Jong Seok Bae

Clinical predictors of steroid-induced exacerbation in myasthenia gravis

Although oral corticosteroids are effective for the treatment of myasthenia gravis (MG), the possibility of steroid-induced exacerbation of symptoms, especially during the initial course of steroid therapy, has limited their use patients with severe MG. However, the factors influencing or predicting in exacerbation are not well understood. The purpose of this study was to identify the clinical factors that predict the initial paradoxical exacerbation of MG in response to steroid therapy. Fifty-five consecutive patients who were administered for the first time high doses of prednisone (40-80 mg) in a tertiary medical centre in Seoul, were included. Prednisone-induced exacerbation was defined as a significant reduction in a patients Myasthenia Gravis Severity Scale (MSS) score within 4 weeks of prednisone administration. We divided the patients into two groups on the basis of whether or not they experienced prednisone-induced exacerbation, and investigated the differences between the two groups with respect to clinical, laboratory and electrophysiological features. Twenty-three patients (42%) experienced definite exacerbation after prednisone therapy. Older age, predominantly severe bulbar symptoms, and low MSS score were found to be significant clinical predictors of exacerbation by multivariate logistic regression analysis. A high daily dosage of prednisone relative to body weight was found to be neither a predictor of exacerbation nor a predictor of early improvement in bivariate correlation analysis. Steroid-induced exacerbation in MG is a frequently encountered and challenging problem. Clinicians should be aware of the possibility of exacerbation of MG when prescribing prednisone, especially when treating elderly, bulbar dominant, or severely myasthenic patients.

Acute bulbar palsy as a variant of Guillain-Barré syndrome

Objective: To categorize a syndrome manifesting as prominent acute bulbar palsy (ABP) without limb motor weakness as a variant form of Guillain-Barré syndrome (GBS) and differentiate it from Miller Fisher syndrome (MFS) and pharyngeal-cervical-brachial (PCB) variants. Methods: We analyzed cases of ABP without limb motor weakness based on a dataset containing clinical information and the results of antiganglioside antibodies assays for acute immune-mediated neuropathies. Results: Eleven cases with an age at onset ranging from 18 to 65 years (mean 33.8 years) were identified as ABP-plus syndrome. All of the enrolled cases manifested with ABP as the predominant symptom, and with no limb weakness. The following features accompanied ABP in order of decreasing frequency: ophthalmoplegia (n = 9, 82%), ataxia (n = 9, 82%), and facial palsy (n = 6, 55%). An enzyme-linked immunosorbent assay study disclosed that immunoglobulin G (IgG) anti-GT1a antibodies were the most frequent (n = 11), followed by IgG anti-GQ1b antibodies (n = 6). Conclusions: We propose that ABP-plus syndrome without neck or limb weakness is a variant of GBS that is distinct from the MFS and PCB variants. The presence of IgG anti-GT1a antibodies can explain the relationships between the distinct clinical characteristics and the underlying pathomechanisms.

Identification of a novel mutation in a Korean patient with oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disorder characterized by progressive dysphagia and bilateral ptosis. Mutations in the polyadenylate binding protein nuclear 1 (PABPN1) gene have been found to cause OPMD. The typical mutation is a stable trinucleotide repeat expansion in the first exon of the PABPN1 gene, in which (GCG)(6) is the normal repeat length. We investigated a Korean patient with OPMD and identified a novel mutation: a heterozygous insertion of a 9-bp sequence [(GCG)(GCA)(GCA); c.27_28insGCGGCAGCA] instead of the (GCG) repeat expansion, resulting in an in-frame insertion of three alanines (p.A10insAAA). To the best of our knowledge, this is the first report of a genetically confirmed case of OPMD in Korea.

Contingent negative variation before and after hemodialysis among patients with end-stage renal disease

OBJECTIVE To investigate changes in contingent negative variation (CNV) induced by uremia and to study the effects of hemodialysis. METHODS Fifteen right-handed healthy subjects and 12 patients with end-stage renal disease (ESRD) were studied. CNV was recorded from the Fz, Cz and Pz (using the International 10-20 System) referenced to linked ear lobes, using an S1 (click)-S2 (flashes)-key press paradigm. The amplitude of initial CNV (iCNV) was calculated as the average amplitude at 550-750 ms after S1. The amplitude of late CNV (lCNV) was the mean amplitude of the last 200 ms before S2. Testing was repeated for the patient group at pre- and post-hemodialysis observations. Neuropsychological measurements, a trail making test (TMT) and mini-mental state examination (MMSE), were conducted at each time. RESULTS The mean amplitudes of iCNV and lCNV at the vertex (Cz) were both significantly lower in the patient group than in the control group (P<0.05). TMT were also significantly different between patient and control groups (P<0.05)), however MMSE showed no significant difference. There were no significant correlations between the values of neuropsychological tests and the parameters of CNV. Both iCNV and lCNV were not significantly different between the pre- and post-dialysis tests. CONCLUSION CNV negativity in patients with ESRD reflects diffuse nonlocalizing neurological symptoms of uremia rather than a selective involvement of the frontal lobes. It is likely to reflect dysfunction in the frontal-subcortical circuit. In addition, hemodialysis seemed to have no significant effect on executive brain function in these patients with ESRD.

A novel in-frame deletion in the CAV3 gene in a Korean patient with rippling muscle disease

Rippling muscle disease (RMD) is a rare form of myopathy that is characterized by percussion-induced rapid muscle contractions, muscle mounding, and rippling. Recently a caveolin-3 gene (CAV3) mutation was identified in patients suffering from autosomal dominant RMD. We encountered a Korean male patient with RMD who had suffered from muscle stiffness for 3 years. Mutation analysis of the CAV3 gene revealed the patient to be heterozygous for a novel in-frame deletion mutation (c.307_312delGTGGTG; Phe103_Phe104del). Further analysis of his family members showed that his mother and elder sister also have the same mutation. To the best of our knowledge, this is the first report of genetically confirmed RMD in Korea.

Conduction slowing in painful versus painless diabetic neuropathy

Motor conduction slowing in diabetic distal symmetrical polyneuropathy (DSP) generally exceeds that in distal axonal polyneuropathy. Additional mechanisms secondary to axonal injury may contribute to motor conduction slowing; however, its clinical and pathophysiological significance has rarely been discussed. The purpose of this study was to evaluate the clinical and pathophysiological significance of conduction slowing in DSP. We analyzed motor conduction in 50 patients with symptomatic painful DSP and 25 patients with asymptomatic painless DSP. Motor conduction data from 40 patients with amyotrophic lateral sclerosis (ALS) were used as controls for pure axonal conduction slowing. Compound muscle action potential amplitude (CMAP), distal motor latency (DL), and conduction velocity (CV) values were converted to a percentage of the upper or lower limits of normal and then presented in square root transformation (SQRT) form. Plots of SQRT-DL and SQRT-CV against SQRT-CMAP were analyzed. Regression analysis showed that DL and CV are amplitude-dependent in both painless DSP and ALS. Changes of DL and CV in painful DSP were not amplitude-dependent except for DL in the lower extremities. Our data support the hypothesis that the mechanism of slowing is similar in both painless DSP and ALS, and that it results from the loss of large, fast-conducting fibres. Lack of amplitude-dependency in conduction slowing in painful DSP may reflect combined axonal and demyelinating changes.

Cerebellar ataxia and acute motor axonal neuropathy associated with Anti GD1b and Anti GM1 antibodies

The anti-GD1b antibody is known to bind to the cerebellar granular layer or spinocerebellar Ia fibers. A few cases of anti-GD1b positive acute inflammatory demyelinating polyneuropathy with prominent cerebellar ataxia were reported. Recently, we encountered a middle-aged woman with Guillain Barré syndrome (GBS) with severe cerebellar ataxia and relatively mild motor weakness. Anti-GD1b Ig G antibody and anti-GM1 Ig G antibody titers were markedly elevated in her serum. She was diagnosed with acute motor axonal neuropathy (AMAN) with prominent cerebellar ataxia based on the results of the serial nerve conduction study suggesting axonal neuropathy. This case presents the clinico-pathogenic role of autoantibodies to the GD1b and the GM1 in acute inflammatory neuropathy.