Neurological disorders associated with COVID-19 in Sri Lanka.

BACKGROUND: Neurological manifestations of SARS-CoV-2 infection have been reported from many countries around the world, including the South Asian region. This surveillance study aimed to describe the spectrum of neurological disorders associated with COVID-19 in Sri Lanka. METHODS: COVID-19 patients manifesting neurological disorders one week prior and up to six weeks after infection were recruited from all the neurology centres of the government hospitals in Sri Lanka from May 2021 - May 2022. Data was collected using a structured data form that was electronically transmitted to a central repository. All patients were evaluated and managed by a neurologist. Data were analysed using simple descriptive analysis to characterise demographic and disease related variables, and simple comparisons and logistic regression were performed to analyse outcomes and their associations. RESULTS: One hundred and eighty-four patients with neurological manifestations associated with COVID-19 were recruited from all nine provinces in Sri Lanka. Ischaemic stroke (31%) was the commonest neurological manifestation followed by encephalopathy (13.6%), Guillain-Barre syndrome (GBS) (9.2%) and encephalitis (7.6%). Ischaemic stroke, encephalitis and encephalopathy presented within 6 days of onset of COVID-19 symptoms, whereas GBS and myelitis presented up to 10 days post onset while epilepsy and Bell palsy presented up to 20 - 40 days post onset. Haemorrhagic stroke presented either just prior to or at onset, or 10 - 25 days post onset of COVID-19 symptomatic infection. An increased frequency of children presenting with encephalitis and encephalopathy was observed during the Omicron variant predominant period. A poor outcome (no recovery or death) was associated with supplemental oxygen requirement during admission (Odds Ratio: 12.94; p = 0.046). CONCLUSIONS: The spectrum and frequencies of COVID-19 associated neurological disorders in Sri Lanka were similar to that reported from other countries, with strokes and encephalopathy being the commonest. Requiring supplemental oxygen during hospitalisation was associated with a poor outcome.

Diagnostic outcome of pro bono neurogenetic diagnostic service in Sri Lanka: A wealth creation.

The inherited disease community in Sri Lanka has been widely neglected. This article aimed to present accumulated knowledge in establishing a pro bono cost-effective national, island-wide, free-of-charge molecular diagnostic service, suggesting a model for other developing countries. The project provided 637 molecular diagnostic tests and reports free of charge to a nation with limited resources. We pioneered the implementation of mobile clinics and home visits, where the research team acted as barefoot doctors with the concept of the doctor and the researcher at the patient's doorstep. Establishing pro bono, cost-effective molecular diagnostics is feasible in developing countries with limited resources and state funding through the effort of dedicated postgraduate students. This service could provide an accurate molecular diagnosis of Duchenne muscular dystrophy, Huntington's disease, Spinocerebellar ataxia, and Spinal muscular atrophy, a diagnostic yield of 54% (343/637), of which 43% (147/343) of the patients identified as amenable for available gene therapies. Initiated human resource development by double doctoral degree opportunities with international collaborations. Established a neurobiobank and a national registry in Sri Lanka, a rich and unique repository, wealth creation for translational collaborative research and sharing of information in neurological diseases, as well as a lodestar for aspiring initiatives from other developing countries.

Levodopa Equivalent Daily Dosage: Geographical Variations and Real-Life Modules in Parkinson's Disease.

BACKGROUND: The Levodopa Equivalent Daily Dosage (LEDD) calculation algorithms help in capturing and harmonization of Parkinson's Disease (PD) therapies. Analyzing these updates is essential for validating their effectiveness. OBJECTIVE: To assess updated LEDD conversion factors in capturing the newer therapies in PD and therapy modules in different geographical cohorts. METHODS: Data were sourced from 10 Centers from 6 countries representing 2 different continents. The study compared the LEDD conversion factors proposed by Tomlinson et al and Jost et al, alongside investigating demographic disparities. RESULTS: The analysis involved 2943 subjects; 87% (n = 2577) met the UK Brain Bank criteria for PD. The LEDD differed significantly across methodologies (Tomlinson vs. Jost, 598 mg vs 610 mg, P < 0.0001). Geographical disparities highlighted variations in PD onset age (P < 0.0001). Jost and Tomlinson's calculations demonstrated consistency within but significant differences across countries (P < 0.0001).Age at onset revealed statistically significant differences in LEDD requirements (P < 0.0001), which were particularly higher in 21-50 years (718 mg vs 566 mg). This subgroup also demonstrated increased usage of non-Levodopa therapies (P < 0.0001). Men exhibited higher total LEDD (P = 0.001). 34% reported dyskinesia, associated with higher LEDD (756 mg, P < 0.0001). Surgically treated patients also had higher LEDD (P < 0.0001) and a significant difference between Jost and Tomlinson dosages (761 mg vs716mg) reflecting the incorporation of newer therapeutic molecules. CONCLUSION: This analysis delineates the importance of updated LEDD algorithms and intricacies in the landscape of PD treatment, underscored by geographical, age-related, and gender-specific variations, in real-life management scenarios.

Gene therapy for selected neuromuscular and trinucleotide repeat disorders - An insight to subsume South Asia for multicenter clinical trials.

Background: In this article, the authors discuss how they utilized the genetic mutation data in Sri Lankan Duchenne muscular dystrophy (DMD), Spinal muscular atrophy (SMA), Spinocerebellar ataxia (SCA) and Huntington's disease (HD) patients and compare the available literature from South Asian countries to identifying potential candidates for available gene therapy for DMD, SMA, SCA and HD patients. Methods: Rare disease patients (n = 623) with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy were genetically confirmed using Multiplex Ligation Dependent Probe Amplification (MLPA), and single plex PCR. A survey was conducted in the "Wiley database on Gene Therapy Trials Worldwide" to identify DMD, SMA, SCA, and HD gene therapy clinical trials performed worldwide up to April 2021. In order to identify candidates for gene therapy in other neighboring countries we compared our findings with available literature from India and Pakistan which has utilized the same molecular diagnostic protocol to our study. Results: From the overall cohort of 623 rare disease patients with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy, n = 343 (55%) [Muscular Dystrophy- 65%; (DMD-139, Becker Muscular Dystrophy -BMD-11), SCA type 1-3-53% (SCA1-61,SCA2- 23, SCA3- 39), HD- 52% (45) and SMA- 34% (22)] patients were positive for molecular diagnostics by MLPA and single plex PCR. A total of 147 patients in Sri Lanka amenable to available gene therapy; [DMD-83, SMA-15 and HD-49] were identified. A comparison of Sri Lankan finding with available literature from India and Pakistan identified a total of 1257 patients [DMD-1076, SMA- 57, and HD-124] from these three South Asian Countries as amenable for existing gene therapy trials. DMD, SMA, and HD gene therapy clinical trials (113 studies) performed worldwide up to April 2021 were concentrated mostly (99%) in High Income Countries (HIC) and Upper Middle-Income Countries (UMIC). However, studies on the potential use of anti-sense oligonucleotides (ASO) for treatment of SCAs have yet to reach clinical trials. Conclusion: Most genetic therapies for neurodegenerative and neuromuscular disorders have been evaluated for efficacy primarily in Western populations. No multicenter gene therapy clinical trial sites for DMD, SMA and HD in the South Asian region, leading to lack of knowledge on the safety and efficacy of such personalized therapies in other populations, including South Asians. By fostering collaboration between researchers, clinicians, patient advocacy groups, government and industry in gene therapy initiatives for the inherited-diseases community in the developing world would link the Global North and Global South and breathe life into the motto "Together we can make a difference".

What We Fail to See in Neuro-Genetic Diseases: A Bird's Eye View from the Developing World.

BACKGROUND: Progressive neurological genetic diseases are not rare. They cause psychosocial damages to its victims. This article focuses on common psychosocial issues faced by those from the developing world. METHODS: A multicentre observational survey of 246 patients from teaching hospitals in Sri Lanka. Participants were clinically and genetically confirmed by neurologists and the Interdisciplinary Centre for Innovation in Biotechnology and Neuroscience (ICIBN) respectively from 2014 to 2018. Convenience sample with random geographical distribution. Factors were equally weighted. ANOVA, Student's t-test and chi-square analysis were used. Statistical Software R Statistics-version 3.5 and one-sample t-test with CI = 95% was used. This study meets the ethical guidelines of the local institutional review boards which are in compliance with the Helsinki Declaration. RESULTS: Sample included 184 males and 62 females of 3-76 years with either Duchenne muscular dystrophy (n=121), spinocerebellar ataxia (n = 87) or Huntington disease (n = 38). Mean income of the affected is lower than the standard average monthly income (P ≤ .001). Consultation visits depend on the monthly income (CI 20421.074-34709.361; P ≤ .001). CONCLUSION: Poverty is inversely proportionate to the patients' living conditions. As developing countries are financially challenged, it is a societal challenge to rebuild our values to enhance their living status.