Navigating the landscape of COVID-19 for Multiple Sclerosis patients and clinicians

The purpose of this literature review was to summarise relevant findings regarding the clinical management of multiple sclerosis (MS) in the COVID-19 pandemic, with the focus on patient risks, and the implications of disease-modifying treatment, both on COVID-19 severity and on the response to the SARS-CoV-2 vaccinations. Although MS per se does not seem to put patients at risk for more severe COVID-19, alongside the risk factors known to apply to the general population, progressive disease course, higher disability status, and B-cell depleting therapies may all negatively affect infection severity. The question of COVID-19 sequelae in patients with MS (pwMS) remains unresolved, challenging researchers to further explore this area. The safety profile of COVID-19 vaccinations in pwMS is similar to that of the general population. The efficacy of the vaccination might be affected by B-cell depletion, as well as by S1PR-modulating medications that attenuate humoral responses to the COVID-19 vaccination. Future research should focus on gathering evidence regarding the clinical course of MS following COVID-19 infection and vaccination in larger studies, as well as on establishing the safest and most efficient schedule of COVID-19 vaccination in pwMS on cell-depleting therapies

Zagadkowe objawy kliniczne: zespół wizji Picka oraz choroba Marchiafava-Bignamiego — opis dwóch przypadków

W pracy omówiono 2 przypadki rzadkich zespołów chorobowych o symptomatologii neuropsychiatrycznej: zespołu wizji Picka oraz metaalkoholowego zespołu/choroby Marchiafava-Bignamiego. W komentarzu dotyczącym historii oraz patomechanizmu tych zespołów podkreślono rolę badań neuroobrazowych, w szczególności tomografii rezonansu magnetycznego mózgowia, w adekwatnym rozpoznaniu tych rzadkich schorzeń o niezwykłej różnorodności występujących objawów

Update on pathology of central nervous system inflammatory demyelinating diseases

Multiple sclerosis (MS) is by far the most common central nervous system inflammatory demyelinating disease (CNS-IDD). It is diagnosed according to detailed criteria based on clinical definitions, magnetic resonance imaging (MRI) and cerebrospinal fluid findings. However, in rare instances, atypical syndromes associated with CNS demyelination, such as unusual MRI findings or poor response to standard treatment, may eventually necessitate a CNS biopsy with neuropathological examination.Pathology remains the gold standard in the differentiation of atypical CNS-IDDs, the recognition of which is essential for establishing the correct prognosis and optimal therapy. However, one must bear in mind that between different CNS-IDDs there are still overlapping features, even in the pathology.In this review, we compare and highlight contrasts within a spectrum of CNS-IDDs from the neuropathological perspective. We characterise pathological hallmarks of active vs chronic multiple sclerosis. Also, we define differences in the pathology of MS, acute disseminated encephalomyelitis (ADEM), aquaporin 4-IgG positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOsd), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Detailed description of the particular CNS-IDD pathology is crucial on an individual patient level (when clinically justified in atypical cases) but also from a broader perspective i.e. to advance our understanding of the complex disease mechanisms. Recent immunobiological and pathological discoveries have led to the description of novel inflammatory CNS disorders that were previously classified as rare MS variants, such as NMOsd and MOGAD. Multiple sclerosis remains an umbrella diagnosis, as there is profound heterogeneity between patients. Advances in neuropathology research are likely to disentangle and define further CNS-IDDs that used to be categorised as multiple sclerosis

Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy

Although neurons are the main source of neurotrophins in the healthy brain, neurotrophins can also be expressed in the immune system. We have previously shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell neurotrophin levels are associated with brain atrophy and cognitive impairment. The aim of the present study was to assess if immune-cell neurotrophin expression is impaired in MS as compared with the healthy controls, and to describe if these levels change in treatment-naïve RRMS patients, following one year of immunomodulation. Fifty treatment-naïve RRMS patients were assessed at baseline and after one year of immunomodulation (beta-interferons/glatiramer acetate). The control group included 39 healthy subjects matched according to age and gender. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA. BDNF levels were significantly lower in MS than in the healthy controls (median 613 vs. 1657pg/mg protein, p<0.001). After one year of immunomodulation, BDNF expression did not change significantly (p=0.06) on the group level. In 70% of patients there was no increase in BDNF level, and in 30% it increased. We observed no differences between treatment groups. Other neurotrophins were detected in a minority of MS samples (as opposed to the controls). To conclude, we have shown that immune-cell production of neurotrophins is impaired in MS patients. In our MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs within one year of therapy

Guidelines of the Polish Medical Society of radiology for the routinely used MRI protocol in patients with multiple sclerosis

Magnetic resonance imaging is widely used in diagnosing multiple sclerosis as a basic method for detecting and monitoring the disease. Introduction: Polish Medical Society of Radiology presents the second version of the recommendations for the routinely conducted MRI in multiple sclerosis, which include new data and practical remarks for radiographers and radiologists. The recommended protocol aims to improve the imaging procedure and, most importantly, to standardize conducting MRI scans in all MRI departments. This is crucial for monitoring the patients with MS, which directly contributes to essential clinical decisions. Aim of the guidelines: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disease of the central nervous system (CNS) with its etiology still unknown. The fundamental requirement of the disease is the CNS destruction process disseminated in time (DIT) and space (DIS). MR imaging detects focal lesions in white and gray matter with high sensitivity and is the best way to assessbrainatrophy in MS patients. It isunquestionably the best diagnostic tool to follow-up the clinical course of the disease and treatment of MS patients. However, to achieve a diagnosis based on MRI scans, and follow-up MS patients according to the latest standards, an MRI scan has to meet certainquality criteria that are the subject of this work

Spatial distribution of white matter degenerative lesions and cognitive dysfunction in relapsing-remitting multiple sclerosis patients

Aim. The aim of this study was to assess degenerative lesion localisation in the course of relapsing-remitting multiple sclerosis (RRMS) and to identify the association between localisation and the frequency of T1-hypointense lesions (black holes) with cognitive dysfunction. We also searched for neuroradiological predictors of cognitive dysfunction in patients. The clinical rationale for the study was previous research, and our own findings suggest that lesion localisation plays an important role in cognitive performance and neurological disability of MS patients. Material and methods. Forty-two patients were included in the study. All subjects underwent neuropsychological examination using Raven’s Coloured Progressive Matrices, a naming task from the Brief Repeatable Battery of Neuropsychological Tests, and attention to detail tests. Magnetic resonance imaging (MRI) was acquired on 1.5 Tesla scanner and black holes were manually segmented on T1-weighted volumetric images using the FMRIB Software Library. Linear regression was applied to establish a relationship between black hole volume per lobe and cognitive parameters. Bonferroni correction of voxelwise analysis was used to correct for multiple comparisons. Results. The following associations between black hole volume and cognition were identified: frontal lobes black hole volume was associated with phonemic verbal fluency (t = –4.013, p < 0.001), parietal black hole volume was associated with attention (t = –3.776, p < 0.001), and parietal and temporal black hole volumes were associated with nonverbal intelligence (p < 0.001). The volume of parietal black holes was the best predictor of cognitive dysfunction. Conclusions. Our approach, including measurement of focal axonal loss based on T1-volumetric MRI sequence and brief neuropsychological assessment, might improve personalised diagnostic and therapeutic decisions in clinical practice

Evaluation of clinical prognostic factors in Polish interferon beta-1b treated multiple sclerosis patients

Introduction. Prompt successful control of disease activity in multiple sclerosis (MS) patients improves outcomes. Therefore, tools to aid drug selection and detect non-responders are urgently needed. Although several biochemical markers for predicting response to treatment have been proposed, clinical markers involving relapses, imaging activity and disability progression in the initial years of therapy remain competitive and appear cost-effective in a real-life setting. The aim of this study was to evaluate the prognostic value of select clinical scores in interferon beta-1b (IFNβ-1b) treated MS patients.Materials and methods. Eighty-eight relapsing-remitting MS (RRMS) patients initiating treatment with IFNβ-1b in a Polish outpatient clinic were followed for a median of 5.5 years. Rio, modified Rio and BREMSO scores, as well as two-year no evidence of disease activity (NEDA), were assessed as predictors of disease activity during the observation.Results. A Rio score of 1 had a Positive Predictive Value (PPV) of 83.3% and a Negative Predictive Value (NPV) of 71.4% for the occurrence of relapses in the first five years. A Rio and modified Rio score of 1 was associated with MRI activity after year 3. A loss of NEDA within the first two years was associated with a failure to maintain NEDA in the next three years. The BREMSO score was higher in patients with early relapse activity. Only baseline EDSS and total number of pre-treatment relapses were significantly associated with disability progression.Conclusions. Rio, modified Rio, early NEDA on treatment and BREMSO score are relatively specific, but insensitive, predictors of relapse activity in the first years of IFNβ-1b treatment. Higher pre-treatment EDSS and relapse activity is associated with disability progression, but not overall NEDA, in subsequent observation. While none of the markers is sufficiently sensitive or specific to make a certain prognosis, they may aid treatment decisions in patients with continued early disease activity

The impact of disease modifying therapies on cognitive functions typically impaired in multiple sclerosis patients: a clinician’s review

ObjectiveOver the last few decades clinicians have become aware that cognitive impairment might be a major cause of disability, loss of employment and poor quality of life in patients suffering from multiple sclerosis [MS].The impact of disease modifying therapies [DMTs] on cognition is still a matter of debate. Theoretically, DMTs could exert a substantial beneficial effect by means of reducing neuroinflammation and brain atrophy, which are established correlates of cognitive dysfunction. The aim of the study was to review the evidence concerning the effect of DMTs on cognitive functions.MethodsPubMed, Scopus, and the European Committee for Treatment and Research in Multiple Sclerosis [ECTRIMS] Library were searched for articles concerning the pediatric and adult populations of patients with multiple sclerosis, including clinical trials and RWD, where psychometric results were analyzed as secondary or exploratory endpoints.ResultsWe reviewed a total of 44 studies that were found by our search strategy, analyzed the psychological tests that were applied, the length of the follow-up, and possible limitations. We pointed out the difficulties associated with assessing of DMTs’ effects on cognitive functions, and pitfalls in cognitive tools used for evaluating of MS patients.ConclusionThere is a need to highlight this aspect of MS therapies, and to collect adequate data to make informed therapeutic decisions, to improve our understanding of MS-related cognitive dysfunction and provide new therapeutic targets

Prevalence and prognostic value of prodromal symptoms in relapsing-remitting multiple sclerosis

Introduction. Several studies have suggested the possibility that disease prodromes might occur months or even years before a multiple sclerosis diagnosis. Objectives. To describe the profile of prodromal symptoms and the possible relationship between the occurrence of individual symptoms and clinical course characteristics in patients with relapsing-remitting multiple sclerosis (RRMS), and to assess their role as predictors of further disease course. Material and methods. The cohort included 564 patients with RRMS. Patients were stratified based on their current EDSS score, and the annual EDSS growth rate was calculated. Logistic Regression Analysis was used to study the relationship between prodromal symptoms and disease progression. Results. The most commonly reported prodromal symptom was fatigue (42%). The following symptoms were significantly more common in women than in men: headache (39.7% vs. 26.5%, p < 0.05), excessive sleepiness (19.1% vs. 11.1%, p < 0.05) and constipation (18.0% vs. 11.1%, p < 0.05). Prodromal urinary and cognitive disturbances, fatigue and pain complaints were significantly more common in patients with the highest annual EDSS increase (p < 0.05). Multivariate analysis revealed some potential predictors of long-term disability progression: hesitancy in starting urination predicted EDSS increase by 0.6 point (p < 0.05), while deterioration in everyday functioning because of cognitive disturbances, and pain complaints, were associated with an EDSS increase of 0.5 (p < 0.05), and 0.4 (p < 0.05), respectively. Conclusions. Prodromal pain, urinary and cognitive complaints (especially when these lead to deterioration of everyday functioning) were associated with a higher EDSS increase rate, and may thus be regarded as possible predictors of worse clinical outcomes in RRMS patients

Recommendations for neurological, obstetrical and gynaecological care in women with multiple sclerosis: a statement by a working group convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society

Introduction. Multiple sclerosis (MS) is the most common non-traumatic neurological cause of disability in young adults, affecting women 1-3 times more often than men. Several specific challenges arise from the fact that young women diagnosed with MS often have to make decisions related to treatment and family planning at the same time. These issues are connected with fertility, the impact of pregnancy on disease course, the choice of pregnancy timing, and the optimal mode of disease-modifying therapy in the context of a planned pregnancy, contraception, urological complaints, and sexual dysfunction.State of the art. While MS does not in itself adversely affect fertility, pregnancy or childbirth, pregnancy needs to be carefully planned. This requires the interdisciplinary co-operation of a neurologist, gynaecologist and psychologist. Data on the impact of disease-modifying drugs on foetal development are very limited, and none of these drugs is 100% safe during pregnancy. In the second and third trimesters, MS relapse rate decreases. Unfortunately, it increases within the first 3-6 months after delivery. Adequate disease control should be achieved before pregnancy, as relapse rate in the period of two years preceding pregnancy is one of the strongest predictive factors for post-partum relapses.Clinical implications. The following is a statement by a working group of experts in neurology, gynaecology, obstetrics and urology, convened by the Section of Multiple Sclerosis and Neuroimmunology of the Polish Neurological Society, addressing the issues that are specific to the female MS population. The aim of this statement is to provide guidance in pregnancy planning and disease management, both during pregnancy and post-partum.Future directions. This statement reflects expert opinion and is not intended to be read as guidelines. It rather provides up-to-date information on how to optimise care of female MS patients of childbearing age