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.

Current evidence of rituximab in the treatment of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system. The immunopathology of MS involves both T and B lymphocytes. Rituximab is one of the anti-CD20 monoclonal antibody therapies which deplete B-cells. Although some anti-CD20 therapies have been approved by the Food and Drug Administration for treatment of MS, rituximab is used off-label. Several studies have shown that rituximab has a good efficacy and safety in MS, including certain specific patient conditions such as treatment-naïve patients, treatment-switching patients, and the Asian population. However, there are still questions about the optimal dose and duration of rituximab in MS due to the different dosing regimens used in each study. Moreover, many biosimilars have become available at a lower cost with comparable physicochemical properties, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Thus, rituximab may be considered as a potential therapeutic option for patients without access to standard treatment. This narrative review summarized the evidence of both original and biosimilars of rituximab in MS treatment including pharmacokinetics, pharmacodynamics, clinical efficacy, safety, and dosing regimen.

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.

Facilities, selection, outcome measurement, and limitations of therapeutic plasma exchange for neuroimmunological disorders: The South East Asian survey study.

INTRODUCTION: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an important role in the Southeast Asian region. This study investigates the challenges of performing TPE within the region. METHOD: A questionnaire-based survey was conducted and launched to 15 South East Asian Therapeutic Plasma Exchange Consortium (SEATPEC) members from seven countries in January 2021. It included demographics, TPE techniques, indications, challenges, timing, outcome measurement, and access to laboratory testing in each local center. RESULTS: A total of 15 neurologists from 12 participating centers were included. They usually perform five sessions of TPE (100.0%), with 1 to 1.5 plasma volume (93.3%), and exchanges via the central catheter (100.0%). Acute relapses of neuromyelitis optica spectrum disorder and myasthenia gravis are the most common indications. They used a combination of normal saline and 5% albumin (60.0%) as replacement fluid. Most (66.7%) used TPE as an add-on treatment in steroid-refractory cases or as first-line treatment for severe attacks. They suggested assessing the TPE efficacy of TPE by the interval to the next attack, post-TPE relapse rates, and TPE-related complications. The major challenges within our region are expense, reimbursibility, and access to TPE. CONCLUSION: Although countrywise differences exist, all share similarities regarding methods, indications, timing, obstacles, and challenges of TPE for neuroimmunological conditions. Regional collaboration will be essential to identify strategies to reduce these barriers to access to TPE in the future.

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.

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.

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.

Cannabis extract for the treatment of painful tonic spasms in a patient with neuromyelitis optica spectrum disorder: A case report.

Painful tonic spasm (PTS) is a common yet debilitating symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), especially those with longitudinally extensive transverse myelitis. Although carbamazepine is an effective treatment, it poses the risk of severe adverse reactions, such as Steven-Johnson syndrome (SJS). In this case report, we describe an NMOSD patient with severe PTS suffering from carbamazepine-induced SJS who responded well to cannabis extract. Since cannabinoids can ameliorate spasticity in an experimental autoimmune encephalomyelitis model through cannabinoid 1 (CB1) receptor activation, cannabis extract which includes delta-9-tetrahydrocannabinol (THC) is a potential treatment option for PTS in NMOSD patients.

Patterns of single photon emission tomography (SPECT) among patients with dementia in the memory clinic at Siriraj Hospital.

OBJECTIVE: The authors hypothesized that there is a pattern difference in cerebralperfusion of the 99-Technitium L, L-ethyl cysteinate dimer Single Photon Emission Computer Tomography (99-Tc ECD SPECT) between mild and moderate to severe dementia. MATERIAL AND METHOD: The authors reported a retrospective study in the Memory Clinic, Siriraj Hospital between January 2001 and October 2003 including only patients with Alzheimer's disease, vascular dementia, and mixed dementia. Clinical dementia rating (CDR) was used to document dementia severity. Patterns of hypoperfusion were classified into no definite hypoperfusion, regional hypoperfusion, and diffused hypoperfusion. RESULTS: One hundred and seven patients were included in the present study. Only mean Thai Mental State Examination (TMSE) score was different between the two groups. There was no significant correlation between pattern of hypoperfusion in brain SPECT and severity of dementia. CONCLUSION: The authors cannot demonstrate the pattern of hypoperfusion of 99-Tc ECD SPECT among patients' difference in dementia severity.

Risk of ischemic stroke among users of the oral contraceptive pill: The Melbourne Risk Factor Study (MERFS) Group.

BACKGROUND AND PURPOSE: Use of oral contraceptives has increased, and there is uncertainty about the stroke risk associated with their use. Our aim was to investigate this issue. METHODS: Using case-control techniques, we identified consecutive women with ischemic stroke from 4 Melbourne hospitals. All patients were between 15 and 55 years of age and had no prior stroke. Neighborhood-based control subjects were individually age-matched (+/-5 years) and geographically matched to subject cases. A questionnaire administered to participants elicited information about prior exposure to various potential risk factors, including the oral contraceptive pill (OCP). RESULTS: We included 234 cases and 234 controls (mean age, 42 years). Compared with noncurrent use, current use of the OCP, in doses of 20 cigarettes per day (OR, 3.68; 95% CI, 1.22 to 11.09). CONCLUSIONS: There was no evidence for an association between ischemic stroke and use of the OCP in low doses (