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.

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.

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.

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.

Knowledge of Stroke, Its Warning Symptoms, Risk Factors and Treatment among the General Public and General Practitioners in a South Asian Population.

BACKGROUND: An adequate stroke literacy among the general public and first-contact physicians is an essential prerequisite to ensure timely treatment and prevention of stroke. Knowledge on stroke pathophysiology, warning symptoms, risk factors and treatment, and its determinants was assessed among general public and general practitioners (GPs) in a South Asian population. METHODS: A cross-sectional study was conducted among relatives of nonstroke patients admitted to the apex tertiary-care hospital in Sri Lanka. Trained doctors administered pretested, structured, open- and close-ended questionnaires. A postal survey using self-administered questionnaires was conducted among all registered GPs in Sri Lanka. RESULTS: The sample of general public (51.7% males; mean age = 40.7 years) from 21 of 25 districts of Sri Lanka was 840 (response-rate = 97.4%) while the sample of GPs (77.6% males; mean age = 59.63 years) was 98 (response-rate = 30%). Of the general public, 83.2% were aware of a vascular aetiology of stroke, but only 46.8% were aware that the affected organ was the brain while 67.5% believed that either the heart or limb muscles die as sequalae of stroke. Over 50% correctly identified stroke warning symptoms while 84.7% would seek immediate Western medical treatment. Approximately, 32%-46% were not aware of the major stroke risk factors. Lower education (adj. OR = 1.7; 95% CI = 1.3-2.3), absence of stroke risk factors (2.6; 1.9-3.7) and nonutility of information sources (1.5; 1.0-2.0) determined poor knowledge on risk factors. Only about 1 in 8 GPs accurately defined stroke and TIA while only 43.9% correctly classified stroke subtypes. Only 1 in 10 GPs were aware of the recommended therapeutic window for thrombolysis. Older age (P = 0.01) and longer service (P = 0.04) of GPs were associated with not requesting brain imaging in stroke. CONCLUSIONS: Strategies to educate both the public and first-contact physicians to improve stroke literacy need to be an integral part of programmes that aim to reduce the burden of stroke in any population.

Selected serum cytokines and nitric oxide as potential multi-marker biosignature panels for Parkinson disease of varying durations: a case-control study.

BACKGROUND: Dopaminergic neuronal loss begins years before motor symptoms appear in Parkinson disease (PD). Thus, reliable biomarkers for early diagnosis and prognosis of PD are an essential pre-requisite to develop disease modifying therapies. Inflammation-derived oxidative stress is postulated to contribute to nigrostriatal degeneration. We evaluated the role of selected serum immune mediators (IFNγ, TNFα, IL-10, and NOx) in PD progression and estimated their usefulness in preclinical diagnosis. METHODS: This case-control study recruited 72 PD patients with varying disease durations (< 1-year, n = 12 patients; 1-3 years, n = 30; > 3 years, n = 30) and 56 age- and gender-matched controls (26 with other neurological disorders as disease controls, and 30 healthy controls). Serum cytokine levels and NOx quantified using Sandwich Enzyme Linked Immunosorbent Assay kits, and the Griess test, respectively, were evaluated for diagnostic accuracy of optimal marker combinations by the CombiROC method. PD patients were clinically evaluated for motor and non-motor symptoms, and staged based on Hoehn and Yahr (H-Y) scale. RESULTS: A significant increase in serum IFNγ and IL-10 was observed in PD compared to healthy controls (p < 0.001). The Th1: Th2 (IFNγ: IL-10) cytokine ratio was higher in PD of 3-12 years compared with PD < 1 year (p < 0.001). Highest levels of NOx manifested during early PD (1-3 years) through a subsequent decline with disease duration. TNFα level was highest at PD onset. A low serum NOx level was associated with cognitive impairment (p = 0.002). The potential of using multi-biomarker panel, IFNγ, IL-10 and TNFα, for detection of PD onset was evident (sensitivity [SE] = 83.3%, specificity [SP] =80.4%, area under curve [AUC] = 0.868), while for early and late PD the multi-biomarker signature of IFNγ, IL-10 and NOx appeared to be more promising (SE = 93.3%, SP = 87.5%, AUC = 0.924). CONCLUSION: A Th1 cytokine-biased immune response predominates with PD progression. Both IFNγ and IL-10 are involved in disease severity. However, TNFα-mediated neurotoxicity appears to occur in early PD.

Cytomegalovirus induced refractory TTP in an immunocompetent individual: a case report.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal disease with multisystem involvement. Cytomegalovirus (CMV) infection as a cause of refractory TTP, has been reported only in immunocompromised individuals. We report a case of CMV-induced refractory TTP in an immunocompetent individual. CASE PRESENTATION: A 35-year-old, previously healthy Sri Lankan man, presented with fever for 3 days with gum bleeding and progressive drowsiness. His Glasgow coma scale score was 10/15. He did not have papilloedema or neck stiffness. Laboratory evaluation showed a severe thrombocytopenia with microangiopathic haemolytic anaemia. There was marginal renal impairment and normal coagulation profile. Non-contrast CT scan of brain was normal. A diagnosis of thrombotic thrombocytopenic purpura was made. Despite daily plasma exchanges and high-dose steroids, he failed to achieve the expected therapeutic response, thus demonstrating refractory TTP. On exploring for possible causes of refractoriness to treatment, a clinically significant PCR titre of CMV was detected. Treatment of CMV infection lead to complete recovery of TTP. His disease course was further complicated with spontaneous spinal haemorrhage leading to neurological sequelae. DISCUSSION AND CONCLUSIONS: This is the first report of CMV induced refractory TTP in an immunocompetent adult. It is also the first report of clinically significant spontaneous spinal haematoma in TTP. These two rare occurrences should be considered when patients with refractory TTP do not improve as expected.

Viral aetiologies of acute encephalitis in a hospital-based South Asian population.

BACKGROUND: The aetiological spectrum of acute encephalitis shows inter- and intra-geographical variations. We aimed to identify the viruses that cause infectious encephalitis in Sri Lanka, which represents a South Asian population. METHODS: A cross-sectional study was conducted among 99 patients with encephalitis/meningoencephalitis admitted to two tertiary-care hospitals in Colombo. Cerebrospinal fluid and serum were tested for conventional and emerging encephalitogenic viruses. Specific nucleic acid amplification and antibody assays were used to identify viruses. Plaque reduction neutralization test was done to confirm the diagnosis of West Nile virus (WNV). RESULTS: Patients' age ranged from 1 month to 73 years (mean = 24.91; SD = 21.33) with a male:female ratio of 1.75:1. A viral aetiology was identified in only 27.3%. These included dengue virus (40.7%), Japanese encephalitis virus (25.9%), varicella zoster virus, WNV and probable Epstein Barr virus (11.1% each). None were positive for herpes simplex viruses or cytomegalovirus. Screening for bacterial aetiologies was negative for all patients. There were no distinguishable clinical or laboratory findings between the different viral aetiologies. The case fatality rate was 7%, which was higher among patients with an identified viral aetiology. CONCLUSIONS: A viral aetiology was identified in only about a quarter of patients with encephalitis. Dengue virus accounted for the majority.

Plasmodium falciparum and Mycoplasma pneumoniae co-infection presenting with cerebral malaria manifesting orofacial dyskinesia and haemophagocytic lymphohistiocytosis.

BACKGROUND: Malaria is a mosquito-borne infectious disease with diverse clinical manifestations caused by a parasitic protozoan of the genus Plasmodium. Complex inter-relationships between Mycoplasma species and Plasmodium parasites have been previously noted in vitro. This is the first report of Plasmodium falciparum and Mycoplasma pneumoniae co-infection in a human host presenting with cerebral malaria manifesting orofacial dyskinesias and haemophagocytic lymphohistiocytosis. CASE PRESENTATION: A 55-year-old Sri Lankan man with a recent visit to South Africa presented with an acute febrile illness, cough and worsening dyspnoea with alveolar-interstitial infiltrates on chest radiography. Serological evaluation confirmed a diagnosis of Mycoplasma infection. He subsequently developed encephalopathy with orofacial dyskinesia. A diagnosis of severe P. falciparum infection with significant parasitaemia was established. Peripheral blood cytopaenia occurred due to haemophagocytic lymphohistiocytosis in the bone marrow. Complete clinical and haematological recovery was achieved with intravenous artesunate. CONCLUSIONS: Plasmodium falciparum and Mycoplasma pneumoniae co-infection occurring in vivo manifests clinical features that are plausibly a result of the interaction between the two microorganisms. This is the first report of orofacial dyskinesia in either infection.

A rare c.183_187dupCTCAC mutation of the acetylcholine receptor CHRNE gene in a South Asian female with congenital myasthenic syndrome: a case report.

BACKGROUND: Congenital myasthenic syndromes (CMSs) occur as a result of genetic mutations that cause aberrations in structure and/or function of proteins involved in neuromuscular transmission. Acetylcholine receptor epsilon (ε) subunit (CHRNE) gene mutations account for about 30-50 % of genetically diagnosed cases. We report a rare CHRNE gene mutation in a South Asian female with CMS. CASE PRESENTATION: A 17-year-old Maldivian female presented with bilateral partial ptosis, fatigable proximal muscle weakness and slurring of speech noted since the age of 2 years. She could not run, had difficulty negotiating stairs and rising from a seated position, and fatigues when speaking at length. Her birth and past medical histories were otherwise unremarkable. There is no parental consanguinity or family history of muscle disorders. On examination, she had a BMI of 18 kg/m2, bilateral fatigable partial ptosis, complete external ophthalmoplegia and fatigable proximal muscle weakness (MRC grade 4/5). Apart from spinal scoliosis the rest of the examination was normal. Haematological and biochemical investigations including serum lactate level and thyroid functions were normal. Acetylcholine receptor antibodies and muscle specific kinase antibodies were not detected in serum. Repetitive nerve stimulation showed marked decrement (>30 %) in nerve-muscle pairs in the face and forearm. Her DNA sequencing revealed a c.183-187dupCTCAC mutation in CHRNE. She remained functionally independent on pyridostigmine treatment. CONCLUSIONS: This case describes a rare mutation of the CHRNE gene in CMS and highlights the relevance of genetic diagnosis in CMS. It further adds to map the occurrence of such mutations in Asian populations.

Prevalence of Stroke and Its Risk Factors in Urban Sri Lanka: Population-Based Study.

BACKGROUND AND PURPOSE: Stroke is a leading cause of disability and death worldwide. In the absence of published population-based prevalence data, we investigated the prevalence and risk factors of stroke in a population of varying urbanization in Sri Lanka. METHODS: A population-based, cross-sectional study was conducted among 2313 adults aged ≥18 years residing in Colombo, selected using a multistage, probability proportionate-to-size, cluster sampling technique. Data were collected using an interviewer-administered questionnaire. Ever diagnosis of stroke was confirmed by medical doctors based on World Health Organization criteria and corroborated by documental evidence. RESULTS: Of the total population (52.4% women; mean age, 44.2 years; SD, 16.6), the prevalence of stroke was 10.4 per 1000 (95% confidence interval, 6.3-14.5) with a 2:1 male:female ratio. Beyond the age of 65 years, the prevalence was higher by 6-fold among men and by 2-fold among women. Ninety two percent had developed hemiparesis, 58.3% had dysphasia, and 16.7% had loss of balance. Hypertension was the commonest risk factor (62.5%) followed by smoking (45.8%), excess alcohol (41.7%), diabetes mellitus (33.3%), and transient ischemic attack (29.2%); 79.2%, predominantly men, had ≥2 risk factors. A percentage of 58.3 had brain computed tomographic scans, of whom 85.7% had ischemic strokes. A percentage of 64.3 had to change or give up working because of stroke-related disability. CONCLUSIONS: Age-adjusted stroke prevalence in urban Sri Lanka lies between high-income and low-/middle-income countries. The prevalence of stroke and its risk factors were higher among men.

Emergence of human West Nile Virus infection in Sri Lanka.

BACKGROUND: West Nile virus (WNV) has emerged as one of the most common causes of epidemic meningoencephalitis worldwide. Most human infections are asymptomatic. However, neuroinvasive disease characterized by meningitis, encephalitis and/or acute flaccid paralysis is associated with significant morbidity and mortality. Although outbreaks have been reported in Asia, human WNV infection has not been previously reported in Sri Lanka. METHODS: Sera and cerebrospinal fluid (CSF) from 108 consecutive patients with a clinical diagnosis of encephalitis admitted to two tertiary care hospitals in Colombo, Sri Lanka were screened for WNV IgM antibody using enzyme-linked immunosorbent assay. Positive results were confirmed using plaque reduction neutralization test (PRNT). Patient data were obtained from medical records and by interviewing patients and care-givers. RESULTS: Three of the 108 patients had WNV IgM antibody in serum and one had antibody in the CSF. The presence of WNV neutralizing antibodies was confirmed in two of the three patients using PRNT. Two patients had presented with the clinical syndrome of meningoencephalitis while one had presented with encephalitis. One patient had CSF lymphocytic pleocytosis, one had neutrophilic pleocytosis while CSF cell counts were normal in one. CSF protein showed marginal increase in two patients. CONCLUSIONS: This is the first report of human WNV infection identified in patients presenting with encephalitis or meningoencephalitis in Sri Lanka. There were no clinical, routine laboratory or radiological features that were distinguishable from other infectious causes of meningoencephalitis.

Selected serum cytokines and vitamin D levels as potential prognostic markers of acute ischemic stroke.

Inflammation-derived oxidative stress is postulated to contribute to neuronal damage leading to poor clinical outcomes in Acute Ischemic Stroke (AIS). We aimed to investigate the association between serum levels of selected cytokines (IL-1ß, IFN-γ, IL-4), and vitamin D in ischemic stroke progression, and their accuracy in predicting AIS prognosis, among Sri Lankans. We compared 60 AIS patients admitted in 4 phases post-stroke onset (<6 h; 6-24 h; 24-48 h; 48-96 h; n = 15/phase), with 15 age- and sex-matched controls. The 30-day functional outcome (FO) was assessed using the modified Rankin Scale (mRS). Serum cytokine and vitamin D levels were quantified using sandwich ELISAs, and competitive ELISA, respectively. The CombiROC web tool established optimal prognostic biomarker combinations. Serum IL-1ß and IFN-γ were elevated in all four phases following stroke onset while IL-4 was elevated exclusively in the recovery phase (48-96 h) (p<0.05). Th1 bias polarization of the Th1:Th2 cytokine (IFN-γ:IL-4) ratio occurred with AIS progression while a Th2 bias occurred during AIS recovery (p<0.05). Lower serum IL-1ß and higher IL-4 levels were associated with a good FO (p<0.05), while lower Vitamin D levels were related to a poor FO (p = 0.001). The triple-biomarker panel, IL-4- IFN-γ -Vit D, accurately predicted AIS prognosis (sensitivity = 100%, specificity = 91.9%, area under the curve = 0.98). Serum immunologic mediators IFN-γ, IL-4, and vitamin D may be useful biomarkers of AIS prognosis and may serve as therapeutic targets in improving stroke outcomes. Vitamin D supplementation may improve the prognosis of AIS patients. Furthermore, binary logistic model fitted for FO indicated Th1:Th2 cytokine ratio (IFN-γ:IL-4), vitamin D status, history of stroke, and ischemic heart disease as significant predictors of AIS prognosis.

Serum IL-10 as a marker of severe dengue infection.

BACKGROUND: Several studies have shown that serum IL-10, IFNγ and MIF are elevated in patients in severe dengue (SD) and could be used as potential biomarkers. We proceeded to determine if these cytokines could be used as biomarkers in a large cohort of adult dengue patients with varying severity of dengue infection. METHODS: Serum IL-10 levels were determined in 259 of whom 40 had severe dengue infection. Serum IFNγ and IFNα levels were done in 78 and MIF levels were done in 65 patients with acute dengue infection. Clinical features and laboratory investigations were undertaken during the febrile and critical phase. RESULTS: We found that serum IL-10 levels were significantly higher (p = 0.001) in patients with SD, when compared to those with non SD. Serum IL-10 levels significantly and inversely correlated with white cell counts (R = -0.23, p = 0.0002) and lymphocyte counts (R = -0.29, p < 0.0001) but significantly and positively correlated with aspartate tranaminase levels (R = 0.16, p = 0.01) and alanine transaminase levels (R = 0.22, p = 0.007). However, IL-10 levels did not have a good predictive value in discriminating those who were likely to develop SD (AUC = 0.66). Serum IFNγ levels were also significantly higher (p = 0.04) in patients with SD when compared to non SD. There was no difference (p = 0.34) in serum IFNα levels and serum MIF levels (p = 0.15) in patients with SD and non SD. CONCLUSION: Although serum IL-10 was significantly elevated in patients with SD it had a poor discriminatory value in identifying those with SD and non SD and therefore, is unsuitable to be used as a robust biomarker in this cohort.

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.