Course Of Multiple Sclerosis Research Articles

CONNECTION BETWEEN COMORBID PRIMARY HEADACHE, DEPRESSION AND ANXIETY IN PATIENTS WITH MULTIPLE SCLEROSIS

SUMMARY. Multiple sclerosis (MS) is a chronic autoimmune disorder of central nervous system that affects young people and progresses to physical disability. Among patient with MS risk of excessive anxiety and depression is quite common. One of the frequent comorbidities of MS is primary comorbid headache. Depression and anxiety might be more prominent on patients with pain comorbidity of MS. The aim – to show the prevalence and frequency of depression and anxiety in a population of patients with MS, with special attention to the group of patients with primary comorbid headache. Material and Methods. MS was confirmed according to the McDonald criteria 2017. Questionnaires Beck Depression Inventory (BDI) for assessment of depression and The Spielberger State-Trait Anxiety Inventory in Hanin`s interpretation (STAI), version for evaluation of reactive anxiety were used. Results. 130 patients with MS were examined with disease duration 8.63±7.49 years. 36.2 % of males (n=47) and 63.8 % of females (n=83) were included. Average score of patients with MS was 40.22±8.89 points that indicates moderate reactive anxiety. BDI score accounted for 14.15±7.58 points that interpretates as mild-to-moderate depression. Patients with MS and comorbid primary headache received the average points of the STAI in Hanin's interpretation – 42.41±7.49 (moderate anxiety); patients with MS without comorbid primary headache – 37.42±9.31 (low or moderate anxiety), but generally this difference did not show statistical significance (p=0.39). Among MS course scores of anxiety was similar between groups, depression score was the highest in group with primary progressive MS (PPMS). Conclusion. The average score of anxiety and depression showed moderate severity among patients with MS. There were not found significance between patients with primary headache comorbidity and without it, although scores between course disease subgroups showed higher points in patients with comorbid primary headache.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study

BackgroundEndometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. ObjectiveTo characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. MethodsWe retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). ResultsUsing a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. ConclusionWhen controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

A mixture model for differentiating longitudinal courses of multiple sclerosis

BackgroundMultiple sclerosis has a broad spectrum of clinical courses. Early identification of patients at greater risk of accumulating disability is essential. ObjectivesIdentify groups of patients with similar presentation through a mixture model and predict their trajectories over the years. MethodsRetrospective study of patients from 1994 to 2019. We performed a latent profile analysis followed by a latent transition analysis based on eight parameters: age, disease duration, EDSS, number of relapses, multi-topographic symptoms, motor impairment, sphincter impairment, and infratentorial lesions. ResultsWe included 629 patients, regardless of the phenotypical classification. We identified three distinct groups at the beginning and end of the follow-up. The three-classes model disclosed the “No disability regardless disease duration” (NDRDD) class with low EDSS and younger patients, the “Disability within a short disease duration” (DSDD) class with the worse disability besides short illness, and the “Disability within a long disease duration” (DLDD) class that achieved high EDSS over a long disease duration. EDSS, disease duration, and no sphincter impairment had the best entropy to distinguish classes at the initial presentation. Over time, the patients from NDRDD had a 52.1 % probability of changing to DLDD and 7.7 % of changing to DSDD. ConclusionsWe identified three groups of clinical presentations and their evolution over time based on considered prognostic factors. The most likely transition is from NDRDD to DLDD.

Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients

Impact of the therapy that changes the clinical course of multiple sclerosis using allogeneic mesenchymal stem cell transplantation on the immunological parameters of patients

Serum Reactive Antibodies against the N-Methyl-D-Aspartate Receptor NR2 Subunit-Could They Act as Potential Biomarkers?

Synaptic dysfunction and disrupted communication between neuronal and glial cells play an essential role in the underlying mechanisms of multiple sclerosis (MS). Earlier studies have revealed the importance of glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor, in excitotoxicity, leading to abnormal synaptic transmission and damage of neurons. Our study aimed to determine whether antibodies to the NR2 subunit of NMDAR are detected in MS patients and evaluate the correlation between antibody presence and clinical outcome. Furthermore, our focus extended to examine a possible link between NR2 reactivity and anti-coagulant antibody levels as pro-inflammatory molecules associated with MS. A cross-sectional study was carried out, including 95 patients with MS and 61 age- and gender-matched healthy controls (HCs). The enzyme-linked immunosorbent assay was used to detect anti-NR2 antibodies in serum samples of participants along with IgG antibodies against factor (F)VIIa, thrombin, prothrombin, FXa, and plasmin. According to our results, significantly elevated levels of anti-NR2 antibodies were detected in MS patients compared to HCs (p < 0.05), and this holds true when we compared the Relapsing-Remitting MS course with HCs (p < 0.05). A monotonically increasing correlation was found between NR2 seropositivity and advanced disability (rs = 0.30; p < 0.01), anti-NR2 antibodies and disease worsening (rs = 0.24; p < 0.05), as well as between antibody activity against NR2 and thrombin (rs = 0.33; p < 0.01). The presence of anti-NR2 antibodies in MS patients was less associated with anti-plasmin IgG antibodies [OR:0.96 (95%CI: 0.92-0.99); p < 0.05]; however, such an association was not demonstrated when analyzing only RRMS patients. In view of our findings, NR2-reactive antibodies may play, paving the way for further research into their potential as biomarkers and therapeutic targets in MS.

Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss

Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the CNS. The disease course in MS is highly variable and driven by a combination of relapse-driven disease activity and relapse-independent disease progression. The formation of new focal demyelinating lesions is associated with clinical relapses; however, the pathological mechanisms driving disease progression are less well understood. Current concepts suggest that ongoing focal and diffuse inflammation within the CNS in combination with an age-associated failure of compensatory and repair mechanisms contribute to disease progression. The aim of our study was to characterize the diffuse microglia activation in periplaque white matter (PPWM) of MS patients, to identify factors modulating its extent and to determine its potential correlation with loss or preservation of oligodendrocytes. We analyzed microglial and oligodendroglial numbers in PPWM in a cohort of 96 tissue blocks from 32 MS patients containing 100 lesions as well as a control cohort (n = 37). Microglia activation in PPWM was dependent on patient age, proximity to lesion, lesion type, and to a lesser degree on sex. Oligodendrocyte numbers were decreased in PPWM; however, increased microglia densities did not correlate with lower oligodendroglial cell counts, indicating that diffuse microglia activation is not sufficient to drive oligodendroglial loss in PPWM. In summary, our findings support the notion of the close relationship between focal and diffuse inflammation in MS and that age is an important modulator of MS pathology.

COMORBID MIGRAINE CHARACTERISTICS IN PATIENTS WITH MULTIPLE SCLEROSIS

Multiple Sclerosis (MS) is a chronic autoimmune disabling disease that is caused by autoimmune attack of myelin in the central nervous system [1]. Disease is not treatable and the progression depends on disease course and presence of comorbidity [2]. Among plenty of comorbid conditions that are present during MS duration, connection between primary headache and MS is well known but still poorly understood. Primary comorbid headache might be a cause of decreased quality of life of patients with MS. Mostly it depends on the type of primary headache and type of MS course (3).

Implementing Shared Decision-Making for Multiple Sclerosis: The MS-SUPPORT Tool

BackgroundDisease modifying therapies (DMTs) offer opportunities to improve the course of multiple sclerosis (MS), but decisions about treatment are difficult. People with multiple sclerosis (pwMS) want more involvement in decisions about DMTs, but new approaches are needed to support shared decision-making (SDM) because of the number of treatment options and the range of outcomes affected by treatment. We designed a patient-centered tool, MS-SUPPORT, to facilitate SDM for pwMS. We sought to evaluate the feasibility and impact of MS-SUPPORT on decisions about disease modifying treatments (DMTs), SDM processes, and quality-of-life. MethodsThis multisite randomized controlled trial compared the SDM intervention (MS-SUPPORT) to control (usual care) over a 12-month period. English-speaking adults with relapsing MS were eligible if they had an upcoming MS appointment and an email address. To evaluate clinician perspectives, participants’ MS clinicians were invited to participate. Patients were referred between November 11, 2019 and October 23, 2020 by their MS clinician or a patient advocacy organization (the Multiple Sclerosis Association of America). MS-SUPPORT is an online, interactive, evidence-based decision aid that was co-created with pwMS. It clarifies patient treatment goals and values and provides tailored information about MS, DMTs, and adherence. Viewed by patients before their clinic appointment, MS-SUPPORT generates a personalized summary of the patient's treatment goals and preferences, adherence, DMT use, and clinical situation to share with their MS clinician. Outcomes (DMT utilization, adherence, quality-of-life, and SDM) were assessed at enrollment, post-MS-SUPPORT, post-appointment, and quarterly for 1 year. ResultsParticipants included 501 adults with MS from across the USA (84.6% female, 83% white) and 34 of their MS clinicians (47% neurologists, 41% Nurse Practitioners, 12% Physician Assistants). Among the 203 patients who completed MS-SUPPORT, most (88.2%) reported they would recommend it to others and that it helped them talk to their doctor (85.2%), understand their options (82.3%) and the importance of taking DMTs as prescribed (82.3%). Among non-users of DMTs at baseline, the probability ratio of current DMT use consistently trended higher over one-year follow-up in the MS-SUPPORT group (1.30 [0.86-1.96]), as did the cumulative probability of starting a DMT within 6-months, with shorter time-to-start (46 vs 90 days, p=0.24). Among the 222 responses from 34 participating clinicians, more clinicians in the MS-SUPPORT group (vs control) trended towards recommending their patient start a DMT (9 of 108 (8%) vs 5 of 109 (5%), respectively, p=0.26). Adherence (no missed doses) to daily-dosed DMTs was higher in the MS-SUPPORT group (81.25% vs 56.41%, p=.026). Fewer patients forgot their doses (p=.046). The MS-SUPPORT group (vs control) reported 1.7 fewer days/month of poor mental health (p=0.02). ConclusionsMS-SUPPORT was strongly endorsed by patients and is feasible to use in clinical settings. MS-SUPPORT increased the short-term probability of taking and adhering to a DMT, and improved long-term mental health. Study limitations include selection bias, response bias, social desirability bias, and recall bias. Exploring approaches to reinforcement and monitoring its implementation in real-world settings should provide further insights into the value and utility of this new SDM tool.

Association between course of multiple sclerosis and polymorphisms of calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232)

Objective. To evaluate the relationship between the frequency of exacerbations and the rate of progression of multiple sclerosis (MS) and polymorphisms of the calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232).Material and methods. Ninety patients with relapsing-remitting MS took part in the study. All patients are Caucasians, were born and lived in the Altai region of the Russian Federation. Genotyping was performed by TaqMan probes.Results. A protective effect of the TT genotype VDR FokI (rs2228570) on the risk of increasing disability of more than 0.75 points per year according to the expanded disability scale was found (p = 0.034). The protective effect of the TT genotype of the TaqI polymorphism (rs731236) on exacerbations of MS more than once a year (p = 0.041) was also revealed. Associations of the MS course with other studied polymorphisms were not found.Conclusions. It can be assumed that the VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms may influence the course of relapsing-remitting MS. The mechanisms of these influences may include the modulation of immune-inflammatory responses in the central nervous system, which are a key link in the MS pathogenesis.

Association of intestinal dysbiosis with susceptibility to multiple sclerosis: Evidence from different population studies (Review).

Understanding the relationship between microorganisms that live in our intestines and neuroinflammatory and neurodegenerative pathologies of the central nervous system (CNS) is essential, since they have been shown to have an immunomodulatory effect in neurological disorders, such as multiple sclerosis (MS). The gut microbiota can be affected by several environmental factors, including infections, physical and emotional stress and diet, the latter known as the main modulator of intestinal bacteria. An abrupt shift in the gut microbiota composition and function is known as dysbiosis, a state of local and systemic inflammation produced by pathogenic bacteria and its metabolites responsible for numerous neurological symptoms. It may also trigger neuronal damage in patients diagnosed with MS. Intestinal dysbiosis affects the permeability of the intestine, allowing chronic low-grade bacterial translocation from the intestine to the circulation, which may overstimulate immune cells and cells resident in the CNS, break immune tolerance and, in addition, alter the permeability of the blood-brain barrier (BBB). This way, toxins, inflammatory molecules and oxidative stress molecules can pass freely into the CNS and cause extensive damage to the brain. However, commensal bacteria, such as the Lactobacillus genus and Bacteroides fragilis, and their metabolites (with anti-inflammatory potential), produce neurotransmitters such as γ-aminobutyric acid, histamine, dopamine, norepinephrine, acetylcholine and serotonin, which are important for neurological regulation. In addition, reprogramming the gut microbiota of patients with MS with a healthy gut microbiota may help improve the integrity of the gut and BBB, by providing clinically protective anti-inflammatory effects and reducing the disease's degenerative progression. The present review provides valuable information about the relationship between gut microbiota and neuroinflammatory processes of the CNS. Most importantly, it highlights the importance of intestinal bacteria as an environmental factor that may mediate the clinical course of MS, or even predispose to the outbreak of this disease.

FRI432 An Interesting Case Of Primary Hypogonadism In A Patient With Multiple Sclerosis

Abstract Disclosure: S. Ahsun: None. P. Lekprasert: None. K.K. Win: None. Introduction: As per the recent data there is an association between low levels of testosterone in men and the risk for multiple sclerosis (MS). Most recent practice involves checking testosterone levels for male patients with newly developed MS and treating with testosterone supplementation if levels are low. CASE PRESENTATION: A 65-year-old male with medical history of multiple sclerosis, prediabetes, hypogonadism, squamous cell carcinoma of left ear, thyroid cancer (unknown type) status post total thyroidectomy and radioiodine therapy; presented to our endocrine office for an initial visit. Patient had been following with Endocrinologist at different state in the past and did not have much of his prior records since that practice closed. He has been on 150 mcg of levothyroxine and his TSH was stable at 1.2 (0.4-4.5 mIU/L). He also had a history of hypogonadism and had been on testosterone supplementation since the age around 50. Patient did not know the underlying cause for his hypogonadism. He has 3 biological children and the youngest one is 26 years old. He had been off of testosterone therapy for 3 months prior to our initial visit. We did some workup which showed total testosterone level of &amp;lt;20 (250-1100 ng/dL). Free testosterone 2.2 (46-224 pg/mL). FSH and LH levels were elevated at 27.1 (1.6-8 mIU/mL) and 17.3 (1.6-15.2 mIU/mL). Prolactin level was 5.1 (5.2-26.5) ng/mL. These labs were consistent with Primary hypogonadism. Repeat testing was done and the patient had redemonstration of very low testosterone levels. Further checking of the karyotype analysis revealed normal male karyotype testing. His physical exam showed normal sized testicles at 20 cc and no gynecomastia. Body hair distribution was normal but there was decreased shaving frequency with decreased muscle strength. Patient never had any chemotherapy or the radiation therapy to the pelvic area. No known history of chronic infection or trauma. Currently, he is on Ocrelizumab for Multiple Sclerosis. His testosterone level is now in the normal range with the testosterone therapy after the work up. CONCLUSION: As per the above case, our patient has an interesting presentation of primary hypogonadism with multiple sclerosis. He has no known reason for his primary testicular failure. We know that testosterone deficiency has been linked to development of MS and MS can lead to secondary hypogonadism. But Primary hypogonadism has not yet been seen with MS although autoimmunity can be postulated to lead to primary testicular failure in these patients, but more studies and investigation will need to be done to establish this cause and effect relationship. REFERENCE: Chitnis T. The role of testosterone in MS risk and course. Mult Scler. 2018 Jan;24(1):36-41. doi: 10.1177/1352458517737395. PMID: 29307293 Presentation: Friday, June 16, 2023

Modern neuroimaging criteria for diagnosing multiple sclerosis in children

The article presents a clinical case of multiple sclerosis (MS) in a 10-year-old female patient, the use of one of the advanced magnetic resonance imaging (MRI) techniques, namely proton magnetic resonance spectroscopy (1H-MRS), in the diagnosis of MS. MRI is an integral part of the diagnostic algorithm for patients with multiple sclerosis according to the McDonald criteria, which were last updated in 2017. In addition, MRI allows assessing the course of the disease, serving as a criterion for confirming the aggravation of the pathological process. Although the McDonald criteria are applied in adults, they are also used to diagnose MS in children, and MS in children has its own particularities. The McDonald criteria include traditional (conventional) MRI sequences: T2-weighted images, T1-weighted images, post-contrast T1-weighted images. With the rapid development of MRI, cutting-edge (advanced) MRI techniques have emerged that allow for a better understanding of changes in the brain matter in MS: brain volumetry, magnetization transfer imaging, cortical imaging, diffusion tensor imaging, 1H-MRS, susceptibility-weighted imaging. In particular, 1H-MRS allows us to assess the degree of white matter integrity by detecting increased resonance of myelin breakdown metabolites. The studies have shown that changes in MS have their own specificity, but there is no consensus on this issue. Currently, there are no agreed guidelines that would include advanced MRI techniques, but we believe they will allow us to better understand the course of MS and to predict the development of the disease. This approach will improve the management of MS in both adults and children and quality of their life.

Features of protein glycosylation in multiple sclerosis

The article presents an analytical review of the published data on the features of protein glycosylation in multiple sclerosis (MS). The search in the PubMed database with the keywords "multiple sclerosis, glycosylation", for the period of 2012-2022, resulted in 12 sources presenting the studies on N-glycosylated plasma proteins and immunoglobulins G in multiple sclerosis, clinically isolated syndrome, neuromyelitis optica spectrum disorders and meningitis of viral etiology in patients' cerebrospinal fluid and blood serum.&#x0D; The studies revealed specific changes in glycoproteins in multiple sclerosis. Glycome changes correlated with the age and sex of patients, with the clinical form of the disease, as well as with the degree of disability on the EDSS scale. These findings can contribute to the early diagnosis of MS, the definition of the form of the disease and its course prediction.&#x0D; Given the diversity of the glycome expression, the differences in its modifications in different environments (serum and blood plasma, cerebrospinal fluid), as well as the variety of approaches to its study (many quantitative and qualitative biochemical methods), there is a prospect of further search for markers and predictors of the course of multiple sclerosis.

Clinical markers for unfavorable course of multiple sclerosis

Objective. To study possible clinical markers associated with the unfavorable course of multiple sclerosis and its transition to a progressive subtype.&#x0D; Materials and methods. This prospective study included healthy volunteers and patients with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS), primary progressive multiple sclerosis (PPMS). For a comprehensive clinical evaluation, the participants completed the Timed 25-Foot Walk Test (T25-FW), Nine-Hole Peg Test (9-HPT), Symbol Digit Modalities Test (SDMT), Fatigue test, and MSProDiscuss questionnaires. Then we compared the results between the groups.&#x0D; Results. We found significant differences between the groups in regard to most of the tests. Furthermore, we proposed a composite clinical score (CCS) based on T25-FW, SDMT, and 9-HPT results (for both hands).&#x0D; Discussion. Our CCS can be a useful clinical tool to determine the most likely course of multiple sclerosis at a certain timepoint.

Cognitive and Emotional Disorders during Multiple Sclerosis – Exogenous and Endogenous Conditions, Contemporary Methods of Treatment and Prevention

Multiple sclerosis (SM) is an autoimmune, demyelinating disease of the central nervous system. The disease affects patients of all ages, with a higher incidence in women. The etiopathogenesis of SM is not fully understood — it is believed that autoreactive lymphocytes play a key role in the development of the disease, although genetic predisposition and environmental factors also play a role. Diagnosis is based on the McDonald criteria, and the disease has different clinical presentations. Treatment is based on immunomodulation, aims to control the disease, and prevent recurrence. Frequent symptoms of the disease are motor, sensory, and cognitive disorders. Cognitive impairment, which is common in multiple sclerosis patients, has numerous consequences in everyday life (mental, social, economic) that significantly reduce the quality of life. Psycho-cognitive dysfunction, which can occur at any stage of the disease, is associated with changes in the central nervous system. Prevention of these disorders includes the early application of treatment methods that modify the natural course of the disease and the implication of pro-health behaviors, such as quitting smoking, proper diet and physical exercise. Pharmacological treatment shows limited effectiveness. Rehabilitation involving the use of compensatory strategies, remedial methods aimed at brain neuroplasticity and cognitive training shaping new functional networks of the brain is important. The aim of this work is to present the problem of cognitive and emotional disorders in the course of multiple sclerosis, with particular emphasis on endo- and exogenous conditions, together with modern methods of their treatment and prevention. (JNNN 2023;12(3):140–146)

Optical coherence tomography with voxel-based morphometry: a new tool to unveil focal retinal neurodegeneration in multiple sclerosis.

Neurodegeneration is the main contributor to disability accumulation in multiple sclerosis. Previous studies in neuro-ophthalmology have revealed that neurodegeneration in multiple sclerosis also affects the neuro-retina. Optical coherence tomography has been used to measure thinning of retinal layers, which correlates with several other markers for axonal/neuronal loss in multiple sclerosis. However, the existing analytical tools have limitations in terms of sensitivity and do not provide topographical information. In this study, we aim to evaluate whether voxel-based morphometry can increase sensitivity in detecting neuroaxonal degeneration in the retina and offer topographical information. A total of 131 people with multiple sclerosis (41 clinically isolated syndrome, 53 relapsing-remitting and 37 progressive multiple sclerosis) and 50 healthy subjects were included. Only eyes with normal global peripapillary retinal nerve fibre layer thickness and no history of optic neuritis were considered. Voxel-based morphometry and voxel-wise statistical comparisons were performed on the following: (i) patients at different disease stages and 2) patients who experienced the first demyelination attack without subclinical optic neuritis, assessed by visual evoked potentials. Standard parameters failed to discern any differences; however, voxel-based morphometry-optical coherence tomography successfully detected focal macular atrophy of retinal nerve fibre layer and ganglion cell/inner plexiform layer, along with thickening of inner nuclear layer in patients who experienced the first demyelination attack (disease duration = 4.2 months). Notably, the atrophy pattern of the ganglion cell/inner plexiform layer was comparable across disease phenotypes. In contrast, the retinal nerve fibre layer atrophy spread from the optic nerve head to the fovea as the disease evolved towards the progressive phase. Furthermore, for patients who experienced the first neurological episode, the severity of retinal nerve fibre layer atrophy at entry could predict a second attack. Our results demonstrate that voxel-based morphometry-optical coherence tomography exhibits greater sensitivity than standard parameters in detecting focal retinal atrophy, even at clinical presentation, in eyes with no history of optic neuritis and with normal latency of visual evoked potentials. Thinning of the ganglion cell/inner plexiform layer primarily concentrated in nasal perifovea in all disease phenotypes, indicating selective vulnerability of retinal ganglion cells and their perifoveal axons. Conversely, the degree of retinal nerve fibre layer thinning seems to be related to the clinical course of multiple sclerosis. The findings suggest bidirectional neurodegeneration in the visual pathway. Voxel-based morphometry-optical coherence tomography shows potential as a valuable tool for monitoring neurodegeneration on a patient level and evaluating the efficacy of novel neuroprotective treatments.

Preventive exercise and physical rehabilitation promote long-term potentiation-like plasticity expression in patients with multiple sclerosis.

Loss of long-term potentiation (LTP) expression has been associated with a worse disease course in relapsing-remitting multiple sclerosis (RR-MS) and represents a pathophysiological hallmark of progressive multiple sclerosis (PMS). Exercise and physical rehabilitation are the most prominent therapeutic approaches to promote synaptic plasticity. We aimed to explore whether physical exercise is able to improve the expression of LTP-like plasticity in patients with multiple sclerosis (MS). In 46 newly diagnosed RR-MS patients, we explored the impact of preventive exercise on LTP-like plasticity as assessed by intermittent theta-burst stimulation. Patients were divided into sedentary or active, based on physical activity performed during the 6 months prior to diagnosis. Furthermore, in 18 patients with PMS, we evaluated the impact of an 8-week inpatient neurorehabilitation program on clinical scores and LTP-like plasticity explored using paired associative stimulation (PAS). Synaptic plasticity expression was compared in patients and healthy subjects. Reduced LTP expression was found in RR-MS patients compared with controls. Exercising RR-MS patients showed a greater amount of LTP expression compared with sedentary patients. In PMS patients, LTP expression was reduced compared with controls and increased after 8 weeks of rehabilitation. In this group of patients, LTP magnitude at baseline predicted the improvement in hand dexterity. Both preventive exercise and physical rehabilitation may enhance the expression of LTP-like synaptic plasticity in MS, with potential beneficial effects on disability accumulation.

Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study

Background/objectiveThe use of natalizumab (NAT) in multiple sclerosis (MS) may be complicated by progressive multifocal leukoencephalopathy (PML), a rare and life-threatening opportunistic brain infection. We aimed to analyze the course of MS after PML recovery together with the long-term outcome of NAT-associated PML (NAT-PML) in Austria.MethodsRetrospective study based on identification of cases in the nationwide Austrian MS treatment registry (AMSTR) and MS centers with review of patient records. The expanded disability status scale (EDSS) was used to measure neurological disability and outcome.ResultsAs of December 2022, we identified 15 NAT-PML cases in Austria; only 20% occurred after 2016, when increased vigilance commenced. Two patients did not survive acute PML, and an additional patient died five years later, yielding a mortality rate of 20%. Seizures occurred exclusively in patients with pronounced EDSS increase. Gadolinium (Gd)-enhancement on brain magnetic resonance imaging (MRI) on PML suspicion was associated with minor changes of post-PML neurological disability. Long-term follow-up of up to 132 months (median 76 months) was available in 11/15. The overall median EDSS increased from 3.5 at pre-PML to 6.5 at the last assessment. Regarding inflammatory MS-related disease activity during the observation period, one single individual experienced an MS relapse and another patient had two Gd-enhancing brain lesions. Three patients converted to progressive MS within three years from PML and the EDSS further increased in 6/11.ConclusionsThe number of NAT-PML cases is decreasing over time. While many patients accumulated severe persistent neurological deficits compared to pre-PML, inflammatory MS-related disease activity after PML recovery was rare.

Internal comorbidities and complications of multiple sclerosis therapy - don't be caught off guard!

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, mainly affecting young adults. Factors positively influencing its course include early antiinflammatory treatment and the influencing of other comorbidities. The most common comorbidities occurring in MS patients with a higher frequency than in the general population are neurological, psychiatric, cardiovascular, metabolic and autoimmune. Just as comorbidity compensation affects the course of MS, in some cases, MS decompensation is associated with a worse course of associated diseases. Due to common risk factors and partially shared immunopathogenesis, treatment covering multiple conditions can be used, especially for some autoimmune diseases. On the other hand, some drugs may potentiate the development of other autoimmunity or disorder. A special topic is the side effects and complications of treatment (especially infections and malignancies) of disease-modifying therapies used in patients with MS. However, the potential treatment discontinuation carries significant risks and should always be discussed with the MS specialist. Therefore, close interdisciplinary collaboration is crucial.

Impact of menopause on relapse rate and disability level in patients with multiple sclerosis (MS): a systematic review and meta-analysis

BackgroundMenopause is a physiologic phase in women’s lives. Findings regarding multiple sclerosis (MS) course through menopause are diverse. So, we designed this systematic review and meta-analysis to estimate the impact of menopause on relapse rate, and disability status in women with MS.MethodsPubMed, Scopus, EMBASE, Web of Science, and google scholar were systematically searched by two independent researchers on January 1st, 2023. They also evaluated conference abstracts, and references of the included studies. In addition, data regarding the total number of participants, name of the first author of the publication, publication year, country of origin, disease duration, disease type, annual relapse rate, and Expanded Disability Status Scale (EDSS) before and after menopause were recorded.ResultsA literature search revealed 1024 records. Twenty-one full texts were evaluated, and finally, four studies were included for meta-analysis. Mean ARR before menopause ranged between 0.21 and 0.37, and after menopause ranged between 0.13 and 0.08. The SMD of mean ARR ranged between − 1.04, and − 0.29, while the pooled SMD was estimated as -0.52(95% CI: -0.88, -0.15) (I2 = 73.6%, P = 0.02). The mean EDSS before menopause ranged between 1.5 and 2, and after menopause ranged between 2 and 3.1. The SMD of EDSS ranged between 0.46, and 0.71. The pooled SMD of EDSS change (after menopause-before menopause) estimated as 0.56(95% CI: 0.38, 0.73)(I2 = 0, P = 0.4).ConclusionThe result of this systematic review and meta-analysis show that menopause can be associated with relapse rate reduction, unlike increase in disease-related disability in women with MS.