Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Multiple Acyl-CoA Dehydrogenase Deficiency: Phenotypic and Genetic Features of a Malaysian Cohort.

BACKGROUND AND PURPOSE: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited disorder of fatty acid oxidation that causes lipid storage myopathy (LSM). This is the first report on MADD that describes the phenotypic and genetic features of a Malaysian cohort. METHODS: Among the >2,500 patients in a local muscle biopsy database, patients with LSM were identified and their genomic DNA were extracted from muscle samples and peripheral blood. All 13 exons of the electron-transfer flavoprotein dehydrogenase gene (ETFDH) were subsequently sequenced. Fifty controls were included to determine the prevalence of identified mutations in the normal population. RESULTS: Fourteen (82%) of the 17 LSM patients had MADD with ETFDH mutations. Twelve (86%) were Chinese and two were Malay sisters. Other unrelated patients reported that they had no relevant family history. Nine (64%) were females. The median age at onset was 18.5 years (interquartile range=16-37 years). All 14 demonstrated proximal limb weakness, elevated serum creatine kinase levels, and myopathic changes in electromyography. Three patients experienced a metabolic crisis at their presentation. Sanger sequencing of ETFDH revealed nine different variants/mutations, one of which was novel: c.998A>G (p.Y333C) in exon 9. Notably, 12 (86%) patients, including the 2 Malay sisters, carried a common c.250G>A (p.A84T) variant, consistent with the hotspot mutation reported in southern China. All of the patients responded well to riboflavin therapy. CONCLUSIONS: Most of our Malaysian cohort with LSM had late-onset, riboflavin-responsive MADD with ETFDH mutations, and they demonstrated phenotypic and genetic features similar to those of cases reported in southern China. Furthermore, we report a novel ETFDH mutation and possibly the first ever MADD patients of Malay descent.

Gastrointestinal Dysfunction in Parkinson's Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem.

Patients with Parkinson's disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.

The Immunobiology of Nipah Virus.

Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that emerged in Malaysia in 1998. It is a human pathogen capable of causing severe respiratory infection and encephalitis. The natural reservoir of NiV, Pteropus fruit bats, remains a continuous virus source for future outbreaks, although infection in the bats is largely asymptomatic. NiV provokes serious disease in various mammalian species. In the recent human NiV outbreaks in Bangladesh and India, both bats-to-human and human-to-human transmissions have been observed. NiV has been demonstrated to interfere with the innate immune response via interferon type I signaling, promoting viral dissemination and preventing antiviral response. Studies of humoral immunity in infected NiV patients and animal models have shown that NiV-specific antibodies were produced upon infection and were protective. Studies on cellular immunity response to NiV infection in human and animal models also found that the adaptive immune response, specifically CD4+ and CD8+ T cells, was stimulated upon NiV infection. The experimental vaccines and therapeutic strategies developed have provided insights into the immunological requirements for the development of successful medical countermeasures against NiV. This review summarizes the current understanding of NiV pathogenesis and innate and adaptive immune responses induced upon infection.

Sequential intermittent therapeutic plasma exchange: A possible induction and maintenance therapy in the management of adult patients with neuromyelitis optica spectrum disorder.

Evidence on the benefits of intermittent therapeutic plasma exchange (TPE) as maintenance therapy in neuromyelitis optica spectrum disorder (NMOSD) is limited. This study explores the possible effectiveness of sequential intermittent therapeutic plasma exchange (SITPE), a novel TPE protocol in the management of adult NMOSD patients. Through retrospective review of medical records in Kuala Lumpur Hospital, Malaysia, NMOSD patients who underwent SITPE, namely, an induction phase of monthly cycle of TPE (1 cycle = five exchange sessions) for three cycles with or without a subsequent maintenance phase of three-monthly cycle of TPE for three cycles, were included in this controlled historical cohort study. We explored their serial improvements in Expanded Disability Status Scale (EDSS), limb power, visual acuity, and annualized relapse rate following SITPE initiation. Statistical significance was set at P < .05. Fifteen adults (mean age: 35.4 years, mean disease duration: 9.5 years, 73% female, 87% AQP4-IgG positive) with corticosteroid-refractory attacks were included. Upon SITPE initiation, significant improvements in EDSS and limb motor power for up to 12 months, in addition to significant improvements in visual acuity for up to 6 months, were recorded. Significant reduction in annualized relapse rates for up to 2 years was documented. These improvements were not significantly influenced by age groups, gender, or presence of cord atrophy. Notably, adverse events of SITPE were infrequent and manageable. Sequential intermittent therapeutic plasma exchange as induction and maintenance therapy may improve the disease outcomes and prevent relapses in adult NMOSD patients with severe, corticosteroid-refractory attacks.

Therapeutic Plasma Exchange in Neuromyelitis Optica Spectrum Disorders and Related Disorders in Resource-Limited Settings: Outcomes in a Multiethnic Single-Center Population.

We evaluated therapeutic plasma exchange (TPE) efficiency in treatment of a single relapse in steroid-refractory patients with neuromyelitis optica spectrum disorders (NMOSD) in a multi-ethnic resource-limited setting. This was a historical cohort study on the clinical outcomes post-TPE in a multiethnic cohort of 53 steroid-refractory NMOSD patients at a single Malaysian tertiary center. Primary outcomes, assessed both pre- and post-TPE, were Medical Research Council scale of muscle power, Modified Rankin Scale, Expanded Disability Status Scale (EDSS), and visual acuity. Secondary outcomes were ambulatory status and target neurological deficit (TND)-based TPE response. Significant improvements in Medical Research Council, Modified Rankin Scale, EDSS, and visual acuity (P < 0.001) were observed at 1-month post-TPE with further improvement of EDSS at 6 months (EDSSΔ6) post-TPE (P < 0.001). At 6 months post-TPE, 87% of patients has successful TND-based TPE response and 69.8% were ambulating without support. Patients with anti-aquaporin 4 seronegativity (P = 0.004), myelitis and brainstem features at first relapse (P = 0.004), longer cord lesions (P = 0.030), higher pre-TPE EDSS of ≥8 (P = 0.018) and delayed TPE initiation of >14 days (P = 0.047) were significantly associated with improved EDSSΔ6. TND-based TPE response was significant in absence of cord atrophy (P = 0.030). TPE is an effective treatment for steroid-refractory acute relapses of NMOSD in a multiethnic Malaysian population despite its resource-limited setting. The predictive factors of EDSSΔ6 improvement were anti-aquaporin 4 seronegativity, longer cord lesions, and higher pre-TPE EDSS. Absence of cord atrophy was predictive of better TND-based TPE response. Unexpectedly, our study showed that delayed TPE initiation of more than 14 days and up to 60 days may also be beneficial.

Knowledge of Parkinson's Disease in a Multiethnic Urban Asian Setting.

BACKGROUND: Public knowledge regarding Parkinson's disease (PD) is important to facilitate good health-seeking behavior, but the literature on this topic is scarce. OBJECTIVE: We aimed to explore the level of public knowledge regarding PD in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller cohort of PD patients and caregivers. METHODS: A Knowledge of PD Questionnaire (KPDQ) was developed and administered to members of the Malaysian general public, and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and general knowledge regarding PD. RESULTS: 1,258 members of the general public completed the KPDQ. Tremor was the most widely recognized symptom (recognized by 79.0% of respondents); however, 83.7% incorrectly believed that all PD patients experience tremor. Memory problem was the most widely recognized NMS. Overall, motor symptoms were better recognized than NMS. Common misperceptions were that there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female gender, Chinese ethnicity, tertiary education, healthcare-related work, and knowing someone with PD were independently associated with higher KPDQ scores. PD patients (n = 116) and caregivers (n = 135) demonstrated superior knowledge compared with the general public group, but one-third of them believed that PD is currently curable. CONCLUSIONS: This is the only study on public knowledge regarding PD in Asia. Important gaps in knowledge were evident, which could present a barrier to early diagnosis and appropriate treatment of PD. This highlights the need for targeted education campaigns and further research in this area.

Impulsive-compulsive behaviors are common in Asian Parkinson's disease patients: assessment using the QUIP.

BACKGROUND: There are limited data on the prevalence of impulsive-compulsive behaviors and subsyndromal impulsive-compulsive behaviors in Asian patients with Parkinson's disease, who are treated with lower dosages of dopaminergic medications. METHODS: The recently-validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease was administered to 200 consecutive patients attending a Malaysian university-based neurology clinic. Informant report was also systematically obtained. RESULTS: A high rate of Questionnaire positivity was found (35.0% by combined patient and informant report; 24.6% by patient report alone; 27.4% by informant report alone), despite usage of relatively low dosages of dopaminergic medications (mean/median total l-dopa equivalent units of 528/450 mg/day; mean/median agonist-only l-dopa equivalent units of 74/37 mg/day). Eating, sexual and punding or hobbyism behaviors were relatively common, while gambling and compulsive medication use occurred less frequently. Agreement between patient- and informant-reporting of impulsive-compulsive behaviors was moderate-to-fair (Kappa values ranging from 0.203 to 0.494). Factors associated with Questionnaire positivity on univariate analysis were male gender, younger age at Parkinson's disease onset, longer disease duration, use of dopamine agonist or amantadine therapy, higher total l-dopa equivalent units and higher dopamine agonist-only l-dopa equivalent units. On multivariate analysis, male gender and longer disease duration independently predicted Questionnaire positivity. No association was found with cognitive or apathy scores. CONCLUSIONS: Our findings suggest that Asian patients with Parkinson's disease may be susceptible to dopaminergic medication-related side effects. The data here also contribute to the understanding of the psychometric properties of the Questionnaire for Impulsive-Compulsive Disorders.