Search

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis. ispartof: Acta Neurologica Belgica vol:118 issue:2 pages:161-168 ispartof: location:Italy status: published

Objective:To investigate the effect of chronic comorbidity on the time of diagnosis of multiple sclerosis (MS) and on mortality in MS.Methods:We conducted a population-based, nationwide cohort study including all incident MS cases in Denmark with first MS symptom between 1980 and 2005. To investigate the time of diagnosis, we compared individuals with and without chronic comorbidity using multinomial logistic regression. To investigate mortality, we used Cox regression with time-dependent covariates, following study participants from clinical MS onset until endpoint (death) or to the end of the study, censuring at emigration.Results:We identified 8,947 individuals with clinical onset of MS between 1980 and 2005. In the study of time of diagnosis, we found statistically significant odds ratios for longer diagnostic delays with cerebrovascular comorbidity (2.01 [1.44–2.80]; Conclusions:An increased awareness of both the necessity of neurologic evaluation of new neurologic symptoms in persons with preexisting chronic disease and of optimum treatment of comorbidity in MS is critical.

Submitted by Dulce Barreto (mdulce.barreto@chlc.min-saude.pt) on 2017-03-30T11:38:17Z No. of bitstreams: 1 Acta Med Port 2016_29_419.pdf: 245517 bytes, checksum: 54bcb833d184e2fdcbaade5d3c204bec (MD5) Made available in DSpace on 2017-03-30T11:38:17Z (GMT). No. of bitstreams: 1 Acta Med Port 2016_29_419.pdf: 245517 bytes, checksum: 54bcb833d184e2fdcbaade5d3c204bec (MD5) Previous issue date: 2016-08 info:eu-repo/semantics/publishedVersion

The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.

Since its initial reports in the 19th century, neuromyelitis optica (NMO) had been thought to involve only the optic nerves and spinal cord. However, the discovery of highly specific anti-aquaporin-4 antibody diagnostic biomarker for NMO enabled recognition of more diverse clinical spectrum of manifestations. Brain MRI abnormalities in patients seropositive for anti-aquaporin-4 antibody are common and some may be relatively unique by virtue of localization and configuration. Some seropositive patients present with brain involvement during their first attack and/or continue to relapse in the same location without optic nerve and spinal cord involvement. Thus, characteristics of brain abnormalities in such patients have become of increased interest. In this regard, MRI has an increasingly important role in the differential diagnosis of NMO and its spectrum disorder (NMOSD), particularly from multiple sclerosis. Differentiating these conditions is of prime importance because early initiation of effective immunosuppressive therapy is the key to preventing attack-related disability in NMOSD, whereas some disease-modifying drugs for multiple sclerosis may exacerbate the disease. Therefore, identifying the MRI features suggestive of NMOSD has diagnostic and prognostic implications. We herein review the brain, optic nerve, and spinal cord MRI findings of NMOSD.

Introduction. Local microstructural pathology in multiple sclerosis patients might influence their clinical performance. This study applied multicontrast MRI to quantify inflammation and neurodegeneration in MS lesions. We explored the impact of MRI-based lesion pathology in cognition and disability.Methods. 36 relapsing-remitting MS subjects and 18 healthy controls underwent neurological, cognitive, behavioural examinations and 3 T MRI including (i) fluid attenuated inversion recovery, double inversion recovery, and magnetization-prepared gradient echo for lesion count; (ii) T1, T2, and T2*relaxometry and magnetisation transfer imaging for lesion tissue characterization. Lesions were classified according to the extent of inflammation/neurodegeneration. A generalized linear model assessed the contribution of lesion groups to clinical performances.Results. Four lesion groups were identified and characterized by (1) absence of significant alterations, (2) prevalent inflammation, (3) concomitant inflammation and microdegeneration, and (4) prevalent tissue loss. Groups 1, 3, 4 correlated with general disability (Adj-R2=0.6;P=0.0005), executive function (Adj-R2=0.5;P=0.004), verbal memory (Adj-R2=0.4;P=0.02), and attention (Adj-R2=0.5;P=0.002).Conclusion. Multicontrast MRI provides a new approach to inferin vivohistopathology of plaques. Our results support evidence that neurodegeneration is the major determinant of patients’ disability and cognitive dysfunction.

Summary Aim : To evaluate vestibular evoked myogenic potentials in patients with multiple sclerosis as method of diagnostic support. Study design Case-control. Material and Method We studied a group of normal individuals (n = 15) and a Studied group (n = 15) that comprised patients with diagnosis of multiple sclerosis. Both groups were submitted to vestibular evoked myogenic potential exam. In each ear it was applied 200 stimuli by clicks and repeated for 2 consecutive cycles with the purpose of evaluating reproducibility. The active electrode of surface was put on the superior S‡of sternocleidomastoid muscle and the reference electrode on the anterior border of the clavicle. The individuals were instructed to rotate theirs head to the opposite side to the stimulated ear. Results Vestibular evoked myogenic potential responses were prompt, reproducible and biphasic. The latency of wave P1 and N2 and P1-N2 amplitude showed a higher value in the studied group when compared with the normal group. There was no significant difference when the ears were compared in P1 and N2 amplitude. We noticed that individuals with multiple sclerosis showed no response in 30% of the cases. In evaluating the individuals of the Studied group with otoneurology symptoms and compared with individuals without symptoms, it was observed that P1 and N2 latencies and P1-N2 amplitude were higher in symptomatic cases. Conclusion Vestibular evoked myogenic potential was considered a good method of diagnostic support of vestibulospinal tract in cases of multiple sclerosis.

BACKGROUND: Animal studies have suggested that drugs inhibiting the enzyme histone deacetylase might have a beneficial effect on multiple sclerosis (MS). Valproic acid (VPA), an anti-epileptic drug, is the only widely used human drug with a histone deacetylase inhibitory effect.OBJECTIVE: The objective of this paper is to examine if VPA use is associated with a reduced risk of MS.METHODS: We conducted a propensity score-matched cohort study in the period 1997-2011 linking nationwide register data on filled VPA prescriptions, MS cases, and several covariates. The VPA users were matched on propensity scores in a 1:4 ratio with non-users of VPA. Incidence rates of MS were compared among VPA users and non-users of VPA using Cox regression to estimate hazard ratios (HRs).RESULTS: Among 16 028 ever-users of VPA and 54 172 non-users, 18 and 26 cases of MS were identified, respectively. Neither current VPA users nor recent users of VPA, who had ceased VPA treatment within the last year, were at a reduced risk of MS compared with non-users of VPA (HR = 1.30 (95% confidence interval, 0.44-3.80), n = 4, and HR = 1.22 (0.28-5.32), n = 2, respectively). Similarly, in an intention-to-treat analysis, ever-users of VPA were not at reduced risk of MS (HR = 2.41 (1.32-4.43), n = 18).CONCLUSION: In the first human study addressing a possible beneficial effect of VPA use on the risk of MS, we found no support for a protective effect. However, given the wide confidence intervals, only large effects can be ruled out with sufficient certainty. Copyright © 2014 John Wiley & Sons, Ltd.

Optic nerve neuritis is one of the most important differential diagnoses of visual loss in young and middle aged adults. The prognosis in terms of functional outcome is generally good. The diagnosis of optic neuritis is clinical. Steroids can reduce the recovery time but do not affect the long-term functional outcome. Magnetic resonance imaging (MRI) is the most important investigation for assessing an associated risk of multiple sclerosis. Optical coherence tomography (OCT) contributes additional details on the course and functional outcome of optic neuritis. In the future OCT may additionally contribute to the relationship between optic neuritis and possible associated multiple sclerosis.

To examine the feasibility and value of 7 T 3D T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) and Double Inversion Recovery (DIR) MR sequences for lesion detection in multiple sclerosis (MS). High-resolution 3D-FLAIR and 3D-DIR MR sequences at 7 T were obtained using magnetisation preparation (MP), and compared with 2D-T2-weighted and 3D-T1-weighted sequences in 10 MS patients and five healthy controls. We determined contrast ratios and counted lesions according to anatomical location. MR imaging at 7 T was safe and allowed multi-contrast imaging within clinically acceptable imaging times. Lesion to white matter (WM) and grey matter (GM) contrast ratios were higher in 3D-MP-FLAIR and 3D-MP-DIR compared with 2D-T2 and 3D-T1. Cortical (mixed+intra-cortical) and total lesion counts were 97/592 on 3D-MP-FLAIR and 100/558 on 3D-MP-DIR compared with 84/384 on 2D-T2 and 42/442 on 3D-T1. More juxta-cortical lesions were seen with 3D-MP-FLAIR (205) and 3D-MP-DIR (133) than with 2D-T2 (125) and 3D-T1 (70). Finally, higher numbers of lesions were found for deep WM lesions: 176 for 3D-MP-FLAIR and 196 for 3D-MP-DIR vs. 155 for 2D-T2 and 131 for 3D-T1. Near isotropic 3D-MP-FLAIR and 3D-MP-DIR allows high quality T2-weighted MR imaging in MS at 7 T, improving (cortical) lesion detection. Key Points • Magnetization prepared 3D-FLAIR and 3D-DIR 7 T MRI provide high quality isotropic images. • MS lesions are well demonstrated by 3D-MP-FLAIR and 3D-MP-DIR at 7 T MRI. • 3D-MP-FLAIR and 3D-MP-DIR at 7 T MRI show many more Virchov-Robin spaces.

Langerhans cell histiocytosis (LCH) with multiple organ involvement is a rare disorder in adults. Extrapituitary involvement of the central nervous system (CNS) is uncommon. We report the unusual case of a 55-year-old woman presenting with a left-sided hemiataxia-hemiparesis, left hemisensory loss and short-lasting episodes of an alien left hand due to lesions of the internal capsule and the right thalamus, extending into the mesencephalon associated with extensive surrounding edema, without pituitary involvement. The neuroradiological image suggested glioblastoma multiforme. Brain biopsy revealed inflammatory tissue and "pseudotumoral" multiple sclerosis was suspected. Biopsy of concomitant lung and bone lesions disclosed Langerhans cell histiocytosis. The treatment with pulsed steroids in association with mycophenolate mofetil led to a sustained, clinical neurological remission.

We studied 200 female patients with multiple sclerosis (MS) to investigate whether pregnancy after the onset of disease influences long term disability. As an index of progression, we used the time between disease onset and wheelchair dependence. Patients who had at least one pregnancy after onset were wheelchair dependent after 18.6 years, versus 12.5 years for the other women (P < 0.0001). This difference remains statistically significant after correction for age at onset of disease.

Background The prognostic value of evoked potentials (EPs) in multiple sclerosis (MS) has not been fully established. The correlations between the Expanded Disability Status Scale (EDSS) at First Neurological Evaluation (FNE) and the duration of the disease, as well as between EDSS and EPs, have influenced the outcome of most previous studies. To overcome this confounding relations, we propose to test the prognostic value of EPs within an appropriate patient population which should be based on patients with low EDSS at FNE and short disease duration. Methods We retrospectively selected a sample of 143 early relapsing remitting MS (RRMS) patients with an EDSS < 3.5 from a larger database spanning 20 years. By means of bivariate logistic regressions, the best predictors of worsening were selected among several demographic and clinical variables. The best multivariate logistic model was statistically validated and prospectively applied to 50 patients examined during 2009–2011. Results The Evoked Potentials score (EP score) and the Time to EDSS 2.0 (TT2) were the best predictors of worsening in our sample (Odds Ratio 1.10 and 0.82 respectively, p=0.001). Low EP score (below 15–20 points), short TT2 (lower than 3–5 years) and their interaction resulted to be the most useful for the identification of worsening patterns. Moreover, in patients with an EP score at FNE below 6 points and a TT2 greater than 3 years the probability of worsening was 10% after 4–5 years and rapidly decreased thereafter. Conclusions In an appropriate population of early RRMS patients, the EP score at FNE is a good predictor of disability at low values as well as in combination with a rapid buildup of disability. Interestingly, an EP score at FNE under the median together with a clinical stability lasting more than 3 years turned out to be a protective pattern. This finding may contribute to an early identification of benign patients, well before the term required to diagnose Benign MS (BMS).