Multi-actor system dynamics in access to disease-modifying treatments for multiple sclerosis in Southeast Asia: A regional survey and suggestions for improvement.

BACKGROUND: Despite the global availability of multiple sclerosis (MS) treatments, accessing and financing them in Southeast Asia (SEA) remains a challenge. This descriptive survey-based study aimed to describe the current state of MS treatment access and local access dynamics within this region. METHODS: The survey questionnaire, comprising of 15 closed-ended and five open-ended questions, was developed by three neurologists with expertise in MS and routine MS patient management, or had training in neuroimmunology. Questionnaire development was guided by the recent Atlas of MS and in alignment with the Access to Treatment framework, focusing on MS diagnosis and treatment issues in SEA. Fifteen neurologists experienced in managing MS across the region were identified as key informants for this study. RESULTS: All fifteen neurologists participated in the survey via email and videoconferencing between January 2020 and February 2023, which included the following countries: Brunei, Cambodia, Indonesia, Malaysia, Myanmar, Lao PDR, Philippines, Singapore, Thailand, Timor-Leste, and Vietnam. All had at least five years of experience in managing MS patients and six had previously completed a neuroimmunology fellowship programme. SEA countries showed disparities in healthcare financing, availability of neurologists, MS treatments, and investigative tools. Access to MS disease-modifying treatments (DMTs) is hindered by high cost, lack of MS specialists, and weak advocacy efforts. On-label DMTs are not listed as essential medicines regionally except for interferon beta1a and teriflunomide in Malaysia. On-label monoclonals are available only in Malaysia, Singapore, and Thailand. Generic on-label DMTs are unavailable due to lack of distributorship and expertise in using them. Off-label DMTs (azathioprine, methotrexate, and rituximab) predominate in most SEA countries. Other challenges include limited access to investigations, education, and knowledge about DMTs among general neurologists, and absence of registries and MS societies. Patient champions, communities, and MS organisations have limited influence on local governments and pharmaceutical companies. Despite its increasing prevalence, there is a lack of concerted priority setting due to MS being perceived as a rare, non-communicable disease. CONCLUSION: This study highlights the distinct dynamics, challenges, and research gaps within this region, and provides suggestions to improve MS diagnosis, education, and medicine access.

Brain waves spectral analysis of human responses to odorous and non-odorous substances: a preliminary study.

OBJECTIVE: The aim of this study was to identify the potential electrophysiological biomarkers of human responses by comparing the electroencephalogram brain wave changes towards lavender versus normal saline in a healthy human population. METHOD: This study included a total of 44 participants without subjective olfactory disturbances. Lavender and normal saline were used as the olfactory stimulant and control. Electroencephalogram was recorded and power spectra were analysed by the spectral analysis for each alpha, beta, delta, theta and gamma bandwidth frequency upon exposure to lavender and normal saline independently. RESULTS: The oscillatory brain activities in response to the olfactory stimulant indicated that the lavender smell decreased the beta activity in the left frontal (F7 electrode) and central region (C3 electrode) with a reduction in the gamma activity in the right parietal region (P4 electrode) (p < 0.05). CONCLUSION: Olfactory stimulants result in changes of electrical brain activities in different brain regions, as evidenced by the topographical brain map and spectra analysis of each brain wave.

Assessment of a 16-Channel Ambulatory Dry Electrode EEG for Remote Monitoring.

Ambulatory EEGs began emerging in the healthcare industry over the years, setting a new norm for long-term monitoring services. The present devices in the market are neither meant for remote monitoring due to their technical complexity nor for meeting clinical setting needs in epilepsy patient monitoring. In this paper, we propose an ambulatory EEG device, OptiEEG, that has low setup complexity, for the remote EEG monitoring of epilepsy patients. OptiEEG's signal quality was compared with a gold standard clinical device, Natus. The experiment between OptiEEG and Natus included three different tests: eye open/close (EOC); hyperventilation (HV); and photic stimulation (PS). Statistical and wavelet analysis of retrieved data were presented when evaluating the performance of OptiEEG. The SNR and PSNR of OptiEEG were slightly lower than Natus, but within an acceptable bound. The standard deviations of MSE for both devices were almost in a similar range for the three tests. The frequency band energy analysis is consistent between the two devices. A rhythmic slowdown of theta and delta was observed in HV, whereas photic driving was observed during PS in both devices. The results validated the performance of OptiEEG as an acceptable EEG device for remote monitoring away from clinical environments.

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.

Neurological manifestations in SARS-CoV-2 infection: A single-center cross-sectional study in Malaysia.

Background: Neurological involvement associated with SARS-CoV-2 infection has been reported from different regions of the world. However, data from South East Asia are scarce. We described the neurological manifestations and their associated factors among the hospitalized COVID-19 patients from an academic tertiary hospital in Malaysia. Methods: A cross-sectional observational study of hospitalized COVID-19 patients was conducted. The neurological manifestations were divided into the self-reported central nervous system (CNS) symptoms, stroke associated symptoms, symptoms of encephalitis or encephalopathy and specific neurological complications. Multiple logistic regression was performed using demographic and clinical variables to determine the factors associated with outcome. Results: Of 156 hospitalized COVID-19 patients with mean age of 55.88 ± 6.11 (SD) years, 23.7% developed neurological complications, which included stroke, encephalitis and encephalopathy. Patients with neurological complications were more likely to have diabetes mellitus (p = 0.033), symptoms of stroke [limb weakness (p < 0.001), slurred speech (p < 0.001)]; and encephalitis or encephalopathy [confusion (p < 0.001), forgetfulness (p = 0.006) and seizure (p = 0.019)]. Unvaccinated patients had a 4.25-fold increased risk of having neurological complications (adjusted OR = 4.25; 95% CI: 1.02, 17.71, p = 0.047). Anosmia and dysgeusia were less associated with neurological complications (adjusted OR = 0.22; 95% CI: 0.05, 0.96, p = 0.044). The odds of neurological complications were increased by 18% in patients with leukocytosis (adjusted OR = 1.18, 95% CI: 1.003, p = 0.0460). Conclusions: Stroke, encephalitis and encephalopathy were the common neurological complications from our study. Diabetes mellitus, presence of symptoms of stroke, symptoms of encephalitis or encephalopathy, leukocytosis, and being unvaccinated against COVID-19 were the associated risk factors of developing neurological complications.

Primary Nonselective Laryngeal Reinnervation in Iatrogenic Acute Recurrent Laryngeal Nerve Injury: Case Series and Literature Review.

Treating an acutely injured recurrent laryngeal nerve by primary nonselective laryngeal reinnervation (LR) during thyroidectomy is encouraged to minimize postoperative morbidity. Performing a concurrent transoral temporary injection laryngoplasty (IL) may improve the patient's voice while waiting for the effect of successful reinnervation. Chronological multidimensional voice outcomes (qualitative and quantitative) and combination of the primary nonselective LR with concurrent transoral IL were not explicitly demonstrated in previous cases that published the literature. In this study, the authors presented the multidimensional voice parameters of 3 patients undergoing primary nonselective LR with concurrent IL during thyroidectomy. The parameters were measured at different time points (2 weeks and 1, 3, 6, and 12 months) following the surgery. Laryngeal electromyography was done at 1 to 2 months and 12 months postsurgery. The results showed that the voices, qualitatively and quantitatively, were within normal range at within 3 months postintervention. The parameters were slightly beyond the normal limit at 3 months and returned to normal at 6 months postintervention and beyond. The LEMG depicted evidence of successful reinnervation in which the motor unit was normal comparable to the opposite normal vocal fold.

Sixteen-Syndrome in a Young Patient with Systemic Lupus Erythematosus.

Sixteen syndrome is rare variant of one and a half syndrome resulting from lesion affecting bilateral dorsal pontine structures. This report describes a case of 16 syndrome in systemic lupus erythematosus (SLE). A 28 year old woman with underlying lupus was presented with sudden left side body weakness and diplopia. Examination showed features of 16 syndrome with one and a half syndrome, facial diplegia and left hemiparesis. Neuroimaging revealed an acute infarct of bilateral dorsal pons. The patient was placed on antiplatelet therapy. However, she developed left leg deep vein thrombosis and pulmonary embolism after one week. She was then given subcutaneous low molecular weight heparin, followed by warfarin and cycles of cyclophosphamide. Her hemiparesis, ocular symptoms, and facial diplegia improved after one year. SLE increases the risk of stroke and thrombotic events in a young patient. Achieving disease remission is important to prevent stroke in SLE patients.

A Classification Model of EEG Signals Based on RNN-LSTM for Diagnosing Focal and Generalized Epilepsy.

Epilepsy is a chronic neurological disorder caused by abnormal neuronal activity that is diagnosed visually by analyzing electroencephalography (EEG) signals. BACKGROUND: Surgical operations are the only option for epilepsy treatment when patients are refractory to treatment, which highlights the role of classifying focal and generalized epilepsy syndrome. Therefore, developing a model to be used for diagnosing focal and generalized epilepsy automatically is important. METHODS: A classification model based on longitudinal bipolar montage (LB), discrete wavelet transform (DWT), feature extraction techniques, and statistical analysis in feature selection for RNN combined with long short-term memory (LSTM) is proposed in this work for identifying epilepsy. Initially, normal and epileptic LB channels were decomposed into three levels, and 15 various features were extracted. The selected features were extracted from each segment of the signals and fed into LSTM for the classification approach. RESULTS: The proposed algorithm achieved a 96.1% accuracy, a 96.8% sensitivity, and a 97.4% specificity in distinguishing normal subjects from subjects with epilepsy. This optimal model was used to analyze the channels of subjects with focal and generalized epilepsy for diagnosing purposes, relying on statistical parameters. CONCLUSIONS: The proposed approach is promising, as it can be used to detect epilepsy with satisfactory classification performance and diagnose focal and generalized epilepsy.

Movement Disorders Resulting From Bilateral Basal Ganglia Lesions in End-Stage Kidney Disease: A Systematic Review.

OBJECTIVE: The basal ganglia (BG) are susceptible to fluctuations in blood urea levels, sometimes resulting in movement disorders. We described patients with end-stage kidney disease (ESKD) presenting with movement disorders associated with bilateral BG lesions on imaging. METHODS: We report four patients and systematically reviewed all published cases of ESKD presenting with movement disorders and bilateral BG lesions (EBSCOhost and Ovid). RESULTS: Of the 72 patients identified, 55 (76.4%) were on regular dialysis. Parkinsonism was the most common movement disorder (n = 39; 54.2%), followed by chorea (n = 24; 33.3%). Diabetes mellitus (n = 51; 70.8%) and hypertension (n = 16; 22.2%) were the most common risk factors. Forty-three (59.7%) were of Asian ethnicity. Complete clinical resolution was reported in 17 (30.9%) patients, while 38 (69.1%) had incomplete clinical resolution with relapse. Complete radiological resolution occurred in 14 (34.1%) patients. CONCLUSION: Movement disorders associated with BG lesions should be recognized as a rare and potentially reversible metabolic movement disorder in patients with ESKD.

Labrune's Syndrome Presenting With Stereotypy-Like Movements and Psychosis: A Case Report and Review.

Labrune's syndrome, or leukoencephalopathy with brain calcifications and cysts (LCC), is a rare genetic syndrome with variable neurological presentations. Psychiatric manifestations and involuntary movements are uncommonly reported. We report the case of a 19-year-old female, initially diagnosed with Fahr's syndrome, who presented to us with acute psychosis, abnormal behavior and involuntary movements. Her brain computed tomography showed extensive bilateral intracranial calcifications without cysts. Genetic testing detected two compound heterozygous variants, NR_033294.1 n.*9C>T and n.24C>T, in the SNORD118 gene, confirming the diagnosis of LCC. We discuss the expanding phenotypic spectrum of LCC and provide a literature review on the current diagnosis and management of this rare syndrome.

Longitudinally Extensive Transverse Myelitis in Highly Active Relapsing-remitting Multiple Sclerosis.

Transverse myelitis in multiple sclerosis is typically a short cord lesion with patchy distribution. Rarely, longitudinally extensive transverse myelitis can be seen in those with highly active disease or frequent relapses. The recognition of this uncommon phenotype in multiple sclerosis is important as the treatment is largely different from other demyelinating diseases. We describe a patient with highly active relapsing-remitting multiple sclerosis on interferon beta-1a who developed LETM after multiple relapses.

Impact of Covid-19 on the therapeutic plasma exchange service within the South East Asian region: Consensus recommendations and global perspectives.

INTRODUCTION: Therapeutic plasma exchange (TPE) for neuroimmunological disorders has played an increasingly important role within the Southeast Asian (SEA) region. The South East Asian Therapeutic Plasma exchange Consortium (SEATPEC) was formed in 2018 to promote education and research on TPE within the region. The advent of the Covid-19 pandemic has produced challenges for the development and expansion of this service. METHODOLOGY: A qualitative and semi-quantitative questionnaire-based survey was conducted by SEATPEC member countries from January to June 2020 (Phase 1) and then from July 2020 to January 2021 in (Phase 2) to assess the impact of Covid-19 on regional TPE. OBJECTIVES: The study's main objectives were to explore the challenges experienced and adaptations/adjustments taken by SEATPEC countries in order to continue safe and efficient TPE during the Covid-19 pandemic. RESULTS: The pandemic was found to disrupt the delivery of TPE services in all SEATPEC countries. Contributing factors were multifactorial due to overstretched medical services, staff shortages, quarantines and redeployments, fear of acquiring Covid-19, movement restriction orders, and patient's psychological fear of attending hospitals/testing for Covid-19. All SEATPEC countries practiced careful stratification of cases for TPE (electives vs emergencies, Covid-19 vs non-Covid-19 cases). SEATPEC countries had to modify TPE treatment protocols to include careful preprocedure screening of patient's for Covid-19, use of personal protective equipment (PPE) and post-TPE sanitization of machines and TPE suites. CONCLUSION: Based on the responses of the survey, SEATPEC countries produced a consensus statement with five recommendations for safe and effective TPE within the region.

Quantitative laryngeal electromyography (LEMG) in unilateral vocal fold paralysis: Developing normative values using the opposite normal mobile vocal fold.

OBJECTIVE: Laryngeal electromyography (LEMG) is used to confirm neuropathy; traditionally, it is evaluated qualitatively. This study aimed to develop normative values for the thyroarytenoid-lateral cricoarytenoid (TA-LCA) muscle complex by determining the mean turns (MT) and mean amplitudes (MA) using the opposite normal mobile vocal fold in unilateral vocal fold paralysis (VFP). This study also compared the MT and MA of the paralyzed vocal fold with that of the normal side and analyzed their correlations. METHODS: This is a cross-sectional study in which 77 patients (18 males, 59 females, mean age of 48) with unilateral VFP with an opposite normal mobile vocal fold underwent LEMG with a standardized protocol. Koufman gradings and MT and MA were used for the qualitative and quantitative evaluations. Mann-Whitney U test was performed to compare the median of the turns and amplitudes between the opposite normal mobile vocal fold and the paralyzed side. A linear-scale graphical "cloud" of the normal TA-LCA muscle complex was generated using logarithmic regression analysis. The qualitative and quantitative parameters were analyzed using multiple analysis of variance and Kruskall-Wallis test. Post-hoc analysis was performed to further determine the differences of the significance between both parameters. The correlation between the qualitative and quantitative parameters was analyzed using Spearman correlation. RESULTS: The MT and MA were significantly higher for the normal TA-LCA muscle complex than the paralyzed side (582 vs. 336; 412 vs. 296, respectively) and the median of the turns and amplitudes were significantly lower in the paralyzed side with p-values <0.001. A significant difference was observed between the Koufman grading and the combination of MT and MA [F (8,144) = 73.254] and between the Koufman grading and MT and MA individually [H (4, 72) = 18.3 and H (4, 72) =33.4], in which both had p-values <0.001. A moderate negative linear relationship was seen between the Koufman grading and MT and MA. On further analysis, it was revealed that only certain pairs of Koufman grading were statistical significant. CONCLUSIONS: This study was the first to present the quantitative normative values and "cloud" of the TA-LCA muscle complex using the opposite normal mobile vocal fold in patients with unilateral VFP in which it is comparable to healthy controls. We concluded that quantitative LEMG supports the qualitative Koufman grading method however it cannot be used independently to determine the severity of neuropathy.

First Reported Case of Neuroleptospirosis Complicated With Anton's Syndrome.

Leptospirosis is a spirochetal zoonotic disease with a wide clinical spectrum, often underdiagnosed especially when presented as an acute neurological manifestation. We report a case of a 24-year-old man with serologically positive leptospirosis, who presented with altered sensorium, seizures and subsequently developed cortical blindness. His brain MRI revealed bilateral occipital and later parietal lobe cerebritis.

A case of Guillain-Barré syndrome (GBS) presenting with acute urinary retention and T6 sensory level.

Guillain-Barré syndrome (GBS) is an acute immune-mediated demyelinating disease. Early recognition of this disease is crucial as it can progress to life-threatening conditions such as respiratory failure or autonomic dysfunction. Typical clinical manifestations of GBS include progressive weakness of the limbs, bulbar, facial muscles and ophthalmoplegia. Sensory level and bladder dysfunction are more suggestive of acute myelopathy. We report a case of GBS presenting with acute urinary retention and T6 sensory level, which was successfully treated with plasma exchange.