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.

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.

An outbreak of Aspergillus meningitis following spinal anaesthesia for caesarean section in Sri Lanka: a post-tsunami effect?

An outbreak of Aspergillus fumigatus meningitis occurred in 5 women following spinal anaesthesia, performed between 21 June and 17 July 2005 for caesarean section, in Colombo, Sri Lanka. The patients' median age was 27 years. Different teams in 2 maternity hospitals gave spinal anaesthesia. Mean incubation period was 11.2 days. Fever, headache and nuchal rigidity were common presentations. Remittent fever continued despite broad-spectrum intravenous antibiotics. Papilloedema, lateral rectus palsy, cerebral infarction and haemorrhage developed later. Three patients died. Cerebrospinal fluid pleocytosis with low glucose yielded negative PCR for fungi. Fungal cultures subsequently grew Aspergillus fumigatus. A post-mortem of the first patient confirmed Aspergillus meningitis, followed by treatment with amphotericin B and voriconazole, that saved the lives of others. Visual and hearing impairment in one and complete recovery in the other were observed a year after treatment. Examination of unused plastic syringes, needles, cannulae, and ampoules of anaesthetic agents confirmed that 43 syringes from three different manufactures were contaminated with Aspergillus fumigatus. The stores for drugs and devices of the Ministry of Health were examined and found to be full of tsunami donations, while regular procurements of the Ministry were kept in a poorly maintained humid warehouse. Inadequate space for tsunami donations was identified as the most plausible explanation for sub-optimal storage. Withdrawal and incineration of all unused syringes controlled the outbreak. The survival of those aggressively treated for Aspergillus meningitis suggests in hindsight that the availability of diagnostic tests and specific treatment, and early recognition of the outbreak could have saved the lives of victims who died. Early life-threatening side-effects and permanent long term sequelae of antifungal medication stress the need to be cautious with empirical treatment in immuno-competent low-risk individuals.