Smoking and multiple sclerosis, cause or coincidence?

Multiple Sclerosis With Childhood Onset: Report of 21 Cases in Taiwan

The purpose of the study: is to conduct a comparative analysis of clinical parameters at different time stages and to assess their prognostic value in sporadic and familial forms of multiple sclerosis using mathematical analysis. Methods: questionnaire-based survey, clinical and neurological, mathematical and statistical (mean values, confidence interval, permutation test, Student’s test, OR value, correlation analysis using Yule’s coefficient), which were used in various combinations and complemented each other. A total of 97 patients were examined: sporadic form — 55 (relapsing-remitting 31 (RR), progressive types of course (PTC) — 24); familial form — 42 (RR — 20, PTC — 22). A comprehensive analysis of the different time stages of the course in RR and PTC in sporadic and familial forms of multiple sclerosis (MS) was carried out (debut, relapsing stage (RS) for RR and secondary progressive course (SPC), progression stage (PS) for SPC and primary progressive course (PPC), current prognosis — favourable, uncertain, unfavourable). The mean values revealed significant differences between clinical parameters at different time stages in the two forms of RR and PTC MS, which prevailed in the familial form and indicated a more severe and unfavourable course (increased severity of debut and relapses in RP, incomplete remissions after debut, short RR, steady progression, uncertain prognosis in RR and unfavourable prognosis in PTC). Using the odds ratio (OR) and permutation test, we obtained significant differences between clinical parameters in the three groups of patients (general, RR and PTC) in the form of differentiated “sets” in each of the study groups, which closely correlated with prognostic options in PTC and testified in favour of an uncertain prognosis in sporadic and unfavourable prognosis in familial forms of MS. A limited number of indicators were obtained in the MS RR, which had no significant informative value. When applying correlation analysis using Yule’s coefficient between clinical indicators within a single nosological form (MS), different levels of organisation of relations (intra- and interstage) were obtained, which were characterised by significant differences in the structural organisation at different stages in sporadic and familial forms of RR and PTC MS.

Clarification of the characteristics and dynamics of changes in the main indicators of visual evoked potentials (VEP) for a reverse chess pattern in patients with multiple sclerosis (MS) at various stages of the disease and severity of disability. The study of VEP was carried out on 477 subjects, 120 of which were healthy volunteers and 357 patients with MS, including those with clinically isolated syndrome (CIS; 22.7%), remitting course (RT; 55.7%), primary progressive course (PPT; 8.4%), secondary progressive course (VPT; 13.2%). Disability was assessed using the Expanded Disability Status Scale (EDSS). A high sensitivity of VEP in the detection of demyelinating damage to the visual pathways, including subclinical, was noted already at the initial stages of MS, which increases with the progression of the disease from 77.8 to 97.8%. There was a significant increase in latency (r=0.42, p<0.05) and a decrease in amplitude (r= -0.26, p<0.05) of the P100 peak as the EDSS score increased. In patients with MS, 5 patterns of VEP were identified depending on the level and severity of damage to the visual pathways, where pattern 1 is normative VEP, pattern 5 is the absence of VEP recording in case of a pronounced axonal-demyelinating lesion of the visual pathways (prechiasmal/postchiasmal levels). Patterns 1 and 2 are most typical for CIS (22.2 and 53.1%) or RT (20.1 and 26.6%). Patterns 3 and 4 are typical for APT (70 and 20%) and VPT (48.9 and 21.3%), pattern 5 - for VPT (19.1%). Patterns 3-5 predominated in patients with higher EDSS (r=0.54, p<0.05). The classification of VEP changes into patterns makes it possible to identify the dissemination of a focal lesion in the projections of the visual pathways, which increases the diagnostic efficiency of the study and makes it possible to assess the severity of MS.

ObjectivesTo stratify patients with multiple sclerosis (pwMS) based on brain MRI-derived volumetric features using unsupervised machine learning.MethodsThe 3-T brain MRIs of relapsing-remitting pwMS including 3D-T1w and FLAIR-T2w sequences were retrospectively collected, along with Expanded Disability Status Scale (EDSS) scores and long-term (10 ± 2 years) clinical outcomes (EDSS, cognition, and progressive course). From the MRIs, volumes of demyelinating lesions and 116 atlas-defined gray matter regions were automatically segmented and expressed as z-scores referenced to external populations. Following feature selection, baseline MRI-derived biomarkers entered the Subtype and Stage Inference (SuStaIn) algorithm, which estimates subgroups characterized by distinct patterns of biomarker evolution and stages within subgroups. The trained model was then applied to longitudinal MRIs. Stability of subtypes and stage change over time were assessed via Krippendorf’s α and multilevel linear regression models, respectively. The prognostic relevance of SuStaIn classification was assessed with ordinal/logistic regression analyses.ResultsWe selected 425 pwMS (35.9 ± 9.9 years; F/M: 301/124), corresponding to 1129 MRI scans, along with healthy controls (N = 148; 35.9 ± 13.0 years; F/M: 77/71) and external pwMS (N = 80; 40.4 ± 11.9 years; F/M: 56/24) as reference populations. Based on 11 biomarkers surviving feature selection, two subtypes were identified, designated as “deep gray matter (DGM)-first” subtype (N = 238) and “cortex-first” subtype (N = 187) according to the atrophy pattern. Subtypes were consistent over time (α = 0.806), with significant annual stage increase (b = 0.20; p < 0.001). EDSS was associated with stage and DGM-first subtype (p ≤ 0.02). Baseline stage predicted long-term disability, transition to progressive course, and cognitive impairment (p ≤ 0.03), with the latter also associated with DGM-first subtype (p = 0.005).ConclusionsUnsupervised learning modelling of brain MRI-derived volumetric features provides a biologically reliable and prognostically meaningful stratification of pwMS.Key Points• The unsupervised modelling of brain MRI-derived volumetric features can provide a single-visit stratification of multiple sclerosis patients.• The so-obtained classification tends to be consistent over time and captures disease-related brain damage progression, supporting the biological reliability of the model.• Baseline stratification predicts long-term clinical disability, cognition, and transition to secondary progressive course.

ABSTRACTObjective: To assess the compliance, satisfaction and adverse effects of immunomodulating drugs in a German multiple sclerosis (MS) population.Research design and methods: A standardised, anonymous questionnaire was sent to the 1985 members with MS of the Berlin section of the German Multiple Sclerosis Association. Patients were questioned with regards to sociodemographic data, MS-related topics, therapy, adverse effects and compliance. The response rate was 51.1%, from which 681 patients were selected who were experienced in therapy with interferon beta 1a or 1b or glatiramer acetate.Results: Most participants were treated with beta-interferons and only one-third with glatiramer acetate. Patients were moderately satisfied with their medication. Approximately 75.5% of patients had used the medication for longer than 2 years, especially those with a relapsing–remitting course (RRMS). Around one-third of all participants had their immunomodulating drug changed, mostly only once. The main reasons for discontinuation of the therapy were adverse effects, physician's recommendation and lack of treatment effect. Mood-related adverse effects (e.g., depression), fever and pain were perceived as most disturbing. Regression analysis revealed that dependence on a wheelchair and a secondary progressive course predicted a low compliance to treatment.Conclusion: Treating MS is a challenge and to positively influence the course of the disease it is necessary to administer medication in a constant manner. Our data showed a moderate compliance and satisfaction with the immunomodulating medication. Adverse effects and perceived lack of treatment effect were reasons for discontinuation of therapy. To increase compliance and satisfaction with treatment, adequate information about MS, the therapeutic options, handling of medication, side-effects and their management are necessary. Additionally, realistic therapeutic aims should be discussed with the patients.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

Anxiety, depression and impaired health-related quality of life (HRQoL) are commonly reported in patients with multiple sclerosis (MS) and are of great interest for therapeutic approaches. Based on regional differences a quantitative assessment of these factors in comparison to the general population, and the consideration of demographic cofactors, would be useful when designing specific interventions. We adopted such an approach in a German cohort of MS patients. Anxiety, depression (HADS) and HRQoL (SF-36) were measured in 49 consecutive outpatients with MS and compared to age- and gender-adjusted control groups (n=1330 for HADS; n=5087 for SF-36) extracted from German National Health Surveys. Patients with MS showed significantly increased levels of anxiety and depression as well as decreased HRQoL with the exception of mental health; the effect sizes ranged from 0.39 (depression) to 1.06 (physical functioning). As could be expected, MS patients with relapsing-remitting clinical course had better physical functioning than patients with secondary progressive MS. There were strong relations between anxiety and depression (r=0.54; P<0.01), and between neurological impairment (EDSS) and physical functioning (r=−0.80; P<0.001) as well as depression (r=0.48; P<0.05). This investigation of MS patients confirms the prevalence and impact of anxiety, depression and most of the HRQoL dimensions in MS patients and provides evidence for the usefulness of a quantitative comparison to a region-specific general population as a starting point for therapeutic approaches.

To develop an electronic registry of patients with MS in the Russian Federation and to analyze the collected epidemiological and clinical data. Patients aged 18 and older with definite multiple sclerosis were included in the study. We designed a specialized electronic individual registration form (registry) to gather information about study participants. This paper presents data collected in the project between September 25, 2017 and March 25, 2020. We collected information on 2728 patients. This paper presents the results of data analysis from the registry of MS patients, including demographic, clinical and epidemiological characteristics, the type and timing of treatment received. Based on the data obtained, certain issues with primary diagnosis of multiple sclerosis and delayed initiation of disease-modifying therapy can be highlighted, which contribute to the transition of the disease to a secondary progressive course and disability increase.

It has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course. Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate:creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate:creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetylaspartate:creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.

Introduction: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that predominantly affects young women. Its clinical manifestations include sensory–motor relapses, monocular optic neuritis, and brainstem syndrome, which may follow a relapsing–remitting, primary, or secondary progressive course. Recently, prodromal symptoms, such as psychiatric alterations, have been described, adding complexity to the initial diagnosis. Objective: The aim of this study was to report a clinical case of MS with an atypical presentation, characterized by acute behavioral changes with fluctuating infantilization, highlighting the importance of an interdisciplinary approach and early diagnosis. Methods: A 23-year-old female patient was referred due to acute behavioral changes. During hospitalization, the mental health team ruled out a primary psychiatric disorder. Neurological investigation included imaging exams, such as computed tomography and brain magnetic resonance imaging, along with cerebrospinal fluid (CSF) analysis for oligoclonal bands. Results: The exams revealed hyperintense lesions in T2 and FLAIR sequences located in the periventricular and subcortical white matter and the posterior fossa, some with peripheral contrast enhancement, in addition to positive oligoclonal bands in the CSF. Despite initial treatment, the patient experienced repeated sensory–motor relapses, requiring plasmapheresis due to high disease activity. Conclusion: MS presents with a wide range of manifestations, with acute psychiatric symptoms being a less common initial presentation. This case highlights the importance of early recognition of atypical presentations for proper diagnosis and treatment, reducing disease progression and functional impairment in the patient.

Melatonin reduces oxidative stress in the erythrocytes of multiple sclerosis patients with secondary progressive clinical course

Objective: The aim of the present study was to assess the size of the third ventricle in a sample of patients with multiple sclerosis (MS) affected by chronic cerebrospinal venous insufficiency (CCSVI), versus size of the third ventricle in a healthy control group. Background: CCSVI, a new nosological vascular pattern, has recently been associated with MS. Methods: We enrolled 33 patients affected by MS (three in the primary progressive clinical course, 23 in the relapsing–remitting clinical course, and seven in the secondary–progressive clinical course). All patients had been affected by CCSVI and were tested using an echo color Doppler (ECD) imaging unit. The group of 33 affected by both MS and CCSVI (MS–CCSVI) was composed of 19 females and 14 males with a mean age of 40±10 years, from a minimum age of 20 years to a maximum age of 66 years, with a median of 40 years and a mode of 32 years. We compared the 33 MS–CCSVI patients with 33 healthy control subjects of similar sex and age. In the MS–CCSVI group, the MS clinical severity was expressed by expanded disability status scale (EDSS) score: light (19 patients, scoring 1, 2, or 3); medium (ten patients with a score of 4, 5, or 6), and severe (four patients with a score of 7, 8, or 9). The average duration of the MS was 10±7 years (from a minimum of 1 to a maximum of 26 years, with a median of 10 years and a mode of 1 year). Results: In the MS–CCSVI group, the third ventricle diameter was 6.2±1.7 mm (from a minimum of 2.5 mm to a maximum of 9.2 mm, with a median of 6.3 mm, and a mode of 6.0 mm). Our data showed that 29 patients (88%) had an increase in third ventricle diameter, whereas only four patients (12%) had physiological size (less than 4 mm) comparable to all healthy control group subjects (27.28%). These results show that the increase in the third ventricle diameter could represent a criterion of positivity of neurological disease in patients with CCSVI.

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a clear nomenclature. We evaluate the proposition that primary progressive MS has a profile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.

The literature data of the last three decades on the problem of comorbidity of multiple sclerosis (MS) and epilepsy have been analyzed, such as issues of pathogenesis, clinical course, prognosis, and treatment of this dual pathology. Epileptic seizures occur in 2–3% to 5.9% of patients with MS, which is 3–6 times more common than in the general population. The incidence of epilepsy raises with increasing duration and severity of MS, with its progressive course, and also depends on the effect of drugs for the treatment of MS. There is no unanimity in the literature on the age and gender characteristics of the occurrence of epileptic seizures in MS. Probable mechanisms of MS comorbidity and epilepsy are analyzed. Data on certain common pathophysiology of MS and epilepsy and the concept according to which the model of epilepsy in MS is considered as a network disease are presented. Data on clinical manifestations and diagnosis of comorbid MS with epilepsy are presented. Epileptic seizures can occur at any stage of MS: before the clinical manifestations, at the onset of the disease, in the late stages, or can indicate exacerbation of MS. Types of epileptic seizures with a dual diagnosis (MS + epilepsy) are diverse. The majority of patients (up to 87.5%) have focal seizures (aware or unaware) or focal seizures to bilateral tonic-clonic, and a small share of patients have seizures of unknown origin. Most researchers believe that patients with MS and epilepsy have a more severe MS course and a worse long-term prognosis. The main directions of MS treatment and the impact of such treatment on the development of epileptic seizures are highlighted. Data on the effect of some disease-modifying drugs for the treatment of MS on the course of epilepsy and, on the other hand, on the impact of some antiseizure medications on the course of MS are presented. It is concluded that patients with MS have individual profiles and inter-individual variability of epileptogenicity. The principles of treatment of epileptic seizures/epilepsy in patients with MS are proposed.

Dementia in multiple sclerosis: is it Alzheimer's or a new entity?