14 patients studied. Side effects comprised lower limb phlebitis (n = 2), pulmonary embolism (n = 1), depression (n = 6), dysarthria and freezing (n = 1), sialorrhea and drooling (n = 1), postural imbalance (n = 1), transient paresthesias and dyskinesias. This study confirms the great value of subthalamic nucleus stimulation in the treatment of intractable PD. Some adverse events such as depression may be taken into account in the inclusion criteria and also in the post-operative outcome.

Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth 1A duplication.

BACKGROUND: A 1.5-Mb microduplication containing the gene for peripheral myelin protein 22 (PMP22) on chromosome 17p11.2-12 is responsible for 75% of cases of the demyelinating form of Charcot-Marie-Tooth disease (CMT1A). Methods for molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of polymorphic poly(AC) repeats (microsatellites) located within the duplicated region, or the detection of junction fragments specific for the duplication. Difficulties with both strategies have led us to develop a new diagnostic strategy with highly polymorphic short tandem repeats (STRs) located inside the CMT1A duplicated region. METHODS: We tested 10 STRs located within the duplication for polymorphic behavior. Three STRs were selected and used to test a set of 130 unrelated CMT1A patients and were compared with nonduplicated controls. The study was then extended to a larger population of patients. Alleles of interest were sequenced. A manual protocol using polyacrylamide electrophoresis and silver staining and an automated capillary electrophoresis protocol to separate fluorescently labeled alleles were validated. RESULTS: We identified three new STRs covering 0.55 Mb in the center of the CMT1A duplication. One marker, 4A, is located inside the PMP22 gene. The two others, 9A and 9B, more telomerically positioned, have the highest observed heterozygosity reported to date for CMT1A markers: 0.80 for 9A, and 0.79 for 9B. Tetra- and pentanucleotide repeats offered clear amplification, accurate sizing, and easy quantification of intensities. CONCLUSIONS: Combined use of the three STRs allows robust diagnosis with almost complete informativeness. In our routine diagnosis for CMT1A, they have replaced the use of other polymorphic markers, either in a manual adaptation or combined with fluorescence labeling and allele sizing on a DNA sequencer.

Glial toxicity in urine and multiple sclerosis.

The biochemical and biological characterization of a cytotoxic activity targeting macroglial cells (oligodendrocytes and astrocytes), in moncyte cultures and in CSF of a patient with multiple sclerosis, has previously been described. In further studies, cell-based tests have shown a good correlation between this glial cytotoxic (gliotoxic) activity, in CSF or in urine, and MS. We now present results obtained with urine samples from 102 MS patients, 51 patients with other neurological disease and 35 healthy subjects using a bioassay set up for the detection of an apoptosis-like effect induced in a glial cell-line. Significant gliotoxicity was detected in urine from 74/102 MS patients while only 4/51 neurological controls (P>0.001) and never in healthy subjects (P>0.001). Given the statistical tendency provided by this bioassay and its technical limitations for routine testing, it is now used for monitoring the molecular characterization of this 'gliotoxic factor'. Its replacement by a specific immunoassay could provide more accurate routine techniques for the detection of this biological marker in MS.

Clinical report of three patients with hereditary hemochromatosis and movement disorders.

Neurologic manifestations are rarely described in hereditary hemochromatosis (HH). We describe three patients with HH and movement disorders. Patient 1, a 69-year-old man, had a 13-year history of disabling cerebellar syndrome, action tremor and myoclonus, and secondary dementia. Patient 2 was a 40-year-old man with a 9-year history of cerebellar syndrome, head and arm tremor, and cervical dystonia. Patient 3, a 75-year-old woman, had a 5-year history of rapidly disabling parkinsonian syndrome unresponsive to levodopa. The diagnosis of HH was established in the three patients by iron tests, evidence of a C282Y mutation, and, in two patients, by liver biopsy. High-field T2-weighted magnetic resonance imaging showed hyperintense signals in hemispheric white matter in patient 1, cerebellar atrophy in patient 2, and cerebellar and cerebral atrophy in patient 3 and no significant hypointense signals in the three patients. Phlebotomies and symptomatic treatments did not change the course of the disease. Our cases are compared with the five previously reported observations of HH with movement disorders. This rare association is one cause of the chronic acquired non-Wilsonian hepatocerebral degeneration syndromes and represents a separate entity from aceruloplasminemia. The pathophysiologic mechanism of movement disorders in HH is unresolved. No hepatic insufficiency and portosystemic encephalopathy is evidenced in our cases, whereas the putative role of abnormal iron load remains to be ascertained. HH should be investigated more systematically in patients with movement disorders.