French validation of the Quality of life in Essential Tremor Questionnaire (QUEST) and the Essential Tremor Embarrassment Assessment (ETEA).

Two scales have been developed and validated in English to evaluate the impact of tremor on daily life, namely Quality of life in Essential Tremor Questionnaire (QUEST) and Essential Tremor Embarrassment Assessment (ETEA). The psychometric properties of the French version of these two scales were assessed for 117 patients with head tremor. Both scales showed excellent acceptability, very good internal consistency (Cronbach's alpha coefficient>0.8) and reproducibility (Lin concordance coefficient>0.8), satisfactory external validity and satisfactory sensitivity to change. In conclusion, the French versions of QUEST and ETEA are comprehensive, valid and reliable instruments for assessing patients with head tremor.

A combined pharmacokinetic/pharmacodynamic model of levodopa motor response and dyskinesia in Parkinson's disease patients.

PURPOSE: Levodopa is the reference treatment for Parkinson's disease. However, after several years of treatment, dyskinesia may occur and strategies to overcome this side effect still need to be explored. We identified a unique population pharmacokinetic/pharmacodynamic model in Parkinson's disease to investigate the relationship and dissociability of motor response and dyskinesia. METHODS: Thirty parkinsonian patients (Hoehn and Yahr stages 3-4), treated with levodopa and suffering from peak-dose dyskinesia, were included in a prospective open-label study. They received a single dose of levodopa equal to 150 % of their usual daily dose. Blood samples, motor evaluations (UPDRS III scale) and peak-dose dyskinesia (Goetz scale) were examined after administration. A population pharmacokinetic/pharmacodynamic (PK/PD) model was developed using NONMEM software. RESULTS: Pharmacokinetic analysis identified a one-compartment model with the following parameter values [bootstrap 95 % CI]: absorption rate constant (KA) 1.86 1/h [1.08-3.25], clearance 36.6 L/h [31.3-42.8], and volume of distribution 42.9 L [34.3-52.3]. Between-subject variability was 122 % [71-183] and 38 % [26-47] for KA and clearance, respectively. Residual variability was 1120 µg/L [886-1290]. UPDRS III and dyskinesia were best described with an effect compartment and similar KE0 values of 1.37 1/h [1.01-1.77]. For UPDRS III, the E0, EC50, Emax, and Hill coefficient were 31.4 [28.4-35.3], 1410 µg/L [1200-1700], 0.72 [0.71-0.75], and 4.26 [3.20-5.58], respectively. For dyskinesia, the EC50 and Emax were 6280 µg/L [3420-37,900] and 17.9 [12.3-80.8], respectively. Residual variability was 3.15 [2.75-3.53] for UPDRS III and 2.66 [1.94-3.51] for dyskinesia. No covariates influenced the parameters. CONCLUSIONS: In patients treated with levodopa and suffering from dyskinesia, the motor response and dyskinesia have close onsets and duration effects. Maximal motor response tends to be inevitably associated with dyskinesia.

[Cerebrotendinous xanthomatosis: a multicentric retrospective study of 15 adults, clinical and paraclinical typical and atypical aspects]. / Étude rétrospective multicentrique de 15 cas adultes de xanthomatose cérébrotendineuse : aspects cliniques et paracliniques typiques et atypiques.

INTRODUCTION: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid. METHOD: We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients. RESULTS: The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died. CONCLUSION: Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology.

Pharmacokinetic and pharmacodynamic analysis of sedative and amnesic effects of lorazepam in healthy volunteers.

This study describes for the first time the pharmacokinetic and pharmacodynamic modeling of the psychomotor and amnesic effects of a single 2-mg oral dose of lorazepam in healthy volunteers. Twelve healthy volunteers were included in this randomized, double-blinded, placebo-controlled two-way crossover study. The effect of lorazepam was examined for a battery of tests that explored mood, vigilance, psychomotor performance, and memory. The pharmacokinetic and pharmacodynamic modeling of these tests was performed using the indirect response model. Vigilance and psychomotor performance were significantly impaired. Short-term memory was not affected, but a paradoxical tendency to improvement of the score was observed 0.4 hours after drug intake. Significant impairment was observed for immediate and delayed cued verbal recall, for immediate and delayed free recall, and for picture recognition as well as for visual-verbal recall, but not for cued visual-spatial recall or priming. Globally, the different effects were greatest between 0.4 to 3 hours after dosing. However, the time course profile of the recovery period suggests a possible dissociation between the kinetics of the effects of lorazepam on vigilance, psychomotor performance, and visual episodic memory, on the one hand, and on verbal episodic memory, on the other. The pharmacokinetic and pharmacodynamic model used two compartments with first-order absorption to describe the lorazepam concentrations and an indirect response model with inhibition or stimulation of Kin to describe the effects. The mean values for calculated median effective concentration (EC50) derived from the pharmacokinetic and pharmacodynamic modeling of the different tests ranged from 11.3 to 39.8 ng/mL. According to these EC50 values, lorazepam seemed to be more potent on the delayed-recall trials than on the immediate-recall trials; similar observations were made concerning the free-recall versus cued-recall trials. The previously stated results suggest that the tests performed in this study represent sensitive measurements of the effects of lorazepam on the central nervous system. Moreover, the parameter values derived from pharmacokinetic and pharmacodynamic modeling, especially, the EC50 values, may provide sensitive indices that can be used to compare the central nervous system effects of benzodiazepines.

[Tremor and abnormal movement in multiple sclerosis: symptomatic therapeutic indications]. / Les tremblements et les mouvements anormaux au cours de la sclérose en plaques: indications thérapeutiques à visée symptomatique.

Tremor and movement disorders in multiple sclerosis (MS) patients cause a severe functional impairment. The different types of tremor observed in MS are: cerebellor tremor with a dominant intention component, Holmes tremor characterized by the addition of rest and postural components and palatal tremor. When no medication can improve the functional status, it is acceptable to discuss the deep brain stimulation in the VIM thalamus, thus making possible a partial attenuation of the rest and postural component, mainly affecting the proximal part of the affected limb. Among the movement disorders, paroxysmal dyskinesias are not rare and a good therapeutic response is obtained with carbamazepine: dystonia and parkinsonism are usually coincidental features during MS.

Pharmacokinetic-pharmacodynamic analysis of mnesic effects of lorazepam in healthy volunteers.

AIMS: To describe the pharmacokinetic-pharmacodynamic modelling of the psychomotor and mnesic effects of a single 2 mg oral dose of lorazepam in healthy volunteers. METHODS: This was a randomized double-blind, placebo-controlled two-way cross-over study. The effect of lorazepam was examined with the following tasks: choice reaction time, immediate and delayed cued recall of paired words and immediate and delayed free recall and recognition of pictures. RESULTS: The mean calculated EC50 values derived from the PK/PD modelling of the different tests ranged from 12.2 to 15.3 ng ml-1. On the basis of the statistical comparison of the EC50 values, the delayed recall trials seemed to be more impaired than the immediate recall trials; similar observations were made concerning the recognition vs recall tasks. CONCLUSIONS: The parameter values derived from PK/PD modelling, and especially the EC50 values, may provide sensitive indices that can be used, rather than the raw data derived from pharmacodynamic measurements, to compare CNS effects of benzodiazepines.

Devic's neuromyelitis optica: a clinicopathological review of the literature in connection with a case showing fatal dysautonomia.

A new clinicopathological case of Devic's neuromyelitis optica, including unusual predominant clinical features (fatal dysautonomia) is described herein: pathological examination showed extensive and severe demyelination mainly involving the optic nerves, the medulla, and spinal cord, which was particularly pronounced in the thoracic segments, and thus explained the unusual vegetative symptomatology. In a review of 45 clinicopathological cases described in the literature as Devic's disease (DD), it turned out that only 22 cases, including the patient described here, fulfilled the recently defined diagnostic criteria [Devic 1980]. Among the other 23 cases, 15 did not fulfill the criteria because of the occurrence of relapses, 3 others had 2 separate pathological locations within the spinal cord, and the remaining 5 showed evidence that a disease other than DD was involved. Among the 22 cases which were definitely taken to be DD, the mean age at clinical onset was 39 years (+/- 14); it was characterized by acute bilateral visual loss and transversal myelitis which gradually led either to death or to partial or complete recovery. The pathological lesions, which mostly were located along the optic tracts and the spinal cord, were characterized by demyelination with inflammation and necrosis; in some cases the pathological process diffused into the medulla (8/22 cases) or the whole brainstem (4/22 cases). The cavitation of the spinal cord was not a key feature of the diagnosis, since it was observed on only 9/22 cases. Devic's neuromyelitis optica may be a separate nosological entity which differs from multiple sclerosis.

Visuospatial ability of parkinsonians and elderly adults in location memory tasks.

Two experiments addressed the question of the spatial deficits of Parkinson disease (PD) patients, using a spatial location task which varied the characteristics of the task along an effortful continuum. In the more effortful task, 11 PD patients, 10 elderly control subjects, and 13 young control subjects were given 3 min to learn the layout of 12 places labeled on a map and then reproduce it. In the less effortful task, 9 new PD patients, 9 new elderly control subjects, and 10 new young control subjects were given 3 min to learn the layout of 12 black dots and then asked to reproduce it. In both cases the task was repeated twice. The results showed that PD patients were less accurate than young and elderly control subjects in the less effortful task. In contrast, the performance of PD patients and elderly control subjects were equivalent in the more effortful task. These results support the idea of a specific visuospatial deficit in Parkinson's disease. Moreover, the deficit in effortful tasks seems to be due to normal aging.

[Guillain-Barré syndrome of axonal type, Campylobacter jejuni infection and anti-ganglioside GM1 antibodies]. / Syndrome de Guillain-Barré de type axonal, infection à Campylobacter jejuni et anticorps anti-ganglioside GM1.

Infection by Campylobacter jejuni (C. jejuni) has been reported in 17 to 55 p. 100 of the GBS. The "axonal" GBS has been recently attributed to such an association. It is characterized by rapid progression to severe widespread paralysis, respiratory failure, poor and delayed recovery. The acute "axonal" form of Guillain-Barré syndrome has been and remains a matter of controversy. A typical case of GBS with serological evidence of recent C. jejuni infection and increased antibodies to GM1 is reported. An immune mechanism remains most likely. Recent studies have suggested the hypothesis of "shared epitope" between C. jejuni and peripheral nervous system cell (Gal beta 1-3 N Acetylgalactosamine epitope). Such a cross-reactivity could provoke a severe form of GBS with a poor recovery in some predisposed hosts (antiganglioside antibodies, HLA "immunogenic" groups such as B8, B35 or DR3).

[Non bacterial thrombotic endocarditis (marantic endocarditis). Apropos of a case and value of transoesophageal echocardiography]. / Endocardite thrombotique abactérienne (endocardite marastique). A propos d'un cas et de l'intérêt de l'échographie transoesophagienne.

Marantic or non-bacterial thrombotic endocarditis is a common complication of terminal malignancy, usually discovered at autopsy. The authors report a case of marantic endocarditis as a presenting sign of pancreatic carcinoma in which the diagnosis was made ante-mortem by transoesophageal echocardiography.

Effects of handedness and sex on the morphology of the corpus callosum: a study with brain magnetic resonance imaging.

In view of conflicting data in the existing literature, we examined 53 normal subjects using a handedness questionnaire and callosal area measurements obtained from midsagittal MRI images. The callosum was found to be significantly larger in nonconsistent right-handers (NCRH), especially in its anterior half and especially for males. A significant hand x sex interaction, favoring consistent right-handed (CRH) females, was also found for the posterior midbody, a region known to house interhemispheric fibers connecting the right and left posterior association cortices. These results (1) confirm Witelson's (1985) first findings on postmortem specimens; (2) validate a dichotomy between CRH and NCRH rather than simply considering the writing hand, as was the case in most other similar studies; and (3) suggest that at least two different sex-related--probably hormonal--factors may be acting during the callosal development, one explaining the larger anterior half in NCRH males and the other the larger posterior midbody in CRH females.

[Meningoencephalitis caused by Coxiella burnetii]. / Méningoencéphalite due à Coxiella burnetii.

Meningoencephalitis caused by Coxiella burnetii is exceptional and its clinical presentation is varied. We report a case which presented as transient central neurological deficits and intracranial hypertension without fever. The condition was diagnosed by indirect immunofluorescence.