Progressive Forms Of Multiple Sclerosis Research Articles

A rapid review of differences in cerebrospinal neurofilament light levels in clinical subtypes of progressive multiple sclerosis.

Multiple sclerosis (MS) is divided into three clinical phenotypes: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). It is unknown to what extent SPMS and PPMS pathophysiology share inflammatory or neurodegenerative pathological processes. Cerebrospinal (CSF) neurofilament light (NfL) has been broadly studied in different MS phenotypes and is a candidate biomarker for comparing MS subtypes. Are CSF NfL levels different among clinical subtypes of progressive MS? A search strategy identifying original research investigating fluid neurodegenerative biomarkers in progressive forms of MS between 2010 and 2022 was applied to Medline. Identified articles underwent title and abstract screen and full text review against pre-specified criteria. Data abstraction was limited to studies that measured NfL levels in the CSF. Reported statistical comparisons of NfL levels between clinical phenotypes were abstracted qualitatively. 18 studies that focused on investigating direct comparisons of CSF NfL from people with MS were included in the final report. We found NfL levels were typically reported to be higher in relapsing and progressive MS compared to healthy controls. Notably, higher NfL levels were not clearly associated with progressive MS subtypes when compared to relapsing MS, and there was no observed difference in NfL levels between PPMS and SPMS in articles that separately assessed these phenotypes. CSF NfL levels distinguish individuals with MS from healthy controls but do not differentiate MS subtypes. Broad biological phenotyping is needed to overcome limitations of current clinical phenotyping and improve biomarker translatability to decision-making in the clinic.

Co-supplementation of synbiotics and anti-inflammatory-antioxidant rich diet in patients with progressive forms of multiple sclerosis: A single-center, randomized clinical trial

BACKGROUND: The relationship between dietary modification and Multiple Sclerosis (MS)-related disability has been emphasized in several researches. AIMS: To determine whether a co-administration of anti-inflammatory-antioxidant rich diet and synbiotics might improve clinical manifestations in progressive MS patients. METHODS: The study involved 70 patients with progressive MS (primary-progressive, secondary-progressive, and progressive-relapsing) who were randomized to receive either intervention (synbiotics capsule plus an anti-inflammatory-antioxidant-rich diet) or placebo. Quality of Life (QOL), Expanded Disability Status Scale (EDSS), and depression-anxiety scores were evaluated before and after the follow-up. Analysis of covariance was performed for final analysis (SPSS v.14). RESULTS: Significant reductions were seen in EDSS (2.6±1.1 to 2.4±1.0, P < 0.001), State Anxiety Inventory (53.7±10.3 to 47.8±10.6, P < 0.001), and QOL scores after four months of intervention. No significant difference was seen across the depression severity (Δ for intervention = –2.2±5.5 vs. Δ for control = –0.6±5.7; P = 0.264). CONCLUSION: This study demonstrates that a combination of synbiotics and diet could be a promising strategy to improve severity and clinical manifestations of progressive MS.

HUMORAL IMMUNITY IN PATIENTS WITH MULTIPLE SCLEROSIS

Introduction. More than 1 million people in the world suffer from multiple sclerosis (MS). The etiology of MS remains not fully understood. The main role in the pathogenesis of MS belongs to the combination of chronic inflammation and neurodegenerative processes, in the genesis of which autoimmune processes play a significant role. Progress in studying the mechanisms of the pathological process of demyelinating diseases has been achieved mainly thanks to immunological research. One of the manifestations of activation of humoral immunity in MS is increased synthesis of immunoglobulins in brain tissue and cerebrospinal fluid
 The aim of the study. To study the state of humoral immunity in multiple sclerosis patients with different types of disease course
 Research methods. 68 patients with a verified diagnosis of multiple sclerosis (MS) based on the MacDonald et al criteria aged 19 to 65 years (37 women, 29 men) were examined. The primary progressive type of the course was established in 19 patients, the secondary-progressive - in 3, the remitting-relapsing type of the course - in 26 patients. The control group consisted of 80 practically healthy male volunteers aged 25-45 years.
 The concentration of immunoglobulins A, G, M in blood serum was determined by the Mancini method (1965). The content of circulating immune complexes (CIC) in blood serum was determined by the method of precipitation in polyethylene glycol.
 Results and discussion. The highest content of Ig A was observed in the group of patients with primary progressive form of MS, which was 3.7 times higher than normal values and 1.2 times higher than in the general group of MS patients. In the group of patients with the secondary progressive form of MS, the content of Ig A was 3.1 times higher than in the control group and 1.2 times lower than in the group with the primary progressive form. In the group of patients with relapsing-remitting form of MS, there was an increase in the level of Ig A three times relative to the normal indicator, and a decrease (by 1.2 times) relative to the level in the group with a primary progressive form of MS.
 The content of Ig M in the blood serum of patients with MS exceeded the norm by 5 times. In the group with the primary progressive form of MS, the level of Ig M was 3.5 times higher than the level in the control group and 1.5 times lower than the level in the group of patients with MS. In patients with secondary progressive form of MS, the content of Ig M was 2.6 times higher than the norm, but 1.3 times lower than the level in the group with primary progressive form of MS and 1.9 times lower than in the group of patients with MS. In patients with the relapsing-remitting form of MS, the level of Ig M was: 4.6 times higher than the level in the control group and 1.7 times higher than the content in patients with the secondary-progressive form of MS, and also 1.3 times higher, than in the group with the primary progressive form.
 In all groups of patients with MS with different types of the course of the disease, the most pronounced increase in the level of Ig G was noted.
 The highest level of CIC was recorded in the general group of patients with MS and in the group with secondary progressive form of MS.
 Conclusions. An imbalance of the humoral link of immunity was observed in patients with multiple sclerosis. A probable increase in the concentration of Ig A in the blood serum of patients with multiple sclerosis indicates the presence of infection of the mucous membranes, which is especially pronounced in patients with the primary progressive form of multiple sclerosis. A significant increase in the content of Ig G in the blood serum of patients with multiple sclerosis indicates a chronic course of the process, which is especially evident in the relapsing-relapsing form of multiple sclerosis. An increased concentration of IgM in the blood serum of patients with multiple sclerosis may indicate an exacerbation of the course of chronic inflammation, especially in the case of relapsing-remitting multiple sclerosis. The detected fluctuations of the average content of CIC in the blood serum of patients with multiple sclerosis did not go beyond the physiological norm.

Why do we so rarely recognise and treat the primary progressive form of multiple sclerosis?

The primary progressive form of multiple sclerosis is characterised by a systematic increase in disability from the onset of the disease, usually without overlapping relapses. It is estimated that it accounts for 10–15% of all cases of multiple sclerosis, occurs with similar frequency in both sexes, and its symptoms appear at an older age, usually after 40. The initial manifestation usually consists of pyramidal symptoms and myelopathy. The most typical symptoms include progressive gait and sphincter function impairment. Symptoms of cerebellar syndrome, truncal syndromes, as well as visual and cognitive disturbances are less common. The clinical course with characteristic symptomatology resulting from the location of the changes primarily in the spinal cord, followed by the occurrence of initial symptoms, means that this form of multiple sclerosis requires careful differential diagnosis. It should be differentiated primarily from diseases causing lower limb paresis (myelopathy associated with vitamin B12 deficiency, amyotrophic lateral sclerosis, spinal cerebellar ataxia, neuromyelitis optica spectrum disorder, Wernicke’s encephalopathy, Lyme disease, and spinal cord tumours). The diagnosis of primary progressive multiple sclerosis should be guided by the current 2017 McDonald diagnostic criteria. Understanding these criteria and being aware of the differences from the most common relapsing-remitting form of multiple sclerosis can be helpful in speeding up the diagnosis and implementing effective treatment. Even though new treatment options have emerged in recent years, primary progressive multiple sclerosis is still little known and too rarely recognised.

OPERA and ORATORIO – how the world has been changed by “music”

Multiple sclerosis is a chronic autoimmune disease that progresses over time, leading to disability. The condition is still incurable, but available therapies are increasingly effective. Ocrelizumab is the first anti-CD20 monoclonal antibody approved for the treatment of relapsing-remitting and primary progressive forms of multiple sclerosis. In the article, based on the results of the OPERA and ORATORIO clinical trials, their extensions, and post-hoc and meta-analyses, the evidence for long-term high effectiveness of the molecule is presented. Aspects including the control of relapses (annual relapse rate and time to relapse), delay in the occurrence of confirmed disability, probability to achieve disability improvement, need to use a wheelchair and loss of upper limb mobility, as well as radiological activity (gadolinium-enhancing lesions, new T2 lesions, brain atrophy), are assessed. An additional advantage of the OPERA studies is that almost similar results, acquired with identical protocols in a different patient populations, were achieved. Moreover, the effects of therapy did not wear off over time. Based on these findings, ocrelizumab can be regarded as a highly effective therapy in multiple sclerosis, with the highest (48%) NEDA-3 index (no evidence of disease activity) and the greatest potential for delaying the onset of confirmed disability. The presented studies also confirm the benefit of introducing the drug in multiple sclerosis therapy as early as possible.

Multiple sclerosis and seizures: A retrospective observational study in a multiple sclerosis autoimmunity center of excellence

PurposeThe prevalence of epilepsy in patients with multiple sclerosis (MS) is three to six times the prevalence in the general population. Mechanisms resulting in increased seizure risk are not fully understood. Our objective is to characterize patients with MS and epilepsy regarding timing of diagnoses, MS and seizure (SZ) type, EEG findings suggesting cortical dysfunction, frequency of status epilepticus (SE), and seizure freedom. MethodsThis was a single center retrospective study. Cases were obtained via DataDirect via the University of Michigan electronic medical record from January 1, 2006 through October, 12, 2016. The University of Michigan Health System is a large academic institute with a tertiary referral center and an Autoimmunity Center of Excellence. Patients were included if chart listed one or more of the top 62 epilepsy, and one or more of the top 2 MS, most frequently entered ICD9 and ICD10 codes. Patients with alternative epilepsy etiology were excluded. 74 of 361 patients were included. We collected information regarding demographics, MS and SZ type, age at diagnosis, imaging, EEG, seizure freedom, medications, and SE. ResultsWe found a high percentage of patients with SE. Most patients with imaging had multiple lesions at seizure onset. 27/54 of patients with EEG data showed electrographic evidence of cortical dysfunction. 6/8 of EEGs in PPMS showed features consistent with cortical dysfunction, followed by 9/17 in SPMS and 11/23 in RRMS. 7/8 of patients with PPMS showed EEG evidence of temporal lobe dysfunction. ConclusionTime of seizure onset relative to MS diagnosis varied with MS type suggesting distinct pathophysiology. EEG results correspond with reports of increased cortical damage and temporal dysfunction in PPMS, but are unique as a functional modality (EEG) as indicator of gray matter dysfunction. EEG findings differed in RRMS and progressive MS suggesting possibility of supportive diagnostic marker. Our data suggests higher risk of SE in progressive MS and diminished rate of seizure freedom for MS patients with SE. We conclude that early treatment with antiseizure medication would be beneficial for MS patients with SE and with progressive MS forms and SZ, in agreement with previous studies.

Claims-based algorithm to estimate the Expanded Disability Status Scale for multiple sclerosis in a German health insurance fund: a validation study using patient medical records.

The Expanded Disability Status Scale (EDSS) quantifies disability and measures disease progression in multiple sclerosis (MS), however is not available in administrative claims databases. To develop a claims-based algorithm for deriving EDSS and validate it against a clinical dataset capturing true EDSS values from medical records. We built a unique linked dataset combining claims data from the German AOK PLUS sickness fund and medical records from the Multiple Sclerosis Management System 3D (MSDS3D). Data were deterministically linked based on insurance numbers. We used 69 MS-related diagnostic indicators recorded with ICD-10-GM codes within 3 months before and after recorded true EDSS measures to estimate a claims-based EDSS proxy (pEDSS). Predictive performance of the pEDSS was assessed as an eight-fold (EDSS 1.0-7.0, ≥8.0), three-fold (EDSS 1.0-3.0, 4.0-5.0, ≥6.0), and binary classifier (EDSS <6.0, ≥6.0). For each classifier, predictive performance measures were determined, and overall performance was summarized using a macro F1-score. Finally, we implemented the algorithm to determine pEDSS among an overall cohort of patients with MS in AOK PLUS, who were alive and insured 12 months prior to and after index diagnosis. We recruited 100 people with MS insured by AOK PLUS who had ≥1 EDSS measure in MSDS3D between 01/10/2015 and 30/06/2019 (620 measurements overall). Patients had a mean rescaled EDSS of 3.2 and pEDSS of 3.0. The pEDSS deviated from the true EDSS by 1.2 points, resulting in a mean squared error of prediction of 2.6. For the eight-fold classifier, the macro F1-score of 0.25 indicated low overall predictive performance. Broader severity groupings were better performing, with the three-fold and binary classifiers for severe disability achieving a F1-score of 0.68 and 0.84, respectively. In the overall AOK PLUS cohort (3,756 patients, 71.9% female, mean 51.9 years), older patients, patients with progressive forms of MS and those with higher comorbidity burden showed higher pEDSS. Generally, EDSS was underestimated by the algorithm as mild-to-moderate symptoms were poorly captured in claims across all functional systems. While the proxy-based approach using claims data may not allow for granular description of MS disability, broader severity groupings show good predictive performance.

Use of interferons in secondary progressive forms of multiple sclerosis. Efficacy, safety and quality of life of patients treated with these therapies

Use of interferons in secondary progressive forms of multiple sclerosis. Efficacy, safety and quality of life of patients treated with these therapies

Biological aging in multiple sclerosis.

Multiple sclerosis (MS) is most likely to adopt a progressive clinical course during middle age or beyond, and the number of older adults with MS is steadily increasing. Developing new strategies to manage progressive forms of MS, which do not respond to currently available disease-modifying therapies (DMTs), will require a deeper understanding of the mechanisms by which biological aging interacts with pathogenic pathways to propel disability accumulation. In experimental autoimmune encephalomyelitis (EAE), a widely used preclinical mouse model of MS, middle-aged animals experience a more severe and protracted clinical course than their younger counterparts. This exacerbated disease course is accompanied by persistent neuroinflammation. Clinical studies of age-related biomarkers, such as telomere length, senescence markers, and DNA methylation, suggest that biological aging is accelerated in people with MS compared with age- and sex-matched healthy controls. Furthermore, distinguishing biological age from chronological may afford more precision in determining aging effects in MS. Here we review the current literature on aging biology and its impact on MS pathogenesis. Future research on this topic may lead to the development of novel biomarkers and senotherapy agents that slow neurological decline in people with progressive MS by targeting relevant aging-related pathways.

Self-reports by persons with multiple sclerosis are an adequate surrogate for healthcare provider data on disease-modifying therapy and multiple sclerosis type

IntroductionSelf-reports are a valuable and cost-effective method of data collection, though they can be influenced by bias. Limited evidence exists on the quality of self-reports by persons with multiple sclerosis (pwMS), particularly since more potent disease-modifying therapies (DMTs) have been introduced. This study aimed to assess the reliability and validity of self-reported DMT use and multiple sclerosis (MS) type in the Swiss Multiple Sclerosis Registry (SMSR) by comparing self-reports with reimbursement approval requests from the Swiss Association for Joint Tasks of Health Insurers. MethodsThe self-reported and reimbursement approval data were linked using privacy-preserving methods based on information available in both databases, i.e., date of birth, canton of residence, sex, and year of MS diagnosis. The SMSR baseline questionnaire data was utilized for the main analysis, while the SMSR follow-up survey data was utilized for the sensitivity analysis. For both analyses, we compared self-reported data with reimbursement approval data that corresponded to the respective periods of the SMSR data collection. Thus, the main analysis included the entirety of the data over the six-year period, while the sensitivity analysis captured a more recent snapshot of the data. To assess reliability, we estimated agreement using Cohen's kappa, and for validity, we estimated accuracy parameters using reimbursement approvals as the reference standard. Univariable and multivariable logistic regression models were employed to investigate factors associated with discordance between self-reports and reimbursement approvals in the main analysis. ResultsThe main analysis included 446 participants, and the sensitivity analysis included 193 participants. The agreement between self-reported and reimbursement approval data for medication use was near-perfect in both analyses (κ = 0.87, 95% confidence interval (CI) 0.85, 0.90 and κ = 0.82, 95% CI 0.76, 0.88). However, the agreement between self-reported and reimbursement approval-documented MS types ranged from fair to moderate (κ = 0.37, 95% CI 0.25, 0.48 to κ = 0.61, 95% CI 0.46, 0.77). The accuracy estimates for self-reported DMT use were generally high (≥ 0.80) with narrow CIs, except for less frequently reported drugs. While the sensitivity and specificity for RRMS were high, there was a notable possibility of false-negative self-reports for RRMS (NPV = 0.33, 95% CI 0.22, 0.45), and false-positive reports for SPMS (PPV = 0.36, 95% CI 0.21, 0.54). Multivariable logistic regression models showed that age (OR = 1.07, 95% CI 1.04, 1.10 per year) and education level (OR = 0.27, 95% CI 0.11, 0.65) were associated with discordance in reported and documented MS types, whereas possession of Swiss citizenship (OR = 0.32, 95% CI 0.14, 0.72) was associated with discordance in DMT use. ConclusionSelf-reported DMT use in pwMS is a reliable and valid information source, with near-perfect agreement and high accuracy. Self-reported MS types showed fair to moderate agreement and varying accuracy, likely reflecting the complexity of diagnosing progressive forms of MS and access to DMTs. In population-based MS research, self-reports of MS types, and particularly DMT use, can serve as a suitable surrogate for healthcare provider data.

Impact of comorbid primary headache on neurological function of patients with multiple sclerosis

Multiple Sclerosis (MS) is a progressive disease affecting the working population. Due to the demyelination process, patients have motor, sensory and cognitive impairments. Often patients with MS complain of headaches. Comorbid primary headache accompanies more than half of patients with MS. The aim of our study was to reveal the relationship between the presence of primary comorbid headache and the progression of MS. For this purpose, the Expanded Disability Status Scale (EDSS), motor testing for 25-Foot Walk Test (25FWT), 9-Hole Peg Test (9HPT) were used. International Classification of Headache - 3 (ICHD-3) scale was used for differential diagnosis of headache types. The obtained data were compared among patients with different types of MS: Relapsing-Remitting (RRMS); primary and secondary progressive, which was combined into Progressive forms of MS (PMS). 130 patients with MS were studied, among whom patients with RRMS prevailed (n=98), primary comorbid headache was found in 56.2% (n=73). Among patients with MS, migraine prevailed (p=0.015), in particular, the most cases were found in patients with RRMS. Among patients with PMS, tension headache prevailed (p&lt;0.05). The 9HPT and 25FWT scores did not differ significantly between the groups with and without primary comorbid headache, however, according to the confidence intervals, the EDSS score exceeded the score in the group of patients with comorbid headache. It was found that patients with comorbid migraine performed the motor test faster than patients with tension type headache. Therefore, it can be concluded that comorbid primary headache may have an impact on motor function indicators among MS patients and requires further investigation to determine the role of comorbid headache in the patterns of initial MS symptoms. Keywords: central nervous system, demyelination, migraine, tension type headache, motor function, comorbidity.

Prospects of treatment of progressive forms of multiple sclerosis by transplantation of stem cells (review)

Prospects of treatment of progressive forms of multiple sclerosis by transplantation of stem cells (review)

NfL and GFAP in serum are associated with microstructural brain damage in progressive multiple sclerosis.

The potential of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) as biomarkers of disease activity and severity in progressive forms of multiple sclerosis (MS) is unclear. To investigate the relationship between serum concentrations of NfL, GFAP, and magnetic resonance imaging (MRI) in progressive MS. Serum concentrations of NfL and GFAP were measured in 32 healthy controls and 32 patients with progressive MS from whom clinical and MRI data including diffusion tensor imaging (DTI) were obtained during three years of follow-up. Serum concentrations of NfL and GFAP at follow-up were higher in progressive MS patients than in healthy controls and serum NfL correlated with the EDSS score. Decreasing fractional anisotropy (FA) in normal-appearing white matter (NAWM) correlated with worsening EDSS scores and higher serum NfL. Higher serum NfL and increasing T2 lesion volume correlated with worsening paced autitory serial addition test scores. In multivariable regression analyses with serum GFAP and NfL as independent factors and DTI measures of NAWM as dependent factors, we showed that high serum NfL at follow-up was independently associated with decreasing FA and increasing MD in NAWM. Moreover, we found that high serum GFAP was independently associated with decreasing MD in NAWM and with decreasing MD and increasing FA in cortical gray matter. Serum concentrations of NfL and GFAP are increased in progressive MS and are associated with distinct microstructural changes in NAWM and CGM.

Wobbly hedgehog syndrome- a progressive neurodegenerative disease

Wobbly hedgehog syndrome (WHS) has been long considered to be a myelin disease primarily affecting the four-toed hedgehog. In this study, we have shown for the first time that demyelination is accompanied by extensive remyelination in WHS. However, remyelination is not enough to compensate for the axonal degeneration and neuronal loss, resulting in a progressive neurodegenerative disease reminiscent of progressive forms of multiple sclerosis (MS) in humans. Thus, understanding the pathological features of WHS may shed light on the disease progression in progressive MS and ultimately help to develop therapeutic strategies for both diseases.

Anti-inflammatory-antioxidant modifications and synbiotics improved health-related conditions in patients with progressive forms of multiple sclerosis: A single-center, randomized clinical trial

Background and purposeThere is growing evidence that dietary modification can improve clinical manifestations in multiple sclerosis (MS) patients. This study aimed to assess the impact of synbiotics and anti-inflammatory-antioxidant-rich diet on fatigue, pain, gut and bladder status, and sexual function in patients with progressive forms of MS. Materials and methodsIn this single-center, single-blind, randomized, controlled clinical trial, seventy participants with three forms of progressive MS (primary-progressive, secondary-progressive, and progressive-relapsing) were randomly assigned to receive either synbiotics supplement and anti-inflammatory-antioxidant-rich diet or a placebo along with their usual diet for a duration of four months. Modified fatigue impact scale (MFIS), global pain scale (GPS), bladder control scale (BLCS), bowel control scale (BWCS), and sexual satisfaction scale (SSS) were assessed at baseline and at the end of the trial. ResultsSixty-nine participants successfully completed the trial, resulting in a 98% adherence rate to the diet, and no reports of serious side effects. Significant mean changes were observed in fatigue (Δ for experimental group = −10.5 ± 10.8 vs. Δ for control group = −0.08 ± 4.1; P < 0.001), pain (−14.1 ± 19.0 vs. 0.9 ± 10.3; P < 0.001), bladder (−0.76 ± 2.1 vs. 0.3 ± 1.1; P = 0.013) and bowel (−6.6 ± 3.2 vs. −0.05 ± 2.3; P < 0.001) control, as well as sexual function (−1.0 ± 2.3 vs. 0.51 ± 0.21; P < 0.001). ConclusionThe anti-inflammatory-antioxidant-rich diet and synbiotics co-supplementation demonstrated improvements in fatigue, pain, sexual function, and bowel/bladder status among patients with progressive MS.

Ferroptosis induces detrimental effects in chronic EAE and its implications for progressive MS

Ferroptosis is a form of lipid peroxidation-mediated cell death and damage triggered by excess iron and insufficiency in the glutathione antioxidant pathway. Oxidative stress is thought to play a crucial role in progressive forms of multiple sclerosis (MS) in which iron deposition occurs. In this study we assessed if ferroptosis plays a role in a chronic form of experimental autoimmune encephalomyelitis (CH-EAE), a mouse model used to study MS. Changes were detected in the mRNA levels of several ferroptosis genes in CH-EAE but not in relapsing–remitting EAE. At the protein level, expression of iron importers is increased in the earlier stages of CH-EAE (onset and peak). While expression of hemoxygenase-1, which mobilizes iron from heme, likely from phagocytosed material, is increased in macrophages at the peak and progressive stages. Excess iron in cells is stored safely in ferritin, which increases with disease progression. Harmful, redox active iron is released from ferritin when shuttled to autophagosomes by ‘nuclear receptor coactivator 4’ (NCOA4). NCOA4 expression increases at the peak and progressive stages of CH-EAE and accompanied by increase in redox active ferrous iron. These changes occur in parallel with reduction in the antioxidant pathway (system xCT, glutathione peroxidase 4 and glutathione), and accompanied by increased lipid peroxidation. Mice treated with a ferroptosis inhibitor for 2 weeks starting at the peak of CH-EAE paralysis, show significant improvements in function and pathology. Autopsy samples of tissue sections of secondary progressive MS (SPMS) showed NCOA4 expression in macrophages and oligodendrocytes along the rim of mixed active/inactive lesions, where ferritin+ and iron containing cells are located. Cells expressing NCOA4 express less ferritin, suggesting ferritin degradation and release of redox active iron, as indicated by increased lipid peroxidation. These data suggest that ferroptosis is likely to contribute to pathogenesis in CH-EAE and SPMS.

Dance for Multiple Sclerosis: A Systematic Review.

Evidence of the benefits of dance for people with Parkinson disease is well established, but only recently has dance been investigated for people with multiple sclerosis (MS). The purpose of this review was to identify and evaluate the feasibility and effectiveness of dance interventions to improve functional, psychosocial, and participation outcomes in people with MS. Eight databases and gray literature sources were searched from inception to March 2022. Quantitative, mixed-methods, and qualitative studies evaluating dance interventions for adults with MS were included. Included studies were critically appraised using the Mixed Methods Appraisal Tool, and results were analyzed through a parallel-results convergent synthesis. Thirteen studies were included, with a total of 174 participants. Various dance genres were investigated, and only 1 mild adverse event was reported. Four to 12 weeks of twice-weekly, 60-minute dance sessions were feasible in those with mild to moderate relapsing-remitting MS. Positive effects were identified mainly in motor outcomes, with qualitative themes indicating psychological and social benefits. A variety of dance interventions are likely feasible and potentially beneficial for people with mild to moderate relapsing-remitting MS, but studies were generally of low-moderate quality. High-quality studies are needed to determine the effectiveness of dance interventions for people with MS, including those with progressive forms of MS and higher levels of disability.

Protocolo diagnóstico de las mielitis y otras mielopatías

The initial strategy to clarify the etiology of a myelopathy is based on a combination of semiology, temporal pattern of onset and magnetic resonance findings. We may divide myelopathies into hyperacute (onset within hours, usually with a traumatic or vascular cause), acute-subacute (onset between one day and three weeks, including neoplastic, immune and infectious causes) and chronic (progression of the symptoms beyond 3 weeks, with metabolic, hereditary degenerative or structural causes such as dural fistulas and spondylosis, among others, although progressive forms of multiple sclerosis may present this temporary pattern). Spinal cord lesions in multiple sclerosis are usually short and peripheral, while in neuromyelitis optica they extend more than three vertebral segments, whereas involvement of the conus medullaris is typical in IgG-MOG disease.

Autologous hematopoietic stem cell transplantation in multiple sclerosis: A 20-year single center’s experience in Mexico. (P14-3.015)

<h3>Objective:</h3> To describe the clinical characteristics and clinical outcomes of AHSCT in Mexican patients. <h3>Background:</h3> Autologous Hematopoietic Stem Cell treatment (AHSCT) is an immune reconstitution treatment option for Multiple Sclerosis (MS) that has grown in clinical evidence over the last decades; detailed efficacy and safety data is still lacking, especially outcomes data from low-income countries. <h3>Design/Methods:</h3> Retrospective single-center observational study of all MS patients that underwent AHSCT in a single reference center in Mexico City from January 2000 to January 2020. <h3>Results:</h3> We identified 24 patients, of which 22 had at least one year of follow-up after AHSCT and underwent analysis for clinical outcome. The median follow-up time was 85 months (range: 12–267); with a median age of 44.0 years (IR 38–52); 62.8% (n=15) were men and 31.8% (n=7) women; 50% were secondary progressive forms of MS (SPMS), and 27.3% were relapsing-remitting MS (RRMS); 59% (n=13) met the criteria for highly active MS (HAMS). The composite score of no evidence of disease activity 3 or NEDA3 (no relapses, no new MRI lesions, and no EDSS progression) was achieved in all the patients at a 24-month follow-up and in 72.1% (n=16) of the patients at the time of the last follow up visit. Relapse-free survival at the last follow-up visit was achieved at 77.3%; MRI event-free survival at 90.9%; Expanded disability status scale score progression-free survival in 95.4%. Only one patient required the re-initiation of disease-modifying therapy. There was no treatment-related mortality. One patient was diagnosed with premature ovarian failure. <h3>Conclusions:</h3> AHSCT in Mexican MS patients is an effective and relatively safe treatment option with no mortality and can be performed with a reasonable degree of safety at experienced centers. <b>Disclosure:</b> Dr. Rodriguez Estrada has nothing to disclose. Dr. Molina Carrion has nothing to disclose.

Impact of a specific consultation for patients with progressive forms of multiple sclerosis on the response to their unmet care needs: a cross-sectional study.

As their disease evolves, most patients with progressive forms of multiple sclerosis (MS) develop particular healthcare needs that are not always addressed with usual follow-up. To adapt neurological care to these patients, we created a specific consultation for patients with progressive MS in our centre in 2019. To explore the main unmet care needs of patients with progressive MS in our setting, and to establish the usefulness of the specific consultation to address them. Literature review and interviews with patients and healthcare professionals were conducted to identify the main unmet needs in routine follow-up. Two questionnaires were developed, assessing the importance of the unmet needs identified and the usefulness of the consultation to meet them, for patients under follow-up in the specific consultation and their informal caregivers. Forty-one patients and nineteen informal caregivers participated. The most important unmet needs were the information about the disease, access to social services and coordination between specialists. A positive correlation was found between the importance of these unmet needs and the responsiveness to each of them in the specific consultation. The creation of a specific consultation may improve attention to the healthcare needs of patients with progressive MS.