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.

Anti-Hu antibody-mediated limbic encephalitis associated with cervical cancer: A case report.

A 55-year-old postmenopausal and multiparous woman presented to our department with recent memory disturbances associated with rapidly progressive positive Anti-Hu antibodies. She was subsequently diagnosed with anti-Hu antibody-related paraneoplastic limbic encephalitis. Clinical examination and imaging studies revealed a bulky cervical tumor with both parametrial and vaginal fornix extension; biopsy confirmed the tumor as cervical squamous cell carcinoma. In this case, we encountered a patient with anti-Hu-mediated paraneoplastic limbic encephalitis with a subsequent diagnosis of cervical cancer.

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.

Aging, hypercoagulability, and leg necrosis in critical limb ischemia.

BACKGROUND: Aging is associated with changes in coagulation status and progression of arterial insufficiency. The purpose of this study was to identify interrelationships among aging, coagulation status, and leg necrosis in patients with critical limb ischemia (CLI). METHODS: Between March 2010 and February 2013, 103 consecutive patients with CLI were enrolled in this study. Retrospective analyses were performed on patient characteristics including age, gender, the presence or the absence of leg necrosis, diabetes mellitus (DM), hypertension, and smoking, and preoperatively measured baseline coagulability factors, which included measurements of coagulation factors anticardiolipin antibodies IgG and IgM, lupus anticoagulant and factor 8, the fibrinolytic factor tissue plasminogen activator (t-PA), and natural anticoagulants proteins C and S and antithrombin III. RESULTS: Among 103 patients with CLI, a total of 49 legs from 41 patients presented varying degrees of necrosis. CLI patients with DM and hypertension showed significantly increased incidences of leg necrosis compared with those without (P = 0.000, 0.039, respectively). Patients with CLI and leg necrosis were significantly older compared with the age of those without necrosis (P = 0.007). Blood levels of anticardiolipin antibodies IgG and IgM, factor 8, lupus anticoagulant, and t-PA tended to increase with age. However, blood levels of proteins C and S and antithrombin III decreased with patient age. Patients with CLI and leg necrosis showed significantly increased levels of lupus anticoagulant (P = 0.049) and significantly decreased levels of proteins C and S (P = 0.009 and 0.018, respectively) compared with patients without leg necrosis. CONCLUSIONS: Patients with CLI and leg necrosis were significantly older compared with those without necrosis; similarly, our results revealed age-related hypercoagulability, with significantly elevated coagulation factor lupus anticoagulant and decreased natural anticoagulants protein C and S levels. From these observations, we conclude that age-related hypercoagulability may be an important mechanism that may facilitate leg necrosis in patients with CLI.

Response to antiepileptic drugs in partial epilepsy with structural lesions on MRI.

OBJECTIVE: Although partial epilepsy with structural lesions on MRI (lesional epilepsy) is less favorably responsive to antiepileptics than those without structural lesions on MRI, the response to antiepileptics in lesional epilepsy is a heterogeneous condition. There is growing evidence that the extent of epileptic network beyond the visible lesion on MRI may be related with the response to antiepileptics. The aims of this study are to clarify whether (1) the epilepsy network beyond the visible lesion on MRI, or (2) duration of lesional epilepsy on MRI are related with the response to antiepileptics or not. METHODS: The inclusion criteria for this study were (1) having structural lesions on MRI, (2) taking antiepileptics for at least 1 year, and (3) age ≥13 years old. The definition for drug-resistance epilepsy was a failure of adequate trials of two tolerated, appropriately chosen and used antiepileptics to achieve sustained seizure freedom. The duration was defined as the interval between the start of antiepileptics and the last follow-up. We defined the lesion-plus group as the structural lesions on MRI that has wider spread of epileptic network beyond the visible lesions on MRI, such as hippocampal sclerosis and malformation of cortical development. Lesion-restriction group was defined as the epileptic network being believed to be limited on the structural lesions. RESULTS: We found 234 patients with lesional epilepsy, who met the inclusion criteria. Of these 234 patients, 115 patients were male (49%) and 119 patients were female (51%). The median age was 22 years old (range 13-78 years old) and the median duration was 131 months (range 12-516 months). Forty percent (90/234 patients) were intractable to antiepileptics. Of the structural lesions on MRI, hippocampal sclerosis was most frequent (N=90). Other structural lesions were malformation of cortical development (N=38), cerebromalatic lesions related with trauma (N=34), tumor (N=19), cystic lesion (N=15), cerebral infarction (N=11), vascular malformation (N=10), and other miscellaneous lesion (N=24). Lesion-plus group had significantly higher drug-resistance epilepsy than cystic lesions on MRI (60/128 vs. 2/15, p=0.013 by Fisher's exact test). There was a tendency of having more drug-resistance epilepsy in the lesion-plus group than the lesion-restriction group (56/121 vs. 30/89, p=0.09 by Chi-square test). The median duration in drug-resistance epilepsy was significantly longer than that of medically controlled epilepsy (178 months (range 23-516 months) vs 102 months (range 12-479 months), p<0.0001 by Mann-Whitney test). In addition, duration was only the significant variable associated with drug-resistance epilepsy in lesional epilepsy by multiple logistic regression analysis (p=0.02 for overall model fit). CONCLUSION: In lesional epilepsy, hippocampal sclerosis and malformation of cortical development are more intractable to antiepileptics, reflecting wider epileptic network beyond the visible lesion. In addition, the response to antiepileptics may be expected to decrease when the duration is prolonged.

Neurological and electrophysiological parameters as outcome measurements for peripheral arterial occlusive disease.

BACKGROUND: Ischemic monomelic neuropathy is not an uncommon complication of peripheral arterial occlusive disease (PAOD). However, many investigators have used revascularization, limb salvage, and complete wound healing rates instead of neurologic and electrophysiological parameters as outcome measurements of PAOD. The aim of the study is to investigate the neurologic and electrophysiological parameters associated with PAOD and to find the ideal tools for assessing PAOD. METHODS: A total of 38 PAOD patients (68.5 ± 8.1 years old, male:female = 32:6) with a total of 76 lower limbs were enrolled in the study. Primary outcomes were neurological symptoms scores (NSSs) and neurological impairment scores (NISs) for the lower extremities. Secondary outcomes were taken from nerve conduction studies (NCSs) and included the following: sensory nerve action potential (SNAP) amplitudes of the sural, superficial peroneal, and medial plantar nerves and the compound muscle action potential (CMAP) amplitudes of the posterior tibial and common peroneal nerves. RESULTS: Female patients with old age, hypertension, low body weights, low body mass indices (BMIs), decreased ankle-brachial indices (ABIs), and poorer Fontaine classifications exhibited worse NSSs and NISs indices. Patients with old age, diabetes mellitus, hypertension, histories of social alcohol consumption, low body weights, low BMIs, and poorer Fontaine classifications exhibited decreased SNAP and CMAP amplitudes in the sensory and motor NCSs. Decreased ABI was associated with decreased SNAP amplitudes in the sensory NCSs. CONCLUSIONS: Neurologic and electrophysiological parameters can be good tools for the assessment of PAOD. NSSs and NISs are particularly good candidates for outcome measures of PAOD.

Secular trends in prevalence of alcohol use disorder and its correlates in Korean adults: results from Korea National Health and Nutrition Examination Survey 2005 and 2009.

The Alcohol Use Disorders Identification Test (AUDIT) has been found to provide an accurate measure for risk of hazardous and harmful alcohol use, as well as possible dependence. Data from 2 representative samples of 7693 adults in the Korea National Health and Nutrition Examination Survey (KNHANES) 2005 and 6276 participants in 2009 were analyzed. The overall age-adjusted prevalence of alcohol use disorder (AUD) in 2009 (38.8%) was higher than that in 2005 (32.7%), with a difference of 6.1% (95% confidence interval [CI], 2.9%-9.3%; P = .0002). Men were about 7 times as likely as women to meet the criteria for AUD (odds ratio [OR] = 7.16; 95% CI, 6.27-8.17). Current smoking was the most important correlate associated with AUD in both genders (women: OR = 6.03; 95% CI, 4.40-8.27; men: OR = 2.83; 95% CI, 2.29-3.48). Among women, unmarried (OR = 1.76; 95% CI, 1.35-2.31), less than high school education (OR = 2.71, 95% CI, 1.86-3.96), and lowest income (OR = 1.45, 95% CI, 1.06-1.97) were associated with AUD. These findings provide the most updated prevalence estimates of AUD in the Korean population and they highlight its strong association with smoking, gender differences, and lower socioeconomic status in the Korean population.