Practical Guidance on the Use of Cladribine Tablets in the Management or Relapsing Multiple Sclerosis: Expert Opinion from Qatar.

The increasing availability of high-efficacy disease-modifying therapies (DMT) for the management of relapsing multiple sclerosis (RMS) has increased the potential for individualised patient management but has added complexity to the design of treatment regimens. The long-term application of immune reconstitution therapy (IRT) is supported by an increasing database of real world studies that have added important information on the long-term safety and efficacy of this approach. Cladribine tablets (CladT) is an IRT given as two annual short courses of treatment, following which a majority of patients then demonstrate no significant MS disease activity over a period of years. Whether, and how, to treat patients beyond the first two years of treatment remains a matter for debate, as clinical evidence accumulates. We, a group of neurologists who manage people with RMS in Qatar, provide our expert consensus recommendations on the application and long-term management of CladT therapy based on our experience with treatment in the last 5 years. These include pragmatic recommendations for people with MS disease activity in years 3 and 4 (ie up to four years following first dose of CladT), and for people with or without MS disease activity in subsequent years. We believe our recommendations will help to ensure the optimal application of CladT-based IRT, with the potential benefit for the patient of achieving prolonged periods free of both MS disease symptoms and the burden of regular applications of immunosuppressive DMT.

A Rare Case of Lambert-Eaton Myasthenia Syndrome Associated with Non-Hodgkin's Lymphoma: A Case Report and Review of the Literature.

Introduction: Lambert-Eaton myasthenia syndrome (LEMS) is a rare autoimmune disorder characterized by autoantibodies targeting presynaptic neuromuscular junctions. It results in muscle weakness and autonomic dysfunction. LEMS can be idiopathic or associated with neoplastic diseases, often small-cell lung cancer. This case report describes a rare instance of paraneoplastic LEMS in a man with non-Hodgkin lymphoma. Case Presentation: A 57-year-old male with non-Hodgkin lymphoma presented with progressive muscle weakness, diminished reflexes, and autonomic symptoms. Diagnosis revealed LEMS with autoantibodies against voltage-gated calcium channels. Immunosuppressive therapy and lymphoma treatment led to significant improvement in his condition. Conclusion: This case highlights the rare occurrence of paraneoplastic LEMS in a patient with non-Hodgkin lymphoma. Recognition and timely management of LEMS alongside lymphoma treatment can lead to significant clinical improvement, emphasizing the need for increased awareness of such complex associations.

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Demyelinating Neurological Adverse Events following the Use of Anti-TNF-α Agents: A Double-Edged Sword.

Background: Tumor necrosis factor antagonists (anti-TNF-α) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported, and literature data suggest a potential role of anti-TNF-α in the induction of demyelination. Case Presentation. In this series, we present three cases of demyelination after the use of anti-TNF-α agents. The first case involved a 21-year-old man with HLA-B27 negative peripheral spondylarthritis who had been taking adalimumab for 2 years. He developed headache, urinary incontinence, and bilateral lower extremity numbness that progressed to the middle of the trunk for 2 days. Magnetic resonance imaging (MRI) showed multiple hyperintense enhancement lesions in the left paramedian anterior pons consistent with multiple sclerosis (MS). The second case included a 17-year-old woman who was on 2 years of adalimumab treatment for juvenile idiopathic arthritis and chronic anterior uveitis and developed new-onset dizziness and tremors. The clinical examination showed signs of cerebellar dysfunction. MRI findings were consistent with multiple sclerosis. The third case was a 34-year-old male who was on 5 years of infliximab treatment for ankylosing spondylitis when he developed left hand numbness and weakness. Cerebrospinal fluid (CSF) analysis and MRI findings were consistent with demyelination. Discontinuation of tumor necrosis factor antagonists (anti-TNF-α) resulted in resolution of the symptoms with no recurrence in the first case, but there was evidence of recurrence in the other 2 cases, where one was managed with rituximab and the second one improved with pulse steroid therapy. Conclusion: Despite the small number of patients, our series adds to the growing body of evidence supporting a causal link between anti-TNF-α agents and demyelination. Thus, we can conclude that on suspicion of any neurological side effects, early discontinuation of the TNF-α blockers and requesting urgent MRI scan to confirm the diagnosis is of utmost importance.

Bilateral Acute Optic Perineuritis Associated With COVID-19 in a Patient With Seronegative Myelin Oligodendrocyte Glycoprotein (MOG) Antibody.

Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) may cause various neuro-ophthalmologic manifestations including optic perineuritis. Optic perineuritis is a rare form of orbital inflammatory disease in which optic nerve sheath is inflamed and nonspecific fibrotic thickening with classic radiological finding is a perineural enhancement of optic nerve sheath. A 45-year-old gentleman with known diabetes mellitus, hypertension and dyslipidemia was admitted with a critically ill COVID-19 infection. During the recovery period, the patient developed sudden onset of painless loss of vision. MRI head and orbit with gadolinium was suggestive of optic perineuritis. Other secondary causes of autoimmune or vasculitis myelin oligodendrocyte glycoprotein (MOG) antibody disease and other common central nervous system (CNS) infection were excluded. The patient had dramatic response with steroids. This is the first rare case report of COVID-19-related optic perineuritis in critically ill COVID-19 patients with seronegative MOG antibody. Optic perineuritis is a rare orbital inflammatory disease and underlying mechanisms may arise from systemic response to COVID-19 infection as well as direct effects of the virus via angiotensin-converting enzyme 2 (ACE-2) receptors on ocular tissues. Optic perineuritis is a rare disease with inflammation restricted to the optic nerve sheath. Neuroimaging of the brain and orbit is the most important modality of choice for visualizing optic nerve sheath and optic nerve. Delay in the diagnosis of COVID-19-related optic perineuritis, may result in permanent optic nerve injury and irreversible vision loss.

Acute Myocardial Injury and Rhabdomyolysis in COVID-19 Patients: Incidence and Mortality.

Background Myocardial injury has been defined as an elevated troponin level. The frequency of acute myocardial injury of hospitalized coronavirus disease 2019 (COVID-19) patients ranges from 7% to 36%. COVID-19 patients with cardiovascular disease (CVD) have a four-fold higher risk of mortality (odds ratio, 4.33; CI 95%, 3.16-5.94). In COVID-19 hospitalized patients' study showed mortality rate was 18.5%. Rhabdomyolysis is considered as muscle necrosis and the release of intracellular muscles elements and enzymes into blood. In one of retrospective cohort study of COVID-19 hospitalized patients, incidence of rhabdomyolysis was 16.7%. Materials and methods This retrospective observational study consisted of 413 COVID-19 hospitalized patients. Patients with rhabdomyolysis was defined as creatine kinase level greater than 1,000 U/L and acute myocardial injury was defined as serum high-sensitivity troponin-T for males greater than 30 ng/l and for female greater than 20 ng/l. The primary outcome was in-hospital mortality of COVID-19 patients with acute myocardial injury and rhabdomyolysis.  Results The incidence of acute myocardial injury and rhabdomyolysis in hospitalized COVID-19 patients was 23.9% (99) and 15.7% (65), respectively. The mortality rate of in hospitalized COVID-19 patients who developed acute myocardial injury (28.3%) was significantly higher in comparison to patients who developed rhabdomyolysis (13.8%). Discussion The binding of SARS-CoV-2 virus to the angiotensin-converting enzyme 2 (ACE2) is a critical step in the pathophysiology in patients with COVID-19. There may be diverse direct and indirect mechanisms of acute myocardial injury in COVID-19 including ischemic injury, hypoxic injury (MI type 2), direct viral myocarditis, stress cardiomyopathy and systemic cytokine storm. Musculoskeletal injury may be caused by direct viral myositis or indirectly by host immune hyperinflammatory cytokine storm response that leads to skeletal muscle fiber proteolysis and fibrosis. Conclusions Acute myocardial injury and rhabdomyolysis were underreported in COVID-19 patients. The incidence and mortality of acute myocardial injury are higher than that of rhabdomyolysis in COVID-19 hospitalized patients. The outcome was worse in COVID-19 patients with severe acute myocardial injury. Patients with acute myocardial injury and rhabdomyolysis may get benefits from rehabilitation programs.

Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19.

This article describes consensus recommendations from an expert group of neurologists from the Arabian Gulf region on the management of relapsing multiple sclerosis (RMS) in the COVID-19 era. MS appears not to be a risk factor for severe adverse COVID-19 outcomes (though patients with advanced disability or a progressive phenotype are at higher risk). Disease-modifying therapy (DMT)-based care appears generally safe for patients with MS who develop COVID-19 (although there may be an increased risk of adverse outcomes with anti-CD20 therapy). Interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab and cladribine tablets are unlikely to increase the risk of infection; fingolimod, anti-CD20 agents and alemtuzumab may confer an intermediate risk. Existing DMT therapy should be continued at this time. For patients requiring initiation of a DMT, all currently available DMTs except alemtuzumab can be started safely at this time; initiate alemtuzumab subject to careful individual risk-benefit considerations. Patients should receive vaccination against COVID-19 where possible, with no interruption of existing DMT-based care. There is no need to alter the administration of interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod or cladribine tablets for vaccination; new starts on other DMTs should be delayed for up to 6 weeks after completion of vaccination to allow the immune response to develop. Doses of the Oxford University/AstraZeneca vaccine may be scheduled around doses of anti-CD20 or alemtuzumab. Where white cell counts are suppressed by treatment, these should be allowed to recover before vaccination.

Expert Consensus and Narrative Review on the Management of Multiple Sclerosis in the Arabian Gulf in the COVID-19 Era: Focus on Disease-Modifying Therapies and Vaccination Against COVID-19.

This article describes consensus recommendations from an expert group of neurologists from the Arabian Gulf region on the management of relapsing multiple sclerosis (RMS) in the COVID-19 era. MS appears not to be a risk factor for severe adverse COVID-19 outcomes (though patients with advanced disability or a progressive phenotype are at higher risk). Disease-modifying therapy (DMT)-based care appears generally safe for patients with MS who develop COVID-19 (although there may be an increased risk of adverse outcomes with anti-CD20 therapy). Interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab and cladribine tablets are unlikely to increase the risk of infection; fingolimod, anti-CD20 agents and alemtuzumab may confer an intermediate risk. Existing DMT therapy should be continued at this time. For patients requiring initiation of a DMT, all currently available DMTs except alemtuzumab can be started safely at this time; initiate alemtuzumab subject to careful individual risk-benefit considerations. Patients should receive vaccination against COVID-19 where possible, with no interruption of existing DMT-based care. There is no need to alter the administration of interferon-ß, teriflunomide, dimethyl fumarate, glatiramer acetate, natalizumab, fingolimod or cladribine tablets for vaccination; new starts on other DMTs should be delayed for up to 6 weeks after completion of vaccination to allow the immune response to develop. Doses of the Oxford University/AstraZeneca vaccine may be scheduled around doses of anti-CD20 or alemtuzumab. Where white cell counts are suppressed by treatment, these should be allowed to recover before vaccination.

Corneal Immune Cells Are Increased in Patients With Multiple Sclerosis.

Purpose: Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that has been used to identify increased corneal immune cells in patients with immune-mediated peripheral neuropathy. Given that multiple sclerosis has an immune-mediated etiology, we have compared corneal immune cell (IC) density and near-nerve distance in different subtypes of patients with multiple sclerosis (MS) to controls. Methods: This is a blinded, cross-sectional study conducted at a tertiary hospital. Patients with clinically isolated syndrome (CIS) (n = 9), relapsing-remitting multiple sclerosis (RRMS) (n = 43), secondary progressive multiple sclerosis (SPMS) (n = 22), and control subjects (n = 20) underwent CCM. The total, mature, and immature corneal IC density and their nearest nerve distance were quantified. Results: The total IC density was higher in patients with MS (P = 0.02), RRMS (P = 0.01), and SPMS (P = 0.04) but not CIS (P = 0.99) compared to controls. Immature IC density was higher in patients with MS (P = 0.03) and RRMS (P = 0.02) but not SPMS (P = 0.10) or CIS (P = 0.99) compared to controls. Mature IC density (P = 0.15) did not differ between patients with MS and controls. The immature IC near-nerve distance was significantly greater in patients with MS (P = 0.001), RRMS (P = 0.007), and SPMS (P = 0.002) compared to controls. Immature IC density correlated with the Symbol Digit Modalities Test (r = -0.281, P = 0.02) and near-nerve distance correlated with the Expanded Disability Status Scale (r = 0.289, P = 0.005). Conclusions: In vivo CCM demonstrates an increase in immature IC density and the near-nerve distance in patients with MS. These observations merit further studies to assess the utility of CCM in assessing neuroimmune alterations in MS. Translational Relevance: Multiple sclerosis is an immune-mediated neurodegenerative disease. Dendritic cells mediate communication between the innate and adaptive immune systems. We have used in vivo CCM to show increased corneal ICs and suggest it may act as an imaging biomarker for disease status in patients with MS.

Real-world experience of ocrelizumab in multiple sclerosis in an Arab population.

OBJECTIVE: Pivotal clinical trials revealed good clinical efficiency of ocrelizumab while having a good safety profile in the management of multiple sclerosis (MS). However, real-world data of ocrelizumab in daily clinical practice remain scarce. The aim of this study was to evaluate the preliminary safety profile and effectiveness of ocrelizumab treatment for MS in an Arab population in a real-world clinical setting. METHODS: In this retrospective single-center observational study in Qatar, we reviewed the medical records and analyzed the clinical and MRI data of all patients with relapsing-remitting MS (RRMS) and active secondary progressive MS (aSPMS)-between October 2017 through December 2020-who had received at least one infusion of ocrelizumab (Q-OCRE). RESULTS: A total of 60 MS patients were included (57 with RRMS, three SPMS). The Median follow-up period was 19 months (range, 1-32). The most common reason for switching to ocrelizumab was increased disease activity and three-quarters of the patients were on a previous disease-modifying drug (DMD). No evidence of disease activity (NEDA) status at year 1 was achieved in 73% of the cohort. Mild infusion-related reactions (IRR) and infections were reported (mainly upper respiratory tract infections followed by urinary tract infection) with a declining percentage over the follow-up applications. No severe side effects were observed. CONCLUSION: Our real-world experience confirms good efficacy, tolerability, and safety of ocrelizumab in our Arab population.

Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis.

Axonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) [(clinically isolated syndrome (n = 9); relapsing-remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21)] underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm2, 95% CI - 18.24 to - 11.59, P < .0001), CNFL [for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm2, 95% CI - 8.94 to - 5.77, P < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm2, 95% CI - 9.55 to - 5.6, P < .0001] and CNFrD [for ACCMetrics: 1.52 ± 0.02 vs. 1.45 ± 0.04, 95% CI - 0.09 to - 0.05, P < .0001; for deepNerve: 1.29 ± 0.03 vs. 1.19 ± 0.07, 95% - 0.13 to - 0.07, P < .0001]. Corneal nerve parameters were comparably reduced in different courses of MS. There was excellent reproducibility between the algorithms. Significant corneal axonal loss is detected in different courses of MS including patients with clinically isolated syndrome.

Emerging Application of Nanorobotics and Artificial Intelligence To Cross the BBB: Advances in Design, Controlled Maneuvering, and Targeting of the Barriers.

The blood-brain barrier (BBB) is a prime focus for clinicians to maintain the homeostatic function in health and deliver the theranostics in brain cancer and number of neurological diseases. The structural hierarchy and in situ biochemical signaling of BBB neurovascular unit have been primary targets to recapitulate into the in vitro modules. The microengineered perfusion systems and development in 3D cellular and organoid culture have given a major thrust to BBB research for neuropharmacology. In this review, we focus on revisiting the nanoparticles based bimolecular engineering to enable them to maneuver, control, target, and deliver the theranostic payloads across cellular BBB as nanorobots or nanobots. Subsequently we provide a brief outline of specific case studies addressing the payload delivery in brain tumor and neurological disorders (e.g., Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.). In addition, we also address the opportunities and challenges across the nanorobots' development and design. Finally, we address how computationally powered machine learning (ML) tools and artificial intelligence (AI) can be partnered with robotics to predict and design the next generation nanorobots to interact and deliver across the BBB without causing damage, toxicity, or malfunctions. The content of this review could be references to multidisciplinary science to clinicians, roboticists, chemists, and bioengineers involved in cutting-edge pharmaceutical design and BBB research.

Pregnancy-related issues in women with multiple sclerosis: an evidence-based review with practical recommendations.

Objective: To review the current evidence regarding pregnancy-related issues in multiple sclerosis (MS) and to provide recommendations specific for each of them. Research design and methods: A systematic review was performed based on a comprehensive literature search. Results: MS has no effect on fertility, pregnancy or fetal outcomes, and pregnancies do not affect the long-term disease course and accumulation of disability. There is a potential risk for relapse after use of gonadotropin-releasing hormone agonists during assisted reproduction techniques. At short-term, pregnancy leads to a reduction of relapses during the third trimester, followed by an increased risk of relapses during the first three months postpartum. Pregnancies in MS are not per se high risk pregnancies, and MS does not influence the mode of delivery or anesthesia unless in the presence of significant disability. MRI is not contraindicated during pregnancy; however, gadolinium contrast media should be avoided whenever possible. It is safe to use pulse dose methylprednisolone infusions to manage acute disabling relapses during pregnancy and breastfeeding. However, its use during the first trimester of pregnancy is still controversial. Women with MS should be encouraged to breastfeed with a possible favorable effect of exclusive breastfeeding. Disease-modifying drugs can be classified according to their potential for pregnancy-associated risk and impact on fetal outcome. Interferon beta (IFNß) and glatiramer acetate (GA) may be continued until pregnancy is confirmed and, after consideration of the individual risk-benefit if continued, during pregnancy. The benefit of continuing natalizumab during the entire pregnancy may outweigh the risk of recurring disease activity, particularly in women with highly active MS. GA and IFNß are considered safe during breastfeeding. The use of natalizumab during pregnancy or lactation requires monitoring of the newborn. Conclusions: This review provides current evidence and recommendations for counseling and management of women with MS preconception, during pregnancy and postpartum.

Management of relapsing-remitting multiple sclerosis in Qatar: an expert consensus.

Healthcare systems vary greatly between countries. International, evidence-based guidelines for the management of multiple sclerosis (MS) may need to be adapted for use in particular countries. Two years ago, the authors published a comprehensive consensus guideline for the management of MS in Qatar. Since that time, the availability of disease-modifying treatments for relapsing-remitting MS (RRMS), and our understanding of how to apply those treatments, has increased. The authors present an update to our guidance, focussing on the management of relapsing-remitting RRMS. In particular, the authors consider the optimal use of different DMTs in patients presenting with mild, medium or high disease activity.

Severe rebound disease activity after fingolimod withdrawal in a pregnant woman with multiple sclerosis managed with rituximab: A case study.

Although pregnancy is potentially protective against relapses of multiple sclerosis, severe rebound of disease activity after withdrawal of fingolimod may occur. We report a woman with multiple sclerosis who discontinued fingolimod in the first month of her pregnancy. She developed severe disease rebound which responded poorly to steroids. She was started on rituximab, which was continued during the rest of her pregnancy and beyond. Rituximab appeared safe and well tolerated by both mother and infant, and could be considered in pregnancy for those patients with multiple sclerosis who are at high risk of gestational and postpartum relapse.

Expert consensus from the Arabian Gulf on selecting disease-modifying treatment for people with multiple sclerosis according to disease activity.

Recent research has expanded our understanding of the natural history and clinical course of multiple sclerosis (MS) in the Arabian Gulf region. In addition, the number of available therapies for MS has increased greatly in recent years, which complicates considerably the design of therapeutic regimens. We, an expert group of physicians practising in Arabian Gulf countries, present pragmatic consensus recommendations for the use of disease-modifying therapy, according to the level of MS disease activity, according to objective criteria, and prior treatment (if any) received by a given patient.

Disease-Modifying Drugs and Family Planning in People with Multiple Sclerosis: A Consensus Narrative Review from the Gulf Region.

Most disease-modifying drugs (DMDs) are contraindicated in pregnancy. Management of MS is especially challenging for pregnant patients, as withdrawal of DMDs leave the patient at risk of increased disease activity. We, a group of experts in MS care from countries in the Arab Gulf, present our consensus recommendations on the management of MS in these patients. Where possible, a patient planning pregnancy can be switched to a DMD considered safe in this setting. Interferon ß now can be used during pregnancy, where there is a clinical need to maintain treatment, in addition to glatiramer acetate. Natalizumab (usually to 30 weeks' gestation for patients with high disease activity at high risk of relapse and disability progression) may also be continued into pregnancy. Cladribine tablets and alemtuzumab have been hypothesised to act as immune reconstitution therapies (IRTs). These drugs provide a period of prolonged freedom from relapses for many patients, but the patient must be prepared to wait for up to 20 months from initiation of therapy before becoming pregnant. If a patient becomes pregnant while taking fingolimod, and requires continued DMD treatment, a switch to interferon ß or natalizumab after a variable washout period may be prescribed, depending on the level of disease activity. Women who wish to breastfeed should be encouraged to do so, and interferon ß may also be used during breastfeeding. There is a lack of data regarding the safety of using other DMDs during breastfeeding.

Oral disease-modifying therapies for multiple sclerosis in the Middle Eastern and North African (MENA) region: an overview.

BACKGROUND: The introduction of new disease-modifying therapies (DMTs) for remitting-relapsing multiple sclerosis (RRMS) has considerably transformed the landscape of therapeutic opportunities for this chronic disabling disease. Unlike injectable drugs, oral DMTs promote patient satisfaction and increase therapeutic adherence. REVIEW: This article reviews the salient features about the mode of action, efficacy, safety, and tolerability profile of approved oral DMTs in RRMS, and reviews their place in clinical algorithms in the Middle East and North Africa (MENA) region. A systematic review was conducted using a comprehensive search of MEDLINE, PubMed, Cochrane Database of Systematic Reviews (period January 1, 1995-January 31, 2018). Additional searches of the American Academy of Neurology and European Committee for Treatment and Research in Multiple Sclerosis abstracts from 2012-2017 were performed, in addition to searches of the Food and Drug Administration and European Medicines Agency websites, to obtain relevant safety information on these DMTs. CONCLUSIONS: Four oral DMTs: fingolimod, teriflunomide, dimethyl fumarate, and cladribine have been approved by the regulatory agencies. Based on the number needed to treat (NNT), the potential role of these DMTs in the management of active and highly active or rapidly evolving RRMS is assessed. Finally, the place of the oral DMTs in clinical algorithms in the MENA region is reviewed.

An Overview of High-Efficacy Drugs for Multiple Sclerosis: Gulf Region Expert Opinion.

This article discusses the opinions of the multiple sclerosis (MS) experts in the Gulf region on the use of high-efficacy disease-modifying drugs (DMDs; natalizumab, fingolimod, alemtuzumab, cladribine tablets, and ocrelizumab) in clinical practice. The experts reviewed the current literature including pivotal clinical trials and meta-analyses for high-efficacy DMDs, supplemented by the expert opinions on the usage of these DMDs in clinical practice. Several criteria were discussed by the panel based on different efficacy, safety, and convenience attributes. The panel concluded that all the DMDs available for the treatment of MS have benefits and risks, which should be considered while discussing the treatment plan with the patient. It is important to have a personalized approach based on the risk-benefit assessment for each case. Common considerations while choosing treatments include effectiveness, side effects/safety, and convenience/route of administration.Funding: Merck Serono Middle East FZ LTD.