Search

The reflection of picosecond ultrasonic pulses from a cell-substrate interface is used to probe cell-biomaterial adhesion with a subcell resolution. We culture monocytes on top of a thin biocompatible Ti metal film, supported by a transparent sapphire substrate. Low-energy femtosecond pump laser pulses are focused at the bottom of the Ti film to a micron spot. The subsequent ultrafast thermal expansion launches a longitudinal acoustic pulse in Ti, with a broad spectrum extending up to 100 GHz. We measure the acoustic echoes reflected from the Ti-cell interface through the transient optical reflectance changes. The time-frequency analysis of the reflected acoustic pulses gives access to a map of the cell acoustic impedance Z c and to a map of the film-cell interfacial stiffness K simultaneously. Variations in Z c across the cell are attributed to rigidity and density fluctuations within the cell, whereas variations in K are related to interfacial intermolecular forces and to the nano-architecture of the transmembrane bonds. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a central nervous system inflammatory disease. Objective: To describe the disease course of CLIPPERS. Design: A nationwide study was implemented to collect clinical, magnetic resonance imaging, cerebrospinal fluid, and brain biopsy specimen characteristics of patients with CLIPPERS. Setting: Academic research. Patients: Twelve patients with CLIPPERS. Main Outcome Measures: The therapeutic management of CLIPPERS was evaluated. Results: Among 12 patients, 42 relapses were analyzed. Relapses lasted a mean duration of 2.5 months, manifested frequent cerebellar ataxia and diplopia, and were associated with a mean Expanded Disability Status Scale (EDSS) score of 4. Besides typical findings of CLIPPERS, magnetic resonance imaging showed brainstem mass effect in 5 patients, extensive myelitis in 3 patients, and closed ring enhancement in 1 patient. Inconstant oligo clonal bands were found on cerebrospinal fluid investigation in 4 patients, with an increased T-cell ratio of CD4 to CD8. Among 7 available brain biopsy specimens, staining was positive for perivascular CD4 T lymphocytes in 5 samples. Thirty-eight of 42 relapses were treated with pulse corticosteroid therapy, which led to improvement, with a mean residual EDSS score of 1.9 (range, 0-7). In 1 patient with untreated relapses, scores on the EDSS progressively increased to a score of 10 at death. Among 5 patients without long-term corticosteroid therapy, the mean annualized relapse rate was 0.5 (range, 0.25-2.8). Among 7 patients taking oral corticosteroids, no relapses occurred in those whose daily dose was 20 mg or higher. No progressive course of CLIPPERS was observed. Four patients with a final EDSS score of 4 or higher had experienced previous severe relapses (EDSS score, ⩾5) and brainstem and spinal cord atrophy. Conclusions: CLIPPERS is a relapsing-remitting disorder without progressive forms. Long-term disability is correlated with the severity of previous relapses. Further studies are needed to confirm that prolonged corticosteroid therapy prevents further relapses. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that intrathecal synthesis of IgM is observed in multiple sclerosis (MS) and correlates with a worse disease course. These results suggest that IgM participates in the formation of MS lesions.Objective: The aim of the present study was to assess the potential association between the level of intrathecal synthesis of IgM measured after a clinically isolated syndrome (CIS) and the subsequent formation of brain lesions.Methods: Fifty seven patients with a CIS and a high risk developing MS were enrolled in a longitudinal study. Examination of cerebrospinal fluid was performed after the CIS and included measures of intrathecal IgM and IgG synthesis. Patients were assessed with the same 1.5 Tesla magnetic resonance imaging (MRI) system at baseline and after a mean follow-up period of 49 months (range 36–60). Spearman Rank correlation was used to assess the potential correlations between levels of intrathecal immunoglobulin synthesis and MRI data.Results: The level of intrathecal IgM synthesis was correlated with the number of gadolinium-enhancing lesions at baseline (p = 0.01) and with accrual of brain lesions during the follow-up period (p = 0.02). By taking into account brain sub-regions, we demonstrated that the level of intrathecal IgM synthesis was only correlated with the increased number of lesions in the periventricular regions (p = 0.004). The level of intrathecal IgG synthesis was not correlated with any MRI data.Conclusion: The present longitudinal study demonstrates that the level of intrathecal IgM synthesis measured after a CIS is associated with subsequent lesion accrual during the first years of MS. This result emphasizes the involvement of IgM in plaque formation. [ABSTRACT FROM AUTHOR]

Background: Few data exist on a possible benign form of neuromyelitis optica (NMO). Objectives: To identify NMO with a good outcome (go-NMO) among a large population of patients and to describe demographic and clinical variables associated with go-NMO vs standard NMO and benign multiple sclerosis. Design: Observational retrospective multicenter study. Setting: Twenty-five medical centers in metropolitan France (MF) and 3 medical centers in the French West Indies (FWI). Patients: A total of 175 patients with NMO were retrospectively analyzed from 2 cohorts: 125 in MF and 50 patients of nonwhite race/ethnicity in the FWI. Patients in MF fulfilled the 2006 NMO criteria, whereas patients in the FWI fulfilled the 1999 or 2006 NMO criteria. Neuromyelitis optica and multiple sclerosis databases were reviewed, and patients with a score of 3 or lower on the Expanded Disability Status Scale after a 10-year follow-up period were considered to have go-NMO. Main Outcome Measures: Clinical, laboratory, and magnetic resonance imaging data and course of disability. Results: In MF, go-NMO was observed in 11 patients, including 3 untreated patients. In the FWI, NMO was severe because of disability related to optic neuritis. Compared with standard NMO, go-NMO was associated with a lower annualized relapse rate (0.3 vs 1.0, P<.01), and 8 of 11 patients with go-NMO showed complete regression of myelitis on magnetic resonance imaging during the disease course. Three patients experienced a disabling attack of NMO after 15 years of follow-up. A good outcome occurred less frequently among patients with NMO than among patients with multiple sclerosis (12.0% vs 22.4%, P=.03). Conclusions: Among patients in MF, go-NMO occurs rarely. However, because a disabling attack may occur after a long follow-up period, a benign form of NMO cannot be defined. [ABSTRACT FROM AUTHOR]

Brain neuronal injury is present in patients suffering from multiple sclerosis (MS) from the earliest stage of the disease; however, the functional counterpart of early neuronal injury is largely unknown. The goal of this study was to assess the potential impact of early neuronal dysfunction affecting white matter (WM), grey matter (GM), or the cerebellum on cognitive deterioration and/or EDSS progression during the first 5 years of MS. Magnetic resonance spectroscopic (MRS) examinations and neuropsychological assessments were performed in 23 patients included after the first clinical attack of MS and 24 healthy controls. The same protocol was performed in patients after a follow-up of 5 years. Metabolic neuronal function was assessed in WM (splenium of corpus callosum), GM (dorsal posterior cingulate cortex), and the cerebellum by evaluating N-acetylaspartate (NAA) levels. During follow-up, 39% of patients showed cognitive deterioration and 43% showed a deterioration in their EDSS. Patients with cognitive deterioration had greater NAA level reductions during follow-up in the cerebellum ( p = 0.003) and WM ( p = 0.02) compared to patients without cognitive deterioration. In addition, patients with cognitive deterioration had higher progression of T2 lesion load (T2LL) during the follow-up period compared to patients without cognitive deterioration ( p = 0.03). No differences between patients with and without EDSS progression in terms of NAA levels or T2LL were observed. The present longitudinal study found evidence that, during the first 5 years of MS, cognitive deterioration is associated with the progression of neuronal dysfunction and tissue injury as assessed by MRS and T2LL, respectively. [ABSTRACT FROM AUTHOR]

Object: While occurrence of motor cortical reorganization has been clearly demonstrated in patients with multiple sclerosis (MS), it is not yet clear whether this cortical reorganization constitutes a response to cortico-spinal lesions or to more diffuse damage affecting the neuronal network involved in motor act preparation, or both. We proposed to investigate the changes in the activation pattern during a simple motor task devoid of cortico-spinal dysfunction occurring in patients with clinically isolated syndrome (CIS) suggestive of MS. Materials and methods: Among 15 right-handed CIS patients, we selected eight patients with a preserved central motor pathway established by motor evoked potentials. Ten healthy right-handed gender- and age-matched volunteers were also included. After morphological MRI, subjects performed calibrated conjugated finger flexion and extension movements during fMRI acquision. Results: In CIS patients, simple movements of the non-dominant hand induced recruitment of the anterior cingulate cortex (BA32) usually involved in complex motor movements. This reorganization was correlated with the diffuse brain tissue damage (brain T lesion load). Conclusion: These results suggest that at least part of the cortical reorganization observed during very simple tasks in the earliest stage of MS occurs whether or not the efferent pathways are intact. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), it seems likely that the variability of the long-term disability might be partly due to the variability of the early gray matter (GM) injury. In the present study, we assessed the variability of GM injury in early MS, using a method designed to determine individual pathological GM patterns. Eighteen patients presenting with a clinically isolated syndrome and 24 healthy matched control subjects were included in this study. Patients were explored using a 1.5 Tesla MR scanner (Magnetom Vision Plus; Siemens). Brain MR protocol included magnetization transfer ratio imaging (MTR). Statistical mapping analyses were performed to compare each subject's GM MTR maps with those of the whole group of control subjects (SPM5). The statistical threshold was taken to be the maximum P value showing no significant cluster when any control individual was compared with the whole control population. GM abnormalities were observed in 83% of the patients, ranging in size from 0.3 to 125 cm3. Among the patients with GM abnormalities, 87% had abnormalities located in the temporal cortex, 80% in the frontal cortex, 80% in the limbic cortex, 73% in the posterior fossa, 53% in the deep GM, 47% in the parietal cortex, and 47% in the occipital cortex. Individual statistical mapping of MTR data, which gives a quantitative assessment of individual GM lesions, demonstrates great variability of grey matter injury in the first stage of multiple sclerosis. J. Magn. Reson. Imaging 2010;32:424-428. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) has considerably improved the diagnosis and monitoring of multiple sclerosis (MS). Conventional MRI such as T2-weighted and gadolinium-enhanced T1-weighted sequences detect focal lesions of the white matter, damage of the blood–brain barrier, and tissue loss and inflammatory activity within lesions. However, these conventional MRI metrics lack the specificity required for characterizing the underlying pathophysiology, especially diffuse damage occurring throughout the whole central nervous system. To overcome these limitations, advanced MRI techniques have been developed to get more sensitive and specific parameters of focal and diffuse brain damage. Among these techniques, magnetization transfer imaging, diffusion MRI, functional MRI, and magnetic resonance spectroscopy are the most significant. In this article, we provide an overview of these advanced MRI techniques and their contribution to the better characterization and understanding of MS. [ABSTRACT FROM AUTHOR]

Abstract: Working memory impairment is frequently observed in patients with early multiple sclerosis (MS). MRI and functional MRI studies have shown that working memory impairment is mostly due to diffuse white matter (WM) damage affecting the connectivity between distant cortical areas. However, working memory deficits in early MS patients can be either completely or partly masked by compensatory functional plasticity. It seems likely that concomitantly with the WM bundle injury resulting from pathological processes, the functional plasticity present in early MS patients may be accompanied by reactive structural WM plasticity. This structural plasticity may effectively compensate for connectivity disturbances and/or contribute to functional brain reorganization. The diffusion characteristics of WM bundles involved in working memory were assessed here by performing quantitative diffusion tensor imaging (DTI) tractography on 24 patients with early relapsing-remitting MS and 15 healthy control subjects. The DTI tractography findings showed that WM connections constituting the executive system of working memory were structurally impaired (the fractional anisotropy was lower than normal and the mean diffusivity, higher than normal). A significantly larger number of connections between the left and right thalami was concurrently observed in the MS patients than in the control subjects, which suggests that the WM is endowed with reactive structural plasticity. [Copyright &y& Elsevier]

Previous MR studies have established that grey matter (GM) atrophy occurs in multiple sclerosis (MS) from clinical onset. However, it is uncertain whether early GM atrophy is global or has certain local predilections: using Voxel-Based Morphometry this study aimed to address this question. Twenty-one patients with early RRMS (mean age 36 years, mean disease duration from symptom onset 25.8 months) and 10 healthy control subjects (mean age 37 years) were studied. T1-weighted three-dimensional MRI images were acquired at baseline and two year follow-up, and analysed with statistical parametric mapping software (SPM2). Two-sample t-tests (p < 0.05 corrected for multiple comparisons at cluster level) were used to compare GM maps from all patients and controls on a voxel-by-voxel basis. At baseline, no GM region appears significantly atrophic in MS subjects compared with controls. However, during the follow-up period significantly greater atrophy occurred in both thalami and the right lateral prefrontal cortex of MS patients when compared with controls. By year two, cross-sectional group comparison revealed GM atrophy in the thalami of MS patients relative to controls. The rate of thalamic atrophy in MS subjects was correlated with changes in EDSS during the follow-up period. This study suggests that early in the clinical course of RRMS, the thalamic atrophy is more consistently apparent than regional cortical atrophy. [ABSTRACT FROM AUTHOR]

Abstract: Following our previous reports based on parametric MRI methods (T2-weighted MRI, statistical mapping analysis of magnetization transfer ratio images and functional MRI) applied to a population of 18 patients with clinically isolated syndrome suggestive of multiple sclerosis, we have reviewed the possible structural and functional surrogates of MS that could explain the subtle cognitive impairment related to attention and working memory deficits evaluated with paced auditory serial addition test (PASAT). We propose that the brain substrates underlying cognitive impairment observed at the very early stage of MS are multifactorial. Several components could influence PASAT performances in patients: i) the extent of diffuse white matter damage, ii) the location of visible and non visible lesions, iii) the connectivity efficiency between distant brain functional areas involved in working memory processes and iv) the cortical reorganization. Nevertheless, individually, each of these parameters may have few influences on PASAT performance in patients. Using a multiregression model built with independent MR parameters, a very good evaluation of PASAT scores has been obtained in this limited number of patients explaining 90% of the variance. In conclusion, the different aspects of tissue and functional pathological brain underpinnings must be accounted to monitor accurately new therapeutic strategies for the treatment of early cognitive deficits related to MS. [Copyright &y& Elsevier]

Abstract: Dysfunction of high controlled information processing is present in patients with multiple sclerosis (MS) right at the beginning of the disease. One hypothesis is that disruption of communication inside large-scale cortical networks, occurring as a consequence of white matter damage, may constitute the anatomical substrate of cognitive impairment at the very early stage of MS. Disturbance of interregional synchronization might be the main pathogenic factor in controlled information processing deficiency in early MS. Preliminary functional MRI studies (fMRI) have provided important clues to corroborate the connectivity hypotheses. First, brain connectivity assessed by fMRI has brought new data about the influence of diffuse white matter damage on connectivity efficiency inside large-scale networks. These studies have suggested that connectivity disturbances occur inside the working memory network in patients at the very early stage of MS and appear related to the extent of structural white matter damage. Also, fMRI studies have suggested that patients may partially compensate for connectivity impairment by a greater cognitive control. Such a compensatory mechanism could limit the determinant functional impact of diffuse white matter damage on high controlled information processing. [Copyright &y& Elsevier]

Functional magnetic resonance imaging (fMRI) using paced auditory serial addition test (PASAT) as paradigm was used to study the functional connectivity in 18 patients at the very early stage of multiple sclerosis (MS) compared with 18 controls, to determine the existence of circuitry disturbance inside the working memory network and its relationship with white matter abnormalities assessed by conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA 45/46 was selected as the seed region to compute correlation maps with other brain regions. After obtaining the correlation map for each subject, between-group comparisons were performed using random effect procedure. Compared with controls, patients did not show any greater functional connectivity between left BA 45/46 and other regions during PASAT. In contrast, decrease in functional connectivity was observed in patients between left BA 45/46 and left BA 9, right BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations were found between altered functional connectivity and clinical data. However, functional connectivity observed between left BA 45/46 and BA 24 in patients was correlated with the MTR of normal appearing white matter, and with brain T2 lesion load. Altered functional connectivity is present inside the working memory network of patients at the very early stage of MS and is related to the extent of diffuse white matter changes.Journal of Cerebral Blood Flow & Metabolism (2005) 25, 1245–1253. doi:10.1038/sj.jcbfm.9600122; published online 20 April 2005 [ABSTRACT FROM AUTHOR]

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT. Hum. Brain Mapping 24:216-228, 2005. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The acoustic field of a homogeneous and isotropic cylinder generated by a laser point source in either ablation or thermoelastic regime is obtained theoretically. A three-dimensional Fourier transform is used to calculate the acoustic displacement at he cylinder surface. Experimental waveforms were measured and analyzed for both regimes. Theoretical normal displacements under either regime are calculated and compared to the experimental signals for aluminum cylinders. Very good agreements are observed in the arrival time, shape, and relative amplitude (i) of the cylindrical Rayleigh waves with different round trips, and (ii) of the various longitudinal and transverse bulk waves propagating through the cylinder or reflected at the free circular surface. [ABSTRACT FROM AUTHOR]

We report on a common-path implementation of conoscopic interferometry in picosecond pump-probe reflectometry for simple and efficient detection of picosecond ultrasounds. The interferometric configuration proposed here is greatly simplified, involving only the insertion of a birefringent crystal in a standard reflectometry setup. Our approach is demonstrated by the optical detection of coherent acoustic phonons propagating through thin metal films under two representative geometries, one a particular case where the crystal slab is part of a sample as substrate of a metal film, and the other a more general case where the crystal slab is independent of the sample as part of the detection system. We first illustrate the former with a 300 nm thin film of polycrystalline titanium, deposited by physical vapor deposition on top of a 1 mm-thick uniaxial (0001) sapphire crystal. A signal-to-noise ratio (SNR) enhancement of more than 15 dB is achieved compared to conventional reflectometry. Next, the general case is demonstrated with a 900 nm-tungsten film sputtered on a silicon wafer substrate. More echoes can be discriminated by using the reported approach compared to standard reflectometry, which confirms the improvement in SNR and suggests broad applications for the reported method. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that cognitive impairment is already present in patients suffering from a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). However, little is known about the course of cognitive impairment after the occurrence of a CIS. In order to characterize the early evolution of cognitive impairment, the authors assessed during a 5-year follow-up period a group of 24 CIS patients with high risk of developing MS. Longitudinal neuropsychological assessment was performed at two time points (baseline and year 5) in patients and controls (baseline and year 1). At year 5, 54% of patients showed cognitive impairment against 29% at baseline. Multiple regression models showed that patients with a higher T2 lesion load at baseline had a higher cognitive impairment at year 5. This longitudinal study performed in CIS patients showed that the frequency of cognitive impairment increases dramatically during the first 5 years following a CIS and that the cognitive status at year 5 was predictable by conventional MRI parameters recorded at baseline. [ABSTRACT FROM AUTHOR]

• Largest study of rituximab in MOG-IgG-associated disorder, includes both adults and children. • Rituximab reduced relapse rates in MOG-IgG-associated disorder by 37%. • Compared to similar studies in AQP4-IgG-associated NMOSD, the efficacy seems lower. • Some patients relapsed despite apparent circulating B-cell depletion. To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3–14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3–24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19–52%, p <0.001) overall, 63% (95%CI=35–79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2–44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+ B -cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

In this work, we show that the use of silica nanoparticles improves the imaging and 3D-morphological measurement down to nanometer thicknesses of fixed cells in solution with picosecond ultrasonics (PU). Synchronized ultrafast fs-laser pulses are used to generate coherent acoustic phonons (CAPs) that evoke the Brillouin light scattering and enable the recording of the time-resolved Brillouin oscillations along with the propagation of the acoustic nanopulses through a thin transparent cell in solution. Silica nanoparticles, whose size matches the phonon wavelength at the frequency of the Brillouin scattering in the solution, are used to strongly scatter the CAPs in the solution. Suppressing the Brillouin signature of the surrounding liquid, this protocol improves significantly the PU imaging and makes it possible to measure the mechanical properties of a transparent cell, including the thin peripheral region where the thickness is less than the Brillouin wavelength, equal to half the probe light wavelength in the cell, and where crucial interaction of the cell with its surroundings occurs. We present experimental evidence of the considerable improvement in the cartography of the entire cell using nanoparticles. The intricate frequency dependence of Brillouin scattering and of resonances for a very thin cell is analyzed using a semi-analytical model leading to the challenging measurement of the 3D-morphology of the immersed cell at thicknesses down to 1 / 9 of the optical wavelength. [ABSTRACT FROM AUTHOR]

Background: The factors underlying the topography of nitrous oxide (N2O)‐induced neurological complications are unknown. Methods: We included all consecutive patients admitted to the university hospital of Marseille for N2O‐induced neurological complications in a prospective observational study. Patients underwent neurological examination, spinal cord magnetic resonance imaging, and nerve conduction studies within the first 4 weeks after admission. Results: In total, 61 patients were included: 45% with myeloneuropathy, 34% with isolated myelopathy, and 21% with isolated neuropathy. On multivariable analysis, the odds of myelopathy were associated with the amount of weekly N2O consumption (~600 g cylinder per week, odds ratio [OR] = 1.11, 95% confidence interval [CI] = 1.001–1.24). The extent of the myelopathy (number of vertebral segments) was correlated with the number of ~600‐g cylinders consumed weekly (ρ = 0.40, p < 0.005). The odds of neuropathy were associated with the duration of consumption (per month; OR = 1.29, 95% CI = 1.05–1.58). Mean lower‐limb motor nerve amplitude was correlated with the duration of consumption (in months; ρ = −0.34, p < 0.05). Conclusions: The odds of myelopathy increased with the amount of N2O consumption, and the odds of neuropathy increased with the duration of N2O exposure, which suggests distinct pathophysiological mechanisms underlying these two neurological complications. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data reveal that 45% of persons with multiple sclerosis (PwMS) in France are more than 50 years. This population more than 50 is more susceptible to cancer, and this risk may be increased by frequent use of immunosuppressive drugs. Consequently, concerns have arisen about the potential increased risk of cancer in PwMS and how patients should be screened and managed in terms of cancer risk. Objective: To develop evidence-based recommendations to manage the coexistence of cancer and multiple sclerosis (MS). Methods: The French Group for Recommendations in MS collected articles from PubMed and university databases covering the period January 1975 through June 2022. The RAND/UCLA method was employed to achieve formal consensus. MS experts comprehensively reviewed the full-text articles and developed the initial recommendations. A group of multidisciplinary health care specialists then validated the final proposal. Results: Five key questions were addressed, encompassing various topics such as cancer screening before or after initiating a disease-modifying therapy (DMT), appropriate management of MS in the context of cancer, recommended follow-up for cancer in patients receiving a DMT, and the potential reintroduction of a DMT after initial cancer treatment. A strong consensus was reached for all 31 recommendations. Conclusion: These recommendations propose a strategic approach to managing cancer risk in PwMS. [ABSTRACT FROM AUTHOR]

Advances in microscopy with new visualization possibilities often bring dramatic progress to our understanding of the intriguing cellular machinery. Picosecond optoacoustic micro‐spectroscopy is an optical technique based on ultrafast pump‐probe generation and detection of hypersound on time durations of picoseconds and length scales of nanometers. It is experiencing a renaissance as a versatile imaging tool for cell biology research after a plethora of applications in solid‐state physics. In this emerging context, this work reports on a dual‐probe architecture to carry out real‐time parallel detection of the hypersound propagation inside a cell that is cultured on a metallic substrate, and of the hypersound reflection at the metal/cell adhesion interface. Using this optoacoustic modality, several biophysical properties of the cell can be measured in a noncontact and label‐free manner. Its abilities are demonstrated with the multiple imaging of a mitotic macrophage‐like cell in a single run experiment. [ABSTRACT FROM AUTHOR]

Background: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) are related to several acquired demyelinating syndromes in adults, but the therapeutic approach is currently unclear. We aimed to describe the response to different therapeutic strategies in adult patients with relapsing MOG-Ab-associated disease.Methods: This is a retrospective study conducted in France and Spain including 125 relapsing MOG-Ab patients aged ≥ 18 years. First, we performed a survival analysis to investigate the relapse risk between treated and non-treated patients, performing a propensity score method based on the inverse probability of treatment weighting. Second, we assessed the annualised relapse rates (ARR), Expanded Disability Status Scale (EDSS) and visual acuity pre-treatment and on/end-treatment.Results: Median age at onset was 34.1 years (range 18.0-67.1), the female to male ratio was 1.2:1, and 96% were Caucasian. At 5 years, 84% (95% confidence interval [CI], 77.1-89.8) patients relapsed. At the last follow-up, 66 (52.8%) received maintenance therapy. Patients initiating immunosuppressants (azathioprine, mycophenolate mophetil [MMF], rituximab) were at lower risk of new relapse in comparison to non-treated patients (HR, 0.41; 95CI%, 0.20-0.82; p = 0.011). Mean ARR (standard deviation) was reduced from 1.05(1.20) to 0.43(0.79) with azathioprine (n = 11; p = 0.041), from 1.20(1.11) to 0.23(0.60) with MMF (n = 11; p = 0.033), and from 1.08(0.98) to 0.43(0.89) with rituximab (n = 26; p = 0.012). Other immunosuppressants (methotrexate/mitoxantrone/cyclophosphamide; n = 5), or multiple sclerosis disease-modifying drugs (MS-DMD; n = 9), were not associated with significantly reduced ARR. Higher rates of freedom of EDSS progression were observed with azathioprine, MMF or rituximab.Conclusion: In adults with relapsing MOG-Ab-associated disease, immunosuppressant therapy (azathioprine, MMF and rituximab) is associated with reduced risk of relapse and better disability outcomes. Such an effect was not found in the few patients treated with MS-DMD. [ABSTRACT FROM AUTHOR]

The original version of this article unfortunately contained a mistake. [ABSTRACT FROM AUTHOR]

Background: Inflammation and demyelination are the main processes in multiple sclerosis. Nevertheless, to date, blood biomarkers of inflammation are lacking. TWEAK, a transmembrane protein that belongs to the TNF ligand family, has been previously identified as a potential candidate.Methods: Twenty-eight patients (9 males, 19 females) were prospectively included after a first clinical episode suggestive of multiple sclerosis and clinically followed during 3 years. Fifty-seven healthy controls were also included. TWEAK serum levels and MRI exams including magnetization transfer imaging were performed at baseline, 6- and 12-month follow-up.Results: TWEAK serum levels were significantly increased in the patient group (mean baseline = 1086 ± 493 pg/mL, mean M6 = 624 ± 302 pg/mL and mean M12 = 578 ± 245 pg/mL) compared to healthy controls (mean = 467 ± 177 pg/mL; respectively p < 0.0001, 0.01 and 0.06). Serum levels of soluble TWEAK were significantly increased during relapses, compared to time periods without any relapse (respectively 935 ± 489 pg/mL and 611 ± 292 pg/mL, p = 0.0005). Moreover, patients presenting at least one gadolinium-enhanced CNS lesion at baseline (n = 7) displayed significantly increased serum TWEAK levels in comparison with patients without any gadolinium-enhanced lesion at baseline (n = 21) (respectively 1421 ± 657 pg/mL vs 975 ± 382 pg/mL; p = 0.02). Finally, no correlation was evidenced between TWEAK serum levels and the extent of brain tissue damage assessed by magnetization transfer ratio.Conclusions: The present study showed that TWEAK serum levels are increased in MS patients, in relation to the disease activity. This simple and reproducible serum test could be used as a marker of ongoing inflammation, contributing in the follow-up and the care of MS patients. Thus, TWEAK is a promising serum marker of the best window to perform brain MRI, optimizing the disease control in patients. [ABSTRACT FROM AUTHOR]

Although multiple sclerosis (MS) is frequently accompanied by visuo‐cognitive impairment, especially functional brain mechanisms underlying this impairment are still not well understood. Consequently, we used a functional MRI (fMRI) backward masking task to study visual information processing stratifying unconscious and conscious in MS. Specifically, 30 persons with MS (pwMS) and 34 healthy controls (HC) were shown target stimuli followed by a mask presented 8–150 ms later and had to compare the target to a reference stimulus. Retinal integrity (via optical coherence tomography), optic tract integrity (visual evoked potential; VEP) and whole brain structural connectivity (probabilistic tractography) were assessed as complementary structural brain integrity markers. On a psychophysical level, pwMS reached conscious access later than HC (50 vs. 16 ms, p <.001). The delay increased with disease duration (p <.001, β =.37) and disability (p <.001, β =.24), but did not correlate with conscious information processing speed (Symbol digit modality test, β =.07, p =.817). No association was found for VEP and retinal integrity markers. Moreover, pwMS were characterized by decreased brain activation during unconscious processing compared with HC. No group differences were found during conscious processing. Finally, a complementary structural brain integrity analysis showed that a reduced fractional anisotropy in corpus callosum and an impaired connection between right insula and primary visual areas was related to delayed conscious access in pwMS. Our study revealed slowed conscious access to visual stimulus material in MS and a complex pattern of functional and structural alterations coupled to unconscious processing of/delayed conscious access to visual stimulus material in MS. [ABSTRACT FROM AUTHOR]

Background: Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal lipid storage disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes. The clinical presentation and evolution of NP-C and the effect of miglustat treatment are described in the largest cohort of patients with adolescent/adult-onset NP-C studied to date.Methods: Observational study based on clinical chart data from adult patients with NP-C (> 18 year old) diagnosed in France between 1990 and 2015. Retrospective data from patients at diagnosis, onset of miglustat therapy (if applicable), and last follow up were analysed.Results: In France, patients with an adolescent-adult neurological form constituted approximately 25% of all NP-C cases diagnosed during the study period. Forty-seven patients (46 with NP-C1 and one with NP-C2; 53% female) were included. Mean ± SD (range) ages at neurological onset and diagnosis were 23.9 ± 12.5 (8-56) years and 34 ± 13.5 (15-65) years, respectively. At presentation, patients mainly had 1) impaired gait due to cerebellar ataxia and/or dystonia, 2) and/or cognitive/behavioural manifestations, 3) and/or psychotic signs. Initially, almost half of patients had only one of the above three neuro-psychiatric manifestations. Vertical supranuclear gaze palsy, usually occurring without patient complaint, was only detected on careful clinical examination and was recorded in most patients (93%) at the time of diagnosis, several years after neurological onset. Thirty-seven patients (79%) received miglustat, among whom seventeen (46%) continued beyond 2 years (at last follow up) to a maximum of 9.8 years. Eight patients (22%) discontinued treatment early due to side effects (n = 3) or perceived lack of efficacy (n = 5).Miglustat treatment duration correlated significantly with reduced neurological worsening (p < 0.001). Treatment for≥2 years was associated with improved patient survival (p = 0.029). Good responses to miglustat were associated with less severe neurological disability at the start of miglustat treatment (p = 0.02).Conclusion: The proportion of adolescent/adult-onset NP-C cases diagnosed in France increased 2.5-fold since 2009 compared with the 2000-2008 period due to improved awareness. Adolescent/adult-onset NP-C frequently presented initially with a non-specific isolated neuro-psychiatric manifestation (motor, cognitive or psychotic). Patients with less severe neurological disability responded better to miglustat therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent studies in adults suggested that extended-interval dosing of rituximab/ocrelizumab (RTX/OCR) larger than 12 months was safe and could improve safety. This was an observational cohort study of very active pediatric-onset multiple sclerosis (PoMS) (median (range) age, 16 (12–17) years) treated with RTX/OCR with 6 month standard-interval dosing (n = 9) or early extended-interval dosing (n = 12, median (range) interval 18 months (12–25)). Within a median (range) follow-up of 31 (12–63) months after RTX/OCR onset, one patient (standard-interval) experienced relapse and no patient showed disability worsening or new T2-weighted lesions. This study suggests that the effectiveness of RTX/OCR is maintained with a median extended-interval dosing of 18 months in patients with very active PoMS. [ABSTRACT FROM AUTHOR]

Background and objective: Myelin-oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) frequently initiates during childbearing years. This study investigated the impact of pregnancy and post-partum on MOGAD activity. Methods: Retrospective analysis of clinical and demographic data from a multicenter French cohort of adult patients with MOGAD. All adult female patients who had a pregnancy after disease onset or in the year before disease onset were included. The annualized relapse rate was evaluated in patients who had a pregnancy after disease onset, to evaluate the impact of pregnancy and post-partum on MOGAD course. Results: Twenty-five informative pregnancies after disease onset were identified. No relapse was recorded during these pregnancies and only three relapses occurred during the first 3 months post-partum. The annualized relapse rate decreased from 0.67 (95% confidence interval: 0.40–1.10) during the pre-pregnancy period to 0 (95% confidence interval: 0–0.21) during pregnancy and to 0.22 (95% confidence interval: 0.09–0.53) during the first year post-partum. Among 144 female patients in their childbearing age recorded in the database, 18 (12.5%) reported their first symptoms during pregnancy or in the 12 months post-partum. Discussion: Our study suggests a marked reduction of MOGAD relapse rate during pregnancy and the post-partum period. Prospective studies on the role of pregnancy and delivery in MOGAD course are needed. [ABSTRACT FROM AUTHOR]

Niemann-Pick disease type C (NP-C) is a fatal progressive neurolipidosis involving neuronal storage of cholesterol and gangliosides. Miglustat, an inhibitor of glycosphingolipid synthesis, has been approved to treat neurological manifestations in adults and children with NP-C. This open-label observational study in adults with confirmed NP-C evaluated the efficacy of miglustat (200 mg t.i.d.) based on composite functional disability (CFD) scores and brain proton magnetic resonance spectroscopy (H-MRS) measurement of choline (Cho)/ N-acetyl aspartate (NAA) ratio in the centrum ovale. Overall, 16 patients were included and received miglustat for a mean period of 30.6 months: 12 continued on miglustat throughout follow up, and 4 discontinued miglustat because of adverse effects ( n = 2) or perceived lack of efficacy ( n = 2). In the 'continued' subgroup, the mean (SD) annual progression of CFD scores decreased from 0.75 (0.94) before treatment to 0.29 (1.29) during the period between miglustat initiation and last follow-up. In the discontinued subgroup, CFD progression increased from 0.48 (0.44) pre-treatment to 1.49 (1.31) at last follow up (off treatment). Mean (SD) Cho/NAA ratio [normal level 0.48 (0.076)] decreased during miglustat treatment in the continued subgroup: 0.64 (0.12) at baseline (miglustat initiation), 0.59 (0.17) at 12-month follow up, and 0.48 (0.09) at 24-month follow up. Cho/NAA ratio remained relatively stable in the discontinued subgroup: 0.57 (0.15), 0.53 (0.04) and 0.55 (0.09), respectively. In conclusion, H-MRS Cho/NAA ratio might serve as an objective, quantitative neurological marker of brain dysfunction in NP-C, allowing longitudinal analysis of the therapeutic effect of miglustat. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients. [ABSTRACT FROM AUTHOR]

Structures made of a metallic film deposited on a substrate are conventionally used as opto-acoustic transducers for picosecond ultrasonic experiments where detection in the time domain of the Brillouin scattering in a transparent sample is sought. In this paper, we substitute the metallic film for a periodic stack of nanometric layers made of gold and lithium fluoride to increase the amplitude, at the Brillouin frequency shift, of the strain generated by the photo-thermal effect. A model is used to analyze the generated strain amplification with the volume fraction and with the total thickness of this structure and to evaluate the gain in terms of sample dynamic reflectivity changes. Amplification by a factor of 20 is measured when using the composite structure with respect to signals detected with a transducer made of a single gold layer. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorder (NMOSD) attacks require an urgent probabilistic anti-inflammatory therapeutic strategy. As inadequately treated attacks result in disability, there is a need to identify the optimal attack-treatment regimen. Our study aimed to identify predictors of outcome after a first attack in patients with an NMOSD presentation and propose the best treatment strategy.Methods: We performed a retrospective cohort study on the French national NMOSD registry (NOMADMUS), a nested cohort of the French multiple sclerosis observatory (OFSEP) recruiting patients with NMOSD presentations in France. We studied the first attack for any independent locations of clinical core characteristic of NMOSD, in treatment-naïve patients. The primary outcome was the evolution of the Expanded Disability Status Scale (EDSS) score at 6 months, stratified in two ways to account for recovery (return to baseline EDSS score) and treatment response (classified as "good" if the EDSS score decreased by ≥ 1 point after a nadir EDSS score ≤ 3, or by ≥ 2 points after a nadir EDSS score > 3). We used ordinal logistic regression to infer statistical associations with the outcome.Results: We included 211 attacks among 183 patients (104 with anti-AQP4 antibodies, 60 with anti-MOG antibodies, and 19 double seronegative). Attack treatment regimens comprised corticosteroids (n = 196), plasma exchanges (PE; n = 72) and intravenous immunoglobulins (n = 6). Complete recovery was reached in 40 attacks (19%) at 6 months. The treatment response was "good" in 134 attacks (63.5%). There was no improvement in EDSS score in 50 attacks (23.7%). MOG-antibody seropositivity and short delays to PE were significantly and independently associated with better recovery and treatment response.Conclusions: We identified two prognostic factors: serostatus (with better outcomes among MOG-Ab-positive patients) and the delay to PE. We, therefore, argue for a more aggressive anti-inflammatory management of the first attacks suggesting an NMOSD presentation, with the early combination of PE with corticosteroids. [ABSTRACT FROM AUTHOR]

Abstract: Background: Acute symptomatic inflammation is a main feature of multiple sclerosis but pathophysiological processes underlying total or partial recovery are poorly understood. Objective: To characterize in vivo these processes at molecular, structural and functional levels using multimodal MR methods. Methods: A neuroimaging 3-year follow-up (Weeks 0, 3, 11, 29, 59 and 169) was conducted on a 41-year-old woman presenting at baseline with a large acute demyelinating lesion of multiple sclerosis. Conventional magnetic resonance imaging (MRI), magnetization transfer imaging, diffusion-weighted imaging, functional MRI and magnetic resonance spectroscopy were conducted at 1.5 T. Results: Patient presenting with subacute left hemiplegia recovered progressively (expended disability status scale 7 to 5.5). The MR exploration demonstrated structural functional and metabolic impairments at baseline. Despite restoration of the blood brain barrier integrity, high lactate levels persisted for several weeks concomitant with glial activation. Slow and progressive structural and metabolic restorations occurred from baseline to W169 (lesion volume −64%; apparent diffusion coefficient −14.7%, magnetization transfer ratio +14%, choline −51%, lipids −78%, N-acetylaspartate +77%) while functionality of the motor system recovered. Conclusions: Multimodal MRI/MRS evidenced long-term dynamics recovery processes involving tissue repair, glial activation, recovery of neuronal function and functional systems. This may impact on customized rehabilitation strategies generally focused on the first months following the onset of symptoms. [Copyright &y& Elsevier]

Abstract: Periventricular white matter damage affecting large bundles connecting distant cortical areas may constitute the main neuronal mechanism for the deficit of controlled information processing observed in patients with early multiple sclerosis (MS). Visual backward masking has been demonstrated to affect late stages of conscious perception involving long-range interactions between visual perceptual areas and higher level integrative cortices while leaving intact early feed-forward visual processing and even complex processing such as object recognition or semantic processing. We therefore hypothesized that patients with early MS would have an elevated masking threshold, because of an impairment of conscious perception whereas subliminal processing of masked stimuli would be preserved. Twenty-two patients with early MS and 22 normal controls performed two backward-masking experiments. We used Arabic digits as stimuli and varied quasi-continuously the temporal interval with a subsequent mask, thus allowing us to progressively “unmask” the stimuli. We finely quantified the visibility of the masked stimuli using both objective and subjective measures, thus obtaining accurate estimates of the threshold duration for access to consciousness. We also studied the priming effect caused by the variably masked numbers on a comparison task performed on a subsequently presented and highly visible target number. The threshold for access to consciousness of masked stimuli was elevated in MS patients compared to controls, whereas non-conscious processing of these stimuli, as measured by priming, was preserved. These findings suggest that conscious access to masked stimuli depends on the integrity of large-scale cortical integrative processes, which involve long-distance white matter projections, and are impaired due to diffuse demyelinating injury in patients with early MS. [Copyright &y& Elsevier]

Objective: As phase III trials have shown interest in innovative but expensive drugs in the treatment of neuromyelitis optica spectrum disorder (NMOSD), data are needed to clarify strategies in the treatment of neuromyelitis optica (NMO). This meta‐analysis compares the efficacy of first‐line strategies using rituximab (RTX), mycophenolate mofetil (MMF), or azathioprine (AZA), which are still widely used. Methods: Studies identified by the systematic review of Huang et al. (2019) were selected if they considered at least two first‐line immunosuppressants among RTX, MMF, and AZA. We updated this review. The Medline, Cochrane Central Register of Controlled Trials, Embase, and ClinicalTrials databases were queried between November 2018 and April 2020. To be included, the hazard ratio (HR) [95% CI] for the time to first relapse after first‐line immunosuppression had to be available, calculable, or provided by the authors. Results: We gathered data from 919 NMO patients (232 RTX‐, 294 MMF‐, and 393 AZA‐treated patients). The risk of first relapse after first‐line immunosuppression was 1.55 [1.04, 2.31] (p = 0.03) for MMF compared with RTX, 1.42 [0.87, 2.30] (p = 0.16) for AZA compared with RTX, and 0.94 [0.58, 1.54] (p = 0.08) for MMF compared with AZA. Interpretation: The findings suggest that RTX is more efficient than MMF as a first‐line therapy. Even if the results of our meta‐analysis cannot conclude that RTX has a better efficacy in delaying the first relapse than AZA, the observed effect difference between both treatments combined with the results of previous studies using as outcome the annualized relapse rate may be in favor of RTX. [ABSTRACT FROM AUTHOR]

Background and objective: The prognosis in myelin oligodendrocyte glycoprotein (MOG) antibody‐associated disease (MOGAD) is a matter of debate. Our aim was to assess the long‐term outcomes of patients with MOGAD. Methods: We retrospectively analysed the clinical and paraclinical data of patients from the French nationwide observatory study NOMADMUS who tested positive for MOG antibodies (MOG‐IgG) and who had clinical follow‐up of at least 8 years from their first episode. Results: Sixty‐one patients (median [range] age at onset 27 [3–69] years), with a median (mean; range) follow‐up of 177 (212.8; 98–657) months, were included. Among 58 patients with a relapsing course, 26.3% relapsed in the first year after onset. Of the 61 patients, 90.2% experienced at least one episode of optic neuritis. At last visit, the median (mean; range) Expanded Disability Status Scale (EDSS) score was 1 (2.12; 0–7.5), 12.5% had an EDSS score ≥6 and 37.5% had an EDSS score ≥3. Of 51 patients with final visual acuity (VA) data available, 15.7% had VA ≤0.1 in at least one eye and 25.5% had VA ≤0.5 in at least one eye. Bilateral blindness (VA ≤0.1) was present in 5.9% of patients. Finally, 12.5% of patients presented bladder dysfunction requiring long‐term urinary catheterization. No factor associated significantly with a final EDSS score ≥3 or with final VA ≤0.1 was found. Conclusion: Overall long‐term favourable outcomes were achieved in a majority of our patients, but severe impairment, in particular visual damage, was not uncommon. [ABSTRACT FROM AUTHOR]

Background: Planning pregnancy in patients with active multiple sclerosis (MS) is highly challenging because treatment withdrawn may be associated with dramatic disease reactivation. Objective: To compare two strategies for women with active MS who were planning pregnancy: stopping natalizumab (1) at the end of the first trimester and (2) at conception. Methods: Standardized strategy for women with active MS was initiated in our department. Maintenance of natalizumab until the end of first trimester was recommended ("secured first trimester" (SFT)). When patients refused, they were advised to continue until conception ("secured conception" (SC)). Predictors of disease activity during pregnancy were assessed. Results: Forty-six pregnancies were prospectively followed (30 with SFT and 16 with SC). One congenital anomaly occurred in the SC group. The proportions of patients with relapse and disability progression during pregnancy were lower in the SFT than in the SC group (3.6% vs 38.5%, p < 0.005 and 3.6% vs 30.8%, p < 0.05, respectively). Predictors of relapse and disability progression during pregnancy were the time when natalizumab was stopped (conception vs end of first trimester) and the number of relapses during the year before natalizumab. Conclusion: Maintaining natalizumab during the first trimester may reduce the risk of disease reactivation during pregnancy in patients with active MS. [ABSTRACT FROM AUTHOR]