[Show abstract][Hide abstract] ABSTRACT: Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder.
Journal of Neurology 11/2015; DOI:10.1007/s00415-015-7952-8 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Despite a growing use of rituximab (RTX) in neuromyelitis optica (NMO), data are lacking in patients with refractory NMO (RNMO), defined as cases with at least one relapse during immunosuppressive therapy.
The purpose of this study was to assess RTX as a maintenance therapy in RNMO.
Out of a total of 305 NMO cases from a population-based cohort, 21 RNMO patients received RTX during a mean follow-up period of 31 months.
After RTX, 11 patients (52.3%) were relapse free, meaning that 47.7% were refractory to RTX. The mean annualized relapse rate decreased from 1.3 to 0.4 (p<0.001) and median EDSS from 5 to 3 (p=0.02). Body mass index (BMI) was predictive of EDSS worsening.
RTX is an effective and well-tolerated treatment in RNMO. BMI could be a predictive factor for efficacy.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The co-occurrence of autobiographical memory (AM) and episodic future thinking (EFT) impairment has been documented in relapsing-remitting multiple sclerosis (RR-MS) patients. On these bases, we aimed at probing the efficacy of a mental visual imagery (MVI)-based facilitation programme on AM and EFT functioning in the context of a randomised-controlled trial study in RR-MS patients.
Using the Autobiographical Interview (AI), 40 patients presenting with an AM/EFT impairment were randomly assigned in three groups: (i) the experimental (n = 17), who followed the MVI programme, (ii) the verbal control (n = 10), who followed a sham verbal programme, and (iii) the stability groups (n = 13), who underwent the AM/EFT test twice, with no intervention in between.
AI's second assessment scores showed a significant improvement of AM and EFT performance only for the experimental group, with a long-term robustness of treatment benefits.
The control and stability groups' results ruled out nursing and test learning effects as explanations of AM/EFT improvement. These benefits were corroborated by the patients' comments, which indicated an effective MVI strategy transfer to daily life. Our results suggest that the MVI programme tackles a common cognitive process of scene construction present in AM and EFT.
Restorative neurology and neuroscience 08/2015; DOI:10.3233/RNN-140461 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Recent clinical investigations showed impaired episodic future thinking (EFT) abilities in multiple sclerosis (MS) patients. On these bases, the aim of the current study was to explore the structural and functional correlates of EFT impairment in nondepressed MS patients.
Twenty-one nondepressed MS patients and 20 matched healthy controls were assessed with the adapted Autobiographical Interview (AI), and patients were selected on the bases of an EFT impaired score criterion. The 41 participants underwent a functional magnetic resonance imaging (fMRI) session, distinguishing the construction and elaboration phases of the experimental EFT, and the categorical control tests. Structural images were also acquired.
During the EFT fMRI task, increased cerebral activations were observed in patients (relative to healthy controls) within the EFT core network. These neural changes were particularly important during the construction phase of future events and involved mostly the prefrontal region. This was accompanied by an increased neural response mostly in anterior, and also posterior, cerebral regions, in association with the amount of detail produced by patients. In parallel, structural measures corroborated a main positive association between the prefrontal regions' volume and EFT performance. However, no association between the hippocampus and EFT performance was observed in patients, at both structural and functional levels.
We have documented significant overlaps between the structural and functional underpinnings of EFT impairment, with a main role of the prefrontal region in its clinical expression in MS patients.
Journal of Clinical and Experimental Neuropsychology 08/2015; 37(10):1107–1123. DOI:10.1080/13803395.2015.1080228 · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies in multiple sclerosis (MS) showed longer survival times from clinical onset than older hospital-based series. However estimated median time ranges widely, from 24 to 45 years, which makes huge difference for patients as this neurological disease mainly starts around age 20 to 40. Precise and up-to-date reference data about mortality in MS are crucial for patients and neurologists, but unavailable yet in France.
Estimate survival in MS patients and compare mortality with that of the French general population.
We conducted a multicenter observational study involving clinical longitudinal data from 30,413 eligible patients, linked to the national deaths register. Inclusion criteria were definite MS diagnosis and clinical onset prior to January, 1st 2009 in order to get a minimum of 1-year disease duration.
After removing between-center duplicates and applying inclusion criteria, the final population comprised 27,603 MS patients (F/M sex ratio 2.5, mean age at onset 33.0 years, 85.5% relapsing onset). During the follow-up period (mean 15.2 +/- 10.3 years), 1569 deaths (5.7%) were identified; half related to MS. Death rates were significantly higher in men, patients with later clinical onset, and in progressive MS. Overall excess mortality compared with the general population was moderate (Standardized Mortality Ratio 1.48, 95% confidence interval [1.41-1.55]), but increased considerably after 20 years of disease (2.20 [2.10-2.31]).
This study revealed a moderate decrease in life expectancy in MS patients, and showed that the risk of dying is strongly correlated to disease duration and disability, highlighting the need for early actions that can slow disability progression.
PLoS ONE 07/2015; 10(7):e0132033. DOI:10.1371/journal.pone.0132033 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease.
[Show abstract][Hide abstract] ABSTRACT: Mental time travel (MTT) entails the ability to mentally travel into autobiographical memory (AM) and episodic future thinking (EFT). While AM and EFT share common phenomenological and cerebral functional properties, distinctive characteristics have been documented in healthy and clinical populations. No report, to our knowledge, has informed on the functional underpinnings of MTT impairment in multiple sclerosis (MS) patients, hence the aim of this work. We studied 22 relapsing-remitting MS patients and 22 matched controls. Participants underwent an AM/EFT assessment using the Autobiographical Interview (Levine et al. 2002), followed by a functional MRI session. The latter consisted in AM and EFT tasks, distinguishing the construction and elaboration phases of events. The results showed impaired performance for AM and EFT in patients, accompanied by increased cerebral activations mostly located in the frontal regions, which extended to the parietal, lateral temporal and posterior regions during AM/EFT tasks, relative to healthy controls. Enhanced brain activations in MS patients were particularly evident during the EFT task and involved the hippocampus, frontal, external temporal, and cingulate regions. The construction phase required greater fronto-parieto-temporal activations in MS patients relative to both healthy controls, and the elaboration phase. Taking together, our results suggested the occurrence of cerebral activation changes in the context of MTT in MS patients, expressed by distinct and common mechanisms for AM and EFT. This study may provide new insights in terms of cerebral activation changes in brain lesion and their application to clinical settings, considering AM/EFT's central role in everyday life.
Brain Imaging and Behavior 05/2015; DOI:10.1007/s11682-015-9394-4 · 4.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Antibodies against myelin oligodendrocyte glycoprotein (MOG) have been identified in a subgroup of pediatric patients with inflammatory demyelinating disease of the central nervous system (CNS) and in some patients with neuromyelitis optica spectrum disorder (NMOSD). The aim of this study was to examine the frequency, clinical features, and long-term disease course of patients with anti-MOG antibodies in a European cohort of NMO/NMOSD. Findings: Sera from 48 patients with NMO/NMOSD and 48 patients with relapsing-remitting multiple sclerosis (RR-MS) were tested for anti-aquaporin-4 (AQP4) and anti-MOG antibodies with a cell-based assay. Anti-MOG antibodies were found in 4/17 patients with AQP4-seronegative NMO/NMOSD, but in none of the AQP4-seropositive NMO/NMOSD (n = 31) or RR-MS patients (n = 48). MOG-seropositive patients tended towards younger disease onset with a higher percentage of patients with pediatric (<18 years) disease onset (MOG+, AQP4+, MOG−/AQP4−: 2/4, 3/31, 0/13). MOG-seropositive patients presented more often with positive oligoclonal bands (OCBs) (3/3, 5/29, 1/13) and brain magnetic resonance imaging (MRI) lesions during disease course (2/4, 5/31, 1/13). Notably, the mean time to the second attack affecting a different CNS region was longer in the anti-MOG antibody-positive group (11.3, 3.2, 3.4 years). Conclusions: MOG-seropositive patients show a diverse clinical phenotype with clinical features resembling both NMO (attacks mainly confined to the spinal cord and optic nerves) and MS with an opticospinal presentation (positive OCBs, brain lesions). Anti-MOG antibodies can serve as a diagnostic and maybe prognostic tool in patients with an AQP4-seronegative NMO phenotype and should be tested in those patients.
Journal of Neuroinflammation 05/2015; 12(46). · 5.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study (n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event.
Journal of Neurology 05/2015; 262(7). DOI:10.1007/s00415-015-7758-8 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Most of the studies used a model of aerobic exercise training at moderate intensity in Multiple Sclerosis (MS) patients. However, it has been shown that interval aerobic exercise associated with strength training may be more efficient in several pathologies. The objectives were to determine whether exercise training (i.e. interval aerobic exercise and strength training) may improve: 1) aerobic and strength capacity 2) quality of life 3) the autonomy to exercise. Methods: 13MS patients have already completed the program. A measurement of maximum oxygen consumption and maximal muscle strength of right (RKE) and left knee extensors (LKE) at 90-180 and 240°/s were made before and after training. Exercise training included one aerobic session on cycle ergometer and one session of muscular strengthening during the first 4 weeks, then one session in autonomy was added. Aerobic exercise started by 10 min warm-up, then 5times 1min at 90% of maximal heart rate following by 3 min of recovery at anaerobic threshold. Results: The muscles strength was increased by 18% on LKE and 9% on RKE at 180°/sec. And by 10% on LKE and 7% on RKE at 240°/sec. VO2peak as well as maximal aerobic power were improved following exercise training respectively by 10 and 8%. The SEP-59 self-questionnaire showed that Role limitation-emotional was enhanced by 13%, energy by 7% and emotional well-being by 10%. Conclusion: Combined exercise training 1) improved strength and VO2peak 2) enhanced emotional well-being 3) encouraged the resumption of physical activity in autonomy for patients.
[Show abstract][Hide abstract] ABSTRACT: Following the publication practice guidelines for multiple sclerosis by a group of neurologists (multiple sclerosis study group [GRESEP]), the primary objective of this study was to compare the reality of practice to the guidelines according to the targeted clinical audit (TCA) method. The study was conducted at 17 neurology sites and was administered during two periods of MS care (diagnostic - TCA-DIAG, and disease course - TCA-EVOL). Two complementary surveys were done on the record keeping and the root causes of the deviations. The percentages of compliance ranged from 8 to 98% for the TCA-DIAG, and from 15 to 99% for the TCA-EVOL, with wide disparity between sites. The audits were able to identify causes of the flaws in traceability or accessibility. At the end of the study, despite its limitations, we think that the sharing of the results from different sites provided interesting approaches for the use of the assessment criteria defined by GRESEP in a complete audit cycle. This study is to our knowledge the first report of an experiment in which guidelines were created, and subsequently followed by the development of assessment criteria and then the performance of targeted clinical audits using them, all by the same participants.