Romain Deschamps

Different HLA class II (DRB1 and DQB1) alleles determine either susceptibility or resistance to NMO and multiple sclerosis among the French Afro-Caribbean population.

Background:Despite similarities, neuromyelitis optica (NMO) can be distinguished from multiple sclerosis (MS) by clinical, radiological and serological findings. Objective:This case-control study aimed to determine whether patients with NMO or with MS in an Afro-Caribbean population originating from French West Indies shared the same or different HLA class I and II pattern distribution. Methods:The association with HLA class II (DRB1 and DQB1) alleles was tested in 42 NMO patients, 163 MS patients and 150 healthy controls. HLA-DRB1 and DQB1 typing was undertaken on genomic DNA extracted from peripheral blood leucocytes. Results:By comparison with healthy controls, significantly increased frequency of HLA-DRB1*03 (26.2% vs. 13%, odds ratio 2.4, 95% confidence interval 1.31–4.28, p after correction, cp 0.045) was observed in patients with NMO. By contrast, in MS patients, HLA-DRB1*15 (24.8% vs. 13%, odds ratio 2.21, 95% CI 1.45–3.36, cp < 0.0015), but not DRB1*03 allele, was positively associated with the disease. Moreover, a modest protective effect of HLA-DRB1*11 in the MS group, independently of DRB1*15 association, was found (13.7% vs. 7% in controls, odds ratio 0.48, p 0.006), but did not survive Bonferroni correction. Conclusion:In conclusion, comparison of the HLA-DRB1 and DQB1 distribution in NMO and MS in this Afro-Caribbean population shows important differences in the HLA associations among NMO and MS.

High prevalence of IgG4-related lymphoplasmacytic infiltrative disorder in 25 patients with orbital inflammation: a retrospective case series

Aims To evaluate retrospectively the prevalence of positive IgG4-immunostaining in orbital tissue of patients with idiopathic orbital inflammation and to compare the clinical, radiographic and pathologic features among patients with and without IgG4-positive cells. Patients and methods 25 patients with biopsy-proven idiopathic orbital inflammation examined from January 2006 through December 2011 were included. Immunohistochemistry with IgG and IgG4 immunostaining from biopsy specimens of all patients was performed. Tissue with more than 10 IgG4-positive plasma cells per high-power field and with a ratio of IgG4+/IgG+ plasma cells of more than 40% was scored as positive. Histopathologic features, demographic and clinical data, radiologic findings, treatment and follow-up information for each patient were analysed. Results Immunohistochemical staining showed 10 cases (40%) were IgG4 positive. The symptoms and signs included eyelid or periocular swelling/mass in all, pain (3/10), extraocular muscle restriction (3/10), proptosis (5/10) and/or decreased vision (4/10). Demographic and clinical findings of these patients did not differ from those with IgG4-negative cells. The presence of positive IgG4-immunostaining in orbital tissue was significantly associated with characteristic pathological features (more background fibrosis, lymphoid hyperplasia, plasma cells and phlebitis). Conclusions Finally, 40% of patients with biopsy-proven orbital inflammation were classified as IgG4-RD, with typical histological features, but without specific clinical or radiological findings.

Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis

Objective To characterise recurrence of multiple sclerosis (MS) inflammatory activity during the year following natalizumab (NTZ) cessation. Methods Thirty-two patients with MS were included in a monocentric cohort study. Data were collected prospectively during and after NTZ, with serial clinical and MRI evaluations. The first relapse occurring after interrupting NTZ was the primary outcome measure. The numbers of gadolinium-enhancing lesions before, during and after NTZ treatment, were compared. Results During the year following NTZ cessation, the cumulative probability of relapses was estimated at 52.9% and an unusually high MRI inflammation was noticed. It was defined by a number of gadolinium-enhancing lesions >5 and exceeding the gadolinium lesions existing before NTZ initiation. Rebound of MS activity after NTZ cessation was characterised by association of relapses and unusual MRI inflammation. Cumulative probability of rebound was estimated at 39% and mostly occurring between 3 months and 9 months after interrupting NTZ. Risk of rebound appears related with a higher annualised relapse rate and a lower Expanded Disability Status Scale score before NTZ initiation. Rebound was associated with severe recurring relapses in 9% of the patients. Conclusions This study identifies rebound after NTZ cessation as an association of relapses and high MRI activity.

Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study.

Background Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity. Methods We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301). Results Men more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate. Conclusion Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials.

CLIPPERS: Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids

A 56-year-old previously healthy man developed progressive cerebellar ataxia and binocular horizontal diplopia, worsening over several weeks. An MR scan of brain showed multiple punctate hyperintensities in T2 weighted images, confined to the pons, medulla oblongata and cerebellum, with curvilinear gadolinium enhancement in T1 weighted images. The clinical and radiological features suggested the CLIPPERS syndrome (Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids). The symptoms and MR findings improved dramatically with high dose parenteral corticosteroids. CLIPPERS syndrome (Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids) is a recently described CNS inflammatory disorder.1 Since 2010, several new possible cases have been published.2,–,5 We report a further patient with features consistent with this syndrome. A previously healthy 56-year-old man was admitted with a several week history of progressive ataxia and binocular horizontal diplopia. On initial neurological examination, he showed dysarthria, left sixth nerve palsy, a right-sided extensor plantar response, right-sided sensory loss and cerebellar limb and gait ataxia; ophthalmoscopy was normal. MR scan of the brain (T2 weighted images) showed multiple punctate hyperintensities in the pons, medulla oblongata and cerebellum (figure 1A), with curvilinear gadolinium enhancement in T1 weighted images (figure 1B, C). Diffusion weighted MR images gave no additional information. MR …

Prognostic value of cerebrospinal fluid analysis at the time of a first demyelinating event

Background and Objective: This study aimed to assess the value of cerebrospinal fluid (CSF) findings for predicting conversion to clinically definite multiple sclerosis (CDMS). Methods: From a database of 447 patients with a first demyelinating event, the records of 208 patients less than 51 years old who had baseline magnetic resonance imaging (MRI) and CSF examinations and a follow-up of at least 1 year were included. A multivariable Cox model was used to assess the short-term risk of CDMS according to baseline CSF findings after adjustment for prognostic factors (including brain MRI) and to provide a simple classification for predicting CDMS. Results: During a median follow-up of 3.5 years, 141 (67.8%) patients converted to CDMS. In multivariate analysis, younger age (hazard ratio [HR]: 1.44 [95% CI 1.02–2.01]), spatial dissemination on brain MRI (HR: 2.07 [95% CI 1.47–2.91]) and more than 4 WBC/mm3 in CSF (HR: 1.44 [95% CI 1.03–2.02]) were independently associated with CDMS. The Cox score obtained from these three predictors enabled patients to be divided into three groups with significant increased risks of CDMS at 1, 2 and 3 years; groups were classified as high-risk (64.7%, 77.4%, 96.1%), intermediate-risk (33.3%, 51.5%, 61.5%), and low-risk (11.1%, 18.3%, 40.3%). Conclusions: Age at onset, spatial dissemination on brain MRI and CSF white blood cell count are independently associated with short-term conversion to CDMS. The three proposed risk group classifications could be a useful tool to select patients for early therapeutic intervention.

Clinical and Radiological Characteristics in Multiple Sclerosis Patients with Large Cavitary Lesions

Background: Large cavitary lesions are not typical for multiple sclerosis (MS). Cavitary white matter changes may be seen in megalencephalic leukoencephalopathy with subcortical cysts, Alexander disease, mitochondrial leukoencephalopathies, vanishing white matter disease, leukoencephalopathy with calcifications and cysts, cytomegalovirus infection, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Objective: To analyze clinical and radiological characteristics in MS patients with large cavitary lesions. Methods: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), Mini Mental State (MMS), corpus callosum lesions, history of segmental myelitis, CSF oligoclonal bands (OCB), visual evoked potentials (VEP), vanishing white matter disease genetic analysis, and characteristics of the cavitary lesions were analyzed. Results: Nine patients were analyzed, 1 man and 8 women. Mean age of disease onset was 38.5 years. Mean disease duration was 9 years. Three patients had initial relapsing-remitting MS and 6 patients had primary-progressive MS. Mean EDSS was 4.5. Mean MMS was 20/30. Segmental myelitis was present in 6 cases. OCB were found in 6 patients. VEP was performed in 6 patients, and pathological in all but one. Vanishing white matter disease genetic analysis was performed and negative in 5 patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance. Conclusion: MS patients with large cavitary lesions seem to represent an MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction.

Absence of consistent association between human leukocyte antigen-I and -II alleles and human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis risk in an HTLV-1 French Afro-Caribbean population

OBJECTIVES Human T-cell lymphotropic virus type 1 (HTLV-1) infection leads to the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in less than 5% of cases. The mechanism of disease progression in HAM/TSP remains unknown. A significant role of certain human leukocyte antigen (HLA) genotypes in determining the risk of HAM/TSP has been reported in Japan, where the HLA-A*02 gene has been found to be associated with a lower HTLV-1 provirus load and with protection from HAM/TSP, whereas HLA-DRB1*0101 has been found to be associated with an increased susceptibility to HAM/TSP. The aim of the present case-control study was to investigate the HLA class I and class II allele distribution in HTLV-seropositive French Afro-Caribbean individuals, originating from the French West Indies. METHODS Associations with HLA class I (A and B) and class II (DRB1 and DQB1) alleles were tested in 123 HAM/TSP patients and 85 asymptomatic HTLV-1 carriers. HLA typing was undertaken on genomic DNA extracted from peripheral blood leukocytes. RESULTS In our cohort, no significant effect on either the risk of developing HAM/TSP or HTLV-1 provirus load was found for HLA class I or class II, including HLA-A*02 (p=0.43). CONCLUSIONS Our findings are in contrast to those in the Japanese population, however the literature on HLA associations in HTLV-1 infections across different populations over the past decade have reported conflicting results and this suggests strong ethnic disparities.

Œdèmes papillaires bilatéraux : étude prospective de 50 patients

In this prospective study, we report fifty consecutive cases of bilateral papilledema without neurosurgical or obvious ophthalmologic etiology, referred to our institution between January 2005 and March 2007. Lumbar puncture with opening CSF pressure measurement distinguished two groups of patients: Group 1 (n=39) with and Group 2 (n=11) without intracranial hypertension. In Group 1, 9/39 patients presented secondary intracranial hypertension mainly due to cerebral venous thrombosis. In 30 patients, after complete investigations, a diagnosis of idiopathic intracranial hypertension was made: as commonly reported, patients were predominantly overweight (96.7% with body mass index>25kg/m2) young (mean age=27.6 years) and women (96.7%). Eleven patients with intracranial hypertension had no headaches. In Group 2, the most common diagnosis was bilateral non-arteritic anterior ischemic optic neuropathy, but rare causes have been identified.

Clinical spectrum and prognostic value of CNS MOG autoimmunity in adults: The MOGADOR study

Objective To describe clinical and radiologic features associated with myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) in a large French nationwide adult cohort, to assess baseline prognostic features of MOG-Ab-associated diseases after a first acute demyelinating syndrome, and to evaluate the clinical value of MOG-Ab longitudinal analysis. Methods Clinical data were obtained from 197 MOG-Ab-positive patients ≥18 years of age. Complete imaging data were available in 108, and 54 serum samples were eligible for longitudinal evaluation. For survival analysis comparison, 169 aquaporin-4 antibody (AQP4-Ab)-positive patients from the NOMADMUS database were included. Results Median age at onset was 36.46 (range 18.0–76.8) years, and patients were predominantly white (92.9%) with male:female ratio, 1.1. Clinical phenotype at onset included optic neuritis or myelitis in 90.86%, isolated brainstem or encephalopathy syndromes in 6.6%, and a combination of syndromes in 2.5%. Distinctive brain MRI findings in MOG-Ab-positive patients were thalamic and pontine lesions. Cortical and leptomeningeal lesions were found in 16.3% and 6.1%, respectively. The probability of reaching a first relapse after 2 and 5 years was 44.8% and 61.8%, respectively. MOG-Ab-positive patients were at lower risk at presentation of further clinical relapse (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.26–0.79) compared to AQP4-Ab-positive individuals. MOG-Ab-positive individuals had a lower risk of reaching Disability Status Scale score of 3.0 (HR 0.46, 95% CI 0.22–0.94) and visual acuity of 20/100 (HR 0.23, 95% CI 0.07–0.72). Finally, MOG-Ab titers were higher at relapse than in remission (p = 0.009). Conclusion In adults, MOG-Ab-associated disease extends beyond clinical and radiologic abnormalities in the optic nerve and spinal cord. Despite the relapsing course, the overall visual and motor outcome is better compared with AQP4-Ab-positive patients.