Prognostic impact of epileptic seizures in multiple sclerosis varies according to time of occurrence and etiology.

BACKGROUND AND PURPOSE: Epileptic seizures occur more often in patients with multiple sclerosis (MS) than in the general population. Their association with the prognosis of MS remains unclear. This study was undertaken to evaluate whether epileptic seizures may be a prognostic marker of MS disability, according to when the seizure occurs and its cause. METHODS: Data were extracted from a population-based registry of MS in Lorraine, France. Kaplan-Meier curves and log-rank tests were used to compare the probability of different levels of irreversible handicap during the course of MS in patients who experience epileptic seizures or do not, according to the chronology and the cause of the first epileptic seizure. RESULTS: Among 6238 patients, 134 had experienced at least one epileptic seizure (2.1%), and 82 (1.2%) had seizures secondary to MS. Patients with epileptic seizure as a first symptom of MS (14 patients) had the same disease progression as other relapsing-remitting MS patients. Patients who developed epileptic seizures during the course of MS (68 patients) had a higher probability of reaching Expanded Disability Status Scale = 3.0 (p = 0.006), 6.0 (p = 0.003), and 7.0 (p = 0.004) than patients without an epileptic background. Patients with a history of epileptic seizures unrelated to MS also had a worse prognosis than patients without an epileptic background. CONCLUSIONS: Epileptic seizures might be viewed as a "classic MS relapse" in terms of prognosis if occurring early in MS, or as a marker of MS severity if developing during the disease. Epileptic diseases other than MS may worsen the course of MS.

Comparative effectiveness of dimethyl fumarate in multiple sclerosis.

AIMS: To assess the effectiveness of dimethyl fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting. METHODS: A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 December 2017, with 4.5 years of database history and 1-3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Negative binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, respectively. RESULTS: Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61-0.86]) and TERI (0.81 [0.68-0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts. CONCLUSION: DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

Cumulative effects of therapies on disability in relapsing multiple sclerosis.

BACKGROUND: Long-term effectiveness of treatment remains a key question in multiple sclerosis (MS) and the cumulative effects of past treatment have not been investigated so far. OBJECTIVE: Explore the relationship between treatment exposure and disability risk in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: A total of 2285 adult patients from the French nationwide cohort were included. Outcomes were irreversible EDSS4, and conversion to secondary progression of multiple sclerosis (SPMS). Associations between treatments and risk of disability were assessed using a novel weighted cumulative exposure model, assuming a 3-year lag to account for reverse causality. This flexible approach accounts for past exposure in a multivariate Cox proportional hazards model by computing a weight function. RESULTS: At baseline, mean ± standard deviation age of patients was 33.4 ± 8.9 years and 75.0% were women. A 15-year continuous treatment starting 20 years ago was associated with a decrease in risk of 26% for irreversible EDSS4, and 34% for SPMS compared to a 5-year treatment starting 10 years ago. The risk of disability decreased with increasing duration of exposure to disease-modifying treatment (DMT). CONCLUSION: Long-term use of treatments in RRMS has a stronger beneficial cumulative impact than only early uses and delays the occurrence of moderate disability and conversion to SPMS.

BEST-MS: A prospective head-to-head comparative study of natalizumab and fingolimod in active relapsing MS.

BACKGROUND: There are few head-to-head studies to compare highly active treatments in multiple sclerosis (MS). OBJECTIVE: The aim of this study was to compare the effectiveness between natalizumab (NTZ) and fingolimod (FTY) in active relapsing-remitting MS. METHOD: Best Escalation STrategy in Multiple Sclerosis (BEST-MS) is a multicentric, prospective study with a 12-month follow-up including patients with active MS. Treatment choice was at the discretion of physician. Clinical and magnetic resonance imaging (MRI) data were collected at baseline and at 12 months. The primary outcome was the proportion of patients reaching no evidence of disease activity (NEDA) at 12 months. Secondary outcomes included annualized relapse rate and MRI activity. RESULTS: A total of 223 patients were included (NTZ: 109 and FTY: 114). Treatment groups were well balanced at baseline. Proportion of NEDA patients was 47.8% in NTZ group versus 30.4% in FTY group (p = 0.015). This superiority was driven by annualized relapse rate and MRI activity. In the multivariate analysis, treatment group was the only factor associated with NEDA at 12 months with a lower probability in FTY group (odds ratio (OR) = 0.49, p = 0.029). CONCLUSION: BEST-MS is a prospective study that compared head-to-head the effectiveness of NTZ and FTY in active relapsing-remitting MS. Our results suggest a superiority of NTZ over FTY.

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study.

BACKGROUND: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. OBJECTIVE: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. METHODS: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. RESULTS: Recruitment was stopped prematurely due to slow inclusions (n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) (p = 0.79)). CONCLUSION: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.

Determinants of therapeutic lag in multiple sclerosis.

BACKGROUND: A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. OBJECTIVES: The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. METHODS: Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. RESULTS: High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5). CONCLUSIONS: Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Clinical and radiological activity of secondary progressive multiple sclerosis in a population-based cohort.

BACKGROUND AND PURPOSE: Patients with secondary progressive multiple sclerosis (SP MS) and clinical and/or radiological activity could be the more likely to benefit from disease-modifying treatments. To evaluate the proportions each year after progression onset, patients with SP MS onset between 2002 and 2012 from a population-based multiple sclerosis registry in northeastern France were studied. METHODS: Progression onset was first identified by the neurologist's diagnosis (N cohort), and then by using an automated data-driven definition (D cohort). In a given year after onset of progression, clinical activity was defined as at least one relapse, and radiological activity as at least one new T2 and/or gadolinium-enhancing lesion. A multivariate mixed logistic regression was used to assess factors associated with activity during the year. RESULTS: In the N cohort, amongst 833 patients with SP MS with a median follow-up of 8 years, 10.0%-14.8% had at least one relapse in a year during the first 5 years of progression. Including both clinical and radiological activity increased these proportions to 11.9%-23.7%, with the proportion having a magnetic resonance imaging scan in the year ranging from 29.8% to 40.5%. The first year of progression, a young age and a high relapse rate during the 5 years before progression were associated with activity in a given year. The D cohort results confirmed these findings. CONCLUSIONS: A substantial proportion of patients with SP MS present disease activity. Further studies should evaluate the impact of disease-modifying treatments on the disease course of these patients.

Assessing the experience of the quality of care of patients living with multiple sclerosis and their caregivers: The MusiCare questionnaire.

BACKGROUND AND PURPOSE: Patients with a chronic illness, such as multiple sclerosis (MS), and their natural caregivers have a specific experience of healthcare and health services. These experiences need to be assessed to evaluate the quality of care. Our objective was to develop a French-language questionnaire to evaluate the quality of care as experienced by MS patients and their natural caregivers. METHODS: Eligible patients had been diagnosed with MS according to the McDonald criteria. Eligible caregivers were individuals designated by the patients. The MusiCare questionnaire was developed in two standard phases: (i) item generation, based on interviews with patients and caregivers; and (ii) validation, consisting of validity, reliability, external validity, reproducibility, and responsiveness measures. RESULTS: In total, 1088 patients (n = 660) and caregivers (n = 488) were recruited. The initial 64-item version of MusiCare was administered to a random subsample (n = 748). The validation process generated a 35-item questionnaire. Internal consistency and scalability were satisfactory. Testing of the external validity revealed expected associations between MusiCare scores and sociodemographic and clinical data. The questionnaire showed good reproducibility and responsiveness. CONCLUSIONS: The availability of a reliable and validated French-language self-report questionnaire probing the experience of the quality of care for MS will allow the feedback of patients and caregivers to be incorporated into a continuous healthcare quality-improvement strategy.

Intra-database validation of case-identifying algorithms using reconstituted electronic health records from healthcare claims data.

BACKGROUND: Diagnosis performances of case-identifying algorithms developed in healthcare database are usually assessed by comparing identified cases with an external data source. When this is not feasible, intra-database validation can present an appropriate alternative. OBJECTIVES: To illustrate through two practical examples how to perform intra-database validations of case-identifying algorithms using reconstituted Electronic Health Records (rEHRs). METHODS: Patients with 1) multiple sclerosis (MS) relapses and 2) metastatic castration-resistant prostate cancer (mCRPC) were identified in the French nationwide healthcare database (SNDS) using two case-identifying algorithms. A validation study was then conducted to estimate diagnostic performances of these algorithms through the calculation of their positive predictive value (PPV) and negative predictive value (NPV). To that end, anonymized rEHRs were generated based on the overall information captured in the SNDS over time (e.g. procedure, hospital stays, drug dispensing, medical visits) for a random selection of patients identified as cases or non-cases according to the predefined algorithms. For each disease, an independent validation committee reviewed the rEHRs of 100 cases and 100 non-cases in order to adjudicate on the status of the selected patients (true case/ true non-case), blinded with respect to the result of the corresponding algorithm. RESULTS: Algorithm for relapses identification in MS showed a 95% PPV and 100% NPV. Algorithm for mCRPC identification showed a 97% PPV and 99% NPV. CONCLUSION: The use of rEHRs to conduct an intra-database validation appears to be a valuable tool to estimate the performances of a case-identifying algorithm and assess its validity, in the absence of alternative.

Observatoire Français de la Sclérose en Plaques (OFSEP): A unique multimodal nationwide MS registry in France.

The care of multiple sclerosis (MS) in France is based on two complementary interlinked networks: MS expert centers in university hospitals and regional networks of neurologists. The routine use of European database for multiple sclerosis (EDMUS) in all those centers has paved the way for the constitution of a national registry, designated as Observatoire Français de la Sclérose En Plaques (OFSEP). It promotes a prospective, standardized, high-quality, and multimodal collection of data. On June 2018, there were 68.097 files, with 71.1% females, representing 761,185 person-years. This huge database is open to the scientific community and might contribute exploring unresolved issues and unmet needs in MS.

Double-blind, randomized controlled trial of therapeutic plasma exchanges vs sham exchanges in moderate-to-severe relapses of multiple sclerosis.

INTRODUCTION: No randomized controlled clinical trial of therapeutic plasma exchanges (TPE) has yet been performed for moderate-to-severe relapses of multiple sclerosis (MS). OBJECTIVE: To compare TPE to sham-TPE in patients with a recent steroid-resistant moderate-to-severe MS relapse. METHODS: Patients presenting with an MS relapse of less than 2 months without improvement and 15 days after a course of steroids were randomized. Specific criteria were used for each relapse type to define moderate-to-severe disability. The primary endpoint was the proportion of patients with at least a moderate improvement based on objective and functional evaluation after 1 month. RESULTS: Thirty-eight patients were randomized. The intention-to-treat analysis included 14 patients in the TPE group and 17 in the Sham-TPE group. The proportion of patients with at least moderate improvement at 1 month did not differ between the groups (P = .72), although 57.1% of the TPE group had full recovery compared with 17.6% of the sham group. Considering optic neuritis (ON), a significant difference in the proportion of different levels of improvement was observed in favor of the TPE group (P = .04). The combined Kurtzke's functional systems scores were significantly more improved in the TPE group than in the sham-TPE group at months 1 (P < .01), 3 (P < .05), and 6 (P < .05). No major side effects were observed. CONCLUSIONS: A significant difference between TPE and Sham-TPE at the primary endpoint was only observed in patients with ON. Neurological function improved significantly more often in the TPE group than in the sham-TPE group.

Memory improvement in multiple sclerosis after an extensive cognitive rehabilitation program in groups with a multicenter double-blind randomized trial.

OBJECTIVE: The aim of this study is to determine the effectiveness of an extended cognitive rehabilitation program in group's sessions in multiple sclerosis. DESIGN: Double-blind multicenter randomized trial. PARTICIPANTS: People with multiple sclerosis of 18 to 60 years, Expanded Disability Status Scale ⩽6.0, mild to moderate cognitive impairment. INTERVENTIONS: They were randomized into cognitive rehabilitation program (ProCog-SEP) or in a placebo program. ProCog-SEP comprises 13 group's sessions over 6 months and includes psychoeducational advices and cognitive exercises. Placebo program included non-cognitive exercises. No strategy and no cognitive advice were provided. MAIN MEASURES: The primary endpoint was the percentage of verbal memory learning measured by the Selective Reminding Test. A comprehensive neuropsychological assessment is carried out before and after interventions by a neuropsychologist blinded to intervention. Effectiveness of the ProCog-SEP versus Placebo has been verified using linear regression models. RESULTS: In total, 128 participants were randomized and 110 were included in the study after planning session in groups; 101 completed this trial (77.2% females); mean age: 46.1 years (±9.6); disease duration: 11.8 years (±7.5). ProCog-SEP was more effective in increasing in learning index (9.21 (95% confidence interval (CI): 1.43, 16.99); p = 0.02) and in working memory on manipulation (0.63 (95% CI: 0.17, 1.09); p = 0.01), and updating capacities (-1.1 (95% CI: -2.13, -0.06); p = 0.04). No difference was observed for other neuropsychological outcomes. Regarding quality of life outcomes, no change was observed between the two groups. CONCLUSION: These findings suggest that ProCog-SEP could improve verbal learning abilities and working memory in people with multiple sclerosis. These improvements were observed with 13 group sessions over 6 months.

Efficacy of rituximab in refractory RRMS.

OBJECTIVE: To investigate the efficacy of rituximab as rescue therapy in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent disease activity confirmed by magnetic resonance imaging (MRI) despite immunosuppressive disease-modifying therapy (DMT). METHODS: In this observational nationwide retrospective multicenter study, we first identified 351 off-label rituximab-treated patients through a cohort of 15,984 RRMS patients. In this group, we identified patients with disease activity prior to rituximab confirmed by MRI (one or more new T2 lesion and/or gadolinium-enhancing lesion) despite immunosuppressive DMT (fingolimod, natalizumab, or mitoxantrone) with a follow-up after rituximab initiation longer than 6 months. Outcome data were collected from the French Observatory of Multiple Sclerosis (OFSEP) register and medical charts. RESULTS: A total of 50 patients were identified. Median rituximab treatment duration was 1.1 (0.5-6.4) year. Mean annualized relapse rate significantly decreased from 0.8 during last immunosuppressive DMT to 0.18 after rituximab ( p < 0.0001). While 72% of patients showed gadolinium-enhancing lesions on the last MRI performed during last immunosuppressive DMT, 8% of them showed gadolinium-enhancing lesions on the first MRI performed 6.1 (range 1.4-18.4) months after rituximab ( p < 0.0001). CONCLUSION: This study provides level IV evidence that rituximab reduces clinical and MRI disease activity in patients with active RRMS despite immunosuppressive DMT.

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS.

BACKGROUND: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. OBJECTIVE: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. METHODS: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. RESULTS: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). CONCLUSION: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

Older Age at Multiple Sclerosis Onset Is an Independent Factor of Poor Prognosis: A Population-Based Cohort Study.

BACKGROUND: Late-onset multiple sclerosis (LOMS) frequently features a primary progressive (PP) course, strongly predicting severe disability. In this population-based cohort, we estimated the prognostic role of age at multiple sclerosis (MS) onset, independent of PP course, on disability progression. METHODS: The association of age at disease onset (adult, <50 years [AOMS], vs. late, ≥50 years [LOMS]) and time to Expanded Disability Status Scale (EDSS) score 4 and 6 was estimated by Cox regression modelling. RESULTS: Among 3,597 patients, 245 had LOMS. Relapsing-remitting (RR) disease was less frequent with LOMS than AOMS (51.8 vs. 90.8%, p < 0.0001). PP course, LOMS and male gender predicted short time to EDSS 4 and 6. Worse outcome with LOMS (time to EDSS 4 and 6, HR 2.0 [95% CI 1.7-2.4] and 2.3 [1.9-2.9]) was independent of PP course or male gender. LOMS had greater impact on RR than PP disease (time to EDSS 4 and 6, HR 3.1 [2.3-4.0] and 4.0 [2.9-5.6]). Only LOMS predicted time from EDSS 4 to 6 (p < 0.0001). CONCLUSIONS: Late onset MS was strongly associated with poor prognosis, independent of initial disease course, in predicting the disability progression along time.

Pixantrone: a B-cell-depleting immunosuppressant for multiple sclerosis patients with active disease.

BACKGROUND: Mitoxantrone has been approved for patients with worsening relapsing-remitting (RR) or secondary progressive multiple sclerosis (SPMS), but its long-term use is limited by its cardiotoxicity. Pixantrone (PIX) is an analog of mitoxantrone. OBJECTIVES: The aim of this open-label, multicenter, noncomparative Phase I/II trial was to explore the immunosuppressive effect of PIX, its impact on clinical disease activity and cerebral gadolinium-enhanced (Gd(+)) lesions, and its safety. METHODS: Eighteen patients with active RRMS and SPMS (⩾ 1 cerebral Gd(+) lesion) despite approved immunomodulatory therapy received four intravenous PIX injections every 21 days. A neurological examination, hematology, lymphocyte subsets, and biochemistry were performed at Day 1, Weeks 3, 6 and 9, and Months 3, 6, 9 and 12. Echocardiography was performed before each infusion, at Months 3, 6 and 12. Cerebral MRI was performed at baseline, and at Months 6 and 12. RESULTS: CD19+ cells were reduced by 95% at Month 3 and by 47% at Month 12. Gd+ lesions were reduced by 86% at Month 12 (p = 0.01). The annual relapse rate was reduced by 87% (p < 10(-4)). Two patients experienced a transient reduction in left ventricular fraction. CONCLUSION: These preliminary data indicate the efficacy of PIX in active RRMS and SPMS.

MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

BACKGROUND: Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. OBJECTIVE: To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. METHODS: Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. RESULTS: A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. CONCLUSION: MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated.

Adult-onset genetic leukoencephalopathies: a MRI pattern-based approach in a comprehensive study of 154 patients.

Inherited white matter diseases are rare and heterogeneous disorders usually encountered in infancy. Adult-onset forms are increasingly recognized. Our objectives were to determine relative frequencies of genetic leukoencephalopathies in a cohort of adult-onset patients and to evaluate the effectiveness of a systematic diagnostic approach. Inclusion criteria of this retrospective study were: (i) symmetrical involvement of white matter on the first available brain MRI; (ii) age of onset above 16 years. Patients with acquired diseases were excluded. Magnetic resonance imaging analysis identified three groups (vascular, cavitary and non-vascular/non-cavitary) in which distinct genetic and/or biochemical testing were realized. One hundred and fifty-four patients (male/female = 60/94) with adult-onset leukoencephalopathies were identified. Mean age of onset was 38.6 years. In the vascular group, 41/55 patients (75%) finally had a diagnosis [including CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, n = 32) and COL4A1 mutation, n = 7]. In the cavitary group, 13/17 (76%) patients had a diagnosis of EIF2B-related disorder. In the third group (n = 82), a systematic biological screening allowed a diagnosis in 23 patients (28%) and oriented direct genetic screening identified 21 additional diseases (25.6%). Adult-onset genetic leukoencephalopathies are a rare but probably underestimated entity. Our study confirms the use of a magnetic resonance imaging-based classification with a final diagnosis rate of 64% (98/154) cases.

No prognostic value of routine cerebrospinal fluid biomarkers in a population-based cohort of 407 multiple sclerosis patients.

BACKGROUND: We aimed to determine the association of clinical and routine cerebrospinal fluid biochemical markers (total protein, IgG index and oligoclonal bands) with disability in multiple sclerosis and whether these biomarkers assessed at diagnosis add prognostic value. METHODS: We followed a cohort of patients included in the Multiple Sclerosis Lorraine Register (eastern France) who had a diagnosis of multiple sclerosis for at least 5 years, as well as biological markers values and MRI findings (Barkhof's criteria). In a Cox regression model, endpoint was time to score of 4 on the Expanded Disability Status Scale (EDSS) (i.e., limited time walking without aid or rest for more than 500 m). RESULTS: For 407 patients included, the median time from multiple sclerosis onset to EDSS score 4 was 4.5 years [2.2-7.2]. Cerebrospinal fluid total protein factor < 500 mg/L was associated with EDSS score 4 on bivariate analysis (hazard ratio 0.66, 95% confidence interval 0.46-0.95, p = 0.02). On multivariate analysis, older age at disease onset (≥50 years) and initial primary progressive course of MS but not biological markers predicted worse prognosis. CONCLUSION: Routine cerebrospinal fluid biological markers at diagnosis were not prognostic factors of multiple sclerosis progression.

Milder multiple sclerosis course in patients with concomitant inflammatory bowel disease.

An association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) has been suggested. The purpose of this study was to compare the disease course of patients with both MS and IBD with that of patients with isolated MS or isolated IBD. Sixty-six MS-IBD patients were identified and were matched with 251 isolated MS and 257 isolated IBD controls. Main outcomes were scores using the Expanded Disability Status Scale (EDSS) in MS and extent of disease extension in IBD at last clinical evaluation. After a median 12 years of disease duration, the median EDSS and the percentages of patients reaching an EDSS of 3.0 and 4.0 were significantly lower in MS-IBD patients than in controls. MS had no impact on IBD. MS course appears to be milder in patients with concomitant IBD.