Thashi Chang

Serum IL-10 as a marker of severe dengue infection

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.

Evaluation of the WHO revised criteria for classification of clinical disease severity in acute adult dengue infection

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.

Immunization against GAD induces antibody binding to GAD-independent antigens and brainstem GABAergic neuronal loss.

Stiff person syndrome (SPS) is a highly-disabling neurological disorder of the CNS characterized by progressive muscular rigidity and spasms. In approximately 60–80% of patients there are autoantibodies to glutamic acid decarboxylase (GAD), the enzyme that synthesizes gamma-amino butyric acid (GABA), the predominant inhibitory neurotransmitter of the CNS. Although GAD is intracellular, it is thought that autoimmunity to GAD65 may play a role in the development of SPS. To test this hypothesis, we immunized mice, that expressed enhanced green fluorescent protein (EGFP) under the GAD65 promoter, with either GAD65 (n = 13) or phosphate buffered saline (PBS) (n = 13). Immunization with GAD65 resulted in autoantibodies that immunoprecipitated GAD, bound to CNS tissue in a highly characteristic pattern, and surprisingly bound not only to GAD intracellularly but also to the surface of cerebellar neurons in culture. Moreover, immunization resulted in immunoglobulin diffusion into the brainstem, and a partial loss of GAD-EGFP expressing cells in the brainstem. Although immunization with GAD65 did not produce any behavioral abnormality in the mice, the induction of neuronal-surface antibodies and the trend towards loss of GABAergic neurons in the brainstem, supports a role for humoral autoimmunity in the pathogenesis of SPS and suggests that the mechanisms may involve spread to antigens expressed on the surface of these neurons.

Sequential antibodies to potassium channels and glutamic acid decarboxylase in neuromyotonia.

A patient with thymoma-associated neuromyotonia and voltage-gated potassium channel (Kv1.2 and Kv1.6) antibodies by immunoprecipitation and rat brain immunolabeling was treated successfully with immunoadsorption and cyclophosphamide. Curiously, glutamic acid decarboxylase antibodies, absent at onset, appeared later. Stiff-person syndrome was absent, but fast blink reflex recovery suggested enhanced brainstem excitability. The range of antibodies produced in thymoma-associated neuromyotonia is richer, and the timing of antibody appearance more complex, than previously suspected.

Cyclophosphamide-induced posterior reversible encephalopathy syndrome (PRES): a case report

IntroductionPosterior reversible encephalopathy syndrome is a clinicoradiologic entity characterized by headache, seizures, decreased vision, impaired consciousness and white matter oedema in bilateral occipitoparietal regions. Hypertensive encephalopathy, eclampsia, immunosuppressive/cytotoxic drugs, organ transplantation, renal disease, autoimmune diseases and vasculitides are reported risk factors of posterior reversible encephalopathy syndrome. Reports of cyclophosphamide-induced posterior reversible encephalopathy syndrome are rare and occurred in a background of renal failure, fluid overload or active connective tissue disease.Case presentationWe report a case of posterior reversible encephalopathy syndrome developing as a direct consequence of intravenous cyclophosphamide therapy in a 33-year-old normotensive Sri Lankan woman with lupus nephritis but quiescent disease activity and normal renal function.ConclusionsThis case report highlights the need for awareness and early recognition of this rare but serious adverse effect of cyclophosphamide that occurred in the absence of other known risk factors of posterior reversible encephalopathy syndrome and that early appropriate intervention leads to a good outcome.

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.

Hashimoto encephalopathy: clinical and MRI improvement following high-dose corticosteroid therapy.

Introduction Hashimoto encephalopathy (HE) is an immune-mediated encephalopathy associated with Hashimoto thyroiditis. Most patients with HE respond to corticosteroids. Diffuse or focal white matter changes suggesting primary demyelination on magnetic resonance imaging (MRI) has been reported in only a few patients with HE. Follow-up imaging studies have been sparse. Case Report We report the case of a 48-year-old woman who presented with progressively declining cognitive function over 6 weeks without neurologic focal deficit on clinical examination. Her Mini-Mental State Examination Score was 3/30, and the MRI showed cortical and subcortical white matter demyelination. Biologic and radiologic investigations did not reveal an infective, vasculitic, or neoplastic etiology. Although her thyroid function tests were normal, thyroid antibodies were detected in high titers in her serum. A diagnosis of HE was made, and the patient was treated with high-dose corticosteroids. Over the next 8 weeks, her Mini-Mental State Examination Score improved to 24/30. The MRI changes showed resolution paralleling her clinical improvement. Conclusions This case illustrates the importance of considering rare but treatable causes of encephalopathy in a patient presenting with acute or subacute cognitive decline.

MuSK-antibody-positive myasthenia gravis in a South Asian population.

BACKGROUND MuSK-antibody-positive myasthenia gravis (MuSK-MG) is diagnosed in 0-40% of cases with generalized seronegative MG in different populations. The presence of anti-MuSK antibodies defines a distinct clinico-immuno-pathological subtype of MG. We analysed for the first time the serology and clinical characteristics of MuSK-MG in a South Asian population. METHODS 113 patients with MG attending Neurology Units in three state hospitals in the district of Colombo, Sri Lanka were studied. AChR antibodies were tested in all patients whilst MuSK antibodies were tested in patients seronegative for AChR antibodies. Sera from patients with other neurological diseases (OND) concurrently attending the same hospitals were obtained as controls. RESULTS Four of 19 AChRAb-negative generalised MG patients (21%) were positive for MuSKAbs. Two were women and in 3, disease onset was before the age of 30 years. Although 3 of 4 had ocular-bulbar involvement at presentation, none had facial or bulbar muscle wasting. Two of the 4 patients (50%) had developed myasthenic crisis and had required ventilation. A good treatment outcome appears to be related to early commencement of immunosuppressive medication. None of the patients with ocular MG or OND were positive for either AChR or MuSK antibodies. CONCLUSIONS MuSK-MG is seen in about a fifth of generalised seronegative MG patients in Sri Lanka. The clinical characteristics are consistent with features described in Caucasian MuSK-MG patients.

Clinical and serological study of myasthenia gravis using both radioimmunoprecipitation and cell-based assays in a South Asian population

BACKGROUND Identification of autoantibodies has defined distinct clinico-immuno-pathological subtypes of myasthenia gravis (MG) such as AChR-antibody-positive-MG and MuSK-antibody-positive-MG. The use of more sensitive assays such as the cell-based assay (CBA) is expected to reduce the proportion of seronegative-MG. We studied the seroprevalence of AChR and MuSK antibodies using both radioimmunoprecipitation (RIA) and CBA amongst MG patients in Sri Lanka and related their antibody status to their clinical subtypes and severity. METHODS 113 patients with MG attending Neurology units in the district of Colombo were studied. Clinical data were obtained using an interviewer-administered questionnaire and medical records. The severity of MG was assessed according to MGFA clinical grading. RIA and CBA were used to detect serum AChR and MuSK antibodies. Patients with other neurological diseases were recruited as controls. RESULTS We detected either AChRAb (85%) or MuSKAb (6.2%) in 91.2% of MG patients. Complementing the RIA with the CBA improved the diagnostic power of detecting AChRAbs by 21% and MuSKAbs by 77%. The clinical characteristics and the occurrence of thymic pathology were similar to other populations except for a male preponderance (1.5:1). The AChRAb titer appeared to parallel the clinical severity. Seven of 11 (63.6%) patients with AChRAb-negative generalized MG had MuSK-MG. CONCLUSIONS Clinical characteristics of MG in Sri Lanka are similar to other populations. Complementing the RIA with CBA increases the diagnostic power of detecting pathogenic autoantibodies.

Hydrogen sulphide inhalational toxicity at a petroleum refinery in Sri Lanka: a case series of seven survivors following an industrial accident and a brief review of medical literature

This case series details clinical observations in 7 survivors of accidental hydrogen sulphide inhalation toxicity at a petroleum refinery in Sri Lanka. One survivor developed status epilepticus and severe neurotoxicity whilst another survivor developed delayed respiratory failure; both patients required intensive care management. One victim manifested mild bronchospasms in the immediate post-exposure period and another developed mild perioral numbness 2 days following the exposure. A brief literature review explores the manifestations, pathophysiology and available modalities of treatment of hydrogen sulphide inhalation toxicity.BackgroundHydrogen sulphide (H2S) is a highly toxic gas. Accidental deaths following H2S exposure is a known hazard amongst petroleum workers exposed to by-products of refineries. Toxicity results mainly due to cellular respiratory poisoning which impairs oxidative phosphorylation. The heart, brain and the lungs are the organs most commonly affected in H2S inhalational toxicity leading to varied clinical presentations.