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Objective: To determine the factors, if any, that are associated with the efficacy of "off-label therapies" (OLTs) for multiple sclerosis (MS). Methods: Consecutive patients (N = 174) with relapsing--remitting MS (RRMS) or secondary progressive MS (SPMS) with relapses, on OLTs with a generic formulation of azathioprine, mycophenolate mofetil, or rituximab biosimilar for ≥2 years were included. Annualized relapse rate (ARR) and expanded disability status score (EDSS) 1 year before and ≥2 years after starting OLTs were recorded. Optical coherence tomography (OCT) was done at baseline and at the end of the study. Results: During a median period of 4.1 years (2.4-24), ARR reduced in all (P < 0.0001) and EDSS improved in RRMS (P < 0.0001) patients but not in SPMS (P < 0.31) patients. Good responders were those who had RRMS (P = 0.001, odds ratio [OR] 0.04, 95% confidence interval [CI] 0.01-0.15), female gender (P 0.008, OR 6.67, 95% CI 1.7-26.8), and had early access to OLT (P = 0.006, OR 1.2, 95% CI 1.05-1.40). Baseline peripapillary retinal nerve fiber layer thickness identified the risk of conversion to SPMS (P < 0.01, OR 1.03; 95% CI 1.01-1.06). Conclusions: This limited prospective study suggests that early identification of patients who could potentially respond to unconventional but accessible therapies may be valuable in the treatment of MS, particularly in resource-poor regions. [ABSTRACT FROM AUTHOR]

Background: Though considered optimal, live cell-based assay (LCBA) is often unavailable for the diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) in resource-poor regions. This study was undertaken to determine the agreement between LCBA and the widely available fixed cell-based assay (FCBA), for recommending testing guidelines within our region. Method: All consecutive patients in our registry with a MOGAD phenotype were tested. The results from a commercially available FCBA (Euroimmun, Germany) were compared with a validated "in-house" LCBA. Clinical and MRI data were available for correlation. Results: Among the 257 patient samples tested, 118 (45.9%) were positive by FCBA titre ≥1:10 and or LCBA titres ≥1:160 titre and 139 samples were negative. There was robust agreement between the two assays (agreement 98.8%, Cohen's kappa 0.98 [95% CI- 0.95-1.00], Spearman correlation 0.97 (p < 0.0001). Among five discordant samples, four had clinical and or MRI data which supported an alternate diagnosis. There was a modest correlation between assay titres, particularly for samples with titres ≥ 1:100 in FCBA (Spearman's Rho 0.26, p 0.005). Thirty samples were positive by FCBA at < 1:100 titre and included 1:80 (20),1:40(7) and 1:10 (3) titres. Among them, 80% had clear positive titres when tested by LCBA. Conclusion: The FCBA tested with serum dilutions of 1:10 was highly predictive of MOGAD in our study and compared well with our "in-house" LCBA. The current recommendations for testing at higher dilutions need to be re-examined in light of our findings. The results of our study should ideally be replicated in a larger dataset but at the same time provide some guidance for the accurate diagnosis of MOGAD in resource-poor settings. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (Hp) persists after colonizing the gut in childhood, and potentially regulates host immune system through this process. Earlier studies have shown that Hp infection in childhood, may protect against MS in later life. Such an association was not seen with AQP4-IgG positive NMOSD, while the association with MOGAD is unclear. Objective: To evaluate frequency of Hp IgG among patients with MOGAD, MS, NMOSD and matched controls and its effect on disease course. To ascertain whether childhood socio economic factors were linked to prevalence of Hp infection. Methods: In all, 99 patients diagnosed to have MOGAD, 99 AQP4 IgG+ NMOSD, 254MS and 243 matched controls were included. Patient demographics, diagnosis, age at disease onset, duration and the last recorded expanded disability status scale (EDSS) were obtained from our records. Socioeconomic and educational status was queried using a previously validated questionnaire. Serum HpIgG was detected using ELISA kits (Vircell, Spain). Result: Frequency of Hp IgG was significantly lower among MOGAD (28.3% vs 44%, p-0.007) and MS (21.2% vs 44%, p-0.0001) but not AQP4-IgG+ NMOSD patients (42.4% vs 44%, p-0.78) when compared to controls. Frequency of Hp IgG in MOGAD & MS patients combined (MOGAD-MS) was significantly lower than those with NMOSD (23.2% vs 42.4%, p-0.0001). Seropositive patients with MOGAD-MS were older (p-0.001. OR -1.04, 95% CI- 1.01- 1.06) and had longer disease duration (p- 0.04, OR- 1.04, 95% CI- 1.002- 1.08) at time of testing. Educational status was lower among parents/caregivers of this study cohort (p- 0.001, OR -2.34, 95% CI- 1.48-3.69) who were Hp IgG+. Conclusions: In developing countries Hp infection may be a significant environmental factor related to autoimmune demyelinating CNS disease. Our preliminary data suggests that Hp may exert a differential influence - a largely protective role for MS-MOGAD but not NMOSD and may influence disease onset and course. This differential response maybe related to immuno-pathological similarities between MOGAD and MS in contrast to NMOSD. Our study further underscores the role of Hp as a surrogate marker for poor gut hygiene in childhood and its association with later onset of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Introduction of international consensus criteria (2015 IPND criteria) for neuromyelitis optica spectrum disorders (NMOSDs) has improved diagnostic accuracy for aquaporin 4 (AQP4)-IgG-associated and seronegative NMOSDs. This study aimed to review relevant publications related to the incidence and prevalence of NMOSDs and provide an updated review of the global epidemiology of NMOSDs in the light of new diagnostic criteria. A comprehensive literature search was performed from January 2015 to June 2021 by using appropriate keywords in PubMed, Scopus, and Web of Science. Relevant papers that fulfilled inclusion criteria were shortlisted and reviewed. Twenty-one papers were selected for this review. Incidence of NMOSDs was 0.04-0.25/100,000 in predominantly white and 0.34-1.31/100,000 in nonwhite populations. Prevalence was 0.70-1.91/100,000 in white and 0.86-4.52/100,000 in nonwhite populations. The 2015 IPND criteria significantly improved the incidence and prevalence rates for NMOSDs when compared to the Wingerchuk 2006 criteria. Incidence of MOG-IgG-associated NMOSDs was 0.12-0.13/100,000, with prevalence in children 0.03-1.4/100,000 and in adults 0.65-2/100,000. In this systematic review, studies that used uniform diagnostic criteria and confirmed cases after testing for AQP4-IgG were included. The prevalence of NMOSDs was estimated to be <5/100,000 globally. A clear bias was seen in favor of nonwhite and indigenous populations. This review highlights the need for prospective population-based epidemiological studies and the importance of surveys in nonwhite populations around the globe. [ABSTRACT FROM AUTHOR]

Objective: Patients with myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease (MOGAD) suffer from severe optic neuritis (ON) leading to retinal neuro-axonal loss, which can be quantified by optical coherence tomography (OCT). We assessed whether ON-independent retinal atrophy can be detected in MOGAD.Methods: Eighty patients with MOGAD and 139 healthy controls (HCs) were included. OCT data was acquired with (1) Spectralis spectral domain OCT (MOGAD: N = 66 and HCs: N = 103) and (2) Cirrus high-definition OCT (MOGAD: N = 14 and HCs: N = 36). Macular combined ganglion cell and inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) were quantified.Results: At baseline, GCIPL and pRNFL were lower in MOGAD eyes with a history of ON (MOGAD-ON) compared with MOGAD eyes without a history of ON (MOGAD-NON) and HCs (p < 0.001). MOGAD-NON eyes had lower GCIPL volume compared to HCs (p < 0.001) in the Spectralis, but not in the Cirrus cohort. Longitudinally (follow-up up to 3 years), MOGAD-ON with ON within the last 6-12 months before baseline exhibited greater pRNFL thinning than MOGAD-ON with an ON greater than 12 months ago (p < 0.001). The overall MOGAD cohort did not exhibit faster GCIPL thinning compared with the HC cohort.Interpretation: Our study suggests the absence of attack-independent retinal damage in patients with MOGAD. Yet, ongoing neuroaxonal damage or edema resolution seems to occur for up to 12 months after ON, which is longer than what has been reported with other ON forms. These findings support that the pathomechanisms underlying optic nerve involvement and the evolution of OCT retinal changes after ON is distinct in patients with MOGAD. ANN NEUROL 2022;92:476-485. [ABSTRACT FROM AUTHOR]

Background: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort.Method: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site.Results: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere.Conclusion: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates. [ABSTRACT FROM AUTHOR]

Background: Co-occurrence of other autoimmune disorders (AID) and autoantibodies in patients with autoimmune demyelinating CNS disorders have not been studied previously in patients of Indian origin. Objective: To determine the frequency of concomitant autoimmune disorders, anti-nuclear antibody (ANA) and antithyroid antibody (ATAb) and to evaluate the impact on clinical course of disease. Materials and Methods: A total of 111 patients with MS and 152 patients with non-MS demyelinating disorders were included. Demographics, clinical course and disability were recorded. History of other autoimmune disorders (AIDs) in patients and first degree relatives was noted. Serum ANA and ATAb were tested. Results: Concomitant AIDs were seen in 21% of MS and 19% of non-MS patients. Autoimmune thyroid disease was most frequent and seen in 10.8% of MS and 6.6% of non-MS disorders. Frequency of ATAb was significantly higher among MS group (MS 25.5% vs non-MS 13.2% P = 0.04) but that of ANA was similar between the 2 groups (MS 19.8% vs non-MS 26.9% P = 0.17). A positive family history of autoimmune disorders was noted in 20% of MS and 15.1% of non-MS disorders. Clinical course was unaffected by presence of concomitant AID and autoantibodies. Conclusion: Cooccurrence of autoantibodies and AID are seen in a significant number of patients with MS and non-MS disorders and influences clinical management. [ABSTRACT FROM AUTHOR]

Epidemiological and clinical features of demyelinating disorders in the Indian context have been sparsely reported. This paper aims to provide a review of literature from the past decade on the same. PubMed, Google scholar, and PubMed search databases were searched using subject headings and key words for data from the past 10 years (1999‐2019). Data from studies that collected Incidence and prevalence of demyelinating disorders were prioritized. In addition, clinical and demographic features of demyelinating disorders were obtained from hospital‐based studies published from different regions within India. The sole epidemiological study from India showed a prevalence of multiple sclerosis (MS) among Indians to be 8.3/100 000 and that of neuromyelitis optica spectrum disorders (NMOSD) to be 2.7/100 000. Clinical features of MS obtained from hospital‐based studies showed female predominance, an onset of disease predominantly in the second decade of life and pyramidal dysfunction as a common initial attack. Aquaporin 4‐IgG‐associated NMOSD were predominantly in woman with myelitis as the most common initial attack. In contrast, MOG‐IgG‐associated disorders showed no gender bias and presented often with optic neuritis. There is growing awareness of demyelinating disorders in India, and the availability of imaging and serological tests has allowed for accurate and early diagnosis. In the absence of large epidemiological studies at the national level, there is likely to be a significant underestimation of prevalence and incidence of these diseases. [ABSTRACT FROM AUTHOR]

Background: The possible interaction between genetic and immunological factors in influencing clinical course of multiple sclerosis (MS) has not been studied previously in Indian population. Aim: In this study we evaluated the association of HLA alleles and OCB in affecting clinical course and disability of MS. Methods: Clinical and demographic features of 145 MS patients who had CSF oligoclonal bands (OCB) tested by isoelectric focussing technique were analyzed, disability status estimated, and HLA DRB1 alleles were genotyped. Results: OCBs were positive in 53.8% (78/145) of all MS cases. Patients with CSF OCB had more frequent relapses and an association with HLA DRB1*15. Early disease onset and a high annualized relapse rate was associated with HLA DRB1*03 allele. A relapsing remitting course for MS was seen with HLA DRB1*03 & 15 while a progressive disease was associated with DRB1*01. Presence of both OCB and HLA DRB1*13 was significantly associated with disability in this cohort. Conclusion: The results of our study suggest that an interaction between immunological and genetic factors may influence disease onset, course, and disability in MS. [ABSTRACT FROM AUTHOR]

Background: The role of viral infections in multiple sclerosis (MS) pathogenesis is unclear.Objective: Certain neurotropic viruses previously linked with MS among white population were studied including Epstein-Barr virus, human herpesvirus-6 (HHV-6) and MS-associated retrovirus (MSRV).Material and Methods: Sixty-two MS patients (37 had a recent clinical relapse) and 65 controls with other neurological disorders were included. Blood and cerebrospinal fluid (CSF) samples were obtained and processed with the primary objective of determining whether there was intrathecal multiplication of viruses under study (EBV, HHV6 A and B and human endogenous retrovirus) or a breach in blood-brain barrier associated with viral presence in both peripheral blood and CSF.Results: Evidence of breach in blood-brain barrier was seen in 86.5% of patients as evidenced by abnormal CSF/serum albumin index and or MRI. EBV nuclear antigen (EBNA1 IgG) was seen in 89% of MS patients and 58% controls (P = <0.001). However, HHV6 IgG was similar in both groups (85% versus 81%; P = 0.45). In affinity immunoblotting reaction intrathecal IgG synthesis against EBNA1 antigen was demonstrable in 26% (16/62) of patients and none against HHV6. A subset of patients showed significant elevation in mean copy number of plasma EBV DNA during relapse and there was a trend for the same among patients harboring HHV-6B. No evidence of isolated intrathecal viral presence or multiplication was seen.Conclusions: The results of our study suggest that viruses studied namely EBV and HHV6 have a role in triggering relapses through a peripheral mechanism, rather than a direct role through intrathecal multiplication. [ABSTRACT FROM AUTHOR]

Knowledge related to SARS-CoV-2 or 2019 novel coronavirus (2019-nCoV) is still emerging and rapidly evolving. We know little about the effects of this novel coronavirus on various body systems and its behaviour among patients with underlying neurological conditions, especially those on immunomodulatory medications. The aim of the present consensus expert opinion document is to appraise the potential concerns when managing our patients with underlying CNS autoimmune demyelinating disorders during the current COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The practice of prescribing off-label therapies has increased over time in both developed and developing nations in low- and middle-income countries (LMICs) for a variety of medical indications including immunological disorders. Generic versions of MS therapies are available in several countries and include dimethyl fumarate, fingolimod, cladribine, teriflunomide among others, including biosimilars for platform therapies which are priced competitively alongside patent-protected drugs. [Extracted from the article]

Objectives: We investigated the clinical characteristics and treatment response in myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disease and looked for evidence of subclinical disease. Methods: We prospectively evaluated the frequency and pattern of relapse, tested afferent visual function and monitored treatment response in 42 south Asian patients from a single centre. Results: Eighteen patients (42.9%) had monophasic and 24 (57.1%) a relapsing course. Disease duration was longer (P<0.02) in those with a relapsing course. Median time to the second attack was prolonged (P<0.04) in patients with recurrent transverse myelitis when compared with neuromyelitis optica spectrum disorder and recurrent optic neuritis. Thirteen out of 17 patients (76.5%) initially presenting with optic neuritis developed recurrent optic neuritis later. After the first attack of transverse myelitis, 17 out of 22 (77.3%) had disease confined to the spinal cord. Optical coherence tomography detected peripapillary retinal nerve fibre layer thickness (P<0.05) and macular ganglion cell complex volume (P<0.005) abnormalities in seven out of 10 (70.0%) patients without clinical optic neuritis. Immunosuppressants induced remission in 17 out of 22 (77.3%) patients during a median follow-up of 48 months and the median Expanded Disability Status Score was 1 (range 1-10). Conclusion: Our study highlighted the tendency for stereotypical attacks in MOG-IgG-associated disease, heterogeneity in clinical course among subtypes, subclinical visual impairment and the need for early and sustained immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

A combined endpoint measure to define no evidence of disease activity (NEDA) is becoming increasingly appealing in the treatment of multiple sclerosis (MS). Initial efforts using a 3 parameter NEDA monitored disease activity using clinical and MRI lesion data. Later refinements, introduced more recently, include brain atrophy measurement and cognitive function analysis in defining NEDA-4. Using these stringent criteria clearly differentiated the usefulness of different disease modifying agents (DMDs) in achieving and sustaining NEDA over time. This in turn has changed attitudes and strategies in management of MS. [ABSTRACT FROM AUTHOR]

Background: In less than a decade, genomewide association studies have identified over 100 single-nucleotide variants that are associated with increased risk of developing multiple sclerosis. However, since these studies have focused almost exclusively on European populations, it is unclear what role these variants might play in determining risk in other ethnic groups. Objective: To assess the effects of European multiple sclerosis–associated risk variants in the south Asian population. Methods: Using a combination of chip-based genotyping and next-generation sequencing, we have assessed 109 European-associated variants in a total of 270 cases and 555 controls from the south Asian population. Results: We found that two-thirds of the tested variants (72/109) showed over representation of the European risk allele in south Asian cases (p < 0.0003). In the rest of the Immunochip array, the most associated variant was rs7318477 which maps close to TNFSF13B, the gene for the B-cell-related protein BAFF. Conclusion: Our data indicate substantial overlap in genetic risk architecture between Europeans and south Asians and suggest that the aetiology of the disease may be largely independent of ethnicity. [ABSTRACT FROM AUTHOR]

Background: Neuromyelitis optica spectrum disorders (NMOSDs) represent 20% of all demyelinating disorders in South India. No studies have determined the seroprevalence to both antibodies against aquaporin‑4* and antimyelin oligodendrocyte glycoprotein antibody (anti‑MOG+) in this population. Objective: To identify and characterize seropositive patients for anti‑aquaporin‑4 antibody (anti‑AQP4+) and anti‑MOG+ in South India. Materials and Methods: We included 125 consecutive patients (15 children) who were serologically characterized using live transfected cells to human M23‑AQP4 or full‑length MOG. Results: Among a total of 125 patients, 30.4% of patients were anti‑AQP4+, 20% were anti‑MOG+, and 49.6% were seronegative. No patient was positive for both. Anti‑MOG+ patients represented 28.7% (25/87) of seronegative NMOSD. In comparison to anti‑AQP4+ patients, anti‑MOG+ patients were commonly male, had less frequent attacks and milder disability on expanded disability status score scale. Seronegative patients were also predominantly male, 36% (9/25) had monophasic longitudinally extensive transverse myelitis and disability was comparable with anti‑AQP4+ patients. Lumbar cord involvement was common in anti‑MOG+ and seronegatives, whereas anti‑AQP4+ patients had more cervical lesions. Conclusion: Anti‑AQP4+/anti‑MOG + patients accounted for nearly half of the patients suspected of having NMOSD in South India, indicating that antibody testing may be useful on the management of subgroups with different prognosis. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) prevalence has increased worldwide. The known genetic association for MS in the west has not been studied in detail in nonwhite populations and particularly Indians. Objective: The objective of this study was to evaluate some known genetic variations outside the major histocompatibility complex (MHC) region associated with MS in patients of Indian origin. Materials and Methods: We investigated 10 gene‑associated single nucleotide polymorphisms (SNP’s) outside the MHC region in 300 patients and 720 unrelated controls. Genotyping was performed on an ABI7500 real‑time polymerase chain reaction genotyping platform using predesigned TaqMan SNP genotyping assays. Results: CD6 gene associated SNP (rs17824933) showed significant association with MS (P = 4.2 × 10−5, odds ratio [OR] = 2.24, confidence interval (CI) = 1.51–3.33). A modest association was also noted for TMEM39A rs1132200 (P = 0.023, OR = 1.41, CI = 1.05–1.91) and IL2RA rs2104286 (P = 0.04, OR = 1.3, CI = 1.006–1.67). In the remaining SNPs, the allele frequencies were overexpressed in patients when compared to healthy controls. Conclusion: Our data illustrate the similarity in risk association between Indian and European populations for MS. [ABSTRACT FROM AUTHOR]

Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low ( p = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher ( p = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder. [ABSTRACT FROM AUTHOR]

Background: Previous efforts to identify Human Leukocyte Antigen (HLA) gene associations with multiple sclerosis (MS) in the South Asian population have been underpowered. Aim: To identify the primary HLA class II alleles associated with MS in Indians. Methods: We typed HLA-DRB1, -DQA1 and -DQB1 in 419 patients and 451 unrelated controls by polymerase chain reaction using sequence specific oligonucleotide probes (PCR-SSOP). Results: At the gene level DRB1 showed significant evidence of association (p=0.0000012), DQA1 showed only marginal evidence of association (p=0.04) and there was no evidence for association at DQB1 (p=0.26). At the DRB1 locus association is confirmed with the *15:01 (p=0.00002) and the *03 (p=0.00005) alleles. Conclusion: Our study confirms that the risk effects attributable to the HLA- DRB1*15:01and DRB1*03 alleles seen in Europeans are also seen in Indians. The absence of any evidence of association with DQB1 alleles reflects the lower linkage disequilibrium between DQB1 alleles and DRB1 risk alleles present in this population, and illustrates the potential value of fine mapping signals of association in different ethnic groups. [ABSTRACT FROM AUTHOR]

Recent advances in the understanding of neuromyelitis optica spectrum of disorders (NMOSD) have expanded. Diagnostic criteria have changed over the years. The clinical spectrum of disease manifestations are now understood to include sites outside the spinal cord and optic nerve. A variety of autoimmune diseases may coexist with this disorder. Non neurological manifestations have been recently reported. Novel biomarkers other than aquoporin 4 Immunoglobulin G (anti AQP4-IgG) have been discovered which may have clinical relevance. In particul myelin associated oligoglycoprotein antibody (MOG-Ab) associated NMOSD may be relatively benign. This update describes some of these new findings highlighting the clinical manifestations, biomarkers associated with the disease and magnetic resonance imaging characteristics of brain and spinal cord. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is less prevalent among Indians when compared to white populations. Genetic susceptibility remaining the same it is possible that environmental associations may have a role in determining disease prevalence. Aims: To determine whether childhood infections, vaccination status, past infection with Helicobacter pylori (H.pylori), diet, socioeconomic and educational status were associated with MS. Material and Methods: 139 patients and 278 matched control subjects were selected. A validated environmental exposure questionnaire was administered. Estimation of serum H.pylori IgG antibody was done by ELISA. Patients and controls were genotyped for HLA-DRB1*15:01. Results: In our cohort a significant association was seen with measles (p <0.007), vegetarian diet (p < 0.001, higher educational status (p <0.0001) and urban living (p <0.0001). An inverse relationship was seen with H.Pylori infection and MS (p <0.001). Measles infection (OR 6.479, CI 1.21- 34.668, p< 0.029) and high educational status (OR 3.088, CI 1.212- 7.872, p< 0.018) were significant risk factors associated with MS. H.pylori infection was inversely related to MS (OR 0. 319, CI 0.144- 0.706, p <0.005). Conclusions: Environmental influences may be important in determining MS prevalence. [ABSTRACT FROM AUTHOR]

Antibodies targeting  myelin oligodendrocyte glycoprotein (MOG) have been recently reported in association with idiopathic inflammatory central nervous system disorders. Initially believed to be a benign disorder, anti MOG-IgG was noted to cause steroid responsive recurrent optic neuritis and isolated longitudinally extensive myelitis. However, there is growing evidence that the disease may be predominantly relapsing, often producing severe visual loss and involving regions other than the spinal cord and optic nerve. We report an adolescent male with an aggressive disease course previously undescribed in anti MOG-IgG‑associated disease that left him with residual cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Visual loss consequent to anterior visual pathway involvement can occur in a variety of clinical settings. In a tropical country like India, apart from the usual suspects, nutritional, infective, and toxic amblyopia have to be considered in the differential diagnosis. The mode of onset (acute/chronic), unilateral versus bilateral involvement, accompanying occular pain or the lack of it, and pattern of visual loss are some of the pointers which help to differentiate optic neuropathy clinically . The presence of concurrent neurological deficits, evidence of other systemic illnesses, and the results of serological and radiological investigations help to confirm the diagnosis. This article briefly describes the important causes of optic neuropathy in the Indian context and outlines a practical approach to management. [ABSTRACT FROM AUTHOR]

The article discusses a study regarding the link between Vitamin D and multiple sceloris (MS). Serum 25-hydroxyvitamin (OH) D levels, body mass index (BMI), and amout of sun exposure were measured among 108 matched controls and 110 MS patients in India. HLA-DR typing was conducted using polymerase chain reaction (PCR). Results show an inverse relationship between serum 25(OH) D and MS.

Background: In resource-poor settings, the management of neuromyelitis optica (NMO) and NMO spectrum (NMOS) disorders is limited because of delayed diagnosis and financial constraints. Aim: To device a cost-effective strategy for the management of NMO and related disorders in India. Materials and Methods: A cost-effective and disease-specific protocol was used for evaluating the course and treatment outcome of 70 consecutive patients. Results: Forty-five patients (65%) had a relapse from the onset and included NMO (n = 20), recurrent transverse myelitis (RTM; n = 10), and recurrent optic neuritis (ROPN; n = 15). In 38 (84.4%) patients presenting after multiple attacks, the diagnosis was made clinically. Only 7 patients with a relapsing course were seen at the onset and included ROPN (n = 5), NMO (n = 1), and RTM (n = 1). They had a second attack after a median interval of 1 ± 0.9 years, which was captured through our dedicated review process. Twenty-five patients had isolated longitudinally extensive transverse myelitis (LETM), of which 20 (80%) remained ambulant at follow-up of 3 ± 1.9 years. Twelve patients (17%) with median expanded disability status scale (EDSS) of 8.5 at entry had a fatal outcome. Serum NMO-IgG testing was done in selected patients, and it was positive in 7 of 18 patients (39%). Irrespective of the NMO-IgG status, the treatment compliant patients (44.4%) showed significant improvement in EDSS (P ≤ 0.001). Conclusions: Early clinical diagnosis and treatment compliance were important for good outcome. Isolated LETM was most likely a post-infectious demyelinating disorder in our set-up. NMO and NMOS disorders contributed to 14.9% (45/303) of all demyelinating disorders in our registry. [ABSTRACT FROM AUTHOR]

Background: Natural history of optic neuritis (OPEN) has not been studied in India. Aim: To study consecutive patients with optic neuritis as the initial manifestation of the neurologic disease and with disease duration of 3 or more years registered in the Mangalore Demyelinating Disease Registry. Materials and Methods: The study included 59 patients with a primary diagnosis of optic neuritis (confirmed by either an ophthalmologist or a neurologist or both). All the patients were investigated and followed-up in the clinic. Results: During the follow-up of the 59 patients, 29 (49%) patients developed multiple sclerosis (MS); 3 (5%) patients neuromyelitis optica (NMO); and 13 (22%) patients chronic relapsing inflammatory optic neuritis (CRION), while the remaining 14 (24%) did not either progress or relapse, monophasic OPN. An initial abnormal magnetic resonance imaging predicted conversion to MS in all 7 patients who had imaging at onset. Patients with NMO were left with significant residual visual loss distinguishing NMO from MS. In this large series of patients with CRION, nearly 50% of patients had deterioration in vision while steroids were being tapered. Long-term immunosuppression was essential for maintaining good visual outcome in both NMO and CRION. Conclusions: Optic neuritis in India appears similar to that in the West with nearly 50% developing MS in the long term. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disorder with a strong genetic component.Objective: The prevalence of MS in India is low compared with white populations of Northern European descent.Methods: In order to ascertain whether disease susceptibility genes are the same across different populations, we completed the first investigation in the Indian MS population of 15 MS loci outside of the major histocompatibility (MHC) region that were previously identified and validated with MS susceptibility through genome-wide association and replication studies in white populations.Results: In total, 197 Indian patients and 197 unrelated controls were analyzed. The most associated single nucleotide polymorphism (SNP) within this study was rs6897932 in the IL7R gene, which showed a strong protective effect in this data set (rs 6897932, OR = 0.5543, 95% CI = 0.37—0.78, p = 0.0009727). Two other SNPs were nominally associated with MS in this dataset, namely CLEC16A rs 12708716 (p = 0.0082, OR = 1.478, 95% CI = 1.106—1.975) and CD226 rs763361 (p = 0.03971, OR = 1.353, CI = 1.014—1.805). For the majority of the remaining SNPs (7/14), the trend for association was in the same direction as in previous studies in the white population.Conclusions: Although the power of this study was limited, our preliminary data suggest that disease susceptibility genes in MS in the Indian population may be similar to those of western populations. [ABSTRACT FROM AUTHOR]

Multiple Sclerosis (MS) is being diagnosed in increasing numbers in metropolitan cities of India for which the availability of specialist neurologists and magnetic resonance imaging (MRI) facilities are primarily responsible. Epidemiological data are unavailable. Existing data have been obtained from small often retrospective studies from different parts of the country. These earlier studies suggested that optic nerve and spinal cord involvement are considerably high, and that perhaps optic spinal MS was the most prevalent form in India. On this basis it was also speculated that neuromyelitis optica (NMO) may be over represented in Indians. However in recent times, prospective studies backed by MRI data have shown no distinct differences between MS seen in the west and India. Sero positivity for NMO IgG is low though NMO phenotype disorders constitute nearly 20% of demyelinating disorders in India. Genetic susceptibility for MS among Indians may be similar to that for white populations. In the major histocompatibility complex (MHC), HLA DR1*1501 has been strongly associated with MS in Indians. A recent study that evaluated the established non-MHC multiple sclerosis loci in a small data set of Indian patients suggested a strong similarity with white populations. This review highlights some of the background information available on MS from India and so also some recent studies that unveiled the disease characteristics in Indian patients. [ABSTRACT FROM AUTHOR]

Acute transverse myelitis (ATM) is an inflammatory demyelinating disorder that affects the spinal cord focally resulting in motor sensory and autonomic dysfunction. Establishing the diagnosis of ATM is not as difficult as determining the possible etiology. There is a difference in the perception of ATM seen in the West as compared to developing countries. In the West multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system. An attack of ATM may be the beginning of MS. However, this may not be the case in developing countries where MS is uncommon. Most often transverse myelitis is monophasic and at best represents a site-restricted form of acute disseminated encephalomyelitis (ADEM). Traditionally the combination of optic neuritis and ATM, occurring as a monophasic illness would have been called as neuromyelitis optica (NMO). Changing concepts in the definition of NMO and the discovery of a biomarker, neuromyelitis optica immunoglobulin (NMO_IgG), has changed the way relapsing autoimmune disorders are being perceived currently. A variety of idiopathic inflammatory disorders such as Japanese form of optic spinal MS, recurrent myelitis, and recurrent optic neuritis have been brought under the umbrella of neuromyelitis spectrum disorders because of the association with NMO-IgG. Complete transverse myelitis accompanied by longitudinally extensive transverse myelitis which is seronegative for this biomarker has also been reported from several countries including Japan, Australia, and India. Thus, ATM is a heterogeneous disorder with a varied clinical spectrum, etiology, and outcome. [ABSTRACT FROM AUTHOR]

In hospitals in the tropics, the availability of magnetic resonance imaging (MRI) facilities in urban areas and especially in teaching institutions have resulted in white matter diseases being frequently reported in a variety of clinical settings. Unlike the west where multiple sclerosis (MS) is the commonest white matter disease encountered, in the tropics, there are myriad causes for the same. Infectious and post infectious disorders probably account for the vast majority of these diseases. Human immunodeficiency virus (HIV) infection tops the list of infective conditions. Central nervous system (CNS) tuberculosis occasionally presents with patchy parenchymal lesions unaccompanied by meningeal involvement. Human T cell leukemia virus (HTLV) infection and cystic inflammatory lesions such as neurocysticercosis are important causes to be considered in the differential diagnosis. Diagnosing post infectious demyelinating disorders is equally challenging since more than a third of cases seen in the tropics do not present with history of past infection or vaccinations. Metabolic and deficiency disorders such as Wernicke's encephalopathy, osmotic demyelinating syndrome associated with extra pontine lesions and Vitamin B12 deficiency states can occassionaly cause confusion in diagnosis. This review considers a few important disorders which manifest with white matter changes on MRI and create diagnostic difficulties in a population in the tropics. [ABSTRACT FROM AUTHOR]

Background: Mycophenolate mofetil (MMF) is an affordable and tolerable drug reported to be beneficial in the treatment of multiple sclerosis (MS). Aim: To determine efficacy of MMF as first line disease modifying drug (DMD) in 40 patients with MS seen in our demyelinating disease registry. Materials and Methods: The annualized relapse rate (ARR) for 1 year prior to starting MMF therapy and 1for1year year post treatment was calculated. Pre- and post-treatment expanded disability status scores (EDSS), age at onset of treatment, disease duration, and type of MS were recorded. Wilcoxon rank sum test was used for comparison of ARRs and EDSS before and after treatment. Results: Forty patients included 27 females and 1 3 males. Mean duration of MMF therapy was 24 months (range 14-33 months). Pre-treatment mean ARR of 0.95 was significantly different from post treatment mean ARR of 0.11 (P = 0.0001). Pre-treatment mean EDSS 3.80 (inter quartile range [IQR] 3.5-4.5) was significantly different from post-treatment mean EDSS 2.66 (IQR 1.5-3.0, P = 0.0001). No adverse effects were reported that required stopping of medication. Five patients discontinued treatment 6-11 months after starting therapy, two of whom relapsed subsequently. Conclusion: Our preliminary results support the use of MMF, a cheap and well-tolerated drug, as first line disease modifying drug in MS. Long-term results in a larger patient cohort is required for validating our preliminary conclusions. [ABSTRACT FROM AUTHOR]

There is a dearth of epidemiological data about multiple sclerosis (MS) and related demyelinating disorders in India. In this study, a registry method was used for collecting data from secure sources and the index cases were verified Seventy nine patients were identified . A crude prevalence of 8.3/100,000 was obtained for MS and 6.2/100,000 for clinically-isolated syndrome (CIS). Age-standardized prevalence of MS relative to the world population was 7.8/100,000. Neuromyelitis optica (NMO) and spectrum disorders (NMOS) constituted 13.9% of all demyelinating disorders, with a prevalence of 2.6/100,000. Larger studies with more refined survey methodologies are required to understand the true prevalence of demyelinating disorders in India. [ABSTRACT FROM PUBLISHER]

The article describes the case of a 58-year-old male patient with a history of giddiness and headache and who was diagnosed with large unruptured proximal anterior cerebral artery (ACA) A1 aneurysm with aplasia. The diagnosis was confirmed after the patient was subjected to neurological examination, computed tomography (CT)-angiography. The patient was further subjected to a left pterional craniotomy, sylvian fissure dissection and internal carotid artery bifurcation.

Non-Hodgkin's lymphoma of T-cell types are rare neoplasms. Central nervous system metastasis is unusual. We are reporting a patient with peripheral T-cell lymphoma unspecified who had extra nodal metastasis into the brain that manifested with extrapyramidal dysfunction. The clinical presentation was exceptional in that the course was indolent and patient had no overt extra neural manifestations of malignancy for nearly 3 years after the onset of Parkinsonism. Striking brain imaging late in the disease supported by pathological findings enabled the diagnosis of this rare condition. [ABSTRACT FROM AUTHOR]

Progressive post-traumatic cystic syringomyelia is an uncommon and increasingly recognized cause of morbidity following spinal cord injury. We hereby report a 35-year-old gentleman who sustained wedge compression fracture of L-1 vertebral body 15 years back and had complete paraplegia with bowel/bladder involvement. The neurological deficit recovered with minimal residual motor deficits and erectile dysfunction. He presented now with increasing neurological deficits associated with pain and paresthesia. The MRI spine showed a syrinx extending from the site of injury up to the medulla. He underwent a syringo-peritoneal shunt and at follow-up his pain and motor functions had improved but erectile dysfunction was persisting. [ABSTRACT FROM AUTHOR]

Leigh syndrome is a rare progressive mitochondrial disorder of oxidative metabolism. Though it has been reported in infancy and childhood, it is rarely described in adults. The authors describe a patient who had clinical and magnetic resonance imaging features diagnostic of Leigh syndrome, with supportive biochemical and muscle histochemistry evidence. [ABSTRACT FROM AUTHOR]

The article presents a study which shows that variations in the geographic distribution of multiple sclerosis (MS) and neuromyelitis optica (NMO) suggest a role for possible environmental and genetic influences in the etiopathogenesis of these diseases. It mentions that the study was conducted to 93 patients with relapsing Neuromyelitis optica spectrum disorders. It is inferred that NMO among both white and non-white population are the same irrespective of ethnicity genetic susceptibility.

The author reflects on the coexistence of autoimmune diseases with a greater prevalence rate within individuals and in families. Topics covered include the percentage of the population affected by autoimmune disorders, the manifestation of myasthenia gravis during the course of the neurological illness and the importance of screening for associated autoimmunity.

In this article the author discusses her sentiments on a study about treatment of patients with multiple sclerosis (MS) with mitoxantrone. She says that the authors of this study have shown reasonably good response to the treatment in a significant number of patients. She emphasizes that mitoxantrone is not a standalone treatment modality in MS. She stresses that the study shows that there is a real need for a safe and affordable treatment.