BackgroundSeveral 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.MethodsSerum 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.ResultsWe 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.ConclusionAlthough 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.

BackgroundThe WHO guidelines were revised recently to identify patients with severe dengue (SD) early. We proceeded to determine the usefulness of the warning signs in the new WHO guidelines in predicting SD and we have also attempted to define other simple laboratory parameters that could be useful in predicting SD.MethodsClinical and laboratory parameters were recorded in 184 patients in 2011, with confirmed dengue viral infections, admitted to a medical ward in two tertiary care hospitals in Colombo, Sri Lanka.ResultsWe found that the presence of 5 or more dengue warning signs were significantly (p = 0.02) associated with the development of SD (odds ratio 5.14, 95% CI = 1.312 to 20.16). The AST levels were significantly higher (p = 0.0001) in patients with abdominal pain (mean 243.5, SD ± 200.7), when compared to those who did not have abdominal pain (mean 148.5, SD ± 218.6). Lymphocyte counts <1,500 cells/mm3 were significantly (p = 0.005) associated with SD (odds ratio 3.367, 95% CI 1.396 to 8.123). High AST levels were also significantly associated (p < 0.0001) with SD (odds ratio 27.26, 95% CI 1.632 to 455.2). Platelet counts <20,000cells/mm3, were again significantly associated (p < 0.001) with severe disease (odds ratio 1.632 to 455.2, 95% CI 3.089 to 14.71). The PCR was positive in 26/84 of the patients and we found that the infecting serotype was DEN-1 in all 26 patients.ConclusionsThe presence of 5 or more warning signs appears to be a predictor of SD. Lymphocyte counts <1,500 cells/mm3, platelet counts <20,000/mm3 and raised AST levels were associated with SD and could be used to help identify patients who are likely to develop SD.

Importance High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of γ-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker. Objective To investigate the characteristics and potential pathogenicity of GAD autoantibodies in patients with SPS and related disorders. Design Retrospective cohort study and laboratory investigation. Setting Weatherall Institute of Molecular Medicine, University of Oxford. Participants Twenty-five patients with SPS and related conditions identified from the Neuroimmunology Service. Exposures Neurological examination, serological characterization and experimental studies. Main Outcomes and Measures Characterization of serum GAD antibodies from patients with SPS and evidence for potential pathogenicity. Results We detected GAD autoantibodies at a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12 patients with classic SPS. The GAD autoantibodies were high affinity (antibody dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The patients’ autoantibodies co-localized with GAD on immunohistochemistry and in permeabilized cultured cerebellar GABAergic neurons, as expected, but they also bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the highest titer (700 000 U/mL) serum with recombinant GAD indicated that these neuronal surface antibodies were not directed against GAD itself. Although intraperitoneal injection of IgG purified from the 2 available GAD autoantibody–positive purified IgG preparations did not produce clinical or pathological evidence of disease, SPS and control IgG were detected in specific regions of the mouse central nervous system, particularly around the lateral and fourth ventricles. Conclusions and Relevance Autoantibodies to GAD are associated with antibodies that bind to the surface of GABAergic neurons and that could be pathogenic. Moreover, in mice, human IgG from the periphery gained access to relevant areas in the hippocampus and brainstem. Identification of the target of the non-GAD antibodies and peripheral and intrathecal transfer protocols, combined with adsorption studies, should be used to demonstrate the role of the non-GAD IgG in SPS.

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.

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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. Electronic supplementary material The online version of this article (10.1186/s12883-019-1286-6) contains supplementary material, which is available to authorized users.

BackgroundSnakebite is an important public health problem in tropical regions of the world. Although devastating effects of envenoming such as kidney failure, tissue necrosis, bleeding diathesis, and neurotoxicity are well known in the acute stage following a snakebite, the long-term effects of snake envenoming have not been adequately studied.Materials and methodsA population-based study was conducted among 8707 residents in a rural district in Sri Lanka to assess the long-term sequelae following snakebite. Health-related complaints that snakebite victims had developed immediately or within 4 weeks of the bite and persisted for more than 3 months, were assessed by interviewer-administered questionnaire and in-depth interviews, and further evaluated by physical examination and relevant investigations.ResultsOf the 816 participants who were identified as ever snakebite victims, 112 (13.7%) presented with at least one snakebite-related long-term health complication. Among them, “migraine-like-syndrome” characterized by headache vertigo, and photosensitivity to sunlight was found in 46 (5.6%); musculoskeletal disorders such as pain, local swelling, muscle weakness, deformities, contractures, and amputations were found in 26 (3.2%); visual impairment in 21 (2.6%); acute kidney injury in 4 (0.5%); skin blisters at the bite site in 5 (0.6%); psychological distress in 2 (0.2%); hemiplegia in 1 (0.1%); right-side facial nerve palsy in 1 (0.1%); paresthesia over bite site in 1 (0.1%); generalized shivering in 1 (0.1%); and chronic nonhealing ulcer in 1 (0.1%). Interestingly, 31 (3.8%) reported nonspecific somatic symptoms such as abdominal colic, chest tightness, wheezing, receding gums, excessive hair loss, and lassitude with body aches following the bite. The average duration of symptoms since snakebite was 12.7 years (SD=11.7).ConclusionThis study highlights that a significant proportion of snakebite victims suffer disabling chronic health sequelae. There is a need to place systems to address these unmet health needs.

BackgroundThe incidence of dengue fever is on the rise in tropical countries. In Sri Lanka, nearly 45,000 patients were reported in 2012. With the increasing numbers, rare manifestations of dengue are occasionally encountered. We report a patient who presented with bilateral cerebellar signs as the presenting feature of dengue.Case presentationA 45-year-old previously healthy female from the suburbs of Colombo, Sri Lanka presented with an acute febrile illness associated with unsteadiness of gait. Clinical examination revealed a scanning dysarthria and marked horizontal nystagmus with bilateral dysmetria, dysdiadokokinesia and incordination more prominent on the right. Her gait was wide-based and ataxic with a tendency to fall to the right more than to the left. Dengue nonstructural protein antigen 1 test and IgM antibody testing both became positive indicating acute dengue infection. She recovered from the febrile episode within 9 days since the onset of fever but cerebellar symptoms outlasted the fever by one week. The magnetic resonance imaging of brain was normal and cerebellar signs resolved spontaneously by day 17 of the illness.ConclusionsCerebellar syndrome in association with dengue fever has been reported in only four instances and our patient is the first reported case of dengue fever presenting with cerebellitis as the first manifestation of disease. This case report is intended to highlight the occurrence of acute cerebellitis as a presenting syndrome of the expanding list of unusual neurological manifestations of dengue infection.