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Daclizumab, a humanised monoclonal antibody, modulates interleukin-2 signalling by blocking the α subunit (CD25) of the interleukin-2 receptor. We assessed whether daclizumab high-yield process (HYP) would be effective when given as monotherapy for a 1 year treatment period in patients with relapsing-remitting multiple sclerosis.We did a randomised, double-blind, placebo-controlled trial at 76 centres in the Czech Republic, Germany, Hungary, India, Poland, Russia, Ukraine, Turkey, and the UK between Feb 15, 2008, and May 14, 2010. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1), via a central interactive voice response system, to subcutaneous injections of daclizumab HYP 150 mg or 300 mg, or placebo, every 4 weeks for 52 weeks. Patients and study personnel were masked to treatment assignment, except for the site pharmacist who prepared the study drug for injection, but had no interaction with the patient. The primary endpoint was annualised relapse rate. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00390221.204 patients were assigned to receive placebo, 208 to daclizumab HYP 150 mg, and 209 to daclizumab HYP 300 mg, of whom 188 (92%), 192 (92%), and 197 (94%), respectively, completed follow-up to week 52. The annualised relapse rate was lower for patients given daclizumab HYP 150 mg (0·21, 95% CI 0·16-0·29; 54% reduction, 95% CI 33-68%; p0·0001) or 300 mg (0·23, 0·17-0·31, 50% reduction, 28-65%; p=0·00015) than for those given placebo (0·46, 0·37-0·57). More patients were relapse free in the daclizumab HYP 150 mg (81%) and 300 mg (80%) groups than in the placebo group (64%; p0·0001 in the 150 mg group and p=0·0003 in the 300 mg group). 12 (6%) patients in the placebo group, 15 (7%) of those in the daclizumab 150 mg group, and 19 (9%) in the 300 mg group had serious adverse events excluding multiple sclerosis relapse. One patient given daclizumab HYP 150 mg who was recovering from a serious rash died because of local complication of a psoas abscess.Subcutaneous daclizumab HYP administered every 4 weeks led to clinically important effects on multiple sclerosis disease activity during 1 year of treatment. Our findings support the potential for daclizumab HYP to offer an additional treatment option for relapsing-remitting disease.Biogen Idec and AbbVie Biotherapeutics Inc.

BACKGROUND--The prevalence of hepatitis C virus (HCV) infection has been estimated at 43 to 84% in patients with essential mixed cryoglobulinaemia in recent large series. Some of these cases have been successfully treated with interferon-alpha. The objective was to evaluate the prevalence and the possible role of HCV infection in essential mixed cryoglobulinaemia. METHODS--Fifteen patients (eight men and seven women; mean age: 61.2 (SD 16.5) years) with peripheral neuropathy (10 polyneuropathies and five multifocal mononeuropathies) and essential mixed cryoglobulinaemia were tested for serum anti-HCV antibodies. RESULTS--Antibodies were found in 10 of 15 patients involving either polyneuropathies (seven patients) or multifocal mononeuropathies (three patients). Electrophysiological studies and teased nerve fibre studies (in seven patients) allowed neuropathies to be classified as predominantly sensory axonopathies. Compared with HCV-negative (HCV -) patients, HCV-positive (HCV +) patients had a more pronounced and more widespread motor deficit; motor nerve conduction velocities in peroneal and median nerves were more impaired in HCV + patients, although significance was not reached except for the mean value of the amplitude of the compound muscle action potentials of the median nerves (P < 0.05); necrotising vasculitis was found in two of nine nerve biopsies from the HCV + patients studied and in none of the three HCV - patients. In addition, HCV + patients had more frequent cryoglobulin related cutaneous signs, higher aminotransferase and serum cryoglobulin concentrations, lower total haemolytic complement concentrations, and more frequent presence of rheumatoid factor. A liver biopsy performed in eight HCV + patients disclosed a range of lesions, from chronic active hepatitis (six patients) to persistent hepatitis (two patients). Lastly, treatment with interferon-alpha conducted over six months in two patients seemed to improve the peripheral neuropathy. CONCLUSIONS--Patients with peripheral neuropathy and essential mixed cryoglobulinaemia should be tested for anti-HCV antibodies to determine the appropriate treatment.

We review here the epidemiologic and clinical aspects of tropical spastic paraparesis, human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (TSP/HAM) as observed in Europe and in Africa. Europe is not an endemic region for HTLV-I (seroprevalence in blood donors, < 0.03%), and TSP/HAM is thus rarely observed in European countries. Most of the few patients suffering from TSP/HAM are first- or second-generation immigrants from HTLV-I endemic areas (mostly the West Indies), and the clinicoepidemiologic aspects of these patients are similar to those seen in endemic areas. However, rare cases occur in European-born subjects with or without risk factors for HTLV-I infection, which raises the possibility of limited foci areas in Europe. Although Africa is considered as a primary HTLV-I endemic area, with at least a few million infected inhabitants, epidemiologic data on the situation of TSP/HAM in Africa remain scarce. Relatively few cases of patients with TSP/HAM have been reported in Africa, including some clusters in Zaire (prevalence, 50/100,000) and in South Africa and sporadically in the main cities of some Western, Central, and Eastern African countries. The paucity of clinical and epidemiologic data on TSP/HAM may be linked to several factors, including the paucity of neurologists, the lack of laboratory and radiologic facilities, and the chronicity of the disease, along with the limited number of field epidemiologic studies performed on this topic and the wide diversity of causes (toxic, nutritional, and infectious) of chronic myelopathies as seen on the African continent.

Demyelination events or multiple sclerosis following hepatitis B virus (HBV) vaccination have been reported. We therefore compared the T-cell response to HBsAg in patients with CNS demyelination following HBV vaccination and in HBV-vaccinated healthy individuals. Our data showed no differences in terms of T-cell proliferation or cytokine production between these groups and may help to allay concerns that HBV vaccination might trigger a deleterious immune response.

The objective of this study was to evaluate the risk of visual outcome after acute optic neuritis (ON) in relation to clinical and MRI findings. Fifty cases of acute ON within one month were retrospectively studied. MRI with Short Tau Inversion Recovery (STIR) sequence of the optic nerve were obtained with a median time onset of 9 days after ON. Mean age of patients was 32.8 years, mean initial visual acuity was 3/10 and orbital pain was present in 86 percent100 of patients. The STIR sequence revealed lesion in 88 percent 100 of acutely symptomatic optic nerves. An initial low visual acuity (less than 2/10), the absence of orbital pain and involvement of the intracanalicular portion of the optic nerve on STIR sequence were statistically correlated with a poorer visual outcome (respectively p=0.0041, p=0.035 and p=0.011).

Andermann syndrome or Agenesis of the Corpus Callosum with Polyneuropathy (MIM 218000) is an autosomal recessive disease almost exclusively found in Québec. Only few cases have been reported in other populations. The locus for Andermann syndrome was assigned to chromosome 15q13-q15 in French Canadian families. We performed a haplotype analysis with two markers of this chromosomal region in an Algerian consanguineous family with two affected sibs. The children were homozygous for both markers, suggesting genetic homogeneity in Andermann syndrome.

MRI is the most powerful imaging technique in managing patients with suspected or confirmed multiple sclerosis (MS). However, conventional MRI variables show nonspecific abnormalities weakly correlated with clinical progression of the disease. New techniques, now routinely available, offer better characterisation of the pathophysiology. We combined conventional MRI, including lesion load, contrast enhancement and "black holes" with magnetisation transfer and diffusion-weighted imaging and localised proton MR spectroscopy (MRS) to study their relationship with disability, course and duration of MS. The variables that were the most significantly linked to the course of the disease (relapsing remitting versus secondary progressive) were lesion load, mean overall magnetisation transfer ratio and apparent diffusion coefficient (MGADC), the percentage of ADC in (PADCIMD), and out of (PAD-COMD) modal distribution, and the ratio N-acetylaspartate and creatine-containing compounds on MRS of the centrum semiovale. MGADC and PADCIMD were the independent factors most related to disability and duration of disease. Combining MRI techniques is clinically relevant and feasible for studies of MS and may be applied to other diseases of the central nervous system.

We report a case of a mitochondrial cytopathy (MERRF) with a late diagnosis because of the absence of Ragged-Red Fibers (RRF) in the first muscular biopsy performed in childhood. Eight years after the onset of the disease the familial history and the clinical manifestations were very suggestive of a mitochondrial cytopathy and a second biopsy was performed confirming the diagnosis of MERRF. The authors discuss several hypotheses to explain the negativity of the first muscular biopsy. The absence of ragged-red fibers does not exclude the diagnosis of a mitochondrial cytopathy and other investigations are justified such as the biochemical study of the respiratory chain and the molecular analysis of mitochondrial DNA.

Recently, genome-wide searches for multiple sclerosis (MS) susceptibility genes have suggested that the chromosome 17q22-q24 region might contain susceptibility genes in two sets of families of different ethnic backgrounds (Finnish and British). Therefore, we decided to test this region in two sets of families of different ethnic backgrounds (American and French), but collected according to the same diagnostic criteria. All lod-score values were non-significant. Moreover, we could exclude that the 17q22-24 region might contain a gene increasing the sibling recurrence risk of MS over 1.4, rendering the existence of such a gene very unlikely, at least in the group of tested families.

The immune system is involved in the pathophysiology of multiple sclerosis (MS) but the initiating antigen(s) is not yet identified. Since cytokines control both the intensity and the quality of the immune response they may be relevant candidates for the genetic susceptibility to MS. To analyze the contribution of type 1 and type 2 cytokine and cytokine receptor genes in the genetic susceptibility to MS, we have examined, in 116 French MS sibpairs, whether there is significant linkage between MS and 15 cytokine or cytokine receptor genes using 31 highly polymorphic genetic markers. The data were analyzed using the maximum likelihood score and the transmission disequilibrium approaches. None of the candidate genes tested was significantly linked to MS on the whole population. However, after stratification of the analysis on the basis of sharing (or not) of the HLA-DRB1*1501 allele, indication of linkage was found for the IL2-RB gene. These findings suggest that the IL2-RB locus contributes to the genetic susceptibility in a subgroup of MS patients.

The interobserver variability of the expanded disability status scale (EDSS) was studied in 59 patients with multiple sclerosis (MS). Interrater agreement was measured by the kappa coefficient. Agreement was low in patients with mild disability (EDSS less than 5); it was higher in patients with EDSS equal to or greater than 5. The difference between ratings of 2 independent examiners was equal to at least 1 point in 34% of the MS cases. This variability must be taken into consideration in designing clinical trials in MS.

Cognitive evaluation of 6 cases of adult adrenoleukodystrophy (ALD) included in a brain magnetic resonance (MR) study are reported: 2 males with adrenomyeloneuropathy and 4 women heterozygous for ALD. Cognition was normal in 4 and MR scan in 2 of them. In the 2 others, there were mild modifications of the white matter. One patient suffered of visual retention disturbances with abnormalities of the white matter in MR scan. In the last, cognitive decline was observed; MR scan showed atrophy of cortex and corpus callosum and periventricular high signal areas. Comparison with leukoaraiosis in healthy adults and with multiple sclerosis suggests that there is probably a relationship between cognition and extension of brain MR abnormalities. Time of appearance and frequency of cognitive dysfunction might be explained by the natural history of each of these diseases.

We investigated neurochemical abnormalities in the normal-appearing white matter (NAWM) on MRI of patients with optic neuritis (ON) and compared them to those of patients with multiple sclerosis (MS). Patients with ON (42) were classified into three groups according to abnormalities on brain MRI. Patients with MS (55) were devided in two groups: relapsing remitting MS (RRMS) and secondary progressive MS (SPMS). All patients underwent MRI of the brain and localised proton magnetic resonance spectroscopy (MRS) of NAWM. The results were compared to those of 15 controls. Patients with MS had significant abnormalities compared with controls and with patients with ON. Patients with RRMS and those with ON had comparable MRS parameters, while patients with SPMS had significant spectroscopic abnormalities in comparison with controls, but also with patients with RRMS. These changes consisted of a decrease in N -acetylaspartate, a neuronal marker, which may reflect axonal dysfunction and/or loss. MRS abnormalities were detected in 14 patients with ON (27 %). The main abnormalities consisted of a decrease in N -acetylaspartate, an increase in choline-containing compounds at long echo times, and the presence of free lipid peaks at short echo times. MRS of the NAWM on MRI may prove useful for detecting neurochemical brain abnormalities in ON not visible on MRI.

Both genetic and environmental factors play a role in the pathophysiology of MS and may influence the clinical expression of the disease.To determine the contribution of familial factors to the clinical expression of MS.The French Multiple Sclerosis Genetics Group identified 87 sibling pairs. For each patient, sex, age at onset, duration of the disease, and disease course from onset were recorded. Disability was determined by the progression index (PI), defined as the ratio of the Expanded Disability Status Scale (EDSS) score disease duration when the latter exceeded 5 years. Statistical analyses were performed either with a group of patients (clinical features, relation between human leukocyte antigen and clinical features) or with a group of sibpairs (concordance for clinical features).The mean age at onset was 29.6 years, the ratio of women to men was 59:28, and the mean PI was 0.27. There was no correlation for disease course and age at onset between sibs with MS. In contrast, we observed a weak but significant correlation of the PI in MS sibpairs (r = 0.234, p = 0.03).This study revealed a concordance in MS sibling pairs for the disease severity, supporting the hypothesis that the degree of disability might be partly influenced by familial factors (environmental or genetic).

To test 23 genes coding for growth factors and their receptors as candidates for MS genetic susceptibility in 84 multiplex families of French origin by linkage analysis.Epidemiologic studies have indicated that genetic susceptibility in MS exists. To identify MS susceptibility genes, association and linkage studies were performed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human leukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pathology have suggested that the oligodendrocyte, the myelin-forming cell in the CNS, and its growth factors might play a crucial role in MS.Fifty-two polymorphic markers within or flanking 23 candidate genes were used. Data were analyzed with the maximum likelihood score (MLS) approach. We also searched for a genetic interaction with HLA.Negative results were obtained for all candidate genes. The lower limits of the relative risk (Xs) possibly excluded for any candidate gene ranged from 1.3 to 2.8. Positive MLS values (up to 0.93) were observed for transforming growth factor beta 3 (TGFbeta3) in HLA DR15-associated families, suggesting a possible role for this growth factor in interaction with HLA.Oligodendrocyte growth factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGFbeta3, the only gene highlighted by this study, deserves further analysis.

Sneddon syndrome is characterized by the association of livedo reticularis and cerebrovascular ischemic events. Clinical and MRI aspects are described in 26 patients with Sneddon syndrome. MRI features were classified in 6 groups according to the aspect and topography of the lesions. No correlation was found between the presence of vascular risk factors, valvulopathy or antiphospholipid antibodies and the presence of dementia or MRI lesions. There was a significant correlation between MRI extension of the lesions and clinical disability. Clinical course and MRI findings are presented according to the treatment.

We report a 73-year-old man who presented with Vernet9s syndrome (involvement of the IXth, Xth, and XIth cranial nerves) as a first manifestation of giant cell arteritis.

Fifty six patients among whom 39 had white matter diseases had MRI of the brain comparing FLAIR sequence to a conventional proton density sequence. Flair sequence allowed to detect 18 additional hypersignal (HS) that were not present on T2 sequence. These HS were located in the periventricular areas for 5 of them, near the cortical sulci in 10, and in the centrum semi-ovale for 3. FLAIR sequence permitted analyze 41 other lesions that were not obvious on proton density sequences. Thirty five of them were thus confirmed to be HS : 31 in the paracortical areas, 3 in the paraventricular regions and one in the internal capsule, whereas the remaining 6 were normal sulci of the brain. FLAIR sequence increases the sensitivity of MRI in white matter diseases.

We report on a 54-year-old man with a sensory-motor polyneuropathy associated with a biclonal IgM-kappa gammopathy, which reacted with the ganglioside GD1b. Examination of nerve biopsy specimens showed some reduction in the density of myelinated fibers and axonal degeneration with a loss of large fibers and a relative increase in the density of small fibers. Immunodetection on thin-layer chromatography of the glycolipid antigens showed strong reactivity of the patient's serum IgM-kappa with GD1b ganglioside and weak binding to GD1a. biclonal IgM antibodies did not react with GM1, asialo-GM1, GT1b, GD2, or GD3. Indirect immunofluorescence staining showed binding of IgM-kappa mainly in a crescent-like pattern on the internal side of myelin sheaths, which could correspond either to an enlarged periaxonal (adaxonal) space or to the internal mesaxon or to both. The immunostaining was abolished after absorption of the serum with GD1b.

Signs of cerebral disconnection, especially left ear suppression to dichotically presented verbal stimuli, have been reported in multiple sclerosis patients and found to be correlated to morphological atrophy of the corpus callosum on magnetic resonance imaging. To reinvestigate this issue, 26 patients satisfying criteria for definite multiple sclerosis were proposed 3 tasks aimed at evaluating interhemispheric function: a dichotic listening task, a motor finger-tapping task and a sensory transfer task. Performance at these tasks suggested impaired callosal function in MS patients, compared to normal controls. Callosal morphology was assessed on midsagittal MRI sections using a digitalised method of partition of the callosal area into 6 subregions and automatized surface measurements. Results of correlations between task performance and callosal areas showed a significant correlation between total callosal atrophy and severity of interhemispheric impairment on each functional task. Moreover, impaired motor transfer was specifically related to atrophy of the anterior callosal regions. These results suggest that MS patients may constitute a suitable population to studying interhemispheric transfer of information through the callosal commissure and that this approach may be useful in the clinical management of MS patients.

Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I-endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2-dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells.

Multiple Sclerosis (MS) cases found at autopsy in patients who had died from other diseases and in whom no sign or symptom could be related to MS are called "asymptomatic". Three cases are reported. The first patient was a 62 year old man who presented with a slowly progressive disturbance of gait, incontinence and deterioration of intellectual function. A falx meningioma was surgically removed. The patient died 3 years later with an acute respiratory illness. Examination of the brain disclosed evidence of the operation and numerous old plaques disseminated through the cerebral hemispheres (centrum semi-ovale, periventricular regions, internal thalamus and junction between cortex and white matter) and in the brain stem. The second case, a 77 year old woman with diabetes mellitus and hypertension, presented with cortical blindness and disturbances of memory of acute onset. She died one year later. Examination of the brain showed multiple infarcts involving the territories of both posterior cerebral arteries and the left middle cerebral artery. Numerous old plaques were seen in the periventricular regions, in the corpus callosum and in the left middle cerebellar peduncle. The third case, a 60 year old woman with mitral and aortic stenosis, presented with cortical deafness and transient right hemiparesis. She died 5 years later. Brain examination showed infarcts involving both middle cerebral artery territories. There was also many old plaques in the periventricular areas, thalamus, internal capsule, centrum semi-ovale, brain stem and right nucleus dentatus. In the 3 cases, the optic tracts were normal. The spinal cord, examined only in the first case, was also normal. The asymptomatic character of these MS cases can be explained first by the location of the plaques and the lack of spinal cord and optic tract involvement. It could also be due to the small size of the plaques and to axonal preservation. Such features are rare since our 3 observations have been selected from a pathological collection of 125 MS cases and 9,300 general neuropathological records. Six other cases have been previously reported by other authors.

A 65 year-old man with an oesophageal carcinoma had an acute polymyositis with an extensive oedema of shoulders and arms which improved spontaneously. The significance of these disorders is discussed.

Four cases of angioimmunoblastic lymphadenopathy associated to peripheral neuropathy are described. The neuropathy was mixed, sensory and motor, more or less extensive, always asymetrical. In two cases, the clinical symptomatology and the clinical course were very peculiar, characterized by sensory disorders of a precise topography, circumscribed and sometimes suspended and by a relapsing and remitting course. In the third case, the neurological signs were acute and rapidly extensive with mandatory respiratory assistance. In this case, death occurred after a few weeks and the exact diagnosis was only attained at post-mortem examination. In the fourth case the neuropathy was very painful but the course was slow. In all four cases marked and extensive pain was present prior to the neurological disorders. Electrophysiological abnormalities were a constant feature with a marked slowing down of nerve conduction velocity. CSF was normal at the beginning in one case but was otherwise markedly pathological with an increased number of cells due to a large number of lymphocytes ranging from 6 to 40 cells while protein ranged from 60 to 160 mg per 100 ml. Nerve and muscle biopsies were non specific, i.e. neurogenous muscular atrophy and demyelination, except in case n. 4 where specific angioimmunoblastic lymphadenopathy infiltrates were present both in nerve and muscle. In cases 1 and 3 a non specific lymphohistiocytic infiltrate was present in spinal roots and meninges. Corticotherapy was used and efficient in two cases. These data are compared with a review of the literature. Since 1976, 7 cases of angioimmunoblastic lymphadenopathy associated to peripheral neuropathy have been reported. Clinical, electrophysiological and biological features are similar. Only one case underwent a post mortem examination of the central nervous system: a non specific lymphocytic infiltration in the spinal roots and meninges was mentioned. The role of the dysproteinemia associated with the AIL in the occurrence of the neuropathies is discussed. It remains a possible factor only. The role of a massive specific localization of the pathological process is well established in only one case (case 4). Such localization in lymphomas are not unusual. In 2 of our cases as well as in 2 from the literature the pathological findings are non specific: mild lymphoplasmocytic infiltrates of spinal roots and meninges. Those lesions are similar to neuropathies associated to non metastasizing neoplasms or malignant hemopathies.

Two anatomo-clinical cases of downward gaze palsy and one case of upward gaze palsy are reported. A tonic and intermittent downward gaze deviation is described. The supranuclear palsies of the downward gaze were related to paramedian lesions of the rostral mesencephalon; the lesions involved the rostral interstitial nucleus of the medial longitudinal fasciculus, the nucleus interstitial of Cajal, and/or their afferent and/or efferent pathways. The supranuclear palsy of the upward gaze was related to lesions of the posterior commissure. Tonic and intermittent downward deviation of gaze and ocular bobbing have opposed features. The former could be related to disinhibited reticular mesencephalic neurones activated by vestibular inputs. Tonic upward deviation of gaze is also related to a vestibulo-ocular reflex. In this case, partial or total damage of the nucleus of Cajal, and/or its input and/or its output fibers appears to have a critical role.

A retrospective study of clinical files of 70 pathologically confirmed cases of Multiple Sclerosis (MS) (53 women and 17 men), selected from the records of the Laboratoire de Neuropathologie Charles Foix (Hôpital de la Salpêtrière) was performed. The following data were recorded and analysed by a computer program (HP 85): sex, age of onset of disease, clinical course (classified into Remittent, Remittent-Progressive, Progressive and Acute) and the date of each new neurological symptom or sign. The mean age of onset was 36.8 +/- 12. In women, the disease began earlier (34.6 +/- 12) and the duration was longer (17.4 +/- 12). In men the age onset was 40.6 +/- 11 and the duration was 12.5 +/- 6. In remittent courses, the mean age of onset was 30.8 +/- 13 and the duration was 21 +/- 10. In progressive courses, the age at onset was 45 +/- 10 and the duration was 2. In women, progressive courses began significantly later (42.3 +/- 9.2) and were shorter (15 +/- 8) than remittent courses which began at 26.8 +/- 8.2 and lasted 23 +/- 10. The histogram of the duration of clinical courses showed three groups: acute courses (8 cases less than 5 years long), intermediate courses (41 cases, between 5 and 20 years long), and long courses (21 cases longer than 20 years). Women were more often affected with acute (7/8 cases) or long courses (20/21 cases). The mean duration of the disease was the same when the symptoms and signs at onset were motor weakness, sensory disturbances, optic neuritis or diplopia.(ABSTRACT TRUNCATED AT 250 WORDS)

Four observations of spinal forms of multiple sclerosis (MS) have been studied by Magnetic Resonance Imaging (MRI) (Magniscan Thomson CGR 0,15 and 0,5 T). They concerned 3 females and 1 male, aged between 29 and 60. Evolution of MS varied between 1 year and 9 years. There were no familial story of neurological illness; there were no signs and symptoms of visual, oculo-motor, labyrinthic and cerebellar disorders in the past. VEP were abnormal in 2 cases (no 1, 3), BAEP in 1 case (no 2). CSF examination showed increased gamma globulins with an oligoclonal pattern in 2 cases (no 3,4). CT Scan performed with iodine contrast injection was normal in 3 cases (no 2,3,4). In all the cases, MRI using T2 weighted-SE sequences, showed high signal lesions in the white matter of the brain and/or the cerebellum, and periventricular patchy white matter lesions. It seems to be no relationship between the duration of MS and the number of abnormal high signals areas, but more important series are necessary to confirm or not such a result. These lesions seem to be without aetiological specificity. They have to be discussed according to the clinical biological, electro-physiological data and sometimes others neuroradiological procedures.

Among 70 pathologically proven MS cases, we found 12 cases with onset before 25. Only females were affected. There was no positive familial history of MS. In every case the diagnosis was considered during life. Mean duration of the disease was 29.1 +/- 12.5 years. This was significantly longer (p less than 0.001) than in the control group (58 pathologically proven cases with onset after 25). There were no acute courses. Progressive courses (1 case) and remittent courses (5 cases) were less frequent than in the control group (p less than 0.001 and p less than 0.01, respectively). The frequency of remittent-progressive courses (6 cases) was similar in both groups. The length of remittent-progressive courses (30.2 +/- 16.2) and remittent courses (28.6 +/- 9.7) was longer than that of control group (p less than 0.001). The symptomatology of onset was similar in both groups and had no predictive value for prognosis. The overall frequency of signs and symptoms was not statistically different in both groups. For each sign, the percentage of affected patients, throughout the course of the disease, was always smaller in early onset MS than in control group, except for optic neuritis which was as frequent in both groups. However, this was statistically significant only for ocular motricity and nystagmus.