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.

A Polypill for primary prevention of cardiovascular disease: a feasibility study of the World Health Organization.

BACKGROUND: The feasibility of conducting a large-scale Polypill clinical trial in developing countries remains unclear. More information is needed regarding the efficacy in reducing the risk factors of cardiovascular disease (CVD), side effects, improvement in adherence and physician/patient "acceptability" of the Polypill. METHODS: We conducted an open-label, parallel-group, randomized clinical trial involving three sites in Sri Lanka that enrolled a total of 216 patients without established CVD. The trial compared a Polypill (75 mg aspirin, 20 mg simvastatin, 10 mg lisinopril and 12.5 mg hydrochlorothiazide) to Standard Practice. After randomization, patients were followed monthly for three months. Pre-specified primary outcomes included reduction in systolic blood pressure, total cholesterol and estimated 10-year CVD risk. We also evaluated the recruitment process and acceptability of the Polypill by both physicians and patients. RESULTS: Patients were recruited in a six-month period as planned. Two hundred three patients (94.0%) completed the treatment program and returned for their three-month follow-up visits. No safety concerns were reported. These findings suggest a high rate of patient acceptability, a finding that is bolstered by the majority of patients completing the trial (90%) indicating that they would take the Polypill "for life" if proven to be effective in reducing CVD risk. Approximately 86% of the physicians surveyed agreed with and supported use of the Polypill for primary prevention and 93% for secondary prevention of CVD. Both the Polypill and Standard Practice resulted in marked reductions in systolic blood pressure, total cholesterol and 10-year risk of CVD. However, the differences between the treatment groups were not statistically significant. CONCLUSIONS: We successfully completed a Polypill feasibility trial in Sri Lanka. We were able to document high acceptability of the Polypill to patients and physicians. We were unable to estimate the risk factor reductions on the Polypill because the control group received similar treatment with individual drugs. The Polypill was however simpler and achieved comparable risk factor reductions, highlighting its potential usefulness in the prevention of CVD. TRIAL REGISTRATION NUMBER: NCT00567307.

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.