Uraemic brainstem encephalopathy mimicking ocular myasthenia: a case report.

BACKGROUND: Uraemia causes a generalised encephalopathy as its most common neurological complication. Isolated brainstem uraemic encephalopathy is rare. We report a case of fatigable ptosis and complex ophthalmoplegia in brainstem uraemic encephalopathy. CASE PRESENTATION: A 22-year-old Sri Lankan man with end stage renal failure presented with acute onset diplopia and drooping of eyelids progressively worsening over one week. The patient had not complied with the prescribed renal replacement therapy which was planned to be initiated 5 months previously. On examination, his Glasgow coma scale score was 15/15, He had a fatigable asymmetrical bilateral ptosis. The ice-pack test was negative. There was a complex ophthalmoplegia with bilateral abduction failure and elevation failure of the right eye. The diplopia did not worsen with prolonged stare. The rest of the neurological examination was normal. Serum creatinine on admission was 21.81 mg/dl. The repetitive nerve stimulation did not show a decremental pattern. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse midbrain and pontine oedema with T2 weighted/FLAIR hyperintensities. The patient was haemodialyzed on alternate days and his neurological deficits completely resolved by the end of the second week of dialysis. The follow up brain MRI done two weeks later demonstrated marked improvement of the brainstem oedema with residual T2 weighted/FLAIR hyperintensities in the midbrain. CONCLUSIONS: Uraemia may rarely cause an isolated brainstem encephalopathy mimicking ocular myasthenia, which resolves with correction of the uraemia.

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.

Adaptation and validation of the Longer-term Unmet Needs after Stroke (LUNS) monitoring tool in Sri Lanka.

BACKGROUND: Globally, stroke is a leading cause of mortality and morbidity. Unmet needs are defined as expressed needs that are not fulfilled by services provided and are considered an important indicator of the adequacy and quality of stroke follow-up care. This study aimed to culturally adapt, modify, translate and validate, the Longer-term Unmet Needs after Stroke (LUNS) monitoring tool, to Sri Lanka. Currently, there is no validated tool in Sri Lanka to assess unmet needs among stroke survivors and unmet needs are not systematically assessed. METHODS: A phased approach followed to culturally adapt, translate, establish its factorial validity and evaluate the convergent and divergent validity, reliability, and overall acceptability. The process of culturally adapting the tool was carried out using two rounds of the modified Delphi technique. The modified tool was translated to Sinhala and pretested among 10 stroke survivors. A descriptive cross-sectional study was conducted among 119 stroke survivors to establish the factorial validity and convergent and discriminant validity using the GHQ-12 and Barthel Index. The Socio-demographic characteristics of the study participants are presented. Communalities were assessed for 21 items and 2 items were dropped. Factor structure was confirmed with varimax and oblique rotations. The correlation coefficient was calculated to assess convergent and divergent validity. Cronbach's alpha value was calculated to assess internal reliability. RESULTS: Following the modified Delphi technique, 5 items of LUNS tool were removed, and 5 items were modified. Three new items were added based on expert recommendation. One item related to driving also removed as it does not fit with the factor structure emerged. In establishing factorial validity 5 factors emerged from the exploratory factor analysis. In assessing the convergent and discriminant validity, test results revealed that both General Health Questionnaire-12 (GHQ-12) and Barthel Index significantly correlated as expected with unmet needs. The results of Cronbach's alpha showed that all the factors were moderately high confirming the reliability of the tool. CONCLUSIONS: The Sinhala version of the LUNS monitoring tool is a valid and reliable instrument to assess the unmet needs of stroke survivors. Assessment of unmet needs will add new insight into evaluation of the quantity, quality, and effectiveness of healthcare interventions received by stroke survivors in Sri Lanka.

Characteristics, management and outcome of stroke: Observations from the Sri Lanka Stroke Clinical Registry.

BACKGROUND: Stroke registries are pivotal to the monitoring and improvement of the quality of stroke care. We report data from the initial phase of a nationally representative hospital-based stroke registry in Sri Lanka. METHODS: Based on an observational cohort design, all consecutive patients aged ≥18 years with a diagnosis of stroke or transient ischemic attack (TIA) presenting to six tertiary-care hospitals in the Western, Eastern, Southern, Northern and Central provinces of Sri Lanka within 14 days of onset were recruited. RESULTS: During a period of 14 months, 5893 patients with a stroke/TIA (58.8% men; mean age 65.22 years, SD=13.28) were entered into the database; 69.8% (n=4111) had an ischaemic stroke (IS); 20.9% (n=1233) had a haemorrhagic stroke (HS); 7.2% (424) had a TIA; and 2.1% (125) had a venous stroke. While IS were more common among women (71.7% vs 68.4%; p=0.006), HS were more common among men (22.3% vs 19.0%; p=0.003). Hemiparesis (86.2% vs 83.2%; p=0.011), headache (29% vs 11.6%; p<0.001), seizures (5.9% vs 4.2%; p=0.013), sphincter dysfunction (11.8% vs 7.7%; p<0.001) and hypertension (72% vs 67.3%, p=0.002) were more common in HS while dysphasia (63.2% vs 50.0%; p<0.001), ataxia (9.6% vs 7.3%; p=0.014), sensory disturbances (10.8% vs 6.0%; p<0.001) and diabetes mellitus (37.9% vs 28.1%; p<0.001) were more common in IS. Thrombolysis was administered in only 2.1% while only 14.6% had access to stroke units. The mean door-to-needle time was 100.2 (SD=46.0) minutes. The hospital mortality rate was 8.3%. Recurrent strokes within three months were more common in HS than IS (3.2% vs 1.6%; p=0.007). CONCLUSIONS: While stroke characteristics in Sri Lanka are similar to that of other populations, the rate of thrombolysis and access to stroke units are inadequate. The stroke registry provides useful data for the appraisal and improvement of stroke services.

Bath-related headache: a case report.

BACKGROUND: Bath-related headache (BRH) is a rare primary headache disorder with only about 50 cases reported from 2000 to 2017 and none since. It is an abrupt onset excruciating headache occurring predominantly in middle-aged Asian women, most commonly following exposure to hot water. This is the first report in a Sri Lankan woman. CASE PRESENTATION: A 60-year-old Sri Lankan woman presented with an abrupt onset, severe throbbing holocephalic headache immediately following a hot-water shower. The headache was not associated with photo- or phonophobia, nausea, or vomiting, and she did not report a past history of migraine. However, she had experienced a similar headache 2 years previously precipitated by a hot-water shower. Her neurological examination, blood investigations, and magnetic resonance imaging of brain and intracranial vessels were normal. She was treated with opioid and nonsteroidal antiinflammatory drug analgesics, but the headache resolved only after treatment with nimodipine. The headache did not recur during a follow-up of 2 years since she avoided hot-water showers. CONCLUSIONS: Bath-related headache is a thunderclap primary headache disorder with a benign prognosis, but its recognition requires awareness to differentiate it from subarachnoid hemorrhage. It warrants inclusion in the International Classification of Headache Disorders.

The first genetically authenticated case of Leber hereditary optic neuropathy in Sri Lanka: a case report and review of the literature.

INTRODUCTION: Leber hereditary optic neuropathy is a genetic disease of mitochondrial inheritance characterized by bilateral irreversible vision loss, predominantly affecting males. We report the first genetically authenticated Sri Lankan case of Leber hereditary optic neuropathy, illustrating its characteristic features of male predominance and variable penetrance. CASE PRESENTATION: A 15-year-old previously healthy Sri Lankan boy presented with painless progressive vision loss in his right eye, followed by vision loss in his left eye within 3 months. There was no history of drug or toxin exposure, or a family history of vision loss. His parents were nonconsanguineous. On examination, he could only perceive light. Funduscopy revealed bilateral optic atrophy. Routine hematological and biochemical blood tests, including inflammatory markers, were normal. Cranial magnetic resonance imaging was unremarkable. Optical coherence tomography, and the clinical presentation, suggested a diagnosis of Leber hereditary optic neuropathy, which was confirmed by detection of m.14484T > C pathogenic variant in the MT-ND6 gene through targeted genetic analysis for the three common pathogenic variants in mitochondrial deoxyribonucleic acid. He was homoplasmic for the variant, and his asymptomatic mother and two female siblings were also found to be harboring the variant with homoplasmy. CONCLUSIONS: This case report is intended to increase awareness of Leber hereditary optic neuropathy, and highlights the need to consider this rare diagnosis in the appropriate clinical context. It also illustrates the phenomena of incomplete penetrance and male predominance, and suggests the possibility of an X-linked gene governing Leber hereditary optic neuropathy disease expression, which warrants further investigation.

Significance of Neuronal Autoantibodies in Comparison to Infectious Etiologies among Patients Presenting with Encephalitis in a Region with a High Prevalence of Infections.

Background: Prevalence of antibody-mediated autoimmune encephalitis (AE) is reported to be comparable to infectious encephalitis in Western populations. We evaluated the frequency and significance of AE and neuronal autoantibodies in comparison to infectious etiologies among patients presenting with encephalitis in a South Asian population. Methods: Ninety-nine consecutive patients with a clinical diagnosis of encephalitis/meningoencephalitis admitted to two of the largest tertiary-care hospitals in Sri Lanka were studied. PCR and ELISA were used to screen viruses while Gram stain and culture were used to screen bacteria. Sera were tested for antibodies binding to primary embryonic rat hippocampal neuronal cultures and cell-based assays for antibodies to NMDAR, LGI1, CASPR2, Contactin2, AMPAR, GABAAR, GABABR, aquaporin-4 and MOG. Results: Patient ages ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male: female ratio of 1.75:1. A viral etiology was identified in 27.3% and bacterial meningoencephalitis was diagnosed in 17.1%. Sera of nine patients had antibodies binding to live primary neurons, but only five had specific antibodies to CASPR2 (n = 1), NMDAR (n = 2) or GABABR-antibodies (n = 2). Moreover, the patients with CASPR2 antibodies and NMDAR-antibodies were also positive for dengue antibodies. Only the two patients with NMDAR-antibodies had features and responses to immunotherapy consistent with AE. Conclusions: Identified infectious forms of meningoencephalitis (44.4%) greatly exceeded the occurrence of neuronal autoantibodies (9.1%) and AE (2%) in Sri Lanka, and this may be common in those regions where infections are prevalent.

Coverage and equity of essential care services among stroke survivors in the Western Province of Sri Lanka: a community-based cross-sectional study.

BACKGROUND: Stroke survivors require continuing services to limit disability. This study assessed the coverage and equity of essential care services received during the first six months of post-stroke follow-up of stroke survivors in the Western Province of Sri Lanka. METHODS: A multidisciplinary team defined the essential post-stoke follow-up care services and agreed on a system to categorize the coverage of services as adequate or inadequate among those who were identified as needing the said service. We recruited 502 survivors of first ever stroke of any type, from 11 specialist hospitals upon discharge. Six months following discharge, trained interviewers visited their homes and assessed the coverage of essential services using a structured questionnaire. RESULTS: Forty-nine essential post-stroke follow-up care services were identified and categorized into six domains: monitoring of risk conditions, treatment, services to limit disabilities, services to prevent complications, lifestyle modification and supportive services. Of the recruited 502 stroke survivors, 363 (72.3%) were traced at the end of 6 months. Coverage of antiplatelet therapy was the highest (97.2% (n = 289, 95% CI 95.3- 99.1)) while referral to mental health services (3.3%, n = 12, 95% CI 1.4-5.1) and training on employment for the previously employed (2.2%, n = 4, 95% CI- 0.08-4.32), were the lowest among the six domains of care. In the sample, 59.8% (95% CI 54.76-64.48) had received an 'adequate' level of essential care services related to treatment while none received an 'adequate' level of services in the category of support services. Disaggregated service coverage by presence and type of limb paralysis within the domain of services to prevent complications, and by sex and education level within the domain of education level, show statistically significant differences (p < 0.05). CONCLUSIONS: Apart from treatment services to limit disabilities, coverage of essential care services during the post-stroke period was inadequate. There were no apparent inequities in the coverage of vast majority of services. However focused policy decisions are required to address these gaps in services.

Short-term pain trajectories in patients with knee osteoarthritis.

AIM: It is unknown if pain in knee osteoarthritis (KOA) follows distinct patterns over the short term. Therefore, the aim of this study was to identify whether persons with a previous history of KOA pain fluctuations have distinct trajectories of pain over 90 days and to examine associations between baseline characteristics and pain trajectories. METHOD: People with a previous history of KOA were selected from a web-based longitudinal study. Baseline variables were sex, age, being obese/overweight, years of KOA, knee injury, knee buckling, satisfactory Lubben Social Support Score, pain and stress scales, Intermittent Constant Osteoarthritis Pain Score (ICOAP), medication use, and physical activity. Participants completed a Knee Injury and Osteoarthritis Outcomes Score (KOOS) pain subscale (KOOS-p, rated 0 = extreme to 100 = no knee problems) at 10-day intervals for 90 days. Short-term KOOS-p trajectories were identified using latent growth mixture modeling and the baseline risk factors for these pain trajectories were examined. RESULTS: Participants (n = 313) had a mean age of 62.2 (SD ± 8.1) years and and a body mass index of 29.8 (SD ± 6.6) kg/m2 . The three-class latent growth mixture modeling quadratic model with best fit indices was chosen (based on lowest sample-size-adjusted Bayesian Information Criterion, high probability of belonging, interpretability). Three distinct pain trajectory clusters (over 90 days) were identified: low-moderate pain at baseline with large improvement (n = 11), minimal change in pain over 90 days (n = 248), and moderate-high pain with worsening (n = 46). Higher ICOAP (intermittent scale), perceived stress, negative affect score, and knee buckling at baseline were associated with a worse knee pain trajectory (P < 0.05). CONCLUSIONS: Persons with KOA showed unique short-term pain trajectories over 90 days, with distinct characteristics at baseline associated with each trajectory.

Autoimmune epilepsy due to N-methyl-D-aspartate receptor antibodies in a child: a case report.

INTRODUCTION: Seizures of autoimmune etiology may occur independent of or predate syndromes of encephalitis. We report a child with "pure" autoimmune epilepsy followed up for 7 years to highlight long-term effects of this epilepsy and the importance of early initiation and appropriate escalation of immunosuppression to achieve a good long-term outcome. CASE PRESENTATION: A previously healthy 5-year-old Sri Lankan boy presented with acute, frequent, brief focal seizures of temporal-lobe semiology without clinical and investigatory findings suggestive of central nervous system infection, tumor, structural abnormality, or metabolic causes. His epilepsy showed poor response to increasing doses and combinations of antiseizure medications. Further investigations detected N-methyl-D-aspartate receptor antibodies in serum, but not cerebrospinal fluid. Treatment with intravenous methyl prednisolone and maintenance on mycophenolate resulted in a rapid reduction, with seizure freedom achieved within 5-6 weeks. He relapsed when immunotherapy and anti seizure medications were reduced after seizure freedom for 24 months. This, and subsequent relapses, showed poor response to modification of anti-seizure medications, but treatment with immunotherapy (methyl prednisolone and rituximab) achieved complete seizure freedom. At 7-years of follow-up, he remains free of seizure for over 3 years, and has average academic performance and satisfactory quality of life. CONCLUSIONS: Autoimmune epilepsy is a recognized independent entity. Diagnostic criteria have been suggested for its early recognition and confirmation of diagnosis. Early diagnosis and initiation of immunosuppression, with prompt escalation of treatment when necessary, remains key to good patient outcome.

Knowledge on prevention, diagnosis and treatment of snakebite envenoming among doctors in snakebite-dense regions in Sri Lanka.

BACKGROUND: Sri Lanka is one of the highest envenoming reporting countries globally with >80 000 snakebites per year. Among other factors, knowledge of snakebite among doctors predominantly determines patient outcomes. METHODS: Using a pretested 72-item self-administered questionnaire, we assessed knowledge on identifying common snake species, signs of envenoming and management of venomous snakebites among 280 doctors working in eight state hospitals in regions where snakebite prevalence is highest in Sri Lanka. RESULTS: Visually, 92.1% correctly identified a cobra and 74.3% identified a Russell's viper, but only 30% could identify a hump-nosed viper (HNV). Syndromic identification of snakes was best for the krait (71.8%) followed by the cobra (59.6%), but poor for the HNV (30%). The median knowledge scores of pictorial and syndromic snake identification, indoor preventive measures and indications of antivenom were <75% of the maximum score. Apart from 62.5% who expected the victim to bring the snake along to the hospital, most doctors selected the correct options of pre-hospital care. The duration of work experience did not influence the competency of syndromic identification. Utilisation of local guidelines was associated with better knowledge in antivenom usage (odds ratio 2.22 [95% confidence interval 1.04 to 5.36]; p=0.03). CONCLUSIONS: Specific deficiencies of core knowledge in snakebite management exist among doctors working in snakebite prevalent regions.

Delayed presentation of postinfectious encephalitis associated with SARS-CoV-2 infection: a case report.

Neurological manifestations of SARS-CoV-2 are increasingly being recognised and can arise as a result of direct viral invasion, para-infectious or postinfectious immune mechanisms. We report a delayed presentation of COVID-19 postinfectious immune-mediated encephalitis and status epilepticus occurring in a 47-year-old woman 4 weeks after SARS-CoV-2 pulmonary disease. SARS-CoV-2-specific IgG and IgM antibodies were detected in her cerebrospinal fluid with features of encephalitis evident in both magnetic resonance imaging of the brain and electroencephalogram. She made a complete recovery following treatment with high-dose intravenous corticosteroids and intravenous immunoglobulins. Diagnosis of COVID-19 postinfectious encephalitis may prove challenging in patients presenting many weeks following the initial infection. A high index of clinical suspicion and testing intrathecal SARS-CoV-2-specific antibodies are key to its diagnosis. Early immunotherapy is likely to result in a good outcome.

Knowledge and attitudes about end-of-life decisions, good death and principles of medical ethics among doctors in tertiary care hospitals in Sri Lanka: a cross-sectional study.

BACKGROUND: Competent end-of-life care is an essential component of total health care provision, but evidence suggests that it is often deficient. This study aimed to evaluate the knowledge and attitudes about key end-of-life issues and principles of good death among doctors in clinical settings. METHODS: A cross-sectional study was conducted among allopathic medical doctors working in in-ward clinical settings of tertiary care hospitals in Sri Lanka using a self-administered questionnaire with open- and close-ended questions as well as hypothetical clinical scenarios. Univariate and logistic regression analysis were used to identify the independent factors associated with knowledge and attitudes. RESULTS: Of the responders who had not been a caregiver for a terminally ill relative (n = 390), 57.9% were men with a mean age of 36.5 years (SD = 8.2). Compared to undergraduate (65.6%; n = 256), only 27.4% (n = 107) had received end-of-life care training at postgraduate level. Only 65.9% of doctors favoured disclosing terminal prognosis to patients; 27.7% of doctors were aware of advance directives; 14.6% were aware of the correct time of death when certifying brain death; 70.3% felt more comfortable in withholding than withdrawing life-sustaining treatment; 61.3% were aware of do-not-attempt cardiopulmonary resuscitation (DNACPR) decisions while 26.7% felt reluctant to administer it; 15.1% thought that all life-sustaining therapy should be withdrawn with a DNACPR decision; and only17.9% were able to name the four principles of medical ethics while 57.9% could not name a single. Participants scored a mean of 9.2 (SD = 3.9) of a maximum 14 points when tested on principles of a 'good death'. Doctors who had pursued postgraduate studies were more likely to be aware of breaking bad news (adjusted-Odds-Ratio:1.99; 95%CI = 1.19-3.32), advance directives (adjusted-OR: 4.15; 95%CI = 2.49-6.94), aware of certifying the correct time of death (adjusted-OR:2.37; 95%CI = 1.33-4.2) and less reluctant to make DNACPR decisions (adjusted-OR:1.74; 95%CI = 1.13-2.68). Doctors who had worked in ICU were more comfortable withholding than withdrawing treatment (adjusted-OR:1.99; 95%CI = 1.2-3.31). CONCLUSIONS: Knowledge and attitudes about end-of-life care, good death and principles of medical ethics among doctors in Sri Lanka were suboptimal. Structured training of end-of-life care needs to be integrated within curricula and in-service training.

Autoimmune encephalitis in a South Asian population.

BACKGROUND: Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. METHODS: Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. RESULTS: One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1-86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1-86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28-71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88-9.09) and deaths (OR = 2.38; 95% CI = 0.67-8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. CONCLUSIONS: NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

A rare mutation in the COLQ gene causing congenital myasthenic syndrome with remarkable improvement to fluoxetine: A case report.

Congenital myasthenic syndromes (CMS) are genetically determined heterogenous disorders of neuromuscular transmission. We report a rare mutation of COLQ causing CMS in an Asian man that remarkably improved with fluoxetine. A 51-year-old Sri Lankan man with slowly progressive fatigable muscle weakness since eight years of age, presented with type 2 respiratory failure that required mechanical ventilation in the acute crisis and subsequent home-based non-invasive ventilation. His birth and family histories were unremarkable. On examination, he had limb girdle type of muscle weakness with fatigability and normal tendon reflexes with no ocular or bulbar involvement. DNA sequencing revealed a pathogenic homozygous mutation in COLQ gene: ENST00000383788.10:exon16:c.1228C>T:p.R410W, the first report in an Asian. Treatment with fluoxetine resulted in remarkable improvement and regain of muscle power and independence from assisted ventilation.

Effective treatment of osmotic demyelination syndrome with plasmapheresis: a case report and review of the literature.

BACKGROUND: Treatment options for chronic osmotic demyelination syndrome are limited to case reports and only a very few show complete recovery. We report a case of complete recovery of chronic osmotic demyelination syndrome with plasmapheresis. CASE PRESENTATION: A 43-year-old Sri Lankan man presented with fever, repeated vomiting, unsteady gait, increased tonicity of his right upper limb and paucity of speech for three days. He was treated in the local hospital with antibiotics and antivirals as per central nervous system infection. He had hyponatraemia, which was rapidly corrected with hypertonic saline from 97 to 119 mmol/L. He was transferred to our hospital because of progressive reduction of consciousness, rapidly worsening rigidity and bradykinesia of all four limbs and worsening dysarthria and bradyphrenia. Magnetic resonance imaging of the brain was compatible with osmotic demyelination syndrome. He was commenced on plasmapheresis twenty-two days after rapid correction of sodium. He regained independent mobility with complete resolution of rigidity, bradykinesia and speech dysfunction after five cycles of alternate day plasmapheresis. CONCLUSION: Plasmapheresis can be considered as an effective treatment modality in chronic osmotic demyelination syndrome.

Is being barefoot, wearing shoes and physical activity associated with knee osteoarthritis pain flares? Data from a usually barefoot Sri Lankan cohort.

AIM: To identify the association between hours of being barefoot/wearing footwear, physical activity (PA) and knee osteoarthritis pain flares (KOAF). METHODS: Persons with a diagnosis of knee osteoarthritis, who reported previous KOAF, were followed up in a 3 months long telephone-based case-crossover study. Exposures to risk factors were assessed every 10 days and whenever the participants experienced a KOAF. Conditional logistic regression examined associations of KOAF with following: hours of being barefoot/using footwear and PA performed (P < .05). RESULTS: There were 260 persons recruited, of whom 183 continued longitudinal follow up. Of them, 120 persons had at least one valid KOAF and control period. Participants were female (90%) with mean (SD) age and body mass index of 59.9 (7.0) years, 28.0 (5.0) kg/m2 respectively. Participants were barefoot for a mean duration of 12.7 hours (SD 4.6) and used footwear for 5.1 (SD 4.7) hours daily; 99% wore heel heights <2.5 cm. Duration of being barefoot, 1 and 2 days before, demonstrated reduced multivariate odds of KOAF (odds ratio [OR] = 0.85; 95% CI 0.80-0.90). Moderate PA performed 1, 2 days prior was associated with a significantly increased risk of KOAF (multivariate OR 4.29; 2.52-7.30 and OR 3.36; 2.01-5.61). Similarly, hours of using footwear 1 and 2 days before flare demonstrated increased odds of KOAF (OR 1.15; 1.07-1.23 and 1.10; 1.03-1.18). CONCLUSIONS: Increased duration of being barefoot 1 to 2 days before is associated with reduced risk of KOAF. Performing moderate PA 1 to 2 days before was associated with an increased risk of KOAF.

Slow-Channel Congenital Myasthenic Syndrome due to a Novel Mutation in the Acetylcholine Receptor Alpha Subunit in a South Asian: A Case Report.

Congenital myasthenic syndromes (CMS) result from genetic mutations that cause aberrations in structure and/or function of proteins involved in neuromuscular transmission. The slow-channel CMS (SCCMS) is an autosomal dominant postsynaptic defect caused by mutations in genes encoding alpha, beta, delta, or epsilon subunits of the acetylcholine receptor resulting in a functional defect which is an increase of the opening time of the receptor. We report a case of SCCMS due to a heterozygous mutation in the M2 domain of the AChR alpha subunit - CHRNA1:ENST00000348749.6:exon7:c.806T>G:p.Val269Gly and corresponding kinetic defect. A substitution of valine with phenylalanine in the same position has been previously described. This is the first reported case of a new CHRNA1 variant in a patient with SCCMS from South Asia. We also highlight the phenotype that would favour a genetic basis over an autoimmune one, in an adult presenting with fatigable weakness.

Prevalence, vulnerability and epidemiological characteristics of snakebite in agricultural settings in rural Sri Lanka: A population-based study from South Asia.

BACKGROUND: The burden of snakebite remains poorly characterised because of the paucity of population-based data. Further, factors determining the vulnerability of individuals within rural communities to snakebite have been rarely investigated. We undertook a population-based study to determine the prevalence, vulnerability and epidemiological characteristics of snakebite in rural Sri Lanka. METHODS AND FINDINGS: A population-based cross-sectional study was conducted among 8707 current residents in the district of Ampara, representing typical rural Sri Lanka. The sample was recruited using multi-stage cluster sampling with probability proportionate-to-size. Snakebite victims were identified using the WHO criteria. Data were collected using a pre-tested interviewer-administered questionnaire. Each household had on average 3.8 persons; mean age 28.3 years (SD = 18.2); 51.3% males. The one-year point prevalence of snakebites was 17.6 per 1000 residents (95% CI: 15-20.6) and 6.12 per 100 households (95% CI: 5.25-7.13), while the lifetime prevalence was 9.4 per 100 residents (95% CI: 8.8-10.0) and 30.5 per 100 households (95% CI: 28.6-32.2) with a case fatality ratio of 0.033. Venomous snakebites accounted for 28.1%; snakes were unidentified among 30.1%. Compared to the non-snakebite victims, being single, males, of Sinhala ethnicity, aged >19 years, low education and socioeconomic status, engaging in farming or unskilled outdoor occupations denoted vulnerability to snakebites. Outdoor bites (77.8%) were more common among males; during daytime; mostly while walking; within the rural terrains and home gardens; on lower limbs; mostly by hump-nosed and Russell viper. Indoor bites were more common among females; during night-time; while sleeping and barefooted; on lower limbs; mostly by hump-nosed vipers, kraits and non-venomous snakes. CONCLUSIONS: The burden of snakebite is considerably high among rural populations. The concept of vulnerability can be useful in healthcare decision-making and resource allocation.

Anemia as a Predictor of Functional Disability in the Early Stage of Ischemic Stroke in a South Asian Population.

BACKGROUND: Reduced hemoglobin concentration has an adverse impact on the ischemic penumbra in patients with ischemic stroke as it causes reduced oxygen delivery to neuronal tissue and predisposes to infarct expansion. There is a paucity of data on the impact of anemia on early functional outcomes. AIMS: To determine the association of anemia on early functional outcomes in a cohort of patients with ischemic stroke. METHODS: This prospective study was conducted among 190 participants with acute ischemic stroke presenting to the National Hospital of Sri Lanka. Data were collected on socio-demographic determinants, clinical presentation, co-morbidities, subtype of stroke, and stroke severity (NIHSS score). Early functional outcomes were assessed by the Modified-Rankin-Score (mRS) and Barthel index (BI) within 48 h of the onset. Anemia was defined as Hb <13 g/dl in males and <12 g/dl in females. RESULTS: The mean age of the population was 62.4 years (SD = 11.8). Most participants (75.8%) were males. Anemia was noted in 56.4% of the total study population (59.0% males; 56.5% females) with a mean Hb of 11.7 g/dl. A total of 20% of patients had moderate to severe stroke severity as defined by an NIHSS of ≥16. Functional status assessment revealed that 67.9% had mRS <3 and 85.8% had BI <75. Furthermore, 85.8% had a composite MRS <3 and/or BI 75. Univariate analysis revealed that anemia was significantly associated with "moderate-severe" functional disability. On logistic regression analyses, this retained significance when the functional disability was assessed by mRS >3 (adjusted OR = 2.36; 95% CI = 1.1-5.1). Receiver operator characteristics (ROC) curves indicated a Hb% of 10.65 g/dl as the cut-off that would predict stroke-related disability assessed by mRS >3 [sensitivity = 86.7%; specificity = 34.2%; and AUC = 0.659 (P < 0.0001)]. CONCLUSIONS: Anemia is an independent determinant of poor functional disability in early acute ischemic stroke.