Acute Psychosis Presenting With Dengue Fever Complicated by Dengue Encephalitis.

Dengue is an infection with a wider spectrum of disease manifestations, ranging from simple dengue fever to expanded dengue syndrome. Expanded dengue syndrome encompasses multiorgan involvement, including neurological manifestations such as dengue encephalitis, seizures, encephalopathy, coma, hemiparesis, etc. Herein, we present a case of a 50-year-old female with a background history of well-controlled type 2 diabetes mellitus and hypertension for five years on oral medication. The patient presented with a one-day history of altered levels of consciousness, agitation, and aggressive behavior. Before admission, she had a history of high-grade fever with chills and rigors for three days. Serial investigations were performed, and the diagnosis of dengue encephalitis was made amidst the absence of positive findings for encephalitis in most of the imaging modalities except in electroencephalogram (EEG), making this case unique. Initially, it was presumed to be meningoencephalitis. Hence, the patient was initiated on intravenous acyclovir and cefotaxime. After the definitive diagnosis of dengue encephalitis, the given medication was stopped after seven days of administration, and with supportive management, the patient made a successful recovery within 10 days.

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.

Stroke systems of care in South-East Asia Region (SEAR): commonalities and diversities.

The Southeast Asia Region (SEAR) accounts for nearly 50% of the developing world's stroke burden. With various commonalities across its countries concerning health services, user awareness, and healthcare-seeking behavior, SEAR still presents profound diversities in stroke-related services across the continuum of care. This review highlights the numerous systems and challenges in access to stroke care, acute stroke care services, and health care systems, including rehabilitation. The paper has also attempted to compile information on the availability of stroke specialized centers, Intravenous thrombolysis (IVT) ready centers, Endovascular therapy (EVT) ready centers, rehabilitation centers, and workforce against a backdrop of each country's population. Lastly, the efforts of WHO (SEARO)-CMCL (World Health Organization-South East Asia region, Christian Medical College & Hospital Ludhiana) collaboration towards improving stroke services and capacity among the SEAR have been described.

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.

Validation of the Sinhala Version of the Addenbrooke's Cognitive Examination-Revised for the Detection of Dementia in Sri Lanka: Comparison with the Mini-Mental Status Examination and the Montreal Cognitive Assessment.

BACKGROUND: Sri Lanka is a rapidly aging country, where dementia prevalence will increase significantly in the future. Thus, inexpensive and sensitive cognitive screening tools are crucial. OBJECTIVES: To assess the reliability, validity, and diagnostic accuracy of the Sinhalese version of the Addenbrooke's Cognitive Examination-Revised (ACE-R s). METHOD: The ACE-R was translated into Sinhala with cultural and linguistic adaptations and administered, together with the Sinhala version of the Montreal Cognitive Assessment (MoCA), to 99 patients with dementia and 93 gender-matched controls. RESULTS: The ACE-R s cutoff score for dementia was 80 (sensitivity 91.9%, specificity 76.3%). The areas under the curve for the ACE-R s, Mini-Mental State Examination (MMSE) and MoCA were 0.90, 0.86, and 0.86, respectively. The -ACE-R s had good interrater reliability (intraclass correlation = 0.94), test-retest reliability (intraclass correlation = 0.99), and internal consistency (Cronbach's α = 0.8442). CONCLUSIONS: The ACE-R s is sensitive, specific and reliable to detect dementia in persons aged ≥50 years in a Sinhala-speaking population and its diagnostic accuracy is superior to previously validated tools (MMSE and MoCA).

Associations between Lifestyle Factors and Parkinson's Disease in an Urban Sri Lankan Clinic Study.

BACKGROUND: Associations between certain environmental and lifestyle factors and Parkinson's disease (PD) have been reported in several studies, but information on these factors and Parkinson's Disease (PD) in South Asia, is limited. OBJECTIVE: To determine associations between lifestyle factors and PD in an urban clinic-based study in Sri Lanka. METHODS: In this case-control study, demographic and lifestyle factor data (including diet, coffee/tea drinking, smoking, alcohol status) was collected from an unselected cohort of PD patients and age and gender-matched controls attending clinics in Greater Colombo, Sri Lanka. Associations between lifestyle factors and PD status were assessed using Logistic Regression analysis, while links with age of PD onset were explored with Kaplan Meier and Cox Regression survival analyses. Results with p<0.05 were considered to be statistically significant. FINDINGS: Of 229 patients with parkinsonism, 144 had Idiopathic PD using standard diagnostic criteria. Controls numbered 102. Coffee drinkers and smokers were significantly less likely to have PD (coffee, p<0.001; Odds Ratio (OR)=0.264; smoking, p=0.043; OR=0.394). Coffee drinkers were older at PD onset (p<0.001). Similar trends seen with tea drinking were not statistically significant. CONCLUSIONS: This is the first formal study of PD and these lifestyle factors in South Asia. It demonstrates an inverse association between coffee drinking, smoking and PD, and an association between coffee drinking and later age of PD onset. This is in line with other studies done worldwide, suggesting biological associations with global relevance.