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.
Amongst 833 French patients with secondary progressive multiple sclerosis 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%.
Neuromyelitis optica (NMO) is a life-threatening disease without any validated treatment strategy. Recent retrospective studies suggested the efficacy of B cell depletion without any distinction ...between first-line or rescue therapy. To assess whether rituximab as first-line therapy in NMO could efficiently control the occurrence of relapses. A retrospective analysis of NMO patients from NOMADMUS network found 32 patients receiving rituximab as first-line therapy. Main measures were number of relapse-free patients, changes in the annualized relapse rate (ARR), and changes in the EDSS. Tolerance was reported. At baseline, NMO patients were 45 ± 12.1 years old, with a sex ratio of 5.4, and 87.5 % of them had AQP4 antibodies. The median disease duration was 6.5 months (1–410), the mean EDSS was 5.8 ± 2.4 and the mean ARR was 3.8 ± 4.3. After rituximab with a mean follow-up of 28.7 ± 21 months, twenty-seven patients (84.3 %) were relapse free. Patients presented a 97 % decrease of ARR (
p
= 0.00001). EDSS decreased significantly to 3.9 ± 2.6 (
p
= 0.01). No relevant side effect was noted. New retrospective data are presented on RTX use in NMOSD. When used as first-line therapy RTX is highly effective and well tolerated.
Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disorder that causes degeneration of upper and lower motor neurons and their axons. ALS is mostly sporadic, but there are familial forms. In ...more than half of the familial forms, a pathogenic variant is found in one of the following genes: C9ORF72, SOD1, TDP-43, FUS, and VCP. SOD1 is the 2nd most common gene involved in genetic forms of ALS. Genotype-phenotype relationships are occasionally established in genetic forms of ALS associated with SOD1 mutations pathogenic variants. The c.281G > T (p.G93V) variant in SOD1 is associated with a rarely described and unexplained anticipation phenomenon. We report a large family from Martinique in whom ALS is associated with a c.281G > T (p.G93V) pathogenic variant in SOD1 and a statistically suggested anticipation. A whole-exome study and detection of CNVs (CoDESeq) from 3 affected members of this family revealed the presence of variants of uncertain signification (VUS) in other ALS genes. VUS in DCTN1 and NEFH were present in patients of the 2nd generation, and CNVs involving UBQLN2 and C21orf2 were found in the youngest case of the family.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Therapeutic options are limited in secondary progressive multiple sclerosis (SPMS). Open-label studies suggested efficacy of monthly IV cyclophosphamide (CPM) without induction for delaying ...progression but no randomized trial was conducted so far.
To compare CPM to methylprednisolone (MP) in SPMS.
Randomized, double-blind clinical trial on two parallel groups. Patient with SPMS, with a documented worsening of the Expanded Disability Status Scale (EDSS) score during the last year and an EDSS score between 4·0 and 6·5 were recruited and received one intravenous infusion of treatment (CPM: 750 mg /m2 body surface area-MP: 1g) every four weeks for one year, and every eight weeks for the second year. The primary endpoint was the time to EDSS deterioration, when confirmed sixteen weeks later, analyzed using a Cox model.
Due to recruitment difficulties, the study was terminated prematurely after 138 patients were included (CPM, n = 72; MP, n = 66). In the CPM group, 33 patients stopped treatment prematurely, mainly due to tolerability, compared with 22 in the MP group. Primary endpoint: the hazard ratio for EDSS deterioration in the CPM in comparison with the MP group was 0.61 95% CI: 0·31-1·22(p = 0·16). According to the secondary multistate model analysis, patients in the CPM group were 2.2 times more likely (1·14-4.29; p = 0.02) to discontinue treatment than those in the MP group and 2.7 times less likely (HR = 0.37, 95% CI: 0.17-0.84; p = 0.02) to experience disability progression when they did not stop treatment prematurely. Safety profile was as expected.
Although the primary end-point was negative, secondary analysis suggested that CPM decreases the risk of progression in SPMS, but its use may be limited by low tolerability.
Clinicaltrials.gov NCT00241254.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The incidence of multiple sclerosis (MS) changes from generation to generation in ethnically different immigrants compared with native-born people. We aimed to determine whether there are ...generational changes in MS phenotypes among North African immigrants in France.
Cohort study with data from a population-based MS registry to compare the clinical characteristics of 80 first (NAG1) and 167 second (NAG2) generation North Africans with MS living in France with 5200 native-born Europeans. Adjusted Cox models were used to test the association between scores of 3 and 6 on the expanded disability status scale (EDSS) and the "origin/generation" variable.
Cox models for EDSS scores 3 and 6 showed a higher risk of score 3 (hazard ratio = 1.738, 95% confidence interval 1.237 to 2.444; P = .002) and 6 (hazard ratio = 2.372, 95% confidence interval 1.626 to 3.462; P<.0001) for NAG1 than Europeans. Being NAG2 was not significantly associated with higher hazards of scores 3 and 6.
We found two different phenotypes among NAG1 and NAG2 MS patients in France. NAG1, but not NAG2, have a higher risk of disability than Europeans. This raises the question of environmental factors in MS expression, and advocates appropriate patient management according to generation in immigrants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights • We describe the largest series of co-occurence of ALS and myasthenia gravis. • This association is rare and requires strict diagnostic criteria. • It may be triggered by a dysfunction of ...the adaptive immune system in both disorders. • False positivity for anti-AChR antibodies is encountered in some ALS patients. • Transient response to acetylcholinesterase inhibitors is also possible in ALS.
Objective
To describe the course of disability in patients with benign multiple sclerosis—i.e., with an expanded disability status scale score < 3 10 years after disease onset—for up to 30 years ...after disease onset. We evaluated the proportion of patients remaining in the benign state on the long term and the factor associated with this favorable outcome and determined the pattern of disability course after the loss of the benign status.
Methods
Patients were selected from the ReLSEP, a French population-based registry. We studied the probability (Kaplan–Meier method) and predictors (multivariate Cox model) of remaining < 3 after year 10, and the course of disability after score 3 according to the duration of the benign phase in patients with ≥ 30 years of follow-up (graphs of the course of the mean expanded disability status scale scores in subgroups of patients).
Results
2295/3440 patients had benign multiple sclerosis (66.7%). The probability of remaining benign at year 30 was 0.26 (95% CI 0.26–0.32). A young age at disease onset and a good recovery after the first relapse were associated with remaining benign. Graphs illustrate that those who lost their benign status between years 10 and 30 follow a two-stage course. Beyond score 3, disability accumulation is similar in all but lower disability scores at advanced age are associated with longer benign periods.
Conclusion
The longer a patient remains in the benign state, the lower the final EDSS at advanced age.
Background:
Younger age, male sex and presence of spinal cord lesion(s) increase the risk of conversion from radiologically isolated syndrome (RIS) to relapsing-remitting multiple sclerosis (RRMS). ...Elevated cerebrospinal fluid (CSF) chitinase-3-like protein 1 (CHI3L1) levels predict conversion from clinically isolated syndrome (CIS) to RRMS.
Objective:
To evaluate the prognostic value of CSF CHI3L1 in RIS patients for conversion to RRMS.
Methods:
We compared CSF CHI3L1 concentrations in RIS, CIS, RRMS and symptomatic controls (SCs). We analysed the influence of epidemiological, radiological and CSF parameters on the risk of clinical event.
Results:
A total of 211 patients (71 RIS, 48 CIS, 50 RRMS and 42 SC) were included. CSF CHI3L1 levels were lower in RIS than in RRMS and higher in RIS with positive CSF versus negative CSF and SC. The presence of at least one spinal cord lesion was the only independent predictor of faster conversion to RRMS. Association of high CSF CHI3L1 levels, positive CSF (presence of oligoclonal bands and/or an elevated IgG index) or four Barkhof criteria with any spinal cord lesion showed a tendency for reduced mean conversion time.
Conclusion:
CSF CHI3L1 correlates with positive CSF but is not an independent predictor of the risk of conversion from RIS to RRMS.
Aujourd’hui, le diagnostic de sclérose en plaques (SEP) secondairement progressive (SP) est souvent tardif, rétrospectif et non reproductible en absence de critère permettant d’objectiver la ...transition en forme SP.
Identifier plus précocement la phase de transition en SEP-SP à l’aide de critères diagnostiques consensuels et définir des critères de suivi afin d’améliorer la prise en charge des patients SP.
Huit boards régionaux impliquant 55 neurologues français spécialistes de la SEP ont été mis en place pour discuter des critères diagnostiques de la SEP-SP et des modalités de suivi des patients. Une réunion nationale, impliquant 13 neurologues dont un représentant de chaque board régional, a ensuite eu lieu afin de discuter des points de convergence et de divergence entre régions et d’émettre un avis d’experts consensuel au niveau national.
Le principal critère diagnostique retenu est l’évolution de l’EDSS (+1 si EDSS ≤5,5 ou +0,5 si >5,5 ; score fonctionnel pyramidal ou cérébelleux ≥2) au cours des 6 mois précédents en absence de toute poussée et à confirmer dans les 3 à 6 mois suivants. En revanche, les activités cliniques et IRM ne sont pas discriminantes pour formuler un diagnostic de SEP-SP.
Même si l’âge et l’EDSS peuvent être des critères pronostiques, il n’y a pas de valeur minimale pour poser le diagnostic. L’écoute du patient à l’anamnèse (altération cognitive, limitation des activités quotidiennes..) reste primordiale comme premier signe d’alerte précédant l’évaluation objective (test de marche chronométré, tests cognitifs..).
Un diagnostic plus précoce de la SEP-SP et une prise en charge adaptée pourront se faire via la surveillance de l’évolution de l’EDSS, des facteurs pronostiques et signes d’alerte.
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