RESUMO
BACKGROUND: Progressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome-wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations. OBJECTIVES: Our goal was to investigate the genetic factors associated with PSP in Southeast Asian PSP patients. METHODS: Next-generation sequencing (whole-exome, whole-genome and targeted sequencing) was performed in two Asian cohorts, comprising 177 PSP patients. RESULTS: We identified 17 pathogenic or likely pathogenic variants in 16 PSP patients (9%), eight of which were novel. The most common relevant genetic variants identified were in MAPT, GBA1, OPTN, SYNJ1, and SQSTM1. Other variants detected were in TBK1, PRNP, and ABCA7-genes that have been implicated in other neurodegenerative diseases. Eighteen patients had a positive family history, of whom two carried pathogenic MAPT variants, and one carried a likely pathogenic GBA1 variant. None of the patients had expanded repeats in C9orf72. Furthermore, we found 16 different variants of uncertain significance in 21 PSP patients in PSEN2, ABCA7, SMPD1, MAPT, ATP13A2, OPTN, SQSTM1, CYLD, and BSN. CONCLUSIONS: The genetic findings in our PSP cohorts appear to be somewhat distinct from those in Western populations, and also suggest an overlap of the genetic architecture between PSP and other neurodegenerative diseases. Further functional studies and validation in independent Asian cohorts will be useful for improving our understanding of PSP genetics and guiding genetic screening strategies in these populations. © 2024 International Parkinson and Movement Disorder Society.
RESUMO
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.
Assuntos
Doenças Autoimunes do Sistema Nervoso , Troca Plasmática , Humanos , Miastenia Gravis/terapia , Troca Plasmática/métodos , Plasmaferese , Estudos Retrospectivos , População do Sudeste Asiático , Doenças Autoimunes do Sistema Nervoso/terapiaRESUMO
This study aimed to: (i) investigate the agronomic properties of biochars derived from selected invasive wetland weeds and (ii) examine the effect of biochar on soil organic carbon (SOC) dynamics and stability of tropical Ultisol soil. The biochars were analyzed for proximate properties, surface characteristics, elemental composition, functional groups, and thermal and carbon stability. Plant growth studies supplemented with biochar under greenhouse conditions for 1 year were conducted. The SOC, its fractions, and its dynamics were studied. The biochar incorporation significantly increased the SOC and its stable fractions like mineral Organic Carbon (MOC), fine-particulate organic carbon (fPOC), and Non-labile Carbon (NLC) by 24.54-7.82, 5.79-2.0, and 9.50-2.16 g kg-1 than control. The labile carbon fractions like Dissolved Organic Carbon (DOC), and coarse-Particulate Organic Carbon (cPOC) showed a substantial reduction by 0.72-0.26 and 2.92-1.29 g kg-1 respectively. However, the easily oxidizable carbon (EOC) and microbial biomass carbon (MBC) content increased by 2.10-4.87 g kg-1 and 28.33-158.55 mg kg-1 respectively. The addition of biochars resulted in the stabilization of soil aggregates. Likewise, substantial CO2 emission reduction (75.24-46.60%) has been achieved during the trials. The carbon pool management index (CPMI) values recorded a substantial increase of 40-7.2% between the trials. The findings imply that the inherent nature of weed biomasses determines the characteristics of the resulting biochar, and their application significantly influenced the carbon dynamics of the tropical Ultisol soil.
Assuntos
Carbono , Solo , Áreas Alagadas , Plantas Daninhas , Carvão VegetalRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing, autoimmune, inflammatory disorder that typically affects the optic nerves and spinal cord. At least two thirds of cases are associated with aquaporin-4 antibodies (AQP4-IgG) and complement-mediated damage to the central nervous system. In a previous small, open-label study involving patients with AQP4-IgG-positive disease, eculizumab, a terminal complement inhibitor, was shown to reduce the frequency of relapse. METHODS: In this randomized, double-blind, time-to-event trial, 143 adults were randomly assigned in a 2:1 ratio to receive either intravenous eculizumab (at a dose of 900 mg weekly for the first four doses starting on day 1, followed by 1200 mg every 2 weeks starting at week 4) or matched placebo. The continued use of stable-dose immunosuppressive therapy was permitted. The primary end point was the first adjudicated relapse. Secondary outcomes included the adjudicated annualized relapse rate, quality-of-life measures, and the score on the Expanded Disability Status Scale (EDSS), which ranges from 0 (no disability) to 10 (death). RESULTS: The trial was stopped after 23 of the 24 prespecified adjudicated relapses, given the uncertainty in estimating when the final event would occur. The mean (±SD) annualized relapse rate in the 24 months before enrollment was 1.99±0.94; 76% of the patients continued to receive their previous immunosuppressive therapy during the trial. Adjudicated relapses occurred in 3 of 96 patients (3%) in the eculizumab group and 20 of 47 (43%) in the placebo group (hazard ratio, 0.06; 95% confidence interval [CI], 0.02 to 0.20; P<0.001). The adjudicated annualized relapse rate was 0.02 in the eculizumab group and 0.35 in the placebo group (rate ratio, 0.04; 95% CI, 0.01 to 0.15; P<0.001). The mean change in the EDSS score was -0.18 in the eculizumab group and 0.12 in the placebo group (least-squares mean difference, -0.29; 95% CI, -0.59 to 0.01). Upper respiratory tract infections and headaches were more common in the eculizumab group. There was one death from pulmonary empyema in the eculizumab group. CONCLUSIONS: Among patients with AQP4-IgG-positive NMOSD, those who received eculizumab had a significantly lower risk of relapse than those who received placebo. There was no significant between-group difference in measures of disability progression. (Funded by Alexion Pharmaceuticals; PREVENT ClinicalTrials.gov number, NCT01892345; EudraCT number, 2013-001150-10.).
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Aquaporina 4/imunologia , Complemento C5/antagonistas & inibidores , Inativadores do Complemento/uso terapêutico , Imunossupressores/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Autoanticorpos/sangue , Inativadores do Complemento/efeitos adversos , Avaliação da Deficiência , Progressão da Doença , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Cefaleia/induzido quimicamente , Humanos , Imunoglobulina G/sangue , Imunossupressores/efeitos adversos , Masculino , Neuromielite Óptica/imunologia , Qualidade de Vida , Infecções Respiratórias/etiologia , Prevenção SecundáriaRESUMO
BACKGROUND: Off-label disease-modifying therapies (DMTs) for multiple sclerosis (MS) are used in at least 89 countries. There is a need for structured and transparent evidence-based guidelines to support clinical decision-making, pharmaceutical policies and reimbursement decisions for off-label DMTs. OBJECTIVES/RESULTS: The authors put forward general principles for the ethical use of off-label DMTs for treating MS and a process to assess existing evidence and develop recommendations for their use. CONCLUSION: The principles and process are endorsed by the World Federation of Neurology (WFN), American Academy of Neurology (AAN), European Academy of Neurology (EAN), Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Middle-East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) and Pan-Asian Committee for Treatment and Research in Multiple Sclerosis (PACTRIMS), and we have regularly consulted with the Brain Health Unit, Mental Health and Substance Use Department at the World Health Organization (WHO).
Assuntos
Esclerose Múltipla , Neurologia , Humanos , Esclerose Múltipla/tratamento farmacológico , Uso Off-Label , Estados UnidosRESUMO
BACKGROUND: Genome-wide association studies (GWAS) have shown that variants in the 3-methylcrotonyl-CoA carboxylase (MCCC1)/lysosome-associated membrane protein 3 (LAMP3) loci (rs10513789, rs12637471, rs12493050) reduce the risk of Parkinson's disease (PD) in Caucasians, Chinese and Ashkenazi-Jews while the rs11248060 variant in the diacylglycerol kinase theta (DGKQ) gene increases the risk of PD in Caucasian and Han Chinese cohorts. However, their roles in Malays are unknown. Therefore, this study aims to investigate the association of these variants with the risk of PD in individuals of Malay ancestry. METHODS: A total of 1114 subjects comprising of 536 PD patients and 578 healthy controls of Malay ancestry were recruited and genotyped using Taqman® allelic discrimination assays. RESULTS: The G allele of rs10513789 (OR = 0.83, p = 0.001) and A allele of rs12637471 (OR = 0.79, p = 0.007) in the MCCC1/LAMP3 locus were associated with a protective effect against developing PD in the Malay population. A recessive model of penetrance showed a protective effect of the GG genotype for rs10513789 and the AA genotype for rs12637471. No association with PD was found with the other MCCC1/LAMP3 rs12493050 variant or with the DGKQ (rs11248060) variant. No significant associations were found between the four variants with the age at PD diagnosis. CONCLUSION: MCCC1/LAMP3 variants rs10513789 and rs12637471 protect against PD in the Malay population.
Assuntos
Doença de Parkinson , Povo Asiático/genética , Carbono-Carbono Ligases , Estudos de Casos e Controles , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Proteínas de Membrana Lisossomal/genética , Malásia , Proteínas de Neoplasias , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
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.
Assuntos
COVID-19 , Troca Plasmática , Sudeste Asiático/epidemiologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/terapia , Consenso , Humanos , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/terapia , Neurologistas , Pandemias , Troca Plasmática/métodos , Troca Plasmática/estatística & dados numéricos , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
A 33-year-old man with a history of chronic toluene abuse through glue sniffing, developed tremors, cerebellar signs and cognitive decline. MR scan of the brain showed global cerebral and cerebellar atrophy with symmetrical T2-weighted hypointensities in the basal ganglia, thalami and midbrain. After stopping glue sniffing, his tremors, ataxia of gait, speech and cognition partially improved. Early recognition and intervention of toluene-induced leukodystrophy could prevent ongoing morbidity and premature mortality.
Assuntos
Abuso de Inalantes , Transtornos Relacionados ao Uso de Substâncias , Adulto , Gânglios da Base , Encéfalo , Humanos , Abuso de Inalantes/complicações , Masculino , Tolueno/efeitos adversosRESUMO
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.
Assuntos
Esclerose Múltipla/patologia , Medula Espinal/patologia , Adulto , Progressão da Doença , Feminino , Humanos , Fatores Imunológicos/farmacologia , Estudos Longitudinais , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Esclerose Múltipla/classificação , Esclerose Múltipla/diagnóstico por imagem , Esclerose Múltipla/tratamento farmacológico , Medula Espinal/diagnóstico por imagemRESUMO
OBJECTIVES: This study looked at observed crude prevalence/incidence of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in Malaysia and identified any inter-ethnic differences for MS/NMOSD. METHODS: This was a nationwide tertiary hospital-based retrospective cross-sectional study using the capture-recapture method. It looked at the estimated crude prevalence of confirmed MS and NMOSD and annual incidence on 29 December 2017. Recapture of data was done between February and March 2018 on 1 March 2018. Public and referring private institutions were accessed. RESULTS: The survey identified 767 MS and 545 NMOSD subjects, with crude prevalence rates of 2.73 per 100,000 (95% confidence interval (CI): 2.53; 2.92 per 100,000 population) and 1.94 per 100,000 (95% CI: 1.77; 2.10 per 100,000 population) with observed crude annual incidence of 0.55 (95% CI: 0.43; 0.58) for MS and 0.39 per 100,000 (95% CI: 0.35; 0.47) for NMOSD. The MS:NMOSD ratios were 1.4:1.0. The capture-recapture method revealed 913 MS (95% CI: 910; 915.9) and 580 (95% CI: 578.8; 581.2) NMOSD with prevalence per 100,000 of 3.26 (95% CI: 3.05; 3.47) and 2.07 (95% CI: 1.90; 2.24), respectively. In the MS group, 59.4% were Malay, 16.6% Chinese, 20.5% Indian, and 3.5% were from indigenous groups. In the NMOSD group, 47.3% were Malay, 46.9% Chinese, 3.5% Indian, and 2.3% were from other indigenous groups. The ratio of NMOSD to MS among the Chinese was 2:1, but the ratio of MS to NMOSD among the Malays was 1.8:1, and that in Indians was 8.3:1. CONCLUSION: There is a modest increase in the prevalence of MS and NMOSD in Malaysia with inter-ethnic differences for MS/NMOSD.
Assuntos
Etnicidade/estatística & dados numéricos , Esclerose Múltipla/epidemiologia , Neuromielite Óptica/epidemiologia , Adulto , Povo Asiático/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Incidência , Povos Indígenas/estatística & dados numéricos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/etnologia , Neuromielite Óptica/etnologia , Prevalência , Estudos Retrospectivos , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
There has been an increase in the use of therapeutic plasma exchange (TPE) in immune-mediated neurological disorders in recent years. However, accessibility and availability of TPE remains low and costly, especially for a country with limited healthcare funding like Malaysia. With expanding clinical indications in neurological disorders, and increasingly expensive conventional immunomodulatory treatment such as intravenous immunoglobulin and monoclonal antibodies, TPE remains an effective part of first or second-line treatment. In this article, we detailed the historical aspects of the use of TPE in neurological disorders in Malaysia over the last four decades and discussed the challenges behind the establishment of the first in-house neurology-driven TPE service in the country. Local TPE database from a national neurology centre in Kuala Lumpur over the past 20 years was analyzed. We observed a remarkable three folds increase in the use of TPE at our center over the past 10 years (total 131 TPE treatments) compared to a decade prior, with expanding clinical indications predominantly for central nervous system demyelinating disorders. Besides using membrane filtration method, centrifugal technique was adopted, providing new opportunities for other clinical beneficiaries such as a neurologist driven "in-house TPE unit". However, there were real world challenges, especially having to provide services with limited funding, human resources, and space. In addition, much has to be done to improve accessibility, availability, and sustainability of TPE services at our center and nationwide. Nevertheless, even with limited resources and support, it is possible with concerted efforts to work within the confines of these limitations to establish a safe, successful, and sustainable TPE service.
Assuntos
Tecnologia Biomédica/métodos , Hospitais Públicos/métodos , Neurologia/métodos , Troca Plasmática/métodos , Anticorpos Monoclonais/uso terapêutico , Doenças Autoimunes do Sistema Nervoso/terapia , Tecnologia Biomédica/tendências , Doenças do Sistema Nervoso Central/terapia , Hospitais Públicos/economia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Troca Plasmática/economia , Troca Plasmática/tendênciasRESUMO
Intravenous immunoglobulin (IVIG), corticosteroids and therapeutic plasma exchange (TPE) are evidence-based conventional treatments for chronic inflammatory demyelinating polyneuropathy (CIDP). In many centres, unconventional treatments are frequently used as alternatives. We evaluated the outcome of conventional and unconventional therapies in 31 CIDP patients. Overall response rate with conventional first-line immunotherapies was 77% (20/26), comparable between IVIG and corticosteroids (80% vs 70%). Use of TPE was limited. Treatment response among typical and atypical CIDP were comparable (76 vs 80%). Non-responders were patients with progressive form of typical CIDP and DADS. Majority (21/26, 81%) of patients with persistent neurological deficits received maintenance therapy. Two subgroups of patients frequently treated with maintenance immunosuppressants were those with improving or stable disease following first-line treatment (12, 57%) and those with progressive form of CIDP (2, 10%). Primary indications for immunosuppressant use were corticosteroids-sparing and additional immunosuppression effects. Nine (64%) patients with improving or stable disease given azathioprine were taken off corticosteroids after a median duration of 14 months (range 12-108). Two (14%) eventually achieved cure or clinical remission without treatment. Maintenance IVIg was given to 6 (29%) relapsing CIDP patients; none of achieved cure or remission after similar median duration of treatment. Less potent immunosuppressant drugs (azathioprine, mycophenolate mofetil, and methotrexate) were frequently used, with moderate adverse effect profiles. In resource limited setting, unconventional treatments were commonly used among CIDP patients with different clinical course of progression. In most cases, careful risk-benefit re-assessment is required to justify its further use.
Assuntos
Corticosteroides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Troca Plasmática/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In December 2017, 79 delegates attended the 2nd regional plasmapheresis conference and workshop for Southeast Asia (SEA) on the immunomodulatory role of plasma exchange in central and peripheral nervous system disorders in Kuala Lumpur, Malaysia. This meeting featured 6 plenary lectures, interactive sessions dedicated for experience sharing, case presentations, and a practical session for paramedics. Clinical experts and researchers from 7 SEA countries and India shared experience and challenges in treating autoimmune neurological disorders. While the spectrum of diseases and neurology practice remained largely similar, there was great disparities in accessibility of therapeutic plasma exchange (TPE) within SEA countries and between urban or rural settings. Costs, human resources, and healthcare policies are common challenges in providing sustainable TPE services. Novel techniques and innovative ideas in performing TPE were explored. A working consortium comprising of key opinion leaders was proposed to improve standards of TPE and enhance future research.
Assuntos
Congressos como Assunto , Troca Plasmática/métodos , Plasmaferese/métodos , Sudeste Asiático , Doenças do Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/terapia , Doenças Desmielinizantes , Humanos , Imunomodulação , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/terapiaRESUMO
We report two cases of neuromyelitis optica spectrum disorder with hypoglossal nerve involvement resulting in a wasted tongue associated with other brainstem symptoms of hypogeusia, hypersalivation, hiccough, increased sweating, hyperemesis and myelitis (in the second patient). This occurred due to involvement of the hypoglossal, tractus solitarius and dorsal vagal nuclei. Though the myelitis and other brainstem signs recovered the hypoglossal nerve involvement resulting in a unilateral wasted tongue did not. It is important to consider neuromyelitis optica and its spectrum disorders in the differential diagnosis of a wasted tongue though its occurrence is rare.
Assuntos
Doenças do Nervo Hipoglosso/etiologia , Neuromielite Óptica/complicações , Doenças da Língua/etiologia , Adolescente , Feminino , Humanos , Pessoa de Meia-IdadeAssuntos
Atenção à Saúde , Fatores Imunológicos/uso terapêutico , Colaboração Intersetorial , Esclerose Múltipla/tratamento farmacológico , Sudeste Asiático , Congressos como Assunto , Acessibilidade aos Serviços de Saúde , Humanos , Internacionalidade , Esclerose Múltipla/epidemiologia , Defesa do PacienteRESUMO
INTRODUCTION: Gaucher's disease is a lysosomal storage disorder caused by the deficiency of glucocerebrosidase. Gaucher's disease has three clinical types: non-neuronopathic (Type 1), Acute Neuropathic (Type 2) and chronic neuronopathic (Type 3). The chronic neuronopathic (Type 3) is characterised by a variety of disease variants with onset in childhood with hepatomegaly, skeletal lesions and later slow horizontal saccades, treatment-resistant generalised tonic-clonic and myoclonic seizures, dementia, progressive spasticity, cognitive deterioration, ataxia and death in the second or third decade of life. CASE PRESENTATION: We describe a case of a 17-year-old girl who was born normally but subsequently developed treatment-refractory seizures at the age of nine with myoclonus, oculomotor apraxia, ataxia and cognitive decline. Enzyme activity of beta-glucocerebrosidase was found to be low without visceromegaly or bone involvement. CONCLUSION: Screening for lysosomal enzyme activity should be done in patients exhibiting features suggestive of progressive myoclonic epilepsy.
Assuntos
Apraxias/diagnóstico , Ataxia/diagnóstico , Transtornos Cognitivos/fisiopatologia , Doença de Gaucher/diagnóstico , Glucosilceramidase/metabolismo , Epilepsias Mioclônicas Progressivas/diagnóstico , Adolescente , Apraxias/fisiopatologia , Ataxia/fisiopatologia , Transtornos Cognitivos/enzimologia , Transtornos Cognitivos/etiologia , Progressão da Doença , Feminino , Neuroimagem Funcional , Doença de Gaucher/enzimologia , Doença de Gaucher/fisiopatologia , Humanos , Epilepsias Mioclônicas Progressivas/enzimologia , Epilepsias Mioclônicas Progressivas/fisiopatologiaRESUMO
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.
Assuntos
Acessibilidade aos Serviços de Saúde , Esclerose Múltipla , Neurologistas , Humanos , Sudeste Asiático , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Neurologistas/estatística & dados numéricos , Inquéritos e Questionários , Fatores Imunológicos/uso terapêutico , Agentes de Imunomodulação/uso terapêuticoRESUMO
BACKGROUND: Differentiating tumefactive demyelinating lesions (TDL) from neoplasms of the central nervous system continues to be a diagnostic dilemma in many cases. OBJECTIVE: Our study aimed to examine and contrast the clinical and radiological characteristics of TDL, high-grade gliomas (HGG) and primary CNS lymphoma (CNSL). METHOD: This was a retrospective review of 66 patients (23 TDL, 31 HGG and 12 CNSL). Clinical and laboratory data were obtained. MRI brain at presentation were analyzed by two independent, blinded neuroradiologists. RESULTS: Patients with TDLs were younger and predominantly female. Sensorimotor deficits and ataxia were more common amongst TDL whereas headaches and altered mental status were associated with HGG and CNSL. Compared to HGG and CNSL, MRI characteristics supporting TDL included relatively smaller size, lack of or mild mass effect, incomplete peripheral rim enhancement, absence of central enhancement or restricted diffusion, lack of cortical involvement, and presence of remote white matter lesions on the index scan. Paradoxically, some TDLs may present atypically or radiologically mimic CNS lymphomas. CONCLUSION: Careful evaluation of clinical and radiological features helps in differentiating TDLs at first presentation from CNS neoplasms.
Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Humanos , Feminino , Masculino , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
BACKGROUND AND OBJECTIVES: Recent data suggest increasing global prevalence of multiple sclerosis (MS). Early diagnosis of MS reduces the burden of disability-adjusted life years and associated health care costs. Yet diagnostic delays persist in MS care and even within national health care systems with robust resources, comprehensive registries, and MS subspecialist referral networks. The global prevalence and characteristics of barriers to expedited MS diagnosis, particularly in resource-restricted regions, have not been extensively studied. Recent revisions to MS diagnostic criteria demonstrate potential to facilitate earlier diagnosis, but global implementation remains largely unknown. METHODS: The Multiple Sclerosis International Federation third edition of the Atlas of MS was a survey that assessed the current global state of diagnosis including adoption of MS diagnostic criteria; barriers to diagnosis with respect to the patient, health care provider, and health system; and existence of national guidelines or national standards for speed of MS diagnosis. RESULTS: Coordinators from 107 countries (representing approximately 82% of the world population), participated. Eighty-three percent reported at least 1 "major barrier" to early MS diagnosis. The most frequently reported barriers included the following: "lack of awareness of MS symptoms among general public" (68%), "lack of awareness of MS symptoms among health care professionals" (59%), and "lack of availability of health care professionals with knowledge to diagnose MS" (44%). One-third reported lack of "specialist medical equipment or diagnostic tests." Thirty-four percent reported the use of only 2017 McDonald criteria (McD-C) for diagnosis, and 79% reported 2017 McD-C as the "most commonly used criteria." Sixty-six percent reported at least 1 barrier to the adoption of 2017 McD-C, including "neurologists lack awareness or training" by 45%. There was no significant association between national guidelines pertaining to MS diagnosis or practice standards addressing the speed of diagnosis and presence of barriers to early MS diagnosis and implementation of 2017 McD-C. DISCUSSION: This study finds pervasive consistent global barriers to early diagnosis of MS. While these barriers reflected a lack of resources in many countries, data also suggest that interventions designed to develop and implement accessible education and training can provide cost-effective opportunities to improve access to early MS diagnosis.