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Climate change, including global warming, will cause poorer global health and rising numbers of environmental refugees. As neurological disorders account for a major share of morbidity and mortality worldwide, global warming is also destined to alter neurological practice; however, to what extent and by which mechanisms is unknown. We aimed to collect information about the effects of ambient temperatures and human migration on the epidemiology and clinical manifestations of neurological disorders. We searched PubMed and Scopus from 01/2000 to 12/2020 for human studies addressing the influence of ambient temperatures and human migration on Alzheimer's and non-Alzheimer's dementia, epilepsy, headache/migraine, multiple sclerosis, Parkinson's disease, stroke, and tick-borne encephalitis (a model disease for neuroinfections). The protocol was pre-registered with PROSPERO (2020 CRD42020147543). Ninety-three studies met inclusion criteria, 84 of which reported on ambient temperatures and nine on migration. Overall, most temperature studies suggested a relationship between increasing temperatures and higher mortality and/or morbidity, whereas results were more ambiguous for migration studies. However, we were unable to identify a single adequately designed study addressing how global warming and human migration will change neurological practice. Still, extracted data indicated multiple ways by which these aspects might alter neurological morbidity and mortality soon. Significant heterogeneity exists across studies with respect to methodology, outcome measures, confounders and study design, including lack of data from low-income countries, but the evidence so far suggests that climate change will affect the practice of all major neurological disorders in the near future. Adequately designed studies to address this issue are urgently needed, requiring concerted efforts from the entire neurological community.
X-linked adrenoleukodystrophy (X-ALD) is a rare, inherited peroxisomal disorder caused by pathogenic variants in the ABCD1 gene, which encodes an ATP-binding cassette transporter located on Xq28. These pathogenic variants result in defective peroxisomal beta-oxidation and accumulation of very long-chain fatty acids (VLCFAs) in plasma and tissues, primarily affecting the adrenal cortex, myelin in the central nervous system, and Leydig cells. The estimated incidence is approximately 1 in 17,000 individuals (Kemp et al. 2016). Clinically, X-ALD is characterized by a broad phenotypic spectrum, including three main presentations: isolated adrenocortical insufficiency, adrenomyeloneuropathy (AMN), and cerebral X-ALD (Raymond et al. 1999). Considerable clinical overlap exists among these forms, and disease severity can vary. The cerebral form most commonly presents in childhood, between ages 4 and 8, whereas adult-onset cerebral X-ALD is rare, representing only about 1% of cases (Bezman et al., American Journal of Medical Genetics. 76(5):415-419, 1998). The parieto-occipital white matter is classically involved, while predominant frontal lobe lesions are unusual. Misdiagnosis is frequent, with rates up to 31%, particularly when cognitive and behavioral changes mimic frontotemporal dementia (Jiang et al., Acta Neurologica Belgica. 123(6):2259-2268, 2023). This report describes a 53-year-old man with an atypical adult-onset cerebral X-ALD presenting with frontal lobe involvement and rapid progression. The case underscores the importance of considering X-ALD in adults presenting with atypical cognitive decline and non-classical MRI patterns.
OBJECTIVE: To evaluate the long-term safety (≥12 months) of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) or its receptor in migraine prevention by synthesising evidence from clinical trials and real-world studies. We focus on drug discontinuation due to adverse events and the type and frequency of adverse events. This is the first review to analyse the effects of the long-term use of all anti-CGRP (receptor) mAbs, aiming to provide novel insights for clinical practice and future treatment strategies. METHODS: We systematically searched PubMed, Cochrane Library, and ClinicalTrials.gov for studies with ≥12 months of anti-CGRP (receptor) mAb use between January 2013 and April 2025. A random-effects meta-analysis of proportions (logit transformation, inverse variance weighting, restricted maximum likelihood) was performed to estimate pooled discontinuation and adverse event rates. Risk of bias was assessed using the ROBINS-I score. RESULTS: From a total of 1,499 records, 14 met the inclusion criteria and were eligible for data analysis. These 14 records corresponded to 11 individual studies with observational durations all exceeding 12 months. Seven studies investigated erenumab, two eptinezumab, and one each fremanezumab and galcanezumab. All studies were judged to have a severe risk of bias due to their underlying design. The overall pooled proportion of treatment discontinuation for any reason among patients receiving anti-CGRP (receptor) mAbs was 23%, whereas the pooled proportion of discontinuation specifically due to adverse events was substantially lower at 3%. Time-trend analysis showed that adverse event–related discontinuation remained low (<5%) beyond the first year, while overall adverse event incidence was high at baseline (>70%) but did not further increase with prolonged follow-up. CONCLUSION: Evidence on long-term use of anti-CGRP (receptor) mAbs over 12 months remains limited, but our analysis indicates good tolerability with consistently low adverse event-related discontinuation, no emergent safety signals, and largely non-serious, stable adverse event profiles. However, heterogeneity and study-level bias warrant cautious interpretation, highlighting the need for long-term clinical studies and continued real-world surveillance (e.g. registries). CLINICAL TRIAL NUMBER: Not applicable.
Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18-39 years), transition onset (40-49 years), LOMS (50-59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93). LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.
Live attenuated measles-mumps-rubella (MMR) and varicella vaccines are recommended for immunocompetent people with multiple sclerosis (MS) lacking immunity. However, concerns about postvaccination relapses may contribute to vaccine hesitancy, and robust data addressing this risk remain limited. To assess whether the risk of MS relapse within 1 year after MMR or varicella vaccination is not unacceptably worse than risk after no such vaccination based on a predefined noninferiority margin. This cohort study used prospectively collected data from July 2016 to October 2024 for people with MS at a tertiary MS center in Barcelona, Spain, who received at least 1 dose of live attenuated MMR and/or varicella vaccine due to serologic susceptibility. Vaccinated patients were matched 1:2 with unvaccinated control individuals with MS by sex, age, and epoch of first demyelinating event. Live attenuated MMR and/or varicella vaccine. Primary outcomes were relapse count and time to first relapse within 1 year of time 0, analyzed using Poisson and Cox proportional hazards regression models with inverse probability weighting based on a propensity score including treatment category, Expanded Disability Status Scale score, and annualized relapse rate in the prior year. Noninferiority was predefined as an annualized relapse rate ratio with an upper bound of the 95% CI less than 1.4. A total of 369 people with MS were included, of whom 123 were vaccinated (mean [SD] age, 28.75 [8.72] years; 85 females [69.1%]) and matched to 246 unvaccinated controls (mean [SD] age, 28.66 [8.60] years; 170 females [69.1%]). Overall, 36 relapse events were observed (15 [41.7%] among vaccinated patients and 21 [58.3%] among unvaccinated controls). In the weighted Poisson model, although relapse incidence was not significantly different between vaccinated and unvaccinated individuals (incidence rate ratio, 0.52; 95% CI, 0.23-1.06), the noninferiority criterion was met. Similarly, weighted Cox proportional hazards regression models showed no difference in hazard of relapse between groups (hazard ratio [HR], 0.55; 95% CI, 0.25-1.17) but the noninferiority criterion was met. Sensitivity and exploratory analyses, including time-dependent adjustment for postbaseline treatment exposure (HR, 0.60; 95% CI, 0.27-1.33), restriction to the high-risk period (n = 15 events), and comparisons of magnetic resonance imaging before (n = 43 events) and after (n = 21 events) exposure in vaccinated patients, revealed findings consistent with those of the primary analysis. In this cohort study of nonimmunosuppressed people with MS, vaccination with live attenuated MMR or varicella vaccine was not associated with increased risk of postvaccination relapse. The results support the administration of these vaccines when indicated and may help reassure clinicians and patients, reducing vaccine hesitancy.
Myasthenia gravis, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are antibody-mediated neuroimmune disorders that frequently affect women in their reproductive years and require careful treatment planning around pregnancy. Disease exacerbations (for myasthenia gravis) and attacks (for NMOSD and MOGAD) can occur during pregnancy, are common postpartum, and can cause preventable, long-term maternal disability. Many drug labels are conservative or recommend unnecessary prolonged washouts or avoidance of breastfeeding, creating uncertainty for physicians and patients. This Personal View integrates available evidence on conventional immunosuppressants and biological therapies, including complement inhibition, B-cell depletion, and neonatal Fc receptor blockade. Although data on pregnancy safety for newer treatments are few, preliminary data suggest that selected therapies could be continued during pregnancy to maintain disease stability and are compatible with breastfeeding. We offer expert recommendations for therapy choice, infant vaccinations, and fetal and infant monitoring in myasthenia gravis, NMOSD, and MOGAD.
Predicting disease progression at the individual level is essential for personalized medicine. We previously developed machine-learning tools to estimate 5-year progression risk in people with multiple sclerosis (PwMS). Such models should account for disease-modifying therapy (DMT) and objective outcome definitions. In a retrospective multicenter case-control study, we evaluated adults with relapsing-remitting multiple sclerosis (RRMS) at baseline. Using machine-learning, we developed two complementary tools for individualized 5-year risk estimation: DAAE-M, optimized for transparency, software-neutral use, and mitigation of indication bias, and ELIE, optimized for dynamic landmark-based modeling, complex treatment histories, and mitigation of immortal-time bias. Disease progression was defined using both a clinical outcome (RRMS-to-progressive MS) and an objective outcome (late-stage confirmed progression independent of relapse activity). Among 34,510 people with RRMS (72.6% female, mean age = 37.1, mean disease duration = 5.8), 9.8% and 21% met clinical and objective progression criteria, respectively, over five years. Both models demonstrated good calibration across risk-groups (Brier scores 0.06-0.16). DAAE-M provided patient-level risk estimates with monotonic risk escalation across risk-groups for clinical (3.1%/11.2%/22.6%/33.0%) and objective (8.4%/14.5%/23.3%/38.8%) progression. For DAAE-M, high-efficacy DMT was associated with approximately half the progression risk compared with low-efficacy DMT (risk-ratios: 0.42-0.59; p < 0.01). ELIE also showed good calibration across risk deciles with increasing incidence for both clinical (0.3%/1.2%/1.7%/2.5%/3.7%/5.5%/7.2%/10.2%/14.3%/21.5%) and objective (0.9%/1.6%/2.5%/4.0%/5.8%/7.8%/10.2%/15.3%/20.9%/32.5%) outcomes. We developed two well-calibrated machine-learning-based tools for individualized 5-year prediction of clinically- and objectively-defined MS progression, each with distinct strengths in usability, bias handling, and treatment modeling. These findings support future tool use in personalized risk stratification and secondary prevention.
Advances in the understanding of multiple sclerosis and the development of biomarkers of pathophysiology prompted a substantial revision of the 2017 McDonald diagnostic criteria. The new 2024 McDonald criteria provide a unified approach for diagnosing multiple sclerosis in individuals with relapsing or progressive courses throughout the lifespan (ie, from paediatric to late-life presentations). The optic nerve can now serve as a fifth anatomical location within the CNS for diagnosis. The central vein sign, paramagnetic rim lesions, and kappa free-light chain concentrations in CSF can be used, when available, to provide supportive evidence and confer specificity for a diagnosis of multiple sclerosis in specific situations. In certain cases, radiologically isolated syndrome or neurological symptoms that do not constitute a clear attack or progression of disability can fulfil the criteria for a multiple sclerosis diagnosis. We also provide guidance for the diagnosis of multiple sclerosis in older individuals (≥50 years) and those with comorbidities. The 2024 revised criteria should expedite the diagnosis of multiple sclerosis, while maintaining specificity.
BackgroundStructural imaging offers insight into migraine pathogenesis. Magnetic resonance imaging (MRI) morphometry plays a crucial role in identifying these alterations, yet the clinical significance remains debated. While gray matter volume and cortical curvature are commonly analyzed, cortical thickness offers a more direct measure of cytoarchitectural differences and neuroplastic changes in migraine. Advanced structural MRI techniques, including surface-based morphometry and voxel-based morphometry, have provided insights into cortical thickness alterations in migraine. These methods enable high-resolution assessment of brain morphometry, revealing dynamic changes associated with migraine phases and treatment.MethodsThis narrative review synthesizes findings from cortical thickness studies, focusing on methodological approaches, variations in imaging sequences and study designs, including cross-sectional and longitudinal studies.ResultsStudies using surface-based morphometry (i.e. SBM) and voxel-based morphometry (i.e. VBM) have reported inconsistent findings. Increased thickness is frequently observed in pain-processing regions, such as the somatosensory cortex, insula and anterior cingulate cortex reflecting hyperexcitability or maladaptive neuroplasticity. by contrast, cortical thinning has been noted in regions such as the orbitofrontal cortex, posterior cingulate cortex and visual cortex, suggesting neuronal loss or impaired cortical integrity. Differences between episodic and chronic migraine further highlight progressive structural changes associated with disease burden. Emerging evidence also suggests that preventive treatments, including calcitonin gene-related peptide monoclonal antibodies and botulinum toxin A, may reverse some of these cortical alterations, particularly in treatment responders.ConclusionsCortical thickness analysis provides valuable insights into migraine pathophysiology, offering a potential biomarker for disease progression and treatment response. However, inconsistencies across studies highlight the need for standardized MRI protocols and larger longitudinal investigations to clarify the clinical relevance of cortical thickness changes in migraine.
In the sustainable development goals (SDG) context of seeking universal health coverage, the expanding gap between the supply of specialized and primary health-care providers of headache-related health care and the care needs of the very large number of people affected by headache is a formidable but not insoluble public-health challenge. Structured headache services provide a cost-effective framework wherein controlled patient flows enable the care needs of people with headache to be met at appropriate levels, but these services may still be overwhelmed by inappropriate demand.Community pharmacists are an underutilized resource, potentially well able to provide the solution. To do so, they must, as a profession, be integrated into structured headache services.What remains to be determined is how to achieve this integration in an encouraging climate for change, which recognises the potential for relieving strained health-care systems and meeting a range of health-care needs by expanding pharmacists' scope of practice.This position statement on behalf of the European Headache Federation (EHF) and Lifting The Burden (LTB) is formally endorsed by the International Pharmaceutical Federation (FIP).
Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.
Soluble urokinase plasminogen activator receptor (suPAR) has garnered attention as a potential blood-based biomarker for low-grade chronic inflammation. However, its specific association with migraine, including its subtypes, remains to be elucidated. We sought to examine the association of plasma suPAR levels with migraine and its subtypes. In this single-centre, cross-sectional study, plasma was collected at a single time point in adults with migraine and sex-matched healthy controls from October 2020 to June 2022. The quantification of plasma suPAR levels was performed in a blinded fashion using a validated enzyme-linked immunosorbent assay. Plasma suPAR levels were compared between participants with migraine (including subgroups) and healthy controls. Plasma samples were analysed from 634 eligible participants with migraine [mean (SD) age, 44.0 (12.2) years; 568 (89.6%) females] and 154 healthy controls [mean (SD), 41.3 (11.8%) years; 132 (86%) females]. Plasma suPAR levels were 6.7% higher (95% CI: 0.1-13.6%; P = 0.045, adjusted for age, sex, body mass index and smoking) in participants with migraine with aura, when compared with healthy controls. Further analysis revealed no difference in plasma suPAR levels between the overall migraine group and healthy controls (3.7%; 95% CI: -0.7-8.2%; P = 0.097), as well as between participants with migraine without aura and healthy controls (2.5%; 95% CI: -2.9-8.3%; P = 0.81). Similarly, plasma suPAR levels did not differ across participants with episodic migraine, chronic migraine and healthy controls. Finally, we found no difference when comparing participants with migraine at time of blood sampling with participants with non-migraine headache (1.0%; 95% CI: -5.7-8.2; P > 0.99), participants without headache (1.2%; 95% CI: -4.2-7.0%; P > 0.99) or healthy controls (4.5%; 95% CI: -1.9-11.3%; P = 0.39). Elevated plasma suPAR levels in migraine with aura indicate the presence of low-grade chronic inflammation. Future research should explore the role of suPAR in the neurobiologic underpinnings of migraine with aura.
Multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can share similar features, posing diagnostic challenges. In this study, we identified sets of conventional MRI lesion distribution criteria proposed for disease differentiation and investigated their clinical utility. We searched five electronic databases for English-written and peer-reviewed diagnostic accuracy studies that included brain MRI at least. Hierarchical and univariate random-effects logistic regression models were employed for diagnostic accuracy meta-analysis. Heterogeneity was explored with subgroup analyses. Certainty of evidence was assessed using the GRADEpro tool. Three sets of criteria ('Matthews', 'Cacciaguerra', 'MS lesion checklist') were investigated in 11 studies (2008 patients; MS, n=1037; NMOSD, n=842; MOGAD, n=129), with low applicability concerns. Overall pooled sensitivity and specificity of the Matthews brain MRI criteria (MS vs seropositive-NMOSD differentiation) were 0.92 (0.86 to 0.96) and 0.85 (0.79 to 0.90), respectively, with higher diagnostic values in non-Caucasian populations and during follow-up. Pooled sensitivity and specificity of the Cacciaguerra brain-spinal cord criteria (seropositive-NMOSD vs MS differentiation) were 0.96 (0.76 to 0.99) and 0.83 (0.71 to 0.90), respectively. The MS lesion checklist (MS vs NMOSD/MOGAD differentiation) had lower diagnostic accuracy measures (sensitivity, specificity: 0.74, 0.79, respectively). The Matthews criteria provided the strongest moderate certainty evidence and also showed high pooled diagnostic accuracy for MS versus seronegative-NMOSD (sensitivity: 0.93 (0.84 to 0.97)); specificity: 0.90 (0.80 to 0.95)) and for MS versus MOGAD differentiation (sensitivity: 0.86 (0.81 to 0.90); specificity: 0.87 (0.76 to 0.93)). Lesion distribution criteria can accurately discriminate between MS, NMOSD and MOGAD. Further optimised validation studies, and revisions or extensions may support sustained implementation. CRD42023472178.
The 2024 McDonald diagnostic criteria for Multiple Sclerosis (MS) introduce kappa free light chains (κ-FLC) detection in cerebrospinal fluid (CSF) which can be used interchangeably with oligoclonal IgG bands (OCB) to demonstrate intrathecal immunoglobulin synthesis. Diagnostic sensitivity and specificity of κ-FLC is equal to OCB on a 95% confidence level. In rare cases determination of both, κ-FLC and OCB should be considered as the concordance rate is around 90%. We recommend calculating the κ-FLC index with values of ≥6.1 performing best for diagnosing MS. Validated turbidimetric or nephelometric assays should be applied for which proficiency testing programs are available. There is some prognostic use of the κ-FLC index with higher values predicting higher disease activity. Neurofilament light (NfL) should not be used for diagnostic purposes although it might be useful for prognosis and disease monitoring. All recommendations apply to paediatric and adult relapsing as well as progressive onset MS.
BACKGROUND: The CGRP pathway targeting antibody fremanezumab is indicated for prevention of migraine in adults with ≥4 migraine days/month. To address the limited availability in real-world long-term data, the FINESSE study was initiated to provide real-world evidence of long-term effectiveness of fremanezumab in clinical practice in an unselected migraine patient cohort. METHODS: FINESSE was a non-interventional, prospective, multicentre, two-country (Germany, Austria) study observing migraine patients receiving fremanezumab over 24 months in clinical routine. The primary endpoint was the proportion of patients reaching ≥50% reduction in the monthly average number of migraine days (MMD) during the 6-month period following fremanezumab initiation. Secondary endpoints included changes from baseline in MMD, MIDAS and HIT-6 scores, and use of concomitant acute migraine medication. Exploratory endpoints comprised assessment of number and classes of concomitant preventive and acute migraine medications, and reduction in migraine severity. All secondary and exploratory outcomes were evaluated at multiple timepoints over the 24-month observation period. Safety data were obtained based on documentation of adverse events reported in normal clinical practice. Data analysis was performed using descriptive and, for comparisons to baseline, inferential statistics. RESULTS: Data of 1016 patients (88.7% female; mean age 45.7 (SD 12.4); 55% episodic migraine; 45% chronic migraine) were evaluable in the full analysis set. Out of 987 patients in the primary endpoint set, the proportion of responders with a ≥ 50% MMD reduction during the 6-month period following fremanezumab initiation was 52.8% in all patients, 57.0% in episodic and 47.8% in chronic migraine patients. Further benefit was observed in terms of clinically meaningful MMD reductions from baseline, decrease in the use of concomitant acute medication, migraine severity, and improvements in disability scores, which were sustained over the 24-month observation period. No new safety signals were identified. CONCLUSIONS: Long-term fremanezumab treatment was associated with rapid, substantial and sustained improvement in both episodic and chronic migraine in a high proportion of patients in a real-world setting throughout the 24-month observation period. Real-world-data on tolerability corroborate the expected favourable safety profile of fremanezumab demonstrated in the pivotal clinical trials. TRIAL REGISTRATION: The FINESSE study was retrospectively registered on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS44606) on December 8, 2021, and previously registered at Paul-Ehrlich-Institut (Federal Institute for Vaccines and biomedicines) on November 11, 2019.
During the COVID-19 pandemic, people with multiple sclerosis (MS) and their healthcare providers have faced unique challenges related to the interaction between SARS-CoV-2, underlying neurological disease and the use of disease-modifying treatments (DMTs). Key concerns arose, primarily related to the possibility that SARS-CoV-2 infection could trigger the initial demyelinating event or exacerbate disease activity. Another major concern was the safety and efficacy of the COVID-19 vaccines, especially for patients undergoing specific treatments that could weaken their antibody responses. In the post-infection phase, identifying long COVID in patients with MS has been complicated due to the large overlap between post-infection sequelae and MS symptoms. In addition, disruptions in health and rehabilitation services have made it difficult for MS patients to access care. This Series article explores current evidence on the interaction between MS and SARS-CoV-2, identifies the challenges posed by the COVID-19 pandemic in the care of patients with MS, and discusses the significant adoption of digital health solutions, including telemedicine and new technology-based rehabilitation approaches. Based on lessons learned, recommendations and future directions are offered for managing patients with MS, rethinking healthcare systems and improving health outcomes in the post-COVID-19 pandemic era.
Idiopathic Normal Pressure Hydrocephalus (iNPH) is a neurological syndrome defined by gait disturbance, cognitive impairment and urinary incontinence. However, its clinical presentation can vary widely due to overlapping syndromes and common comorbidities in older adults. This study aims to provide practical guidance to aid in the clinical suspicion and support the diagnostic and therapeutic processes for these patients. Six quantitative variables regarding clinical, functional, and demographic aspects were considered for a large sample of patients with diagnosed iNPH. Principal component analysis (PCA) was adopted to define the main dimensions explaining the variability of the phenomenon. Then, two clusters of iNPH patients were described. 178 patients were included in the analysis. The PCA produced two dimensions covering 61.8% of the total variability. The first one relied mainly on both clinical (mRS, iNPHGs) and functional (TUG, Tinetti) variables, while the second one was represented mainly on the demographic pattern (age and education). Cluster analysis depicted two main groups of patients. Cluster n.1 is composed of individuals who are older, more disabled, with poor functional performances, and highly symptomatic. Cluster n.2 patients are slightly younger, more educated, fitter, and with more nuanced clinical aspects. Profiling iNPH patients using quantitative variables and cluster analysis can help identify distinct characteristics of these patients, aiding in the guidance of both medical and surgical interventions.
Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.