Clinical pitfalls and serological diagnostics of MuSK myasthenia gravis.

BACKGROUND: We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG. METHODS: A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups. RESULTS: After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation. CONCLUSION: While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.

A multicenter prospective observational study on the safety and efficacy of tacrolimus in patients with myasthenia gravis.

INTRODUCTION: Several clinical studies using tacrolimus revealed reasonable therapeutic mechanisms and efficacy in patients with myasthenia gravis (MG). However, long-period studies in a large number of patients with MG are limited; therefore, the aim of this study was to investigate the therapeutic efficacies and safety of tacrolimus in patients with MG during a 12-month follow-up period. METHODS: Tacrolimus was administered to 150 patients with MG who were recruited based on the inclusion criteria. Fifteen medical centers in Korea participated in this study. The efficacy of tacrolimus was assessed using MG composite scales (MGCS) and the prednisolone-sparing effect. And the adverse drug reactions (ADRs) of tacrolimus were monitored in each patient from the beginning of tacrolimus treatment to the end of the follow-up period. RESULTS: After starting tacrolimus, the 32 patients were affected by ADRs, and consequentially 134 patients of the enrolled patients were followed up for 12months. They showed that the mean prednisolone dosage significantly decreased (6.1±7.6mg/day), compared to that in the baseline (11.3±9.5mg/day), and MGCS significantly improved after 12months of tacrolimus treatment, compared to that at the baseline. CONCLUSIONS: Our study showed that tacrolimus would be an effective immunosuppressant as an initial therapeutic agent in patients with MG; in addition, it showed tolerable safety profiles during the 12-month follow-up evaluation.

Widely varying TNF-alpha levels in patients with myasthenia gravis.

Animal studies have indicated an important role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of myasthenia gravis (MG), and trials of monoclonal antibodies that block TNF-alpha have shown clinical improvement. However, before a TNF-alpha blocking agent is proposed for treatment of MG, whether serum TNF-alpha level correlates with the patient's condition should be confirmed. Therefore, we evaluated the relationship between the serum TNF-alpha level and clinical factors, including the quantitative MG score and the anti-acetylcholine receptor antibody level, in 33 MG patients. TNF-alpha levels ranged from 0.44 to 3.63 pg/mL and did not correlate with clinical factors. Overall, we found that serum TNF-alpha levels varied greatly among MG patients.

Can aspirin resistance be clinically predicted in stroke patients?

OBJECTIVES: Aspirin resistance is one of several possible explanations for limited efficacy or treatment failure of aspirin. However, the predictors of aspirin resistance are not well known. We therefore conducted a study of laboratory-defined aspirin resistance in Korean patients with ischemic stroke and considered a wide range of factors as possible predictors. PATIENTS AND METHODS: A total of 88 patients taking aspirin daily for the secondary prevention of stroke were included. Platelet function was assessed using the Rapid Platelet Function Assay-Aspirin (RPFA-ASA) system and the level of urinary thromboxane B2 (TX-B2). The result of the RPFA-ASA system was expressed as an aspirin reaction unit (ARU). We analyzed a wide range of factors including demographic data, stroke risk factors, and laboratory findings to identify the clinical predictors of aspirin resistance. RESULTS: Eleven (12%) patients were identified as aspirin resistant by the ARU criteria. Univariate analysis showed that an older age, lower LDL cholesterol levels, and concurrent use of angiotensin converting enzyme inhibitors or receptor blockers were related to aspirin resistance by ARU criteria. Aspirin resistance by urinary TX-B2 criteria was observed in 18 (25%) patients and associated with an older age, metabolic syndrome, diabetes, cigarette smoking, and the use of angiotensin-converting enzyme inhibitors or receptor blockers. In multivariate analysis, this association lost significance by ARU criteria, and only lower fibrinogen levels were associated with increased risk by TX-B2 criteria. In addition, the stroke subtypes and the degree of atherosclerosis were not associated with aspirin resistance. The correlation between the two criteria was poor (r=-0.115, p=0.34). CONCLUSION: Despite the comprehensive analysis of this study, we failed to identify independent predictors for laboratory-defined aspirin resistance. Additionally, little overlap was found between the two criteria with which to assess aspirin resistance.

A novel mutation (C67Y)in the NOTCH3 gene in a Korean CADASIL patient.

We report a 52-yr-old Korean woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) whose diagnosis was confirmed by skin biopsy and the presence of a novel mutation in the NOTCH3 gene. The patient's clinical features were rather unusual in that 1) clinical presentations were only two episodes of stroke and mild dementia unaccompanied by mood disturbances or migraine, and 2) there was no family history. Brain MRI showed T2 hyperintensities in both temporal pole areas in line with the recent suggestion by O'Sullivan et al. that the abnormality could be a radiologic marker of CADASIL. FDG-PET also showed a hypometabolism in the temporal pole areas with an abnormal finding on MRI in addition to the hypometabolism in cortical and subcortical regions. We could learn from this case that CADASIL may be included in the differential diagnoses in patients with vascular dementia associated with a small vessel disease, even in the absence of a family history, especially when there are no known stroke risk factors and when the MRI shows T2 hyperintensity in the temporal pole regions.