Anti–Glial fibrillary acidic protein (GFAP) encephalomyelitis is a recently described entity and while the spectrum of this disease has been explored, further research is needed to fully describe its ...phenotype. Area postrema syndrome (APS) is usually associated with neuromyelitis optica spectrum disorders (NMOSDs), whereas no case of APS has been previously reported with anti-GFAP encephalomyelitis. In this article, we report a case of APS in a 41-year-old woman in the context of anti-GFAP encephalomyelitis. This case was not associated with additional anti-AQP4 IgG and therefore extends the clinico-radiological spectrum of anti-GFAP encephalomyelitis.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Objectives:
We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin ...oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis.
Material and Methods:
We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0.
Results:
Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0–4.0)) compared to SM patients (2.0, (1.0–3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01–1.95, p = 0.046).
Conclusion:
SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
The Brief Computerized Cognitive Assessment in Multiple Sclerosis (BCCAMS) is a short neuropsychological battery for persons with multiple sclerosis (PwMS).
Objectives:
The main objective ...of the study is to validate the BCCAMS.
Methods:
PwMS and healthy subjects (HS) were evaluated using the BCCAMS which include two computerized tests, the Computerized Speed Cognitive Test and the Computerized Episodic Visual Memory Test (CEVMT), a newly developed visuospatial memory test, and the French learning test. The Minimal Assessment of Cognitive Function in MS (MACFIMS), including the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) tests, was also administered. Regression-based norms of the BCCAMS were calculated in 276 HS. BCCAMS was compared with BICAMS and MACFIMS for detection of cognitive impairment (CI).
Results:
Out of 120 PwMS, CI was detected using the BCCAMS, BICAMS (one impaired test), and MACFIMS (two impaired tests) in 59.1%, 50%, and 37.9%, respectively. The BCCAMS produced the same predictive value as that of the BICAMS battery for detecting CI in the MACFIMS.
Conclusion:
This study validated the BCCAMS as a validated computerized short assessment for information processing speed and learning in MS.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression.
Objective:
We aimed to develop and validate a dynamic ...score to guide the early decision to switch from first- to second-line therapy.
Methods:
Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs).
Results:
From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09–0.22) for the waiting group and 0.40 (95% CI 0.32–0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30–0.46) and 0.44 (95% CI 0.37–0.52), respectively.
Conclusions:
By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Biotin is thought to improve functional impairment in progressive multiple sclerosis (MS) by upregulating bioenergetic metabolism. We enrolled 19 patients suffering from progressive MS (5 primary and ...14 secondary Progressive‐MS). Using cerebral multinuclear magnetic resonance spectroscopy (MMRS) and clinical evaluation before and after 6 months of biotin cure, we showed significant modifications of: PME/PDE, ATP, and lactate resonances; an improvement of EDSS Neuroscore. Our results are consistent with metabolic pathways concerned with biotin action and could suggest the usefulness of MMRS for monitoring.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Author Affiliation: (1) Unite de Medecine Interne: Maladies Auto-immunes et Pathologie Vasculaire (UF 04), Centre de Reference des Maladies auto-immunes systemiques Rares d'Ile-de-France MATHEC ...(FAI2R), Assistance Publique-Hopitaux de Paris, 75010, Paris, France (2) Service de Medecine Interne et Maladies Infectieuses, CHU de Poitiers, 2, rue de la Miletrie, 86021, Poitiers cedex, France (3) CIC-1402, CHU de Poitiers, 2, rue de la Miletrie, 86021, Poitiers cedex, France (4) Service de Neurologie, National Reference Center for Familial Amyloid Polyneuropathy and Other Rare Neuropathies, Hopital Bicetre, Assistance Publique-Hopitaux de Paris, 94275, Le Kremlin-Bicetre, France (5) U1195, INSERM, Universite Paris-Saclay, 94276, Le Kremlin Bicetre, France (6) Service de Neurologie, CHU de Poitiers, 2, rue de la Miletrie, 86021, Poitiers cedex, France (7) Centre Hospitalier Universitaire de Nice, Systeme Nerveux Peripherique et Muscle, Universite Cote D'Azur, Hopital Pasteur, 2, 30 voie Romaine, CS 51069, 06001, Nice Cedex 1, France (8) Service de Neurologie, Hopital Rangueil, CHU Toulouse, Avenue Jean Poulhes, 31300, Toulouse, France (9) Service de Medecine Interne, Hopital Purpan, CHU Toulouse, Place du Docteur Joseph Baylac, 31300, Toulouse, France (10) Faculte de Medecine de Toulouse, 37 Allee Jules Guesde, 31000, Toulouse, France (11) Institut Gustave-Roussy, Service d'hematologie, 114, rue Edouard-Vaillant, 94800, Villejuif, France (12) IRSL, Recherche Clinique Appliquee a l'Hematologie, EA3518, Universite de Paris, Paris, France (13) Department of Medicine, H3A 1A1, McGill University, Montreal, QC, Canada (a) fanny.urbain@aphp.fr Article History: Registration Date: 02/06/2021 Received Date: 11/26/2020 Accepted Date: 02/05/2021 Online Date: 03/02/2021 Byline:
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk ...stratification with PML incidence has not been evaluated. OBJECTIVE: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013. DESIGN, SETTING, AND PARTICIPANTS: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018. EXPOSURES: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation. MAIN OUTCOMES AND MEASURES: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016). RESULTS: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD range) age at MS onset of 28.5 (9.1 1.1-72.4) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016. CONCLUSIONS AND RELEVANCE: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.
To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy.
This was a retrospective cohort study from 2 large observational MS ...registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation.
A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80).
The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod).
This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy.
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