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OBJECTIVE: To electrophysiologically characterize the Na(v)1.4 mutant N440K found in a Korean family with a syndrome combining symptoms of paramyotonia congenita, hyperkalemic periodic paralysis, and potassium-aggravated myotonia. METHODS: We characterized transiently expressed wild-type and mutant Na(v)1.4 using whole-cell voltage-clamp analysis. RESULTS: N440K produced a significant depolarizing shift in the voltage dependence of fast inactivation and increased persistent current and acceleration in fast inactivation recovery, which gave rise to a 2-fold elevation in the dynamic availability of the mutant channels. In addition, the mutant channels required substantially longer and stronger depolarization to enter the slow-inactivated state. CONCLUSIONS: N440K causes a gain of function consistent with skeletal muscle hyperexcitability as observed in individuals with the mutation. How the same mutation results in distinct phenotypes in the 2 kindreds remains to be determined.

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BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease (CMT) type 1A (CMT1A) is the demyelinating form of CMT that is significantly associated with PMP22 duplication. Some studies have found that the disease-related disabilities of these patients are correlated with their compound muscle action potentials (CMAPs), while others have suggested that they are related to the nerve conduction velocities. In the present study, we investigated the correlations between the disease-related disabilities and the electrophysiological values in a large cohort of Korean CMT1A patients. METHODS: We analyzed 167 CMT1A patients of Korean origin with PMP22 duplication using clinical and electrophysiological assessments, including the CMT neuropathy score and the functional disability scale. RESULTS: Clinical motor disabilities were significantly correlated with the CMAPs but not the motor nerve conduction velocities (MNCVs). Moreover, the observed sensory impairments matched the corresponding reductions in the sensory nerve action potentials (SNAPs) but not with slowing of the sensory nerve conduction velocities (SNCVs). In addition, CMAPs were strongly correlated with the disease duration but not with the age at onset. The terminal latency index did not differ between CMT1A patients and healthy controls. CONCLUSIONS: In CMT1A patients, disease-related disabilities such as muscle wasting and sensory impairment were strongly correlated with CMAPs and SNAPs but not with the MNCVs or SNCVs. Therefore, we suggest that the clinical disabilities of CMT patients are determined by the extent of axonal dysfunction.

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PURPOSE: Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. MATERIALS AND METHODS: In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. RESULTS: We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. CONCLUSION: In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

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In addition to chronic hyperglycemia, insulin resistance itself has been proposed to cause a diabetic neuropathy. We evaluated the role of insulin resistance in the pathogenesis of peripheral and autonomic neuropathy in patients with type 2 diabetes. Eighty-six patients with type 2 diabetes were evaluated for the anthropometric and biochemical profiles, and Kitt value was calculated from insulin tolerance test to assess the insulin resistance. Various autonomic function tests, nerve conduction velocity, and quantitative sensory tests were performed to assess autonomic and peripheral neuropathy. In univariate analysis, both autonomic and peripheral neuropathy were significantly associated with glycemic exposure index (GE index), HDL-cholesterol, duration of DM, and Kitt value. In stepwise linear regression analysis, GE index was an independent predictor of autonomic and peripheral neuropathy (ß = 0.643, P < 0.001; ß = 0.207, P = 0.013, respectively), and Kitt value was also an independent factor for the autonomic and peripheral neuropathy (ß = - 0.306, P < 0.001; ß = - 0.329, P < 0.001, respectively). Low HDL-cholesterol increased the odds ratio for peripheral neuropathy. Insulin resistance is independently associated with peripheral and autonomic neuropathy in Korean Type 2 diabetic patients along with hyperglycemia and HDL-cholesterol.

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PURPOSE: Nemaline myopathy (NM) is a clinical heterogeneous congenital myopathy characterized by the presence of subsarcolemmal or cytoplasmic rod-like structures that call nemaline bodies in the muscle fibers. The purpose of this study was to investigate the clinical diversity and pathological features of Korean patients with NM. MATERIALS AND METHODS: Eight patients underwent analyses of clinical manifestations by a structured protocol. Diagnoses were established by a muscle biopsy. RESULTS: Two patients had the typical congenital type, which exhibited neonatal hypotonia and delayed motor milestone, and five patients had the childhood onset type, which exhibited mild gait disturbance as a first symptom. One patient had the adult onset type, which showed acute respiratory failure. Limb weakness was proximal-dominant occurred in six patients. Hyporeflexia was observed in most patients. Elongated faces and high arched palates and feet were also observed. On light microscopy, the nemaline bodies were observed in type 1 and 2 fibers. All patients showed type 1 predominance and atrophy. In the two cases in which ultrastructural studies were performed, typical nemaline rods and disorganized myofibrillar apparatus were detected. CONCLUSION: In conclusion, the eight Korean patients in this study with NM shared common clinical expressions such as proximal limb weakness, reduced deep tendon reflex, and dysmorphic features. This study, however, showed that clinical heterogeneity ranged from typical congenital, mildly affected childhood to the adult onset form with acute respiratory failure. The pathological findings in this study were in accordance with those of other previous reports.

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OBJECTIVES: The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements. METHODS: Clinical Data Repository (CDR) of u-Severance involved implementing electronic medical records (EMR) as the basis of EHR and the management of individual health records. EHR were implemented with service enhancements extending to the clinical decision support system (CDSS) and expanding the knowledge base for research with a repository for clinical data and medical care information. RESULTS: The EMR system of Yonsei University Health Systems (YUHS) consists of HP integrity superdome servers using MS SQL as a database management system and MS Windows as its operating system. CONCLUSIONS: YUHS is a high-performing medical institution with regards to efficient management and customer satisfaction; however, after 5 years of implementation of u-Severance system, several limitations with regards to expandability and security have been identified.

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BACKGROUND AND PURPOSE: At least 100 Ryanodine receptor type 1 (RYR1) mutations associated with malignant hyperthermia (MH) and central core disease (CCD) have been identified, but 2 RYR1 mutations accompanying multiminicore myopathy in an MH and/or CCD family have been reported only rarely. METHODS: Fifty-three members of a large MH family were investigated with clinical, histopathologic, RYR1 mutation, and haplotyping studies. Blood creatine kinase (CK) and myoglobin levels were also measured where possible. RESULTS: Sequencing of the entire RYR1 coding region identified a double RYR1 mutation (R2435H and A4295V) in MH/CCD regions 2 and 3. Haplotyping analysis revealed that the two missense heterozygous mutations (c.7304G>A and c.12891C>T) were always present on a common haplotype allele, and were closely cosegregated with histological multiminicores and elevated serum CK. All the subjects with the double mutation showed elevated serum CK and myoglobin, and the obtained muscle biopsy samples showed multiminicore lesions, but only two family members presented a late-onset, slowly progressive myopathy. CONCLUSIONS: We found multiminicore myopathy with clinical and histological variability in a large MH family with an unusual double RYR1 mutation, including a typical CCD-causing known mutant. These results suggest that multiminicore lesions are associated with the presence of more than two mutations in the RYR1 gene.

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Familial ALS (FALS) is mostly inherited as an age-dependent autosomal dominant trait. Since the discovery of mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), testing for SOD1 gene mutations has become a routine part of the investigation into ALS patients with a family history. This study reports the results of mutation evaluation and clinical features examination in a Korean family with ALS. The clinical symptoms, signs and neurological findings of a four-generation pedigree with 34 members were collected. Five exons of the Cu/Zn SOD gene were analyzed by polymerase chain reaction. The clinical signs and symptoms of ALS patients began in the lower extremities and spread to the upper extremities and bulbar muscles. The mode of transmission was determined to be autosomal dominant, and low penetrance was seen in females. The age at onset varied from 37 to 77 years. ALSFRS-R testing showed variability in the clinical progression of the disease. A point mutation in exon 1 of the SOD1 gene, resulting in an amino acid change from phenylalanine 20 to cysteine (F20C), was identified. This is the first report of clinical features resulting from the Phe20Cys mutation in the SOD1 gene.

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BACKGROUND AND PURPOSE: Chemokines participate in the regulation of immune and inflammatory responses by interacting with their receptors, which are primarily expressed on immune and inflammatory cells such as B- and T-lymphocytes and antigen-presenting cells. Chemokines and their receptors are therefore considered to mediate inflammation and tissue damage in autoimmune disorders. Chemokine receptor (CCR) genotypes were recently identified, and the importance of their genetic polymorphisms in some autoimmune and infectious disorders has been demonstrated. To define the roles of the polymorphism of the CCR2 gene at codon 64 (CCR2-64I) and the 32-bp deletion in the coding region of CCR5 (CCR5Delta32) in Korean patients with myasthenia gravis (MG), we compared these genotypes in MG cases and healthy controls and investigated the clinical features associated with these genotypes. METHODS: One hundred and fifteen healthy controls (51 men and 64 women) and 109 MG patients (44 men and 65 women) from three University hospitals were included. We examined each patient for clinical features using electrophysiology tests, laboratory tests, and thymic pathology. The CCR2-64I and CCR5Delta32 polymorphisms were determined by the PCR-RFLP method. RESULTS: We detected no difference in the frequencies of CCR2-64I polymorphism between MG patients and healthy controls. All of the MG patients and the healthy controls were homozygous for the wild-type CCR5 genotype. The results of electrophysiological tests and thymic pathologies were not influenced by the type of CCR2-64I polymorphism. However, the anti-acetylcholine-receptor (AChR) antibody titer was higher in the CCR2 G/G genotype (13.34+/-12.71 nmol/L) than in the CCR2 A/A genotype (5.83+/-2.56 nmol/L). CONCLUSIONS: We found no evidence of an increased risk for MG associated with the CCR2-64I and CCR5Delta32 polymorphisms. However, the increased anti-AChR antibody titer in the patients with the CCR2 G/G genotype suggests that the CCR2 gene play a role in the pathophysiology of MG.

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This study aimed to clarify the morphologic variations of the Martin-Gruber anastomosis (MGA) by tracing the anastomotic fascicles. We used 102 upper limbs, and MGA was found in 39.2%. Among 12 instances of MGA between the branches innervating the flexor digitorum profundus muscle, eight anastomotic branches solely innervated the muscle without crossover from median to ulnar nerve. The results of the present study showed three morphologic features of MGA that could not be detected by an electrodiagnostic method.

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