Variant Of Multiple Sclerosis Research Articles

Balo concentric sclerosis, an emerging variant of multiple sclerosis: A case-series and literature review

Balo concentric sclerosis, an emerging variant of multiple sclerosis: A case-series and literature review

Risk factors and prevalence of strokes in patients with multiple sclerosis

Introduction. Numerous data on increased risk of stroke in people with multiple sclerosis (MS) needs clarification in view of shared pathogenesis and immunotherapy risks.The objective was to assess risk factors, prevalence and misdiagnosis of stroke in MS patients for future prevention optimization.Methods and materials. Cross-sectional retrospective study of risk factors, prevalence and misdiagnosis of stroke in cohort of 563 MS patients aged 40 years and older.Results. The cohort under study was representative in terms of gender ratio and MS variants. Stroke rate established as 1.78 % in MS type and gender representative cohort. Ischemic stroke was in 9/10 cases and ischemic venous stroke with hemorrhage in 1/10. Stroke misdiagnosis at MS first presentation estimated as 1.95 %. Stroke risk factors seems to be less prevalent in MS cohort compared to general population, with ischemic heart disease (OR=23.9) and arterial hypertension (OR=7.2) as most significant risk indicators.Conclusion. Stroke prevalence in MS patients may be lower than that in general population. Low rate of arterial hypertension (25.4 %), ischemic heart disease (3.4 %), smoking (10.7 %), diabetes mellitus (3.2 %), and obesity (9.1 %) may influence stroke low rate in MS. Arterial hypertension and ischemic heart disease are the most significant stroke risk factors in MS.

Role of clinicoradiological correlation in evaluation of various demyelinating disorders: A Systematic review

Background: There are mainly three types of white matter disorders resulting from defective myelination (dysmyelinating), destruction of myelin (demyelination) and decreased myelination (hypomyelinating). Each of these disorders require MRI and specific imaging for diagnosis. However, diagnosis of white matter disorders cannot solely rely on imaging. Objective: In this review we aim to correlate clinical presentation, history, laboratory investigations, and imaging as a tool rather than diagnostic modality to highlight the importance of clinical and radiological collaboration to diagnose the exact disease process. We would specifically discuss variants of multiple sclerosis, acute disseminated encephalomyelitis, neuromyelitis Optica spectrum disorder, progressive multifocal leuckoencephalothy, and osmotic demyelination syndrome. This study also includes specific signs of different demyelination white matter disorders on MRI which are characteristic of that disease process. However, we also highlight what clinical correlation and investigations may further aid to confirm the diagnosis, prognosis and extent of disease progression. Methods: In this review article we used Prisma guidelines we extracted studies where there was evidence of better patient outcome in terms of clinicoradiological collaboration in diagnosing various demyelinating white matter disorders. Results: We found that timely diagnosis and better patient outcomes can be achieved if clinicians also take in accord their own clinical judgement and based on that order relevant radiological investigations resulting better clinician to clinician communication, judicious use of hospital resources and overall better outcome in disease process. Conclusion: Our study concludes that solid clinical judgement, laboratory investigations along with radiological features of disease process would enhance clinical outcomes in terms of timely diagnosis, specific treatment and tracking disease prognosis.

Tumefactive Multiple Sclerosis: The Lethal Chameleon.

Tumefactive multiple sclerosis is an uncommon variant of multiple sclerosis that presents a substantial diagnostic challenge due to its potential to resemble the clinical and radiological characteristics of other central nervous system (CNS) pathologies, including neoplasms, granulomatous diseases, abscesses and vasculitis.Despite the fact that multimodal imaging studies may help narrow the differential diagnosis, a biopsy is often required to reach a definitive diagnosis and should not be delayed.Awareness of this condition among non-neurologists is critical since a timely and accurate diagnosis prompts aggressive immunomodulatory treatments that may delay a second demyelinating event or progression to clinically definite multiple sclerosis.

Baló concentric sclerosis: Literature review and report of two cases

BackgroundBaló's concentric sclerosis (BCS) is a rare variant of multiple sclerosis characterized by unique pathological features of alternating demyelination and preserved myelin. ObjectivesTo describe two cases of BCS, radiological and pathological findings and its clinical course. ResultsWe report two distinct cases of BCS that presented with unique MRI findings suggestive of BCS, but with different clinical courses and responses to treatment. The first case demonstrated substantial recovery following corticosteroid therapy, while the second case, initially suspected to be a malignant tumour, showed improvement after surgical intervention and immunoglobulin therapy. ConclusionThese cases highlight the variability in presentation and course of BCS, underscoring the challenges in diagnosis and the importance of considering BCS in the differential diagnosis of demyelinating and tumefactive lesions. The cases also emphasize the potential for favourable outcomes with appropriate management, challenging the traditional view of BCS as uniformly severe.

Possible Roles of Extracellular Vesicles in the Pathogenesis and Interventions of Immune-Mediated Central Demyelinating Diseases.

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are two of the most devastating immune-mediated central demyelinating disorders. NMOSD was once considered as a variant of MS until the discovery of an antibody specific to the condition. Despite both MS and NMOSD being considered central demyelinating disorders, their pathogenesis and clinical manifestations are distinct, however the exact mechanisms associated with each disease remain unclear. Extracellular vesicles (EVs) are nano-sized vesicles originating in various cells which serve as intercellular communicators. There is a large body of evidence to show the possible roles of EVs in the pathogenesis of several diseases, including the immune-mediated central demyelinating disorders. Various types of EVs are found across disease stages and could potentially be used as a surrogate marker, as well as acting by carrying a cargo of biochemical molecules. The possibility for EVs to be used as a next-generation targeted treatment for the immune-mediated central demyelinating disorders has been investigated. The aim of this review was to comprehensively identify, compile and discuss key findings from in vitro, in vivo and clinical studies. A summary of all findings shows that: 1) the EV profiles of MS and NMOSD differ from those of healthy individuals, 2) the use of EV markers as liquid biopsy diagnostic tools appears to be promising biomarkers for both MS and NMOSD, and 3) EVs are being studied as a potential targeted therapy for MS and NMOSD. Any controversial findings are also discussed in this review.

Proposed Diagnostic Criteria and Management of Marburg Variant Multiple Sclerosis: A Meta-analysis (P2-6.011)

Proposed Diagnostic Criteria and Management of Marburg Variant Multiple Sclerosis: A Meta-analysis (P2-6.011)

Gene–environment interactions: Epstein–Barr virus infection and risk of pediatric-onset multiple sclerosis

Background and Objective: Prior Epstein–Barr virus (EBV) infection is associated with an increased risk of pediatric-onset multiple sclerosis (POMS) and adult-onset multiple sclerosis (MS). It has been challenging to elucidate the biological mechanisms underlying this association. We examined the interactions between candidate human leukocyte antigen (HLA) and non-HLA variants and childhood EBV infection as it may provide mechanistic insights into EBV-associated MS. Methods: Cases and controls were enrolled in the Environmental and Genetic Risk Factors for Pediatric MS study of the US Network of Pediatric MS Centers. Participants were categorized as seropositive and seronegative for EBV-viral capsid antigen (VCA). The association between prior EBV infection and having POMS was estimated with logistic regression. Interactions between EBV serostatus, major HLA MS risk factors, and non-HLA POMS risk variants associated with response to EBV infection were also evaluated with logistic regression. Models were adjusted for sex, age, genetic ancestry, and the mother’s education. Additive interactions were calculated using relative risk due to interaction (RERI) and attributable proportions (APs). Results: A total of 473 POMS cases and 702 controls contributed to the analyses. Anti-VCA seropositivity was significantly higher in POMS cases compared to controls (94.6% vs 60.7%, p < 0.001). There was evidence for additive interaction between childhood EBV infection and the presence of the HLA-DRB1*15 allele (RERI = 10.25, 95% confidence interval (CI) = 3.78 to 16.72; AP = 0.61, 95% CI = 0.47 to 0.75). There was evidence for multiplicative interaction (p < 0.05) between childhood EBV infection and the presence of DRB1*15 alleles (odds ratio (OR) = 3.43, 95% CI = 1.06 to 11.07). Among the pediatric MS variants also associated with EBV infection, we detected evidence for additive interaction (p = 0.02) between prior EBV infection and the presence of the GG genotype in risk variant (rs2255214) within CD86 (AP = 0.30, 95% CI = 0.03 to 0.58). Conclusion: We report evidence for interactions between childhood EBV infection and DRB1*15 and the GG genotype of CD86 POMS risk variant. Our results suggest an important role of antigen-presenting cells (APCs) in EBV-associated POMS risk.

Chapter 21 - Pediatric inflammatory leukoencephalopathies

Acquired demyelinating syndromes (ADS) represent acute neurologic illnesses characterized by deficits persisting for at least 24hours and involving the optic nerve, brain, or spinal cord, associated with regional areas of increased signal on T2-weighted images. In children, ADS may occur as a monophasic illness or as a relapsing condition, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Almost all young people with MS have a relapsing-remitting course with clinical relapses. Important strides have been made in delineating MS from other ADS subtypes. Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin 4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) were once considered variants of MS; however, studies in the last decade have established that these are in fact distinct entities. Although there are clinical phenotypic overlaps between MOGAD, AQP4-NMOSD, and MS, cumulative biologic, clinical, and pathologic evidence allows discrimination between these conditions. There has been a rapid increase in the number of available disease-modifying therapies for MS and novel treatment strategies are starting to appear for both MOGAD and AQP4-NMOSD. Importantly, there are a number of both inflammatory and noninflammatory mimics of ADS in children with implications of management for these patients in terms of treatment.

B-cell activating factor gene variants in multiple sclerosis: Possible associations with disease susceptibility among females

Although B cells and B cell activating factor (BAFF) have been previously implicated in MS pathogenesis, data regarding the genetic influence of BAFF polymorphisms on MS susceptibility are limited. Here we aim to explore whether BAFF polymorphisms could contribute to MS susceptibility.156 RRMS patients fulfilling the revised McDonald criteria for MS diagnosis and 220 HCs were enrolled. Clinical, laboratory, and imaging characteristics were recorded. BAFF rs9514827, rs1041569, and rs9514828 polymorphisms were assessed by RFLP-PCR in DNA samples extracted from whole peripheral blood.The BAFF rs1041569 TT genotype along with the CTT and TTC haplotypes were associated with significantly increased risk for MS development in female MS patients compared to healthy female counterparts. These findings were not confirmed in males. The rs1041569 BAFF variant together with the CTT and TTC BAFF haplotypes derived from the BAFF rs9514827, rs1041569, and rs9514828 polymorphisms may represent novel genetic contributors to the development of MS in females.

Glutamate as a new path in discrimination between neuromyelitis optica spectrum disorder and multiple sclerosis

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) used to be considered as a variant of multiple sclerosis (MS), however the recent detection of a highly specific serum biomarkers for NMOSD have made clear that NMOSD is a condition distinct from MS. The aim was to explore the role of serum glutamate level in the discrimination between NMOSD and relapsing remitting (RR) MS patients during and in between relapses. The study comprised two groups; first group, a total of 30 NMOSD patients, they were furtherly subdivided into NMOSD in remission, 15 patients without recent relapses in the last 3 months, NMOSD with relapse, 15 patients with recent relapses in the last 3 months, the second group, 30 definite, RRMS patients, they were further subdivided into RRMS in remission, 15 patients without recent relapses in the last 3 months RRMS with relapse, 15 patients with recent relapses in the last 3 months.ResultsWithout relapse, NMOSD patients have higher level of serum glutamate than RRMS patients with (P values = 0.005), a significant difference between EDSS in NMOSD patients and RRMS patients (P = 0.0001), The cut-off value of glutamate serum level between NMOSD in remission and RRMS in remission was > 10.3 μg/mL, yet its level for differentiation between group RRMS in remission and RRMS with relapse was > 12.6 μg/mL.ConclusionGlutamate cut-off value might be a reliable tool to discriminate between NMOSD and RRMS.

Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study

Background: Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. Objective: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). Methods: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. Results: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients’ cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus (pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. Conclusion: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an “incidental finding” but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.

B-101 Aquaporin 4 and Neuromyelitis Optica Spectrum Disorders

Abstract Background Neuromyelitis óptica (NMO) is a rare demyelinating inflammatory disease of the central nervous system, characterized by acute optic neuritis (ON) and transverse myelitis (TM). Previously, it was considered as a variant of multiple sclerosis (MS), however, there are now several clinical, laboratory, neuroimaging and pathological anatomical features that distinguish it from MS as the presence of a specific autoantibody in blood called IgG-NMO or anti-AQP4 that binds to water channels named aquaporin-4 (AQP4) expressed on astrocytes and plays a key role in the pathogenesis of this disease. Some patients remain seronegative for AQP4-IgG despite a definite diagnosis of NMO and the use of the finest methods for antibody detection. In anti-AQP4 seronegative forms, antibodies against myelin oligodendrocyte glycoprotein (MOG) may be identified. We have carried out a review of those patients with anti-AQP4-IgG detected in the autoimmunity laboratory during the last 3 years. Methods Each year we receive an average of 260 samples from patients with suspected demyelinating pathology with or without visual impairment. For the detection of antibodies against AQP-4 specifically HEK293 cells transfected were used as the standard substrate. Anti-MOG antibody can be detected in the same test. Measurement range: The dilution starting point for this measurement system is 1:10 (serum/plasma) and 1:1 (CSF, undiluted). Results A total of 5 patients were positive for anti AQP-4 antibody in serum samples, all women aged between 23 and 78 years. All patients except the youngest, who presented to the neurology department for loss of visual acuity, had other autoimmune diseases: systemic lupus erythematosus (SLE) in conjunction with rheumatoid arthritis, SLE in conjunction with Graves’ disease and hypothyroidism, the two oldest (59 and 78 years), respectively. The oldest patient was admitted to the internal medicine department for persistent nausea, vomiting and hiccups and was diagnosed as NMO spectrum disorder. In all cases, the oligoclonal immunoglobulin G bands study in CSF was negative. None of the CSF samples tested were positive for anti AQP-4 antibody. All patients were treated with methylprednisolone, but treatment with azathioprine or rituximab was necessary in 3 patients. Conclusion Titers of antibodies against AQP-4 are significantly higher in serum than in CSF, with serum being the most sensitive simple. NMO is more prevalent in women than men, with a female predominance usually higher than observed in MS. The median age of onset is also higher than MS, with a median of 35–45 years. Since the discovery of AQ-4 antibodies, there has been an increase in the number of clinical and radiological manifestations of NMO beyond involvement of the optic nerve and the spinal cord, including manifestations in the brain. It is important to recognise them in order to make an early diagnosis, to avoid unnecessary complementary tests and to establish the most suitable treatment. Persistent and intractable hiccups and nausea may occur in 17%–43% as in our oldest patient’s case. Associations with organ-specific autoimmune diseases such as autoimmune thyroiditis, and non-organ-specific diseases such as SLE and Sjögren’s syndrome have been described.

Tumefactive demyelinating disorders as stroke mimics: Description of cases and systematic review of the literature.

tumefactive multiple sclerosis (TmMS) is a rare subtype of a demyelinating disease that develops over time. Cases of hyperacute presentations mimicking cerebrovascular disorders have been reported; however, detailed clinical and demographic data are lacking. this study aimed to systematically review the literature on tumefactive demyelinating disorders presenting as strokes. After screening the PubMed, PubMed Central, and Web of Science databases, 39 articles describing 41 patients were identified, including 2 historical patients from our center. 23 (53.4%) patients were diagnosed with multiple sclerosis variants (vMS), 17 (39.5%) with inflammatory demyelinating variants (vInf), and 3 with tumors; however, only 43.5% of cases were verified histologically. In subgroup analysis, vMS differed from vInf in several aspects. Inflammatory cerebral spinal fluid parameters, including pleocytosis, proteinorachia was more commonly observed in vInf [11 (64.7%) vs. 1 (5.2%), P=0.001 and 13/17 (76.4%) vs. 6/23 (31.5%), P=0.02] than that in vMS. Neurological deterioration and fatal outcomes were more commonly observed in vInf [13/17 (76.4%) vs. 7/23 (30.4%), P=0.003, and 11/17 (64.7%) vs. 0/23 (0%), P=0.0001] than that in vMS. Clinicodemographic data might aid in recognizing different subtypes of TmMS and warrant consideration of unconventional therapies because outcomes may be poor in the vInf of TmMS.

A Young Lady with Quadriparesis

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease, causing multifocal CNS inflammation affecting the optic nerves &amp; spinal cord. In the 20th century, ‘Devics disease’ was considered as a variant of Multiple sclerosis(MS) that spared the brain. However, the discovery of IgG-class antibodies that bind to the water channel aquaporin-4 (AQP4-IgG) in serum from patients with Devic’s disease, but not from those with typical MS, established NMO as a distinct entity with a chronic, relapsing course. Our patient, a 42-year-old woman has been suffering from vomiting for 2 months followed by inability to move all extremities for last 7 days. It was the very 1st episode of such type of illness. We are reporting this case to highlight the presentation of NMOSD, which is itself a rare disease, outcropped as ‘Area postrema syndrome’, an inaugural manifestation in this patient. J MEDICINE 2023; 24(2): 158-161

Cognitive impairment, fatigue and depression in multiple sclerosis: Is there a difference between benign and non-benign MS?

Multiple Sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system (CNS). The severity of disability in people with MS (PwMS) is generally measured with the Expanded Disability Status Scale (EDSS). A variant of MS known as 'benign MS' (BMS) has been defined as an EDSS score of 3 or lower, combined with a disease duration of 10 years or longer; however, there is disagreement in the field about whether BMS really exists. Given that the EDSS does not capture cognitive issues, communication dysfunction, fatigue, depression, or anxiety properly, its ability to accurately represent disability in all PwMS, including BMS, remains questionable. In this study, 141 persons with BMS (PwBMS) were included, consisting of 115 females (82%) and 26 males (18%) with a mean age of 50.8 (±8.68). A computerized test battery (NeuroTrax®) was used to assess cognition, covering seven cognitive domains (memory, executive function, visual-spatial processing, verbal function, attention, information processing, and motor skills). Fatigue was measured using the Fatigue Severity Scale (FSS). The Beck Depression Inventory (BDI) was used to assess symptoms of depression. Cognitive impairment was defined for this study as when someone has a score lower than 85 in at least two subdomains of the cognitive test battery. Rates of impairment were compared to 158 persons with non-benign MS (PwNBMS; with a disease duration of 10 years and longer and an EDSS score higher than 3) and 487 PwMS with a disease duration of fewer than 10 years. Cognitive impairment was found in 38% of PwBMS and in 66% of PwNBMS (p<0.001). In PwBMS, the lowest rate of impairment was found in the verbal function domain (18%) and the highest rate of impairment in the domain of information processing (32%). Fatigue and depression were found in 78% and 55% of all PwBMS, with no difference in these rates between PwBMS and PwNBMS (p=0.787 and p=0.316 resp.) CONCLUSION: Cognitive impairment, fatigue and depression are common among people with an EDSS-based definition of benign MS. These aspects should be incorporated into a new and better definition of truly benign MS.

High-dose cyclophosphamide as a rescue treatment for fulminant Marburg multiple sclerosis: A case report (P12-3.014)

<h3>Objective:</h3> To describe the presentation of a life-threatening multiple sclerosis variant and the positive response to cyclophosphamide induction. <h3>Background:</h3> The rare Marburg variant of MS is characterized by life-threatening severity and a fulminant disease course. Many treatment regimens have been proposed to combat this disease process, but the most promising results have been demonstrated with high-dose induction cyclophosphamide 50 mg/kg/day for four days (HiCy). <h3>Design/Methods:</h3> N/a <h3>Results:</h3> A previously healthy 39-year-old woman presented with confusion and aphasia. She rapidly became minimally conscious, only intermittently withdrawing to pain. CSF was unrevealing. MRI brain showed widespread subcortical and infratentorial T2 hyperintense lesions. After diagnosis of acute encephalitis, she was treated with IV steroids, 11 sessions of plasma exchange, and 5 sessions of IVIG with little to no clinical response. Further MR imaging revealed spinal cord and open ring-enhancing juxtacortical lesions. After ruling out alternative causes, she was diagnosed with Marburg variant MS and started on HiCy. As early as day two of treatment, she became alert and oriented and was consistently able to follow commands for the first time. She demonstrated steady clinical improvement thereafter, and was discharged with an EDSS of 1. At three-month follow up, she had ongoing disability-free stability and started ocrelizumab for maintenance therapy. <h3>Conclusions:</h3> Though rare and diagnostically elusive, early recognition of Marburg and initiation of rescue treatment with cyclophosphamide can be lifesaving. Given its many potential adverse reactions, the decision to use of HiCy should not be taken lightly and must be weighed against other treatment modalities. We propose that despite these risks, the risk of not treating or delaying treatment in the face of fulminant MS is far greater. This case represents the swiftest and most significant clinical recovery (EDSS 9 to 0) in a patient with Marburg MS treated with HiCy. <b>Disclosure:</b> Dr. Roberts has received intellectual property interests from a discovery or technology relating to health care. Dr. Abdullah has nothing to disclose. Miss Shoga has nothing to disclose. Dr. Reyna has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Reyna has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Reyna has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Reyna has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Celgene. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Genentech. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Serono. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Reyna has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Bristol Myers Squibb. An immediate family member of Dr. Parker has received personal compensation for serving as an employee of Rochal Industries, Rochal Parners. An immediate family member of Dr. Parker has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Sanara Med Tech. An immediate family member of Dr. Parker has stock in Sanara Med Tech. An immediate family member of Dr. Parker has stock in Rochal Industries. An immediate family member of Dr. Parker has stock in Rochal Parnters. The institution of Dr. Parker has received research support from Texas Alzheimer’s Research and Care Consortium. The institution of an immediate family member of Dr. Parker has received research support from Rochal Industries. An immediate family member of Dr. Parker has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Parker has received publishing royalties from a publication relating to health care. Dr. Parker has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Speaker with Univ of Texas Tyler. An immediate family member of Dr. Parker has received personal compensation in the range of $0-$499 for serving as a NIH Review Committees Member with NIH. An immediate family member of Dr. Parker has a non-compensated relationship as a Chairwoman of the Board - Ann Salamone with BioMed SA that is relevant to AAN interests or activities.

In silico prioritisation of microRNA-associated common variants in multiple sclerosis

BackgroundGenome-wide association studies (GWAS) have highlighted over 200 autosomal variants associated with multiple sclerosis (MS). However, variants in non-coding regions such as those encoding microRNAs have not been explored thoroughly, despite strong evidence of microRNA dysregulation in MS patients and model organisms. This study explores the effect of microRNA-associated variants in MS, through the largest publicly available GWAS, which involved 47,429 MS cases and 68,374 controls.MethodsWe identified SNPs within the coordinates of microRNAs, ± 5-kb microRNA flanking regions and predicted 3′UTR target-binding sites using miRBase v22, TargetScan 7.0 RNA22 v2.0 and dbSNP v151. We established the subset of microRNA-associated SNPs which were tested in the summary statistics of the largest MS GWAS by intersecting these datasets. Next, we prioritised those microRNA-associated SNPs which are among known MS susceptibility SNPs, are in strong linkage disequilibrium with the former or meet a microRNA-specific Bonferroni-corrected threshold. Finally, we predicted the effects of those prioritised SNPs on their microRNAs and 3′UTR target-binding sites using TargetScan v7.0, miRVaS and ADmiRE.ResultsWe have identified 30 candidate microRNA-associated variants which meet at least one of our prioritisation criteria. Among these, we highlighted one microRNA variant rs1414273 (MIR548AC) and four 3′UTR microRNA-binding site variants within SLC2A4RG (rs6742), CD27 (rs1059501), MMEL1 (rs881640) and BCL2L13 (rs2587100). We determined changes to the predicted microRNA stability and binding site recognition of these microRNA and target sites.ConclusionsWe have systematically examined the functional, structural and regulatory effects of candidate MS variants among microRNAs and 3′UTR targets. This analysis allowed us to identify candidate microRNA-associated MS SNPs and highlights the value of prioritising non-coding RNA variation in GWAS. These candidate SNPs could influence microRNA regulation in MS patients. Our study is the first thorough investigation of both microRNA and 3′UTR target-binding site variation in multiple sclerosis using GWAS summary statistics.

Cross-Trait Mendelian Randomization Study to Investigate Whether Migraine Is a Risk Factor for Multiple Sclerosis.

Migraine is common among people with multiple sclerosis (MS), but the reasons for this are unknown. We tested 3 hypothesized mechanisms for this observed comorbidity, including migraine is a risk factor of MS, genetic variants are shared between the conditions, and migraine is because of MS. Data were from 2 sources: publicly available summary statistics from genome-wide association studies of MS (N = 115,748) and migraine (N = 375,752 and N = 361,141) and a case-control study of MS recruited from the Kaiser Permanente Northern California Health Plan (N = 1,991). For the latter participants, migraine status was ascertained using a validated electronic health record migraine probability algorithm or self-report. Using the public summary statistics, we used 2-sample Mendelian randomization to test whether a migraine genetic instrumental variable was associated with MS. We used linkage disequilibrium score regression and LOGODetect to ascertain whether MS and migraine shared genetic variants across the genome and regionally. Using the Northern California MS cohort, we used logistic regression to identify whether people with both MS and migraine had different odds of clinical characteristics (e.g., age at MS onset, Perceived Deficits Questionnaire, and depression) or MS-specific risk factors (e.g., body mass index, smoking status, and infectious mononucleosis status) compared with people with MS without migraine. We did not find evidence supporting migraine as a causal risk factor of MS (p = 0.29). We did, however, identify 4 major histocompatibility complex (MHC) loci shared between MS and migraine. Among the Northern California MS cohort, 774 (39%) experienced migraine. People with both MS and migraine from this cohort were more likely to ever smoke (odds ratio [OR] = 1.30, 95% CI: 1.08-1.57), have worse self-reported cognitive deficits (OR = 1.04, 95% CI: 1.02-1.06), and ever experience depression (OR = 1.48, 95% CI: 1.22-1.80). Our findings do not support migraine as a causal risk factor of MS. Several genetic variants, particularly in the MHC, may account for some of the overlap. It seems likely that migraine within the context of MS is because of MS. Identifying what increases the risk of migraine within MS might lead to an improved treatment and quality of life.

Marburg variant of multiple sclerosis masquerading as glioma: a case report

Marburg variant of multiple sclerosis is a rare demyelinating disease with a rapid and often fulminant course. It may disguise as a cerebral ring-enhancing lesion, hence presenting a diagnostic dilemma. Treatment may be challenging due to its rarity, aggressive course and dearth of diagnostic facilities in our environment. To the authors´ best knowledge, this is the first reported case of the Marburg variant of multiple sclerosis in sub-Saharan Africa. We present a 35-year-old woman with clinical and radiological features of intracranial space-occupying lesion who had two recurrences over four months despite total gross excisions. The fulminant, recurrent nature of this disease, coupled with positive oligoclonal bands, led to the Marburg variant of multiple sclerosis diagnosis. Physicians saddled with managing neurological diseases should consider this a differential diagnosis, especially when the clinical course and laboratory findings have ruled out more common neoplastic and infective causes.