Predictors of relapse risk and treatment response in AQP4-IgG positive and seronegative NMOSD: A multicentre study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD. METHODS: This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate. RESULTS: A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group. CONCLUSION: Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.

Routine CSF parameters as predictors of disease course in multiple sclerosis: an MSBase cohort study.

BACKGROUND: It remains unclear whether routine cerebrospinal fluid (CSF) parameters can serve as predictors of multiple sclerosis (MS) disease course. METHODS: This large-scale cohort study included persons with MS with CSF data documented in the MSBase registry. CSF parameters to predict time to reach confirmed Expanded Disability Status Scale (EDSS) scores 4, 6 and 7 and annualised relapse rate in the first 2 years after diagnosis (ARR2) were assessed using (cox) regression analysis. RESULTS: In total, 11 245 participants were included of which 93.7% (n=10 533) were persons with relapsing-remitting MS (RRMS). In RRMS, the presence of CSF oligoclonal bands (OCBs) was associated with shorter time to disability milestones EDSS 4 (adjusted HR=1.272 (95% CI, 1.089 to 1.485), p=0.002), EDSS 6 (HR=1.314 (95% CI, 1.062 to 1.626), p=0.012) and EDSS 7 (HR=1.686 (95% CI, 1.111 to 2.558), p=0.014). On the other hand, the presence of CSF pleocytosis (≥5 cells/µL) increased time to moderate disability (EDSS 4) in RRMS (HR=0.774 (95% CI, 0.632 to 0.948), p=0.013). None of the CSF variables were associated with time to disability milestones in persons with primary progressive MS (PPMS). The presence of CSF pleocytosis increased ARR2 in RRMS (adjusted R2=0.036, p=0.015). CONCLUSIONS: In RRMS, the presence of CSF OCBs predicts shorter time to disability milestones, whereas CSF pleocytosis could be protective. This could however not be found in PPMS. CSF pleocytosis is associated with short-term inflammatory disease activity in RRMS. CSF analysis provides prognostic information which could aid in clinical and therapeutic decision-making.

Safety and effectiveness of disease-modifying therapies after switching from natalizumab.

INTRODUCTION: One strategy to mitigate progressive multifocal leukoencephalopathy (PML) risk is to switch to other highly effective disease-modifying therapies (DMTs). However, the optimal switch DMT following natalizumab (NTZ) discontinuation is yet to be determined. OBJECTIVE: The objective of the study is to determine the most effective and tolerable DMTs to switch to following NTZ discontinuation due to John Cunningham virus (JCV) antibody positivity. METHODS: This is a multicenter observational cohort study that included all stable relapsing-remitting multiple sclerosis (MS) patients who were treated with NTZ for at least 6 months before switching therapy due to JCV antibody positivity. RESULTS: Of 321 patients, 255 switched from NTZ to rituximab/ocrelizumab, 52 to fingolimod, and 14 to alemtuzumab, with higher annualized relapse rate (ARR) in fingolimod switchers (0.193) compared with rituximab/ocrelizumab or alemtuzumab (0.028 and 0.032, respectively). Fingolimod switchers also had increased disability progression (p = 0.014) and a higher proportion developed magnetic resonance imaging (MRI) lesions compared with rituximab/ocrelizumab (62.9% vs. 13.0%, p < 0.001, and 66.6% vs. 24.0%, p < 0.001, respectively). Mean drug survival favored rituximab/ocrelizumab or alemtuzumab over fingolimod (p < 0.001). CONCLUSION: Our study shows superior effectiveness of rituximab/ocrelizumab and alemtuzumab compared with fingolimod in stable patients switching from NTZ due to JC virus antibody positivity.

Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry.

BACKGROUND: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. OBJECTIVES: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. METHODS: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). RESULTS: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. CONCLUSION: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.

A global survey on the attitudes of neurologists and psychiatrists about functional/psychogenic/dissociative/nonepileptic-seizures/attacks, in the search of its name.

PURPOSE: We conducted an observational study to investigate the opinions of neurologists and psychiatrists all around the world who are taking care of patients with seizures [epilepsy and functional seizures (FS)]. METHODS: Practicing neurologists and psychiatrists from around the world were invited to participate in an online survey. On 29th September 2022, an e-mail including a questionnaire was sent to the members of the International Research in Epilepsy (IR-Epil) Consortium. The study was closed on 1st March 2023. The survey, conducted in English, included questions about physicians' opinions about FS and anonymously collected data. RESULTS: In total, 1003 physicians from different regions of the world participated in the study. Both neurologists and psychiatrists identified "seizures" as their preferred term. Overall, the most preferred modifiers for "seizures" were "psychogenic" followed by "functional" by both groups. Most participants (57.9%) considered FS more difficult to treat compared to epilepsy. Both psychological and biological problems were considered as the underlying cause of FS by 61% of the respondents. Psychotherapy was considered the first treatment option for patients with FS (79.9%). CONCLUSION: Our study represents the first large-scale attempt of investigating physicians attitudes and opinions about a condition that is both frequent and clinically important. It shows that there is a broad spectrum of terms used by physicians to refer to FS. It also suggests that the biopsychosocial model has gained its status as a widely used framework to interpret and inform clinical practice on the management of patients.

Counseling about sudden unexpected death in epilepsy (SUDEP): A global survey of neurologists' opinions.

OBJECTIVE: To investigate the opinions and attitudes of neurologists on the counseling about sudden unexpected death in epilepsy (SUDEP) worldwide. METHODS: Practicing neurologists from around the world were invited to participate in an online survey. On February 18th, 2021, we emailed an invitation including a questionnaire (using Google-forms) to the lead neurologists from 50 countries. The survey anonymously collected the demographic data of the participants and answers to the questions about their opinions and attitudes toward counseling about SUDEP. RESULTS: In total, 1123 neurologists from 27 countries participated; 41.5% of the respondents reported they discuss the risk of SUDEP with patients and their care-givers only rarely. Specific subgroups of patients who should especially be told about this condition were considered to be those with poor antiseizure medication (ASM) adherence, frequent tonic-clonic seizures, or with drug-resistant epilepsy. The propensity to tell all patients with epilepsy (PWE) about SUDEP was higher among those with epilepsy fellowship. Having an epilepsy fellowship and working in an academic setting were factors associated with a comfortable discussion about SUDEP. There were significant differences between the world regions. CONCLUSION: Neurologists often do not discuss SUDEP with patients and their care-givers. While the results of this study may not be representative of practitioners in each country, it seems that there is a severe dissociation between the clinical significance of SUDEP and the amount of attention that is devoted to this matter in daily practice by many neurologists around the world.

Complementary and alternative medicine in epilepsy: A global survey of physicians' opinions.

PURPOSE: To investigate the opinions of physicians on the use of complementary and alternative medicine (CAM) in patients with epilepsy (PWE) worldwide. METHODS: Online survey addressed to neurologists and psychiatrists from different countries. RESULTS: Totally, 1112 physicians from 25 countries (different world region: Europe, North America, South America, Middle-East, Africa, Former Soviet Union Republics) participated; 804 (72.3%) believed that CAM might be helpful in PWE. The most commonly endorsed CAM included meditation (41%) and yoga (39%). Female sex, psychiatry specialization, and working in North and South America were associated with the belief that CAM is helpful in PWE. Two-hundred and forty five out of 1098 participants (22.3%) used/prescribed CAM to PWE; among them, 174 (71%) people perceived CAM to be less effective and 114 (46.5%) people found CAM to be safer than conventional antiseizure medications (ASMs). The most common reasons to prescribe CAM for PWE were: to satisfy the patient (49.9%), dissatisfaction with the efficacy (35.6%), and dissatisfaction with the adverse effects (31.2%) of conventional therapies. CONCLUSION: Although the evidence supporting the use of CAM for the treatment of epilepsy is extremely sparse, most physicians worldwide believe that it could be integrated with the use of conventional ASMs, at least in some patients. High-quality controlled trials are warranted to provide robust evidence on the usefulness of CAM options in PWE.

Epilepsy and school in the Middle East and North Africa (MENA) region: The current situation, challenges, and solutions.

Education is a human right that plays a key role in social and economic development. Children having active epilepsy may not be properly schooled in ordinary school structures. Students with epilepsy (SWE) are often faced with academic barriers. The lack of information about the current status of special education for SWE obliged the researchers to try to describe the existing reality of the special education practices in the Middle East and North Africa (MENA) region. We disseminated a simple self-administered questionnaire via email to main healthcare professionals involved in epilepsy care in the MENA region, and we also did a literature search on the PubMed, Google Scholar, and Embase engines. We ranked the countries in terms of their educational system. The 1st group contains the most advanced educational system, including specialized schools for SWE. The 2nd group contains an educational system with specialized but less structured schools. The 3rd group includes countries using integrated classes or classes mixing many children with cognitive disabilities. The 4th group includes countries with ordinary classes for SWE, and finally, the 5th group with no schooling for children with epilepsy (CWE). This study indicates that 60% of the countries in the MENA region belong to the 3rd group; there is only one country in each of the first two groups. This work highlights the need to develop structured environments for schooling for SWE in the MENA region.

CERAD Neuropsychological Battery-Arabic Version: Regression-Based and Stratified Normative Data and Effects of Demographic Variables on Cognitive Performance in Older Omanis.

BACKGROUND AND OBJECTIVES: Normative data on cognitive performance for the Omani population are scarce. In this study, we tested a sample of older (≥50 years) community-dwelling Omanis on the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery-Arabic version (CERAD-ArNB). We analyzed the participants' cognitive performance and how it was affected by their sex, age, and level of education. METHODS: We enrolled 150 older Arabic-speaking Omanis from March 2014 to June 2015. Most of the participants were visitors to patients admitted to a tertiary referral center in the Sultanate of Oman. All participants underwent screening to ensure normal cognitive function before taking the CERAD-ArNB. We used multiple regression analysis and stratification according to demographic variables to illustrate the normative data. RESULTS: A total of 125 participants, 65 men (52%) and 60 women (48%), met the inclusion criteria and completed the testing. Multiple regression and univariate analyses showed that although sex and age significantly affected cognitive performance on some CERAD-ArNB subtests, education level had by far the greatest effect. CONCLUSIONS: Lower education level was associated with poorer CERAD-ArNB performance in a sample of cognitively normal Omanis aged 50 years and older. The normative data obtained from this study will help clinicians correctly interpret cognitive performance in the Omani elderly population, and probably in other, culturally similar Arabic-speaking communities.

Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer's disease.

Alzheimer disease (AD) is one of the most common forms of dementia in the elderly. Several reports have suggested neurotoxic effects of amyloid beta protein (Aß) and role of oxidative stress in AD. Figs are rich in fiber, copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good source of proanthocyanidins and quercetin which demonstrate potent antioxidant properties. We studied the effect of dietary supplementation with 4% figs grown in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice) mice model for AD. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 months and after 15 months using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. Tg mice that were fed a control diet without figs showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial, position discrimination learning ability, and motor coordination compared to the wild-type control mice on the same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our results suggest that dietary supplementation of figs may be useful for the improvement of cognitive and behavioral deficits in AD.

Magnitude and concurrence of anxiety and depression among attendees with multiple sclerosis at a tertiary care Hospital in Oman.

BACKGROUND: Anxiety, depression and functional impairments are commonly reported by persons with multiple sclerosis (PwMS) but no data, to our knowledge, has emerged from an Arab Islamic population. The study aims to investigate the prevalence of anxiety, depression and related disabilities among PwMS attending tertiary care in Sultan Qaboos University Hospital (SQUH), one of the urban hospitals in Oman. METHODS: Consecutive and consenting PwMS (n = 57) and healthy subjects (n = 53) completed the following measures: Hospital Anxiety and Depression Scale (HADS) which was used to measure anxiety (cut-point >7) and depression (>7); and Expanded Disability Status Scale (EDSS) to measure the level of disability (≥5). Characteristics such as socio-demographic and clinical variables were also explored. RESULTS: Fifty seven subjects with multiple sclerosis (MS) met the inclusion criteria. The majority of them were females who were 40 years old or younger and the majority were employed and unmarried. Approximately 86 % of the participants were using beta interferon, 96 % scored ≥5 in EDSS. MS of the Relapsing-Remitting type constituted the majority of the cohort (94 %). Approximately 35 % and 51 % endorsed symptoms of anxiety and depression respectively. The MS group scored significantly higher than controls on HADS measurements of depression and anxiety. CONCLUSION: Disability and symptoms of anxiety and depression are common among the PwMS attendees of tertiary care hospital in Oman. Such psychosocial variables have been largely unreported emerging from non-western populations. As these variables are strong indicators of the burden of MS, resolute effort is needed to address such psychosocial dysfunctions in the algorithms of care for PwMS in the Arab Islamic part of the world.

Effect of dietary supplementation of dates in Alzheimer's disease APPsw/2576 transgenic mice on oxidative stress and antioxidant status.

Oxidative stress may play a key role in Alzheimer's disease (AD) neuropathology. Changes in the oxidative stress, antioxidants, and membrane-bound enzymes were investigated in the cerebral cortex and hippocampus of AD transgenic mice model after long-term dietary supplementation of date palm fruits from Oman. The 4-month-old mice with double Swedish APP mutation (APPsw/Tg2576) were purchased from Taconic Farm, NY, USA; mice were fed two different doses of dates (such as 4 and 2%) or control diet for 15 months and then assessed for the influence of diet on oxidative stress. Significant increase in oxidative stress in terms of enhanced levels of lipid peroxidation (LPO) and protein carbonyls and parallel decrease in the activity of antioxidant enzymes were observed in control diet-treated Tg2576 AD mice. Dates (4 and 2%) treated APPsw/Tg2576 AD mice exhibited significantly attenuated oxidative damage, evidenced by decreased LPO and protein carbonyl levels and restoration in the activities of the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione reductase). The activities of membrane-bound enzymes (Na(+), K(+)-ATPase and acetyl cholinesterase) were altered in control diet-treated APPsw/Tg2576 AD mice brain regions. Meanwhile, both the percentages of date supplementation were able to restore the activity of enzymes to comparable values observed in controls. In summary, we have shown that chronic dietary supplementation of date palm fruits grown in Oman showed possible beneficial effects concomitant with oxidative stress reduction and increased antioxidant enzymes in AD transgenic mice model. These results warrant further exploration of how anti-reactive oxygen species properties of dates offer such beneficial effects on the AD-like brain.

Medical Tourism and Neurological Diseases: Omani Patients' Experience Seeking Treatment Abroad.

Objectives: There is a dearth of research regarding the motivations and experiences of Omani nationals who travel abroad for medical treatment, especially for neurological diseases. The primary objective was to examine and draw comparisons between Omani adults and children with neurological disorders who pursued medical treatment abroad after being evaluated by local specialists. The study also aimed to gain insights into these patients' motivations and experiences. A related objective was to explore the sociocultural factors and family dynamics that shape the attitudes towards illness and treatment seeking. Methods: In this cross-sectional study, Omani patients treated at a major tertiary hospital in Muscat for neurological disorders and subsequently traveled overseas for treatment were identified and administered a structured questionnaire. Results: The participants were 116 Omani nationals (62 children and 54 adults) with neurological disorders, diagnosed predominantly with epilepsy (71.6%) followed by developmental delay, muscular dystrophy, and encephalopathy. Only 19.8% of patients received government sponsorship. The majority (69.8%) followed the recommendations of family members. Most (63.8%) participants reported positive outcomes after treatment abroad, though 4.3% developed complications and 5.2% acquired nosocomial infections. Most (83.6%) participants opined that the treatment they received overseas was comparable to what they would have received in Oman. There were no significant differences between children and adults in most of these aspects. Conclusions: Public awareness should be increased regarding the pros and cons of medical tourism. Patients must be made aware of the advanced treatment facilities available locally. Efforts should be made to enhance patient outcomes and satisfaction by adopting more efficient and patient-friendly processes.

Seasonal Variations in Multiple Sclerosis Relapses in Oman: A Single Tertiary Centre Experience.

(1) Background and Aims: The seasonal factors influencing multiple sclerosis (MS) relapses remain elusive. This study aims to investigate the seasonal variation of MS relapses in Oman and compare it globally. (2) Subject and Methods: This retrospective study was conducted on N = 183 Omani MS patients treated at Sultan Qaboos University Hospital, a tertiary hospital in Muscat, Oman, over sixteen-year period (2007-2022). Demographic and clinical data of all MS patients were juxtaposed with the monthly weather data during this period, using descriptive and inferential statistical techniques. (3) Results: Among the N = 183 MS patients studied, 508 relapses were recorded during the study period. The average number of relapses per patient was 2.8 (range: 1-15). There were significant seasonal variations in MS relapse rate, with the highest prevalence in the winter months of January and February. However, no correlation was found between MS relapses and other climatic parameters (humidity, temperature, and rainfall). (4) Conclusion: The seasonal patterns of MS relapses in Oman differ from other parts of the world, which the local clinicians should take into account while diagnosing and making management decisions. The potential impact of climate change on the anomalous changes in the seasonality of MS relapses warrants further investigation.

Complementary and Alternative Medicine for People with Epilepsy: Opinions of Physicians in Oman.

Objectives: Several studies have explored the opinions of healthcare workers on the use of complementary and alternative medicine (CAM) in epilepsy treatment. We sought to survey the views of non-neurologist and non-psychiatrist physicians in Oman on the use of CAM for epilepsy. Methods: We used convenience sampling to recruit physicians (except neurologists and psychiatrists) from all 11 governorates of Oman. The online questionnaire was open to physicians from 5 January 2022 to 15 February 2023. This study collected anonymous data on their demographics, discipline, work settings, geographical area, and years of practice. Additionally, participants were asked to answer questions about their perception of CAM use and its effectiveness in treating epilepsy. Results: A total of 190 physicians participated, of whom 69.5% were men. Respondents were mostly 36 to 45 years old (51.1%). The majority (52.1%) were general practitioners, 21.1% were internists, 17.9% were pediatricians, and 8.9% were family physicians. Most participants (n = 144; 75.8%) believed that CAM may help treat patients with epilepsy (PWE). The most common therapies that participants considered helpful were meditation (46.0%), prayers (44.7%), yoga (32.6%), and exercise (31.1%). Conclusions: While the evidence supporting the use of CAM for the treatment of epilepsy is scarce, this survey showed that most physicians (non-neurologists and non-psychiatrists), who manage PWE in Oman, believed that some CAM modalities would help treat epilepsy. Well-designed controlled trials are needed to provide reliable evidence on the usefulness of CAM options in PWE.

A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.

Synaptic dysfunction is recognized as an early step in the pathophysiology of parkinsonism. Several genetic mutations affecting the integrity of synaptic proteins cause or increase the risk of developing disease. We have identified a candidate causative mutation in synaptic "SH3GL2 Interacting Protein 1" (SGIP1), linked to early-onset parkinsonism in a consanguineous Arab family. Additionally, affected siblings display intellectual, cognitive, and behavioral dysfunction. Metabolic network analysis of [18F]-fluorodeoxyglucose positron emission tomography scans shows patterns very similar to those of idiopathic Parkinson's disease. We show that the identified SGIP1 mutation causes a loss of protein function, and analyses in newly created Drosophila models reveal movement defects, synaptic transmission dysfunction, and neurodegeneration, including dopaminergic synapse loss. Histology and correlative light and electron microscopy reveal the absence of synaptic multivesicular bodies and the accumulation of degradative organelles. This research delineates a putative form of recessive parkinsonism, converging on defective synaptic proteostasis and opening avenues for diagnosis, genetic counseling, and treatment.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

BACKGROUND AND OBJECTIVES: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods. METHODS: We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods. RESULTS: A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse. DISCUSSION: Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies.

Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study.

BACKGROUND: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. METHODS: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. FINDINGS: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. CONCLUSIONS: Good discrimination and calibration performance on an external validation set is achieved, using only routinely collected variables. This suggests machine-learning models can reliably inform clinicians about the future occurrence of progression and are mature for a clinical impact study.

A multi-centre longitudinal study analysing multiple sclerosis disease-modifying therapy prescribing patterns during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic raised concern amongst clinicians that disease-modifying therapies (DMT), particularly anti-CD20 monoclonal antibodies (mAb) and fingolimod, could worsen COVID-19 in people with multiple sclerosis (pwMS). This study aimed to examine DMT prescribing trends pre- and post-pandemic onset. METHODS: A multi-centre longitudinal study with 8,771 participants from MSBase was conducted. Two time periods were defined: pre-pandemic (March 11 2018-March 10 2020) and post-pandemic onset (March 11 2020-11 March 2022). The association between time and prescribing trends was analysed using multivariable mixed-effects logistic regression. DMT initiation refers to first initiation of any DMT, whilst DMT switches indicate changing regimen within 6 months of last use. RESULTS: Post-pandemic onset, there was a significant increase in DMT initiation/switching to natalizumab and cladribine [(Natalizumab-initiation: OR 1.72, 95% CI 1.39-2.13; switching: OR 1.66, 95% CI 1.40-1.98), (Cladribine-initiation: OR 1.43, 95% CI 1.09-1.87; switching: OR 1.67, 95% CI 1.41-1.98)]. Anti-CD20mAb initiation/switching decreased in the year of the pandemic, but recovered in the second year, such that overall odds increased slightly post-pandemic (initiation: OR 1.26, 95% CI 1.06-1.49; Switching: OR 1.15, 95% CI 1.02-1.29. Initiation/switching of fingolimod, interferon-beta, and alemtuzumab significantly decreased [(Fingolimod-initiation: OR 0.55, 95% CI 0.41-0.73; switching: OR 0.49, 95% CI 0.41-0.58), (Interferon-gamma-initiation: OR 0.48, 95% CI 0.41-0.57; switching: OR 0.78, 95% CI 0.62-0.99), (Alemtuzumab-initiation: OR 0.27, 95% CI 0.15-0.48; switching: OR 0.27, 95% CI 0.17-0.44)]. CONCLUSIONS: Post-pandemic onset, clinicians preferentially prescribed natalizumab and cladribine over anti-CD20 mAbs and fingolimod, likely to preserve efficacy but reduce perceived immunosuppressive risks. This could have implications for disease progression in pwMS. Our findings highlight the significance of equitable DMT access globally, and the importance of evidence-based decision-making in global health challenges.

Types and sociodemographic correlates of complementary and alternative medicine (CAM) use among people with epilepsy in Oman.

Nonpharmacological treatment strategies that originate from sociocultural teachings and are beyond the scope of allopathic medicine are commonly used among people with epilepsy (PWE) in many parts of the world. The present study explored the types and sociodemographic correlates of complementary and alternative medicine (CAM) use among PWE in Oman among attendees of a neurological unit at a tertiary care center. Data on the types of CAM were gathered from telephone interviews. The relevant demographic and clinical characteristics of the participants were obtained from electronic medical records. Of the total of 101 participants, 73.3% were CAM users. The majority of these participants have not disclosed their CAM use to their allopathic health-care providers. The most common types of CAM reported were those falling under the 'mind-body' type (incantations and fumigation) and biologically based (herbal concoctions) or a combination of them. Compared to non-CAM users, a significant and greater proportion of CAM users attributed the etiology of their illness to nonbiomedical factors such as 'evil eyes' (P=0.04). The multivariate logistic regression model indicated that the use of CAM was highly associated with age of <30years (OR=3.09; 95% CI: 1.10, 5.46), unemployment (OR=2.04; 95% CI: 1.15, 6.39), having basic school education (OR=2.21; 95% CI: 0.83, 5.18), low family income (OR=1.52; 95% CI: 0.91, 2.11), and the presence of hypersalivation (OR=2.20; 95% CI: 1.01, 4.39). Further studies are needed to harmonize these two healing practices. On the whole, this study indicates that among attendees of tertiary care utilization, CAM is common among PWE in Oman. The most utilized type of CAM falls under the umbrella of mind-body practice.