Catastrophic tumefactive acute disseminated encephalomyelitis in patient with dengue virus: a case report.

Tumefactive demyelinating lesions (TDL) are a rare occurrence among inflammatory demyelinating diseases of the central nervous system, distinguished by tumor-like lesions exceeding 2 cm in diameter. While various etiologies have been associated with TDL, only a limited number of case reports document the coexistence of acute disseminated encephalomyelitis (ADEM) and TDL. Here, we present the case of a female diagnosed with dengue fever two weeks prior, who subsequently developed left hemiparesis and encephalopathy. Both her brain magnetic resonance imaging (MRI) and clinical course align with the characteristics of tumefactive ADEM.

Use of Complementary and Alternative Medicine in Patients With Idiopathic Inflammatory Demyelinating Diseases of the Central Nervous System: A Cross-Sectional Study in Thailand.

Background: Complementary and alternative medications (CAM) are common among patients with multiple sclerosis (MS) for physical and psychological support. However, there is insufficient data regarding the application of CAM in the different cultures and beliefs of each community as well as patient's status. Objective: To evaluate the prevalence and modalities of the use of CAM among patients with central nervous system idiopathic inflammatory demyelinating diseases (CNS-IIDD) in a tertiary care hospital. Methods: A cross-sectional study was conducted at Siriraj Hospital from June to December 2021 involving patients with MS, neuromyelitis optic spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), idiopathic transverse myelitis (iTM), and optic neuritis (ON) to examine the prevalence and mode of CAM use and its correlation with patient characteristics. Results: There were 107 patients. The diagnoses were MS (38), NMOSD (55), MOGAD (5), iTM (7), and ON (2). Most of the patients were female (89.7%), and 61.7% were diagnosed over 5 years. The mean Expanded Disability Status Scale was 2.63 (S.D., 2.38), and the median ambulation index was 0 (range 0-8.5). There were 68 patients (63.6%) with a history of CAM use for at least 3 months, while those with current use decreased to 62 (58.5%). Vitamins and minerals were the most commonly used, particularly vitamin D (97.1%) and calcium (47.7%). Both treatments were primarily prescribed (95.3%) rather than self-administered (24.3%). The main reasons for the use of CAM were to strengthen their health (48.6%) and relieve existing symptoms (28.0%). Conclusions: The use of CAM is common among patients with Thai CNS-IIDD. Further exploration of patient perspectives and preferences regarding CAM usage may contribute to a more comprehensive management approach for patients with CNS-IIDD.

Efficacy and safety of rituximab in multiple sclerosis and neuromyelitis optica spectrum disorder.

In Thailand, resource limitations lead many multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients to use off-label immunosuppressants. This study assesses the efficacy and safety of rituximab (RTX) with a CD19-based reinfusion regimen among Thai MS and NMOSD patients. A retrospective review of patients at the Faculty of Medicine Siriraj Hospital from January 1994 to April 2023 was conducted. The primary outcome assessed was the change in annualized relapse rate (ARR) for patients using RTX for over a year. Secondary outcomes included changes in the Expanded Disability Status Scale (EDSS) scores, time to the first relapse after RTX initiation for patients using RTX for over a year, and an evaluation of the safety of RTX. The study encompassed 36 MS and 39 NMOSD patients. A majority of patients (91.7% of MS and 79.5% of NMOSD) experienced no relapses during a median follow-up of 30 months (Interquartile range [IQR] 20-46) and 31 months (IQR 23-41), respectively. The median ARR significantly decreased in both MS (from 0.77 [IQR 0.42-1.83] to 0 [IQR 0-0], p < 0.001) and NMOSD (from 0.92 [IQR 0.68-1.78] to 0 [IQR 0-0.17], p < 0.001) patients after switching to RTX, with no difference between those following a fixed 6-month time point regimen and a CD19-based reinfusion regimen. Median EDSS scores improved significantly at the last follow-up visit in both groups. The mean time to the first subsequent relapse was 8.3 ± 3.0 months in MS and 6.8 ± 1.7 months in NMOSD. Mild adverse drug reactions occurred in 44% of patients. RTX effectively prevents relapses in Thai MS and NMOSD patients, with no observed serious adverse drug reactions.

Tumefactive demyelinating lesions: a retrospective cohort study in Thailand.

Tumefactive demyelinating lesions (TDL), characterized by large (≥ 2 cm) demyelinating lesions mimicking tumors, are a rare manifestation of the central nervous system inflammatory demyelinating diseases (CNS-IDD). Distinguishing TDL from other brain lesions can be challenging, often necessitating biopsy or advanced diagnostics. The natural history of TDL varies among races. This study aimed to assess demographics, clinical and radiological features, laboratory findings, management, and outcomes of Thai patients with TDL. We retrospectively reviewed records of twenty-six patients with TDL from the Multiple Sclerosis and Related Disorders registry from two tertiary medical centers. Among 1102 CNS-IDD patients, 26 (2.4%) had TDL. The median age at TDLs onset was 34.5 years (range 17-75); 69.2% were female. Over 70% manifested TDL as their initial CNS-IDD presentation. Common presenting symptoms included motor deficits, sensory disturbances, and cognitive problems. About two-fifths exhibited multiple lesions, most frequently in the frontoparietal region (46.2%). Half of the patients showed an incomplete ring on post-contrast T1-weighted imaging, with peripheral diffusion-weighted imaging restriction in twenty-one patients. T2-hypointense rims were present in thirteen (56.5%) patients. Brain biopsy was performed in 12 cases (46.1%). Serum aquaporin-4 immunoglobulin was positive in 16.7% of tested (4/24) cases. Serum myelin oligodendrocyte glycoprotein immunoglobulin was negative in all thirteen patients tested. Twenty patients (76.9%) received intravenous corticosteroids for TDL attacks. After the median follow-up period of 48 months (range 6-300), 23.1% experienced CNS-IDD relapses. Median Expanded Disability Status Scale at TDL diagnosis was 4.3 (range 0.0-9.5), and improved to 3.0 (range 0.0-10.0) at the last follow-up. This study suggested that TDL were rare among Thai CNS-IDD patients, frequently presenting as a monophasic condition with a favorable outcome.

Infliximab in neurosarcoidosis: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the clinical outcomes and relapse rates in neurosarcoidosis patients administered infliximab. METHODS: A systematic review was conducted using the MEDLINE, EMBASE, SCOPUS, and Cochrane Library databases. The search included studies from their inception to March 2023. We included case-series studies with at least 10 neurosarcoidosis patients undergoing any treatment type. Studies were also required to report at least one of the following outcomes: response rate, overall survival rate, or relapse rate. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model facilitated the analysis of proportional treatment outcomes. Study quality was evaluated using the modified Newcastle-Ottawa quality assessment scale, while a funnel plot helped detect any publication bias. RESULTS: Seven studies comprising 237 patients with neurosarcoidosis were included in the analysis. Of these patients, 184 (77.6%) received treatment with infliximab. The pooled proportion of patients showing clinical improvement after infliximab treatment was 0.74 (95% CI 0.64-0.84, I2 = 49.73%). Relapse rates, derived from four studies, stood at 0.38 (95% CI 0.22-0.55, I2 = 56.92%). Most studies reported successful tapering or cessation of corticosteroid dosage in patients receiving infliximab. Adverse effects were reported in 52 (29.4%) patients, of which 39 out of 54 events (72.2%) were linked to infections. INTERPRETATION: Infliximab demonstrated potential improvement in clinical outcomes for patients with refractory neurosarcoidosis and showed potential for reducing the dosage of concurrent corticosteroids. However, a degree of relapse was observed, with infections being the primary concern for adverse events.

Familial neuromyelitis optica spectrum disorders: Case series and systematic review.

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) is considered a complex multifactorial disorder. Most cases are sporadic, and familial NMOSD is assumed as a rare occurrence. However, few studies reported familial aggregation of the disorder. OBJECTIVES: To report familial NMOSD cases in Thailand and conduct a systematic review of familial NMOSD. METHODS: A retrospective chart review of familial NMOSD patients at the university hospital was performed. Articles related to "genetic" and "NMOSD" were systematically searched and reviewed. We included NMOSD patients whose one or more relatives were diagnosed with the same disease or multiple sclerosis (MS). Data regarding demographics, clinical features, disease outcomes, and genetic testing were collected and analyzed using descriptive statistics. RESULTS: We identified 6 familial cases from 165 NMOSD cases (3.6%) at our hospital and gathered 77 cases from a systematic review, totaling 83 cases from 40 families. The mean (SD) age at onset was 37.2 (18.0) years. Familial NMOSD involved 1-2 generations with mainly 2 affected individuals. The most common kinship pattern was siblingship in 21 families (52.5%). Initial syndromes were mostly optic neuritis and transverse myelitis. Serum aquaporin-4 IgG was positive in 79.7% of cases. Median number of relapses was 3 (range 1-26). Median expanded disability status scale in the last visit was 2 (range 0-8). Reported human leukocyte antigens (HLA) alleles shared between familial cases were HLA-A*01 and HLA-DRB1*03. CONCLUSION: Familial clustering of NMOSD is more common than would be expected in the general population. The demographic, clinical, and outcome profiles of familial cases were not different from sporadic cases. Certain specific HLA haplotypes were shared among familial cases. Our systematic review highlighted complex genetic predisposition to NMOSD.

Lymphomatosis cerebri with coexistent anti-N-methyl-D-aspartate receptor antibody: A case report.

Diagnosis of lymphomatosis cerebri (LC) is usually delayed because of its rarity and the need for pathological confirmation. The association of LC with humoral immunity has scarcely been reported. Herein, we present a woman with a 2-week history of dizziness and gait ataxia, followed by diplopia, altered mental status, and spasticity of all limbs. Magnetic resonance imaging (MRI) of the brain showed multifocal lesions involving bilateral subcortical white matter, deep gray structures, and brainstem. Oligoclonal bands and anti-N-methyl-D-aspartate receptor (NMDAR) antibodies were present in cerebrospinal fluid (CSF) twice. She was initially treated with methylprednisolone but still worsening. A stereotactic brain biopsy confirmed the diagnosis of LC. This is a report on the distinctive coexistence of the rare CNS lymphoma variant and the anti-NMDAR antibody.

The epidemiology and burden of neuromyelitis optica spectrum disorder, multiple sclerosis, and MOG antibody-associated disease in a province in Thailand: A population-based study.

BACKGROUND: Central nervous system inflammatory demyelinating diseases (CNSIDDs) have notable interracial heterogeneity. The epidemiology of CNSIDDs in Thailand, a mainland Southeast Asian country, is unknown. OBJECTIVES: To determine the cumulative incidence, point prevalence, and disease burden of neuromyelitis optica spectrum disorder (NMOSD) and other CNSIDDs in Thailand using population-based data of Chumphon. METHODS: Searching for CNSIDD patients at a public secondary care hospital in Chumphon, the only neurology center in the province, from January 2016 to December 2021 was implemented using relevant ICD-10-CM codes. All diagnoses were individually ascertained by a retrospective chart review. Cumulative incidence, point prevalence, attack rate, mortality rate, and disability-adjusted life years (DALYs) were calculated. RESULTS: Aquaporin 4-IgG-positive NMOSD was the most prevalent CNSIDD in the Thai population at 3.08 (1.76-5.38) per 100,000 persons. The prevalence of multiple sclerosis (MS) followed at 0.77 (0.26-2.26) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) at 0.51(0.14-1.87) per 100,000 adults. In the pediatric population, the incidence of acute disseminated encephalomyelitis was 0.28 (0.08-1.02) per 100,000 persons/year. Among other idiopathic demyelinating diseases, idiopathic optic neuritis had the highest incidence at 0.58 (0.24-0.92) per 100,000 persons/year, followed by acute transverse myelitis at 0.44 (0.14-0.74). Idiopathic demyelinating brainstem syndrome was also observed at 0.04 (0.01-0.25) per 100,000 persons/year. Although most had a fair recovery, disability was worst among NMOSD patients with DALYs of 3.61 (3.00-4.36) years per 100,000 persons. Mortality rate was the highest in NMOSD as well. CONCLUSION: CNSIDDs are rare diseases in Thailand. The prevalence is comparable to that of East Asian populations. A nationwide CNSIDDs registry would better elaborate the epidemiology of these diseases.

Myelitis features and outcomes in CNS demyelinating disorders: Comparison between multiple sclerosis, MOGAD, and AQP4-IgG-positive NMOSD.

Inflammatory myelopathies can manifest with a combination of motor, sensory and autonomic dysfunction of variable severity. Depending on the underlying etiology, the episodes of myelitis can recur, often leading to irreversible spinal cord damage and major long-term disability. Three main demyelinating disorders of the central nervous system, namely multiple sclerosis (MS), aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4+NMOSD) and myelin oligodendrocyte glycoprotein-IgG associated disease (MOGAD), can induce spinal cord inflammation through different pathogenic mechanisms, resulting in a more or less profound disruption of spinal cord integrity. This ultimately translates into distinctive clinical-MRI features, as well as distinct patterns of disability accrual, with a step-wise worsening of neurological function in MOGAD and AQP4+NMOSD, and progressive disability accrual in MS. Early recognition of the specific etiologies of demyelinating myelitis and initiation of the appropriate treatment is crucial to improve outcome. In this review article we summarize and compare the clinical and imaging features of spinal cord involvement in these three demyelinating disorders, both during the acute phase and over time, and outline the current knowledge on the expected patterns of disability accrual and outcomes. We also discuss the potential implications of these observations for patient management and counseling.

AQP4-IgG-positive neuromyelitis optica spectrum disorder and temporally detected neoplasms: case report and systematic review.

BACKGROUND: An increasing number of reports on associations between neoplasms and neuromyelitis optica spectrum disorder (NMOSD) have been published over the past decade. However, types of neoplasms and temporal relationships have not been widely studied. OBJECTIVE: To report cases and determine the associations between neoplasms and NMOSD. METHOD: A retrospective chart review of possible paraneoplastic NMOSD patients at a university hospital was performed. Articles related to "neoplasm" and "NMOSD" were systematically searched and reviewed. We included aquaporin-4 (AQP4)-IgG-seropositive NMOSD patients whose onset of NMOSD and cancer diagnosis or recurrence were within 24 months of one another. Temporal relationship, types of neoplasms involved, treatments, and outcomes of both NMOSD and neoplasms were determined. The subgroup analysis was based on the AQP4 expression of neoplasm histology. RESULTS: We identified 3 cases (1.3%) from a cohort of 224 AQP4-IgG-seropositive NMOSD at our hospital and retrieved 68 cases from a systematic review, totaling 71 cases of possible paraneoplastic NMOSD. The median age at onset of NMOSD was 55 (IQR 41-64) years. Eighty percent were female. The most frequently identified types of neoplasms were lung and breast, accounting for 21.1% and 18.3%, respectively. The other tumor types were ovarian tumors and hematologic malignancy, both at 12.7%. The most commonly identified tissue histology was adenocarcinoma (52.1%). We also reported the first case of melanoma in an NMOSD patient. Twenty-eight patients (39.4%) were diagnosed with cancer before the onset of NMOSD with a median duration of 9.5 (range 1-24) months. Of those, eight patients had NMOSD after surgical removal of neoplasms, and one patient had NMOSD after radiotherapy of prostate adenocarcinoma. Twenty-three patients (32.4%) had NMOSD before cancer diagnosis by a median of 3 (range 1-24) months, and the rest were diagnosed concurrently during the same admission. Three cases were diagnosed with NMOSD around the time of tumor recurrence. Tumor tissue expressed AQP4 in 82.4%. CONCLUSION: A small proportion of AQP4-IgG-positive NMOSD is associated with malignancy. In newly diagnosed NMOSD patients without symptoms of neoplasms, screening for age- and risk-appropriate cancer should be recommended, similar to the general population. The occurrence of NMOSD in cancer patients might suggest tumor recurrence.

Author's response to the commentary: Neuromyelitis optica complicating COVID vaccinations and additional case reports.

Our article Newly diagnosed neuromyelitis optica spectrum disorders following vaccination: Case report and systematic review had instigated a critique that there were more cases of post-COVID-19-vaccination NMOSD. Indeed, after the systematic review was performed in July 2021, many reports have been published, and we have seen two new patients at our center as well. However, Finsterer's question on the subclinical activity of NMOSD prior to vaccination, although an interesting notion, was debatable. NMOSD is a relapsing disease with severe attacks. Investigations in our patients did not reveal robust evidence of prior subclinical attacks so far.

A quarter-century report on neuromyelitis optica spectrum disorder in Thailand: A single-center tertiary care cohort.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating astrocytopathy with a high relapse-related disability. This is the largest long-term study of Thai NMOSD patients. OBJECTIVES: To compare characteristics and outcomes of aquaporin 4 (AQP4)-IgG-positive and AQP4-IgG-negative patients. METHODS: A retrospective review of NMOSD patients at a university hospital was performed from January 1994 to July 2021. RESULTS: From 165 NMSOD patients, the overall female-to-male ratio was 14:1. The mean onset age was 37.5 ± 14.3 years, and the median disease duration was 10.2 years. Transverse myelitis (46.1%) and optic neuritis (39.4%) were the most common presentations. Around 60% remained fully ambulatory at the last follow-up. Severe visual loss and ambulation aids were comparable in both groups, but the AQP4-IgG-positive had severe bowel and/or bladder dysfunction more often than the AQP4-IgG-negative (p = 0.026). The mortality rate was 6.7%, mainly from infection. Multivariate analysis showed that longer time-to-diagnosis and higher disability scores were associated with death. Diagnosis within one year yielded better visual and motor outcomes and lower annualized relapse rate. CONCLUSIONS: Thai AQP4-IgG-positive and AQP4-IgG-negative NMOSD patients had similar baseline characteristics. Relapse and mortality rates were comparable to global NMOSD patients. Diagnosis within one year promises better outcomes.

The efficacy and safety of mycophenolate mofetil in Thai neuromyelitis optica spectrum disorder patients.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) often leaves patients with a residual disability after each attack. Several studies have demonstrated that mycophenolate mofetil (MMF) effectively prevents relapse in NMOSD. So far, there has been no data on the effectiveness, dosage, and safety of MMF in the Thai population. OBJECTIVES: To analyze the efficacy and safety of MMF in Thai NMOSD patients. MATERIALS AND METHODS: We performed a retrospective review of NMOSD patients at Siriraj Hospital from January 1994 to December 2020. The primary outcomes were changes in annualized relapse rate (ARR) and time to relapse after MMF. Pre- and post-MMF Expanded Disability Status Scale (EDSS) scores and visual functional system scores were also compared. RESULTS: Fifty-eight NMOSD patients taking MMF were included. The median dose required was 1,250 (IQR 1,000 - 1,500) mg/day or 23.1 (IQR 17.6-30.8) mg/kg/day. Thirty-five patients (65.5%) were relapse-free after MMF with a median follow-up period of 46.8 months (IQR 24.0-60.9). The median ARR was reduced from 0.80 (IQR 0.45-1.39) to 0 (IQR 0-0.31) after MMF treatment (p < 0.001). Over 90% had either stabilized or improved EDSS. The median EDSS score decreased from 3.5 (IQR 3-6) to 3 (IQR 2-6) (p = 0.004). Nine patients experienced adverse events from MMF, with lymphopenia and infection observed in 8.6% and 5.1% of the cohort, respectively. No serious adverse events were observed. A subgroup analysis of 25 patients switching to MMF after azathioprine failure showed a significant ARR and EDSS reduction. CONCLUSIONS: MMF is effective for relapse prevention in Thai NMOSD patients and has a low risk of adverse events. It could be a salvage therapy for patients with azathioprine failure.

Newly diagnosed neuromyelitis optica spectrum disorders following vaccination: Case report and systematic review.

INTRODUCTION: The pathogenesis of neuromyelitis optica spectrum disorder (NMOSD) has been vigorously illustrated, but triggers of the disease remain unclear. Viral infection and vaccination have been observed to precede certain cases of NMOSD. Amidst the Coronavirus disease 2019 (COVID-19) pandemic, mass vaccination takes place across the globe. We report two cases of newly diagnosed NMOSD following COVID-19 vaccination and systematically review previous reports. METHOD: Searching of Ovid MEDLINE and EMBASE databases was done using predefined search terms related to NMOSD and vaccination. Duplicates were removed. Newly diagnosed NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis criteria with symptoms presenting between 2-30 days after vaccination were included. Data on age, sex, comorbidity, vaccine name, type, and dose number, duration from vaccination to symptom onset, clinical phenotype(s), MRI findings, CSF profiles, severity of attack, initial and maintenance treatment, number of relapses after vaccination, and clinical outcomes were extracted using a standardized table and compared. RESULT: Ten cases of postvaccination NMOSD were identified. Patients aged between 15-46 years old. Nine patients (90%) presented with transverse myelitis and 3 (30%) with optic neuritis. The mean duration from vaccination to clinical onset was 8.2 days (median 9 days). Five patients (50%) tested positive for aquaporin 4 (AQP4) antibody. One patient had a family history of NMOSD. Three-fourths of AQP4-IgG seropositive patients with myelopathy had short transverse myelitis. The reported vaccines included CoronaVac, ChAdOx1 nCoV-19, yellow fever, quadrivalent influenza, H1N1 influenza, quadrivalent human papillomavirus, Japanese encephalitis, rabies, and recombinant hepatitis B virus together with tetanus-diphtheria-pertussis vaccines. All patients received high-dose steroids for initial treatment and 2 received additional therapeutic plasma exchange. Maintenance therapy was given in 4 patients. Five patients (50%) experienced no subsequent relapses within the follow-up period ranging between 3-34 months. Almost all patients returned to baseline functional status. DISCUSSION: The temporal relationship between vaccination and onset of symptoms suggests that vaccine might be a trigger of NMOSD. Genetic predisposition could be a risk factor for postvaccination NMOSD as there are evidences of family history and presence of an associated HLA allele. The prevalence of short-segment transverse myelitis seems to be higher than in typical cases of NMOSD, but the natural history is otherwise similar. All patients received acute treatment with high-dose corticosteroids, most with excellent response. Long-term immunomodulation therapy should be initiated for relapse prevention. Limitations of this study are lack of some relevant data, precision of temporal relationship, and the small number of reports. CONCLUSION: Postvaccination NMOSD is a rare condition that can occur with various types of vaccines. The short temporal relationship between vaccination and onset of NMOSD and the history of NMOSD in one patient's sibling indicate that vaccine might be a trigger for genetically predisposed individuals.

A comparison between subjective and objective measurements of spasticity in neuromyelitis optica spectrum disorder patients.

BACKGROUND: Spasticity is a common and disabling problem in multiple sclerosis (MS), but its effect in other CNS inflammatory demyelinating diseases (CNSIDDs), such as neuromyelitis optica spectrum disorder (NMOSD) is not widely studied. This study aims to compare subjective and objective measurements of spasticity in NMOSD patients and determine associated factors. METHODS: A prospective cross-sectional study was performed on CNSIDD patients attending the Multiple Sclerosis and Related Disorders Clinic at Siriraj Hospital, a tertiary hospital in Thailand, from June to November 2020 was performed. MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) patients were included. Patients' self-rated Numeric Rating Scale (NRS) for spasticity and clinician-evaluated Modified Ashworth Scale (MAS) scores on the same visit were compared and assessed for correlations. Data on characteristics of patients including demographics, number of transverse myelitis (TM) attacks, disease duration, and Expanded Disability Status Scale (EDSS) score were collected. RESULTS: Seventy-nine CNSIDD patients were included with 25 MS, 53 NMOSD, and 1 MOGAD. There was a statistically significant correlation between NRS and MAS scores (r = 0.934, p < 0.001). Spasticity was more commonly observed in NMOSD patients compared to MS (34% vs 8%, p = 0.016). Clinical characteristics strongly associated with spasticity were higher number of TM attacks (p < 0.001), severe TM attacks (p < 0.001), longitudinally extensive transverse myelitis attacks (p < 0.001), longer disease duration (p = 0.025), higher EDSS (p < 0.001), and pyramidal Functional System Scale scores (p = 0.001). CONCLUSIONS: Patients' self-reported NRS score had a good correlation with clinician-evaluated MAS score for spasticity assessment in NMOSD and CNSIDD patients overall. Number and severity of TM attacks were associated with spasticity. Spastic patients had more disability measured by EDSS.

Paraneoplastic neurological syndrome: an evolving story.

Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Several classic PNS have been described, such as limbic encephalitis, paraneoplastic cerebellar degeneration, encephalomyelitis, opsoclonus-myoclonus, sensory neuronopathy, Lambert-Eaton Myasthenic syndrome, and chronic gastrointestinal dysmotility. It is now recognized that PNS can have varied nonclassical manifestations that extend beyond the traditional syndromic descriptions. Multiple onconeural antibodies with high specificity for certain tumor types and neurological phenotypes have been discovered over the past 3 decades. Increasing use of immune checkpoint inhibitors (ICIs) has led to increased recognition of neurologic ICI-related adverse events. Some of these resemble PNS. In this article, we review the clinical, oncologic, and immunopathogenic associations of PNS.

Asian and African/Caribbean AQP4-NMOSD patient outcomes according to self-identified race and place of residence.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy characterized by aquaporin-4 antibodies, whose prognosis is influenced by onset age, race, environmental exposures and immunosuppression. Distinguishing the contribution of environment from genetics is challenging. We aimed to compare neuromyelitis optica spectrum disorder (NMOSD) patient outcomes according to self-identified racial group and place of residence. METHODS: This retrospective analysis of prospectively collected data included non-white anti-aquaporin-4 antibody positive NMOSD patients under follow-up from 15 centers [United Kingdom, France, Germany, Denmark, Martinique, United States of America, Japan, South Korea, Singapore, Thailand, China (including Hong Kong) and India]. Racial groups were designated: African/Caribbean; South Asian; East Asian (including Southeast Asia). Patients from these racial groups residing outside Africa/Caribbean or Asia were compared with those living in the Caribbean or the Asian areas. Kaplan-Meier survival curves and Cox models were generated using time to sustained Expanded Disability Status Scale≥6.0 or death; time to sustained Kurtzke Visual Function Score≥3.0 or a composite endpoint of all three. RESULTS: Among 821 patients, African/Caribbean patients (n = 206) had the shortest time to immunosuppression and higher visual disability at onset. South Asian patients (n = 65) were younger, had lower visual disability at onset and higher mortality rate. East Asians (n = 550) had the lowest relapse rate and lowest accrued motor disability. Survival analysis of African/Caribbean outside Africa/Caribbean vs those in the Caribbean showed a significant difference in the composite endpoint (p = 0.024,log-rank test), not apparently related to treatment differences. No significant differences between native and those residing outside Asia were found for other racial groups. CONCLUSION: This NMOSD study reports the effects of place of residence on the outcomes in different races. Place of residence may not be a significant driver of disability among Asian patients, while it may influence African/Caribbean patient outcomes. Validating these findings could help distinguish between genetic causes and potentially modifiable environmental factors.

Efficacy and safety of mycophenolate mofetil therapy in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis.

Mycophenolate mofetil (MMF) is an immunosuppressive agent (IS) which is widely prescribed in neuromyelitis optica spectrum disorder (NMOSD) patients. We aim to assess the efficacy and safety of MMF in controlling relapse and disease severity. Eligible studies obtained from the EMBASE and Ovid MEDLINE databases were studies of NMOSD patients treated with MMF, which reported treatment outcomes as Annualized Relapse Rate (ARR) or Expanded Disability Status Scale (EDSS) before and after treatment. Fifteen studies included 1047 patients, of whom 915 (87.4%) were aquaporin-4 immunoglobulin seropositive. The total number of patients that received MMF was 799. A meta-analysis on ARR was conducted in 200 patients from 4 studies and on EDSS in 158 patients from 3 studies. The result showed a significant improvement with a mean reduction of 1.13 [95% confidence interval (CI) 0.60-1.65] in ARR, and a mean reduction of 0.85 (95% CI 0.36-1.34) in EDSS after MMF therapy. Adverse events occurred in 106 (17.8%) of 594 patients during MMF therapy. This systematic review and meta-analysis showed that using MMF as a preventive therapy in NMOSD patients can significantly reduce relapse rates and improve disease severity with acceptable tolerability.