Biomedical subjects
Publications and source records attributed to M Clanet.
We have studied HLA markers in family with 2 "Probable" and 2 "possible" cases of Alzheimer disease over 3 generations. Three of them (two brothers and the father) present A29 C-B12 DR2 haplotype. It seems that it exists an association between HLA system and Alzheimer disease but we cannot define the character of this genetic linkage; the study of many families and sporadic cases will allow to define it.
The present paper reports the isolation of multiple sclerosis and the evolution of ideas about this disease since the end of the 19th century. Charcot and Vulpian were close friends during their university years and both were appointed physicians at the Salpêtrière in 1862. It is difficult to sort each other part in the beginning of researches which both devoted to "tremors". When Vulpian left the Salpêtrière in 1865 the main point was settled: a clear cut distinction between paralysis agitans vs patients whose tremor appeared during movement and in whom post-mortem had disclosed disseminated lesions "en plaques". For the 20 ensuing years Charcot built up an impressive corpus of pathological and clinical data which were the basis of his celebrated "Leçons". This history shows the pathological clinical method at ist acme in the hands of a physician of genius. Pathogenetic hypotheses, from vascular to toxic and infectious, the role of immunological, genetic and viral factors are also briefly reviewed.
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Bromocriptine (mean dose: 48 mg daily) was studied during 38 months (mean value) in 20 patients with Parkinson's disease who had never received levodopa treatment. Eight of these 20 patients were treated during a period up to 4 years. Fourteen patients had an "excellent" or "good" improvement with a significant decrease of extrapyramidal symptoms. The side effects were those seen with levodopa but they did not lead to stop the treatment. The most important finding was the lack of long term side effects similar to those usually seen under levodopa treatment: in this group, dyskinesia, oscillations in performance (and specially "on-off" effect) were not noted. A tendency for deterioration of therapeutic efficiency was observed in 2 (or 3) cases. Bromocriptine could be an useful antiparkinsonian drug for previously untreated patients. The pharmacological (importance of the post-synaptic action of bromocriptine) and therapeutic (indications of bromocriptine versus levodopa) implications are discussed.
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Since 1975, various entrapment neuropathies have been reported in patients undergoing periodic haemodialysis, the most frequent being the carpal tunnel syndrome. Ten patients on chronic haemodialysis developing 15 carpal tunnel syndromes (5 unilateral and 5 bilateral) are reported. Various causes for the renal failure were present and clinical signs of the carpal tunnel syndrome developed at a late stage. The arteriovenous fistula required for extrarenal epuration was antebrachial and of the laterolateral type, except in one case when it was lateroterminal. The carpal tunnel syndrome was always on the same side as the fistula, developing at a later stage on th contralateral side in the 5 cases of bilateral disorders. Lesions were severe, in 11 of the 15 cases. Some patients noted fluctuations in pain symptoms during haemodialysis, either improving or becoming worse. Gross pathological findings during operation (13 cases) were tenosynovitis with epineural hypervascularisation on the opposite side. In 9 cases, however, atypical hypertrophic tenosynovitis was observed. Histological examination in 12 cases demonstrated typical tenosynovitis in 3 patients, but granulomatous tenosynovitis with amyloid deposits was reported in 9 patients. Lesions were bilateral in 2 cases thus present, on the side opposite to the fistula. Ultrastructural study confirmed the amyloid nature of the deposits in 3 cases, the microfibrillary appearance (80 to 100 A) being characteristic of amyloid substance. This rare complication does not represent a common carpal tunnel syndrome, and three mechanisms may be involved in its induction : peripheral uraemic neuropathy, haemodynamic modifications resulting from the antebrachial arteriovenous shunt, and amyloid formation in the flexor synovial sheaths. In the latter case, the type of amyloid disease may be a primary systemic amyloidosis not previously detected, or an elective amyloid process localised to the tenosynovial and periarticular tissues.
The authors use the term "complicated migraine" to describe the onset of neurological disorder occurring during an acute attack in a patient with chronic migraine. The disturbance may last for long periods or may be permanent, and these irreversible cerebral lesions have to be differentiated from the transient neurological effects characteristic of ophthalmic on secondary migraine. Patients with migraine and retinal lesions, as well as those with ophthalmoplegic or familial hemiplegic migraine, were excluded from the study. The seven cases reported included 5 women and 2 men with an average age of 30 years (from 14 to 51 years). A more or less severe lesion in a hemisphere was present, which led to sensory-motor signs of a hemiplegia (4 cases), an aphasia (4 cases), and a homonymous lateral hemianopia (3 cases). Exploration revealed the presence of an ischemic cerebral lesion in all cases. One or more arterial occlusions were also noted in 5 out of the 6 patients who were investigated by angiography. All cases showed the presence of the criteria thought to be essential for associating the cerebral ischemic lesion with migraine. 1) the patient had true migraine, 2) there was a close chronological relationship between the migraine attack and the lasting neurological disorder, 3) no other associated vascular disease was present (atheroma, cardiopathy). The very severe and prolonged spasm, which could be the cause of neurological disturbances in secondary and ophthalmic migraine, does not appear to be sufficient for producing an irreversible ischemic lesion and, more especially, a persistent vascular obstruction. The roles played by edema of the arterial wall and parietal changes in the vessels are discussed. It could be that thrombosis formation is encouraged by the changes in blood coagulability which may be associated with a migraine attack. The fact that anomalies in platelet aggregation have been demonstrated merits closer study.
Using a leucocyte migration test (Clausen's direct agarose gel migration method) hypersensitivity to human encephalitogenic protein has been examined in 50 multiple sclerosis patients (group 1), 50 healthy persons (group 2) and 25 patients with other neurological diseases (group 3). In group 1, 30 MS patients (60%) show an abnormal migration index, manifested either as inhibition or stimulation of migration; 29 controls in group 2 (58%), 11 O.N.D. patients in group 3 (44%) show an abnormal migration index. These results mean that lymphocyte hypersensitivity to myelin basic protein appears neither to be constant nor specific to multiple sclerosis. Three migration index curve types at different antigen concentration are obtained: monophasic curves within the normal index zones; monophasic curves staying in the inhibition or stimulation zone and biphasic curves with dose-effect relationship. Whatever the antigen used, this dose-effect relationship implies that the test must be carried out at different concentrations. The meaning of spontaneous sensitisation in healthy controls is discussed.
BRomocriptine (15-75 mg per day) alone or with L-dopa was studied during five to 29 months on 44 patients with Parkinson's disease. Used as sole therapeutic agent, it was found excellent in 12 patients who had never received regular L-dopa treatment either because it was never attempted or because of intolerance from the outset. Its anti-Parkinsonism activity was comparable with L-dopa. The gain was stable in the long term until this report. The side effects of L-dopa were not seen after bromocriptine. In cases where L-dopa had ceased to be active, bromocriptine produced a further improvement if mental deterioration was not associated. In very advanced forms of Parkinson's disease with associated dementia, bromocriptine did not produce durable results. Bromocriptine did not improve the "on-off" effects but reduced a number of the side effects of L-dopa, in particular cardiac, painful contractions, and dyskinesia without "on-off" effects.
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Using a panel of antigens (actin, myosin, tubulin, albumin, transferrin, peroxidase, thyroglobulin, DNA, prolactin, TNP and myelin basic protein (MBP], we have tested the antibody activity of serum and cerebrospinal fluid (CSF) from healthy individuals, patients with multiple sclerosis (MS) and individuals with other neurological diseases. No differences in the concentrations and specificities of the serum antibodies were observed among the 3 groups. In contrast, we found that MS patients often had elevated CSF antibody levels against many antigens of the panel. The MS patients with local immunoglobulin production in the central nervous system (CNS) had the highest antibody levels. Restricted antibody activity against a given antigen of the panel was not observed. Compared to the two other groups, the MS group had equivalent titres of anti-MBP antibodies in the CSF. These results suggest that, in MS, a general immune dysregulation exists which leads to a local expansion of B lymphocytes producing autoantibodies with reactivities similar to those of serum natural autoantibodies.
We performed a prospective study in 21 patients to evaluate the cost of treatment of spasmodic torticollis (cervical dystonia) before and after botulinum toxin type A (BTA) treatment and to assess the impact of BTA treatment on quality of life. Data were recorded for the analysis over a period starting 8 months before and ending 7.2 +/- 0.2 months (mean +/- SEM) after the first injection of BTA. All patients received at least two BTA injections (2.9 +/- 0.2 injections per patient). We studied direct medical costs (drugs, outpatient and inpatient visits, diagnostic procedures, physiotherapy), clinical effects of BTA (clinical rating scale and patient's global assessment), quality of life (French version of the Nottingham Health Profile [NHP]), and adverse reactions. Costs associated with the treatment of spasmodic torticollis before the first BTA injection were 479 +/- 143 French Francs (FF)/patient/month (97 +/- 29 US $/pt/mo). During BTA treatment, costs were 1,126 +/- 147 FF/pt/mo (228 +/- 30 US $/pt/mo), including a mean cost of BTA of 771 +/- 131 FF/pt/mo (157 +/- 27 US $/pt/mo). Treatment with BTA significantly decreased clinical symptoms of spasmodic torticollis and improved the emotional, social, and pain-related domains of the quality of life assessment. Botulinum toxin type A treatment increases the cost of treating spasmodic torticollis but improves quality of life in terms of pain, social, and psychologic functioning in patients with spasmodic torticollis.
We report 3 cases of young patients, 2 women and 1 man, who presented a cerebral venous thrombosis following intravenous treatment with high doses of corticosteroids. All of them presented a probable multiple sclerosis according to clinical, biological (CSF) and MRI criteria and were treated for the first time by a bolus of 1,000 mg of methylprednisolone OD during 5 days. All the usual causes of cerebral venous thrombosis were systematically excluded in all of them. The role of corticosteroid treatment in cerebral thrombophlebitis is discussed. All of them underwent a lumbar puncture a few days before corticosteroid treatment and the relationship between lumbar puncture and cerebral thrombophlebitis is also discussed. Cerebral venous thrombosis associated with corticosteroid treatment has rarely been reported. The relationship between corticosteroids and venous thrombosis has already been suggested but has never been clearly understood.
Pure motor hemiplegia (PMH) is a well defined syndrome usually caused by ischemic lesions of lacunar type located either in the internal capsule or in the pons. Angiography and isotope scanning are usually normal. CT scan reveals small deep infarcts and appears to be the most reliable investigative method. The CT scan findings are described of thirty patients with PMH of rapid onset (less than 36 hours). In 29 of the 30 cases a lesion was found which could explain the PMH. Small hemorrhages (2 cm in diameter) in the posterior limb of the internal capsule were noted in two cases. Ischemic lesions were found in 27 patients, 22 patients had a single lesion (20 capsular and 2 pontine), while 5 patients had 2 lesions (2 bi-capsular, 3 capsular and pontine). Three varieties of ischemic capsular lesions were observed. We found in 15 cases a capsulo-putamine-caudate infarct (type I); in 8 cases a capsulo-pallidal infarct (type II); and in 2 cases an anterior capsulo-caudate infarct (type III). Type I corresponded to the area of the lateral lenticulostriate branches of the middle cerebral artery. Type II involved the territory of the perforating branches of the anterior choroidal artery. We suggest that type III involves the territory of the internal lenticulostriate branches of the anterior cerebral artery. Lacunes are generally linked to arterial systemic hypertension. However, only 16 of 30 patients in this series were chronically hypertensive.
A historical study of the prescription of midodrine was carried out at the university hospital of Toulouse (France) between 1994 and 1998. The aim was to compare the observed prescriptions and the ideal prescriptions in accordance with the Summary of Product Characteristics (SPC). The analysis of 97 consecutive medical reports found discrepancies in prescription concerning the non-respect of contraindications and of potentially hazardous drug associations. Fifty-four (55.7 per cent) patients would have been excluded from prescription if the physicians had strictly respected the SPC. The inappropriate prescription of midodrine was associated with an increase in adverse drug reactions (ADRs). ADRs occurred in 34.0 per cent of cases overall and required drug discontinuation in 15.5 per cent.
The ability of flunarizine in inducing or worsening extrapyramidal symptoms is well documented. The relation with age or dose of such symptoms as their clinical characteristics remain controversial. We report 6 cases of extrapyramidal syndromes induced by flunarizine in five women and one man (mean age 71.5 +/- 5 years). The daily dose was 10 mg in five cases (as recommended by the marketing laboratory) and 20 mg in one patient. These observations allow to discuss the dose-dependent occurrence of this adverse reaction. In only three cases the reason for treatment was compatible with the official french indication. These side effects appeared after 7.0 +/- 1.6 months and disappeared after 2.2 +/- 0.5 months respectively. Flunarizine-induced extrapyramidal symptoms are mainly characterized by tremor (which was the main symptom in 4 cases and the only one in 2 cases).