Identification of demyelinating lesions and application of McDonald criteria when confronted with white matter lesions on brain MRI.

INTRODUCTION: White matter lesions (WML) on magnetic resonance imaging (MRI) are common in clinical practice. When analyzing WML, radiologists sometimes propose a pathophysiological mechanism to explain the observed MRI abnormalities, which can be a source of anxiety for patients. In some cases, discordance may appear between the patient's clinical symptoms and the identification of the MRI-appearing WML, leading to extensive diagnostic work-up. To avoid misdiagnosis, the analysis of WML should be standardized, and a consensual MRI reading approach is needed. OBJECTIVE: To analyze the MRI WML identification process, associated diagnosis approach, and misinterpretations in physicians involved in WML routine practice. METHODS: Through a survey distributed online to practitioners involved in WML diagnostic work-up, we described the leading causes of MRI expertise misdiagnosis and associated factors: clinical experience, physicians' subspecialty and location of practice, and type of device used to complete the survey. The survey consisted of sixteen T2-weighted images MRI analysis, from which ten were guided (binary response to lesion location identification), four were not shown (multiple possible answers), and two were associated with dissemination in space (DIS) McDonald criteria application. Two independent, experienced practitioners determined the correct answers before the participants' completion. RESULTS: In total, 364 participants from the French Neuro Radiological (SFNR), French Neurological (SFN), and French Multiple Sclerosis (SFSEP) societies completed the survey entirely. According to lesion identification, 34.3% and 16.9% of the participants correctly identified juxtacortical and periventricular lesions, respectively, whereas 56.3% correctly identified non-guided lesions. Application of the 2017 McDonald's DIS criteria was correct for 35.3% of the participants. According to the global survey scoring, factors independently associated with correct answers in multivariate analysis were MS-expert subspecialty (P<0.001), young clinical practitioners (P=0.02), and the use of a computer instead of a smartphone to perform WML analysis (P=0.03). CONCLUSION: Our results highlight the difficulties regarding WML analysis in clinical practice and suggest that radiologists and neurologists should rely on each other to ensure the diagnosis of multiple sclerosis and related disorders and limit misdiagnoses.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

Infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society.

INTRODUCTION: Viral, bacterial, or fungal infections are suspected of triggering multiple sclerosis (MS) and promoting relapses of the disease and are likely to be promoted by immune-active treatments. This raises questions about the infectious workup and preventive treatment of these infections prior to their initiation. OBJECTIVES: To establish recommendations on infections and MS. Provide information to patients and healthcare professionals on the minimal infectious workup to be performed in an MS patient at diagnosis and prior to initiation of immuno-active therapy in MS. METHODS: The recommendation attempts to answer four main questions about infections and MS. The French Group for Recommendations in Multiple Sclerosis (France4MS) did a systematic review of articles from PubMed and universities databases (from January 1975 to June 2020), using the RAND/UCLA formalized consensus method. The RAND/UCLA method has been developed to synthesize the scientific literature and expert opinions on health care topics and was used for reaching a formal agreement. Twenty-three experts contributed to the detailed review and a group of 63 multidisciplinary health professionals validated the final version of 36 recommendations. RESULTS: It is recommended that MS patients undergo a minimal infectious workup, check their vaccination status at diagnosis, and repeat it during follow-up and before starting immunotherapy. Screening and preventive treatment of viral (group Herpes virus, HPV, JCV, HCV, HBV), bacterial (mycobacteria) and fungal (Cryptococcus) infections is recommended prior to the initiation of certain immuno-active MS therapies. DISCUSSION AND CONCLUSIONS: At diagnosis of MS and prior to the choice of therapeutic strategy, it is recommended to update the vaccination schedule of MS patients in reference to the HCSP vaccination schedule and the SFSEP recommendations. Before starting immunosuppressive treatment, it is recommended to inform patients of the risks of infections and to look for a constitutive or acquired immune deficiency. Health professionals and patients should be informed of the updated recommendations on infections and MS.

Alexithymia in multiple sclerosis: Clinical and radiological correlations.

BACKGROUND: Alexithymia, meaning no words for emotions is a common problem that could affect up to 53% of patients in multiple sclerosis (MS). OBJECTIVES: To determine the frequency of alexithymia in MS and investigate MS-related abnormalities in structural magnetic resonance imaging (MRI) and their associations with fatigue and cognitive functions. METHODS: Ninety-five patients at all stages of the disease were examined: 21 with clinically isolated syndromes (CIS), 30 with relapsing-remitting MS (RRMS), 21 with primary (PP) and 23 with secondary progressive MS (SPMS). Alexithymia was measured with the Toronto alexithymia scale (TAS-20) and correlated to cognitive functions, depression, and fatigue. Voxel-based morphometry MRI was analyzed to determine lesion load, cerebral and regional atrophy. RESULTS: Fifty-seven of patients had alexithymia with no significant difference between the clinical phenotypes. Alexithymic patients differed from non-alexithymic patients on fatigue, depression and information processing speed. Compared to non-alexithymic patients, alexithymic patients had decreased volumes of cerebral and cerebellar white matter and there was a significant relationship between alexithymia and decreased brainstem, thalamic and corpus callosum volume. CONCLUSION: Regardless of the phenotype of MS, alexithymia is associated with atrophy of cerebral and cerebellar white matter, brainstem, corpus callosum, and thalami.

Pregnancy with multiple sclerosis.

Multiple sclerosis (MS) is usually diagnosed between twenty and forty years of age, when people often plan to have children. A lot has been said about the effect of pregnancy on the course of MS. The individual factors responsible for the disease modifying effect of pregnancy are not well determined. Having MS neither affects the fertility or the course of pregnancy itself. During pregnancy, many women find that their symptoms stay the same or even improve. Epidural and spinal analgesia appear to be safe and in general are not contraindicated for patients with MS. The management of disease-modifying treatments (DMTs) in pregnancy is a new issue for consideration in the clinical practice. There is limited information available into the safety of DMT use during pregnancy, especially for the most recent ones. In general, discontinuation of DMTs is recommended before conception to minimize risk of fetal harm. Women with very active MS before pregnancy who stop second-line treatments may show an increase in disease activity during pregnancy. Therefore, it might be discussed to maintain patients on DMTs until pregnancy is confirmed, and sometimes throughout pregnancy, to avoid a rebound of disease activity and severe relapses during pregnancy in very active patients.

Urinary tract infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society.

OBJECTIVES: Establish recommendations for the management of UTIs in MS patients. BACKGROUND: Urinary tract infections (UTIs) are common during multiple sclerosis (MS) and are one of the most common comorbidities potentially responsible for deaths from urinary sepsis. METHODS: The recommendations attempt to answer three main questions about UTIs and MS. The French Group for Recommendations in MS (France4MS) did a systematic review of articles from PubMed and universities databases (01/1980-12/2019). The RAND/UCLA appropriateness method, which has been developed to synthesize the scientific literature and expert opinions on health care topics, was used for reaching a formal agreement. 26 MS experts worked on the full-text review and a group of 70 multidisciplinary health care specialists validated the final evaluation of summarized evidences. RESULTS: UTIs are not associated with an increased risk of relapse and permanent worsening of disability. Only febrile UTIs worsen transient disability through the Uhthoff phenomenon. Some immunosuppressive treatments increase the risk of UTIs in MS patients and require special attention especially in case of hypogammaglobulinemia. Experts recommend to treat UTIs in patients with MS, according to recommendations of the general population. Prevention of recurrent UTIs requires stabilization of the neurogenic bladder. In some cases, weekly oral cycling antibiotics can be proposed after specialist advice. Asymptomatic bacteriuria should not be screened for or treated systematically except in special cases (pregnancy and invasive urological procedures). CONCLUSION: Physicians and patients should be aware of the updated recommendations for UTis and MS.

Thalamic atrophy correlates with dysfunctional impulsivity in multiple sclerosis.

BACKGROUND: Recent studies highlight the central role of thalamic atrophy in Multiple Sclerosis (MS) related disorders. Behavioural aspects of (MS) are rarely explored but their investigation is of high interest. Dickman's Impulsiveness Inventory (DII) allows distinguishing functional impulsivity (FI) which is the ability to react fast and properly when necessary, from dysfunctional impulsivity (DI) which is a behavioural symptom corresponding to the tendency to miss forethought before acting. OBJECTIVE: This paper aims to explore whether MS patients show significantly high and pathological DI, and to evaluate the impulsivity frequency in the different forms of MS including at the early stage of the Clinically Isolated Syndrome. Furthermore, this study focused on the factors that may induce abnormal impulsivity, and the link between thalamic atrophy and dysfunctional impulsivity in patients with MS. METHODS: 95 patients with demyelinating diseases including 21 Clinically Isolated Syndrome (CIS), 30 Relapsing-Remitting MS (RRMS), 23 Secondary Progressive MS (SPMS) and 21 Primary Progressive MS (PPMS) were prospectively recruited, and covered by extensive cognitive evaluation including the BCCogSEP (French version of the Brief Repeatable Battery for Neurological disease), the CSCT (Computerized Speed Cognitive Test) for processing speed of information (PSI), the DII to measure FI and DI, the Fast BDI to evaluate depression, and the EMIF-SEP scale to study physical, cognitive and social fatigues. 3D T2-FLAIR and 3D T1-weighted MRI were analyzed using automatic segmentation tools to quantify the T2 lesion load and to measure the whole and regional brain atrophy. RESULTS: 7% showed a pathologically high DI. The level of DI tended to differ significantly depending on the MS phenotype. There was no significant difference between RRMS, SPMS and PPMS, but RRMS showed significantly higher DI than CIS patients. Cognitive fatigue (r:-0.27, p<.01), depression (r:-0.21, p=.04) but mainly PSI (r:.33, p<.001) showed a significant correlation with DI. Among the brain regions of interest, the strongest significant correlation with DI was with thalamic atrophy (r:.33, p<.001). CONCLUSION: Some MS patients show a pathologically high DI, mainly RRMS compared to CIS. Previous study highlighted impulsive traits in MS patients only in relation with the presence of depression. The present study demonstrates that depression tends to correlate with DI, but that cognitive fatigue, and mainly slowing of PSI, which is the most early and severe cognitive impairment in MS, have a stronger impact on the rise of pathological impulsive behaviour. DI in MS is linked to frontal regions but even more strongly to thalamus atrophy. This is in line with the hypothesis of a disconnection syndrome in MS that causes cognitive impairment to trigger and could have the same impact on behaviour. Hence, impulsive behaviour should be evaluated and taken into account in the care of patients with MS.

Video-oculography in multiple sclerosis: Links between oculomotor disorders and brain magnetic resonance imaging (MRI).

BACKGROUND: Eye movement abnormalities (EMA) are common in multiple sclerosis (MS). However, type and severity according to the MS stage are poorly known, especially in Radiologically Isolated Syndrome (RIS) and in Clinically Isolated Syndrome (CIS). Although MRI has been included in the MS diagnostic criteria, there may be clinical-radiological dissociation. OBJECTIVE: To analyze by video-oculography (VOG) prevalence of EMA in different MS phenotypes and study correlations with brain and cervical cord MRI T2 lesions location. METHODS: 76 participants were prospectively recruited (12 RIS, 10 CIS, 11 relapsing-remitting-MS, 10 secondary progressive-MS, 10 primary progressive MS and 23 gender and age-matched healthy controls). We analyzed fixations, anti-saccades, horizontal and vertical reflex saccades and smooth pursuit. RESULTS: EMA were frequent and of gradual severity from RIS to progressive forms. Internuclear ophthalmoplegia (INO) and centripetal hypermetria were strong arguments for the diagnosis of a demyelinating disorder versus a control population. Some EMA were linked to infratentorial T2 lesion location, but others like INO were not. CONCLUSION: This study confirm that EMA are common in all MS phenotypes, even at the earliest stages. VOG can be useful to detect demyelinating process at preclinical stage by highlighting subclinical EMA even in absence of characteristic lesions visible on MRI.

Infectious myelitis.

Infectious pathogens can directly affect the spinal cord or trigger autoimmune reactions, which may result in permanent damage to cord structures. The most common aetiology comes from virus but depend on age, location of the patient and co-morbidities. Acute Flaccid paralysis and acute transverse myelitis are considered as emergencies. Differential diagnosis is mainly relapses of autoimmune diseases, which can mimic infectious myelopathies.

Multiple immune disorders after natalizumab discontinuation: After the CIRIS, the SIRIS?

Natalizumab (NTZ) is an effective treatment for patients with highly active relapsing remitting multiple sclerosis (MS). However, when the therapy must be interrupted, it is important to anticipate the withdrawal to avoid reactivation or disease rebound. Described here is the case of a 35-year-old woman, with a past history of beta thalassemia, bulimia and asthma, who was diagnosed with MS at age 26. She was treated initially with first-line subcutaneous (sc) immunomodulatory treatments. However, due to liver toxicity, interferon beta-1a sc was interrupted and replaced by glatiramer acetate treatment, which was well tolerated and used for several years. Unfortunately, disease progression with numerous relapses and contrast enhancement on brain MRI led to initiation of NTZ treatment. After more than 2 years of treatment, NTZ was interrupted because of pregnancy, and the patient was again put on glatiramer acetate. Eight weeks after interruption of NTZ therapy, the first signs of diabetes were observed, together with an increase in blood levels of hepatic enzymes, skin reactions such as angioedema and giant urticaria, and hypothyroidism requiring hormone supplementation. The patient delivered her baby without complications, and NTZ was reintroduced several months later. At the present time, the patient's hypothyroidism, diabetes and increased blood levels of hepatic enzymes persist, although no new skin reactions have been observed. Withdrawal of NTZ can not only lead to reactivation of the disease or its rebound, but also to autoimmune manifestations within the framework of immune reconstitution inflammatory syndrome (IRIS). This risk needs to be considered when therapy has to be interrupted, especially when a personal and/or familial past history of autoimmune disease is present.

A decreasing CD4/CD8 ratio over time and lower CSF-penetrating antiretroviral regimens are associated with a higher risk of neurocognitive deterioration, independently of viral replication.

Persistent immune activation is one of the suspected causes of HIV-associated neurocognitive disorders (HAND) in cART era. The CD4/CD8 ratio has been recently showed as a marker of immune activation and HAND. Our aim was to analyze if a decrease in the CD4/CD8 ratio over time could have an impact on neurocognitive deterioration. Randomly selected HIV-infected patients were followed for neuropsychological (NP) testing during a period of almost 2 years. Tests were adjusted for age, gender, and education. Patients were divided into 5 groups: normal tests (NT), neuropsychological deficit (ND, one impaired cognitive domain), asymptomatic neurocognitive disorders (ANI), mild neurocognitive disorders (MND), and HIV-associated dementia (HAD). Risk factors for neurocognitive deterioration were analyzed. Two hundred fifty-six patients underwent NP tests and 94 participated in the follow-up. The groups were comparable. Upon neuropsychological re-testing, six patients showed clinical improvement, 30 had worsened, and 58 were stable, resulting in 42 patients presenting with HAND (45 %). The majority of HAND cases consisted of ANI (26 %) and MND (16 %). In patients whose NP performance worsened, CPE 2010 score was lower at inclusion (7.13 vs 8.00, p = 0.003) and CD4/CD8 decrease more frequent (60 vs 31 %, p = 0.008) than in those who were stable or improved. Multivariate analysis confirmed these results. A decreasing CD4/CD8 ratio during a longitudinal follow-up of randomly selected HIV-infected patients and lower CSF-penetrating regimens were independently associated with cognitive decline. Monitoring trends in CD4/CD8 ratio could contribute to identifying patients at higher risk of neurocognitive deterioration.

Neuromyelitis optica: Contribution of therapeutic responses markers monitoring in patients given rituximab.

Neuromyelitis optica (NMO) is a central nervous system inflammatory autoimmune disease characterized by medullary and/or optical nerve damage. It is rare but life-threatening. Concerning the treatment of NMO, many drugs have been used in background therapy. Some studies have shown efficacy of rituximab (an antiCD20 monoclonal anti-body) either on the reduction of the annual number of exacerbation or the mean score EDSS. In 2013, a Korean team reported a new protocol during which they administered rituximab only when memory B lymphocytes CD27+ were detectable in the bloodstream. In our patient, institution of this protocol led to clinical benefit with a major decrease in the EDSS score over time (7 in August 2012 vs. 1 in October 2015), a reduction of the total administered dose (4g in 2013 vs. 1.375g in 2014 vs. 0g in 2015) and side effects. Compared with the rate of theoretical administration, health expenditure savings reached 1700 Euros per month over the 11-month treatment. Monitoring therapeutic response markers with memory B lymphocyte counts appear to be an efficient cost-effective way to measure clinical efficiency, reduce total doses, and limit side effects.

Isolated tumefactive demyelinating lesions: diagnosis and long-term evolution of 16 patients in a multicentric study.

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.

Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.

Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects.

OBJECTIVES: The aim of this study was to investigate whether the quadrivalent human papillomavirus (HPV) vaccine Gardasil is associated with a change in the risk of autoimmune disorders (ADs) in young female subjects. DESIGN: Systematic case-control study of incident ADs associated with quadrivalent HPV vaccination in young women across France. PARTICIPANTS AND SETTING: A total of 113 specialised centres recruited (from December 2007 to April 2011) females aged 14-26 years with incident cases of six types of ADs: idiopathic thrombocytopenic purpura (ITP), central demyelination/multiple sclerosis (MS), Guillain-Barré syndrome, connective tissue disorders (systemic lupus erythematosus, rheumatoid arthritis/juvenile arthritis), type 1 diabetes mellitus and autoimmune thyroiditis. Control subjects matched to cases were recruited from general practice. ANALYSIS: Multivariate conditional logistic regression analysis; factors included age, geographical origin, smoking, alcohol consumption, use of oral contraceptive(s) or vaccine(s) other than Gardasil received within 24 months before the index date and personal/family history of ADs. RESULTS: Overall, 211 definite cases of ADs were matched to 875 controls. The adjusted odds ratio (OR) for any quadrivalent HPV vaccine use was 0.9 [95% confidence interval (CI) 0.5-1.5]. The individual ORs were 1.0 (95% CI 0.4-2.6) for ITP, 0.3 (95% CI 0.1-0.9) for MS, 0.8 (95% CI 0.3-2.4) for connective disorders and 1.2 (95% CI 0.4-3.6) for type 1 diabetes. No exposure to HPV vaccine was observed in cases with either Guillain-Barré syndrome or thyroiditis. CONCLUSIONS: No evidence of an increase in the risk of the studied ADs was observable following vaccination with Gardasil within the time periods studied. There was insufficient statistical power to allow conclusions to be drawn regarding individual ADs.

A prospective observational post-marketing study of natalizumab-treated multiple sclerosis patients: clinical, radiological and biological features and adverse events. The BIONAT cohort.

BACKGROUND AND PURPOSE: BIONAT is a French multicentric phase IV study of natalizumab (NTZ)-treated relapsing-remitting multiple sclerosis (MS) patients. The purpose of this study was to collect clinical, radiological and biological data on 1204 patients starting NTZ, and to evaluate the clinical/radiological response to NTZ after 2 years of treatment. METHODS: Patients starting NTZ at 18 French MS centres since June 2007 were included. Good response to NTZ was defined by the absence of clinical and radiological activity. Data analysed in this first report on the BIONAT study focus on patients who started NTZ at least 2 years ago (n = 793; BIONAT2Y ). RESULTS: NTZ was discontinued in 17.78% of BIONAT2Y. The proportion of patients without combined disease activity was 45.59% during the first two successive years of treatment. Systematic dosage of anti-NTZantibodies (Abs) detected only two supplementary patients with anti-NTZ Abs compared with strict application of recommendations. A significant decrease of IgG,M concentrations at 2 years of treatment was found. CONCLUSIONS: The efficacy of NTZ therapy on relapsing-remitting MS in a real life setting is confirmed in the BIONAT cohort. The next step will be the identification of biomarkers predicting response to NTZ therapy and adverse events.

[Symptomatic giant Virchow-Robin spaces]. / Dilatations géantes des espaces de Virchow-Robin symptomatiques.

INTRODUCTION: Perivascular spaces, known as Virchow-Robin spaces (VRS), may become massively enlarged but are usually an incidental finding. However, a few reports on patients with unusually large VRS have mentioned association with neurological symptoms. We report a series of three symptomatic patients with extremely wide Virchow-Robin spaces documented on brain magnetic resonance imaging (MRI). METHODS: We retrospectively analyzed the medical records and brain MRI of three symptomatic patients, who had been diagnosed with VRS widening. CASE REPORTS: In all three patients, the unusual widening of the VRS was located within the subcortical white matter with asymmetric distribution. Their neurological symptoms were epilepsy and neurological deficits which correlated well with the lesions seen on the MRI. Two patients had associated white matter hyperintensities: in the first case associated gliosis and in the second case, with vascular leukoencephalopathy. CONCLUSIONS: Enlarged symptomatic VRS are rare. The underlying pathophysiological mechanisms remain uncertain. We report three cases with symptomatic giant dilatation of the Virchow-Robin spaces.