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Biomedical subjects

P Clavelou

Publications and source records attributed to P Clavelou.

At least 19 recordsLinked to original sources

[From prospective molecular diagnosis of enterovirus meningitis...to the prevention of antibiotic resistance].

Meningitis initially presents with intense manifestations that are not generally specific to a given etiology. The first major question for the physician is to decide whether to initiate a probabilistic treatment. Enteroviruses are a major cause of aseptic meningitis, which is benign in immunocompetent patients. Molecular diagnosis is now becoming the gold standard and its prospective use at the time of patient admission, on the sole basis of clinical suspicion of meningitis, has yielded more reliable data. Cytological and biochemical data from CSF analyses are of low predictive value to influence the initial decision to treat with antibiotics. In addition, cases of meningitis during winter are not uncommon. Adults are concerned in about 25% of cases. Thus, if molecular diagnostic tools are not rapidly available, patient management may be inconsistent, leading to unnecessary scans, laboratory investigations and treatment (including overconsumption of antibiotics). Current progress in the automation and practicability of viral genomic detection yields the result within a few hours after admission. Rapid molecular viral diagnosis of a benign disease that does not require treatment but which is initially worrying is of unquestionable advantage. It is of benefit to both the patient and the community because of its input on health economics, the needless consumption of drugs and, as a result, resistance to antibiotics. The diagnosis of meningitis can no longer remain a retrospective diagnosis after elimination of all the possible causes, since not prescribing unnecessary laboratory tests and not treating are true therapeutic decisions.

Adolescent↗

[Neurological aspects of Fabry's disease].

Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. Progressive accumulation in lysosomes of the undegraded glycosphingolipids leads to a multi-system disease with dermatological, ocular, renal, cardiac, and neurological manifestations. Peripheral nerve involvement, neuropathic pain and chronic acroparesthesiae, are frequent and early-onset signs revealing the disease. They are due to the involvement of small nerve fiber, thus explaining the normality of electroneuromyography. Cochleo-vestibular and autonomic nervous system involvement is frequent. Besides rare aseptic meningitis, central nervous system involvement is essentially represented by cerebrovascular events (stroke, transient ischemic attack). Affecting essentially the posterior circulation, their etiologies have to be clarified: progressive stenosis of small vessels with globotriasocylceramide deposits, arterial remodeling, endothelial dysfunction, pro-thrombotic state, cerebral hypoperfusion consecutive to dysautonaumy, cardiac embolism. MRI shows numerous silent lesions, increasing with age, mainly in small perforant arteries (periventricular white matter, brainstem, cerebellum, basal ganglia). Pulvinar calcifications, due to an increase in cerebral hyperperfusion, could be specific of Fabry disease. Positon tomography analysis shows a reduced cerebral flow velocity and impaired cerebral autoregulation, secondary to the glycosphingolipid storage in vascular endothelial cells. Enzyme replacement therapy has to be carefully monitored.

Brain↗

[Cognitive impairment and quality of life in multiple sclerosis patients].

INTRODUCTION: Cognitive disorders may bias perception of quality-of-life in patients with multiple sclerosis (MS). METHODS: Neuropsychological tests (WAIS-vocabulary, Gröber and Buschke, Stroop, WCST, WAIS-similitude, fluency, Hamilton's depression scale) along with a French health-related quality of life self questionnaire for MS patients (the SEP59) were performed by 117 MS patients with a minor cognitive impairment (Mini Mental State over 24) in order to explore the links between quality of life perception and cognitive functioning. RESULTS: Main Component Analysis and correlation analysis showed that cognitive impairment produced an overrating of the self perception of quality of life. Threshold analysis, splitting patients between the most and the less cognitively impaired, confirmed this relationship. CONCLUSION: The level of cognitive functioning must be considered with caution when analyzing health-related quality of MS patients.

Adult↗

[Symptomatic treatments in amyotrophic lateral sclerosis].

ALS is a progressive, fatal, degenerative motor neuron disease of unknown cause. Although advances in understanding pathophysiology of ALS have stimulated the development of new therapies, most of them remain few efficient or ineffective and the main management of ALS patient, to improve quality of life by alleviating symptoms, is symptomatic treatment. This article discusses the approaches now in use to manage some of the most common symptoms of ALS including the following: spasticity, cramps, pain, laryngospasm, pseudobulbar syndrome, salivation and drooling, sleep disorders and fatigue, constipation and trophic troubles.

Amyotrophic Lateral Sclerosis↗

[Post-polyiomyelitis syndrome].

Postpoliomyelitis syndrome is a clinical syndrome characterized by late progression of symptoms, neuromuscular weakness, fatigue and pain, several (more than 20) Years after acute anterior poliomyelitis. In the United States, where it has been mainly described, frequency is estimated between 20 and 30p.100 in patients with sequelae of poliomyelitis. Although the cause is still unknown, postpoliomyelitis syndrome is likely due to degeneration and dysfunction of terminal axons of enlarged post-polio units, with a possible role of inflammatory reaction driven by persistence of the polio virus. Due to lack of specific therapy, rational therapeutic approaches are symptomatic, including exercise, reassurance and life-strategies for fatigue.

Cerebrospinal Fluid↗

Cerebral venous thrombosis in four patients with multiple sclerosis.

We report four new cases of cerebral venous thrombosis (CVT) occurring in patients with multiple sclerosis (MS). Each patient had undergone lumbar puncture at varying times prior to clinical presentation (4 days to over 1 year). Only two of the patients had received intravenous (i.v.) methylprednisolone 48 h prior to CVT and were under oral contraception, a risk factor for cerebral thrombophlebitis. The other two patients had not undergone recent lumbar puncture, were not taking corticosteroids and did not present vascular risk factors. The patients all had normal routine blood work-ups and none had thrombophilia. All patients dramatically improved with full systemic heparinization. Minor sequelae were noticed in two patients. The pathogenesis underlying the occurrence of CVT in MS patients remains unclear and we discuss the relationship between lumbar puncture, steroid treatment and CVT.

Adult↗

[Enteroviral meningitis in adults, underestimated illness: description of 30 observations from 1999 to 2000, and evolution of clinical practices during 2001].

Enteroviral meningitis is well documented in children but underestimated in adults. The analysis of 30 cases of adult meningitis prospectively diagnosed by enterovirus genome detection (RT-PCR) in cerebrospinal fluid (CSF) between 1999 and 2000 in routine practice showed diagnosis to be problematic. Characteristic symptoms were inconstant (the association of fever/headache/stiff neck absent in 41%) and sometimes misleading (the presence of peribuccal lesions). CSF data showed a predominance of lymphocytes in only 44% of patients. The most reliable criterion was normal constant CSF glucose levels. Thirty three per cent of patients were admitted during cold months. Management of patients varied markedly between departments, and included computed tomography (33%), and the prescription of aciclovir (20%) or antibiotics (53%). A report of positive enterovirus RT-PCR had only low impact on management because it took 6 days to obtain the results (versus 3 days in children during the same period). These findings were communicated to all hospital physicians concerned and as a result, the number of RT-PCR in adults increased significantly during 2001. Again, enteroviral meningitis was diagnosed in adults despite a much lower incidence of the illness in 2001 compared to 2000. Thus this pathology should not be underestimated in adults. Considerable medical expenditure might be avoided (cumulative numbers of 172 days in hospital and 82 days of antibiotics in this study), if rapid and accurate diagnostic techniques were available.

Acyclovir↗

[Validation of the combined SF36/MSQOL test of evaluation of quality of life in migraine patients in France].

The impact of migraine on patients quality of life is great, even between attacks. The aim of this study was to assess the properties of a French language quality of life questionnaire, which associates the Medical Outcome Study Short Form (MOS SF 36) with the Migraine-Specific Quality of Life (MSQOL). Data were obtained from 110 consultant patients of neurology units located in three University hospitals in the center of France. The results indicated a good acceptability of the association of the two questionnaires with a 84p.cent response rate. The Principal Component Analysis showed no change in both SF-36 and MSQOL structures. It also suggested that the two questionnaires were complementary. The high values of the Cronbach alpha coefficients for each scale indicated a high level of internal consistency. The quality of life scores were correlated with external parameters such as frequency, intensity and length of migraine attacks, and social activity reduction due to these attacks. In conclusion, the association of the SF-36 with the MSQOL has the interest of associating generic and specific questionnaire, in a complementary way. This association has good psychometric properties, and can be used to evaluate migraineurs quality of life in French speaking countries.

Adult↗

Compound heterozygous D90A and D96N SOD1 mutations in a recessive amyotrophic lateral sclerosis family.

We describe a French amyotrophic lateral sclerosis (ALS) family with two distinct mutations in the Cu/Zn superoxide dismutase (SOD1) gene. The D90A mutation has been well described and clearly shown to cause recessive ALS. In this family, affected individuals are heterozygous for the D90A mutation and also carry a single copy of a novel SOD1 mutation, D96N. We propose that in this family both mutations are required for the development of disease.

Adult↗

Spontaneous internal carotid artery dissection with lower cranial nerve palsy.

BACKGROUND: Typical presentation of spontaneous internal carotid artery (ICA) dissection is an ipsilateral pain in neck and face with Horner's syndrome and contralateral deficits. Although rare, lower cranial nerve palsy have been reported in association with an ipsilateral spontaneous ICA dissection. CASE STUDIES: We report three new cases of ICA dissection with lower cranial nerve palsies. RESULTS: The first symtom to appear was headache in all three patients. Examination disclosed a Horner's syndrome in two cases (1 and 2), an isolated XIIth nerve palsy in two patients (case 1 and 3) and IX, X, and XIIth nerve palsies (case 2) revealing an ipsilateral carotid dissection, confirmed by MRI and angiography. In all cases, prognosis was good after a few weeks. CONCLUSIONS: These cases, analysed with those in the literature, led us to discuss two possible mechanisms: direct compression of cranial nerves by a subadventitial haematoma in the parapharyngeal space or ischemic palsy by compression of the ascending pharyngeal artery.

Anticoagulants↗

[Quality of life in multiple sclerosis].

The insensitivity of the clinical scales usually performed in MS patients led to measure the quality of life (QoL). QoL includes several important domains of health which are regarded by patients as being more important determinants of their overall health states. Some aspects of QoL of MS patients (early collapse in the disease, impact of interferons therapy) suggested that its measurement is relevant in assessing the effect of treatment and progression of the disease.

Follow-Up Studies↗

[A familial case of chronic progressive external ophthalmoplegia associated with mitochondrial disease].

Mitochondrial myopathies are rare hereditary diseases that affect the energy functions of the mitochondria. Clinical manifestations are variable and sometimes multisystemic. Progressive external ophthalmoplegia constitutes the most frequent clinical form. Unfortunately, the diagnosis and the treatment of these mitochondrial abnormalities stay, today, even difficult. We report ophthalmic findings and the course of the disease in members of a family with chronic progressive external ophthalmoplegia presenting with severe acquired blepharoptosis. From study at the family background, the inheritance seemed autosomal dominant. In one case, a comprehensive workup, including muscular biopsy and molecular genetics disclosed a mitochondrial myopathy. During the 30-year follow-up, the patients were operated on for their ptosis several times, because of recurrences and uneven results.

Adult↗

Evidence for functional compartmentalization of trigeminal muscle spindle afferents during fictive mastication in the rabbit.

Primary afferent neurons innervating muscle spindles in jaw-closing muscles have cell bodies in the trigeminal mesencephalic nucleus (NVmes) that are electrically coupled and receive synapses. Each stem axon gives rise to a peripheral branch and a descending central branch. It was previously shown that some spikes generated by constant muscle stretch fail to enter the soma during fictive mastication. The present study examines whether the central axon is similarly controlled. These axons were functionally identified in anaesthetized and paralysed rabbits, and tonic afferent firing was elicited by muscle stretch. For the purpose of comparison, responses were recorded extracellularly both from the somatic region and from the central axon in the lateral brainstem. Two types of fictive masticatory movement patterns were induced by repetitive stimulation of the masticatory cortex and monitored from the trigeminal motor nucleus. Field potentials generated by spike-triggered averaging of action potentials from the spindle afferents were employed to determine their postsynaptic effects on jaw-closing motoneurons. Tonic firing of 32% NVmes units was inhibited during the jaw-opening phase, but spike frequency during closing was almost equal to the control rate during both types of fictive mastication. A similar inhibition occurred during opening in 83% of the units recorded along the central branch. However, firing frequency in these was significantly increased during closing in 94%, probably because of the addition of antidromic action potentials generated by presynaptic depolarization of terminals of the central branch. These additional spikes do not reach the soma, but do appear to excite motoneurons. The data also show that the duration and/or frequency of firing during the bursts varied from one pattern of fictive mastication to another. We conclude that the central axons of trigeminal muscle spindle afferents are functionally decoupled from their stem axons during the jaw-closing phase of mastication. During this phase, it appears that antidromic impulses in the central axons provide one of the inputs from the masticatory central pattern generator (CPG) to trigeminal motoneurons.

Action Potentials↗

Coexistence of dominant and recessive familial amyotrophic lateral sclerosis with the D90A Cu,Zn superoxide dismutase mutation within the same country.

The Cu,Zn superoxide dismutase (Cu,Zn SOD) mutations described in amyotrophic lateral sclerosis (ALS) have, for the most part, a dominant influence. However, while a few cases with a heterozygous D90A mutation have been described in different countries, D90A has been recently proven to be recessively inherited with a common founder effect in Scandinavia. We screened French ALS families for Cu,Zn SOD mutations. The presence of the D90A allele was found in two index-cases, and their families were subsequently studied. In the first family the ALS patients were homozygotes for D90A, while in the second, all ALS patients were heterozygotes. In both families the disease was found to initially involve the lower limbs with slower progression than in sporadic cases, and frequent atypical signs such as paresthesia and urgency of micturition. We determined the D90A allele frequency in controls (n = 200) and sporadic ALS patients (n = 408). No D90A allele was found. This is the first report of coexistence of dominant and recessive families with the D90A Cu,Zn SOD mutation within the same country.

Adult↗

[Quality of life and multiple sclerosis: validation of the french version of the self-questionnaire (SEP-59)].

We conducted a prospective study among 166 multiple sclerosis (MS) patients (103 from an university hospital, 63 from a MS rehabilitation center) to assess the properties of the French version of the Multiple Sclerosis Quality Of Life - 54 items (MS QOL-54) which combines the MOS SF36 together with MS specific items. The SF-36 had been translated into French through the IQOLA project. We translated and adapted the MS specific items with the help of three different teams. The translation into French has an addition of five items, because we kept the MS specific items of an earlier unpublished form. Acceptability is excellent with a response rate over 90p.100. Test-retest reliability is good except for the "role limitation-emotional" scale of the SF-36. Construct validity, based on factor analysis, shows no change in the SF-36 internal consistency and the specific items provided their own information. External validity, tested against both medical (Expanded Disability Status Scale, Kurtzke scale, Mini-Mental-State and disease stage) and rehabilitation (Functional Independence Measure) parameters is excellent. The French MS QOL questionnaire contains 59 items including both the SF-36 and the MS QOL-54 items. This will permit international comparisons of MS patients' care and therapy.

Adolescent↗