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.

Intraoperative Neurophysiologic Testing of the Perigastric Vagus Nerve Branches to Evaluate Viability and Signals along Nerve Pathways during Gastrectomy.

PURPOSE: The perigastric vagus nerve may play an important role in preserving function after gastrectomy, and intraoperative neurophysiologic tests might represent a feasible method of evaluating the vagus nerve. The purpose of this study is to assess the feasibility of neurophysiologic evaluations of the function and viability of perigastric vagus nerve branches during gastrectomy. MATERIALS AND METHODS: Thirteen patients (1 open total gastrectomy, 1 laparoscopic total gastrectomy, and 11 laparoscopic distal gastrectomy) were prospectively enrolled. The hepatic and celiac branches of the vagus nerve were exposed, and grabbing type stimulation electrodes were applied as follows: 10-30 mA intensity, 4 trains, 1,000 µs/train, and 5× frequency. Visible myocontractile movement and electrical signals were monitored via needle probes before and after gastrectomy. Gastrointestinal symptoms were evaluated preoperatively and postoperatively at 3 weeks and 3 months, respectively. RESULTS: Responses were observed after stimulating the celiac branch in 10, 9, 10, and 6 patients in the antrum, pylorus, duodenum, and proximal jejunum, respectively. Ten patients responded to hepatic branch stimulation at the duodenum. After vagus-preserving distal gastrectomy, 2 patients lost responses to the celiac branch at the duodenum and jejunum (1 each), and 1 patient lost response to the hepatic branch at the duodenum. Significant procedure-related complications and meaningful postoperative diarrhea were not observed. CONCLUSIONS: Intraoperative neurophysiologic testing seems to be a feasible methodology for monitoring the perigastric vagus nerves. Innervation of the duodenum via the celiac branch and postoperative preservation of the function of the vagus nerves were confirmed in most patients. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0000823.

Myasthenia gravis seronegative for acetylcholine receptor antibodies in South Korea: Autoantibody profiles and clinical features.

Acquired myasthenia gravis (MG) is a prototype autoimmune disease of the neuromuscular junction, caused in most patients by autoantibodies to the muscle nicotinic acetylcholine receptor (AChR). There seem to be ethnic and regional differences in the frequency and clinical features of MG seronegative for the AChR antibody. This study aimed to describe the autoantibody profiles and clinical features of Korean patients with generalized MG seronegative for the AChR antibody. A total of 62 patients with a high index of clinical suspicion of seronegative generalized MG were identified from 18 centers, and we examined their sera for antibodies to clustered AChR, muscle-specific tyrosine kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (LRP4) by cell-based assays (CBA) and to MuSK by radioimmunoprecipitation assay (RIPA). We also included 8 patients with ocular MG, 3 with Lambert-Eaton myasthenic syndrome, 5 with motor neuron disease, and 9 with other diagnoses as comparators for the serological testing. Antibodies were identified in 25/62 (40.3%) patients: 7 had antibodies to clustered AChR, 17 to MuSK, and 2 to LRP4. Three patients were double seropositive: 1 for MuSK and LRP4, and 2 for MuSK and clustered AChR. The patients with MuSK antibodies were mostly female (88.2%) and characterized by predominantly bulbar involvement (70%) and frequent myasthenic crises (58.3%). The patients with antibodies to clustered AChR, including 2 with ocular MG, tended to have a mild phenotype and good prognosis.

Clinical manifestation of cancer related stroke: retrospective case-control study.

Cancer related stroke may have different phenotypes from non-cancer stroke, especially in terms of stroke progression and recurrence. We performed a case-control study to identify their incidences and risk factors in cancer related stroke. Between January 2001 and December 2009, we conducted a retrospective review of acute ischemic stroke patients with cancer who were admitted to Seoul National University Hospital, Seoul, Korea. The stroke patients without cancer served as control. We collected demographic variables, vascular risk factors, stroke phenotype, clinical course, and cancer information including diagnosis, stage, and treatment status. Among cancer stroke patients, the potential risk factor of stroke recurrence was evaluated. The mean age of the 102 cancer patients was 66.4 ± 10.8 years, and 64.7 % were men. The mean time interval from cancer diagnosis to stroke onset was 39.7 ± 60.9 months. The principal lesion pattern of cancer stroke was multiple dots extending single vascular territory (39.2 %), and they were associated with low hemoglobin and high fibrinogen levels. Stroke progression and recurrence were noted in 9.8 and 27.5 % of cancer stroke patients, and in 9.3 and 12.7 % of control patients, respectively. The stroke subtype was independently associated with recurrence of cancer stroke after multiple logistic regression (odds ratio = 3.165, 95 % confidence interval = 1.080-9.277, p = 0.036). Cancer related stroke has a distinct phenotype in terms of infarction pattern and laboratory findings. Stroke recurrence is frequently observed among cancer stroke patients, and its risk is related with stroke subtype.