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.

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".

Ischemic Stroke Subtypes: Socio-demographic Factors, Risk Factors, and Outcomes in Southern Sri Lanka.

BACKGROUND: Stroke is a heterogeneous, catastrophic disease. A comprehensive clinical analysis of ischemic stroke (IS) risk factors and outcomes is crucial for optimum management in resource-poor settings. METHODS: A prospective cross-sectional study of acute cerebrovascular disease (ACVD) involving 592 patients was conducted in a tertiary care center in Sri Lanka from November 2018 to May 2019. We aimed to describe the ACVD subtypes and the relationship of IS subtypes and subtype-categories (as defined by the Oxfordshire Community Stroke Project clinical classification) with risk factors, severity, and outcome. RESULTS: The majority (63.3%) had IS. Partial anterior circulation syndromes (PACS), total anterior circulation syndrome (TACS), posterior circulation syndromes (POCS), and lacunar syndromes (LACS) accounted for 102 (29.7%), 58 (16.9%), 88 (25.7%) and 95 (27.7%) of the cases, respectively. The most common PACS sub-category was higher-cerebral-dysfunction-with-homonymous-hemianopia (HCD+HH,39 cases;38.2%). Cerebellar-signs-without-long-tract-signs (CS-LTS) sub-category constituted the highest among POCS (47 cases; 53.4%). The leading sub-category within LACS was pure-motor (PM) strokes (43 cases; 45.3%).Patients aged ≥50 years (adjusted-OR [AOR]2.439; 95%CI,1.163-5.116;P=.018), IHD(AOR 2.520; 95%CI,1.347-4.713; P=.004) and BMI>23kg/m2(AOR 2.607; 95% CI,1.420-4.784; P=.002) were 2.5 times more likely to associate with TACS. Patients with a history of TIA (AOR 1.910; 95%CI,1.036-3.524; P=.038) and arrhythmias (AOR 5.933; 95%CI,3.294-10.684; P<.001) were 1.9 and 5.9 times more likely to be associated with POCS respectively. Those with hypertension were 2.3 times more likely to associate with LACS (AOR 2.233; 95%CI,1.270-3.926; P=.005).NIHSS(P<.001), mRS on admission (P=.001) and in 3 months (P<.001), deaths during hospital stay (P=.003) and within 28 days (P<.001) had a stronger relationship with individual stroke subtypes. CONCLUSION: The comparative risk of different IS subtypes depends on different risk factors. The findings of this study demonstrate that sub-categories within each stroke subtype may behave independently with regard to risk factors and outcomes, thus warranting the need for individual assessment.

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.

Chorioretinitis: a potential clue to the early diagnosis of subacute sclerosing panencephalitis.

We describe a 36-year-old man with subacute sclerosing panencephalitis (SSPE) presenting with chorioretinitis two years before onset of other neurological features. He had neither myoclonus nor the typical EEG features of SSPE. The diagnosis was confirmed in the appropriate clinical setting by detecting elevated measles antibody titres in cerebrospinal fluid and serum. Clinicians should consider SSPE among the differential diagnoses in chorioretinitis. This is particularly so if there is macular or perimacular involvement with concurrent involvement of the optic nerve in young patients, even without other characteristic neurological symptoms.