Clinical Heterogeneity in Korean Patients with Nemaline Myopathy

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.

Clinical Features and Genetic Analysis of Fascioscapulohumeral Muscular Dystrophy

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with contractions of the polymorphic D4Z4-repeat array in 4q35 and has the distinctive clinical presentation of an initial involvement of the facial, shoulder-girdle, and upper-arm muscles. The aim of the present study was to determine clinical characteristics in Korean patients with FSHD and potential relationships between contracted D4Z4-repeat size and the FSHD phenotype. METHODS: We studied 34 genetically confirmed patients who had repeat sizes less than 38 kb, and analyzed their clinical manifestations with a structured protocol. The expressed phenotypes were scored according to the Clinical Severity Score formulated by Ricci and van Overveld. RESULTS: The clinical spectrum ranged widely, from asymptomatic individuals with minimal signs to wheelchair- bound patients. The initial affects were mainly in the facial muscles (68.8%), followed by the shoulder-girdle muscle (28.1%). Asymmetric features of the face and shoulder girdle were also important findings (71.9% and 90.0%, respectively). Winging scapular (87.5%), transverse smile (84.4%), Beevor's sign (68.8%), and sleeping with eyes opened (59.4%) were clinically important signs. There was a significant negative correlation between repeat size and clinical severity (r=-0.38, p=0.03). CONCLUSIONS: Distinctive clinical characteristics of FSHD are descending progression and asymmetric distribution of the muscle weakness. Our results also confirmed that the severity of FSHD increases with decreasing D4Z4-repeat size.

Two Cases of Delayed Post-radiation Lower Cranial Nerve Palsies

Radiation-induced lower cranial neuropathy shows a clinical presentation similar to tumor recurrence or amyotrophic lateral sclerosis. We experienced two patients with bulbar palsies several years after radiotherapy for nasopharyngeal cancer. Brain magnetic resonance imaging showed no evidence of tumor recurrence. Electrophysiologic studies demonstrated mild denervation changes and myokymic discharges in muscles innervated by cranial nerves. Bulbar palsies progressed for 1 year then became stable. We emphasize the importance of myokymic discharges in the differential diagnosis of radiation-induced cranial neuropathy as radiation plexopathies.

Lower Leg MRI Features in Axonal Charcot-Marie-Tooth Patients with MFN2 Mutations

BACKGROUND: Mutations in mitofusin2 (MFN2) are a major underlying cause of axonal Charcot-Marie-Tooth neuropathy (CMT). It has been reported that patients with an early age of onset ( or =10 years, LO) in CMT2A with MFN2 mutations. There are few studies about CMT patients with MRI studies and we performed leg MRIs for better understanding of CMT2A. METHODS: We identified 19 patients (EO=10; LO=9) with MFN2 mutations. We used functional disability scales and CMT neuropathy scales for the grading of disability. Nerve conduction studies and MRIs of the lower leg were performed in all patients. RESULTS: We confirmed that EO had more severe leg muscle involvement than LO by leg MRI. In 7 out of 9 in LO, there were some degree of asymmetric leg muscle weakness and MRI findings explained the nature of asymmetry, that is, asymmetric cross-sectional areas or fatty infiltration. MRI of EO showed marked fatty infiltration on all three compartments whereas that of LO showed rather selective involvement of the posterior compartment. These results were well correlated with clinical findings that in LO, five patients could not do toe walking whereas only one could not do heel walking. CONCLUSIONS: MRI of the leg may be a useful tool for evaluating axonal CMT neuropathy, and asymmetric leg muscle weakness may be the characteristics of an axonal CMT. In addition, more prominent involvement of the posterior leg in LO is a very interesting phenomenon, which is in contrast to the length-dependent involvement in congenital demyelinating neuropathy.

A Family of Bethlem Myopathy

Bethlem myopathy (BM) is an early-onset benign autosomal dominant myopathy characterized by proximal muscle weakness and multiple contractures. It is caused by mutations in the three genes encoding collagen VI, which is a ubiquitous extracellular matrix protein forming a microfibrillar network in close association with the basement membrane. Here, we present a family with BM which is the first reported Korean case.

Prevalence and Risk Factors of Silent Cerebral Infarction in Normal Adults: Single Institute Study

BACKGROUND: Silent cerebral infarcts (SCI) are commonly seen in the elderly and are associated with clinically apparent stroke and vascular dementia. Known cardiovascular risk factors, such as arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia and heart disease may increase the risk of SCI. We investigated the prevalence of, and risk factors for, SCI in an apparently normal adult population. METHODS: Two hundred eighty seven neurologically normal adults (mean age, 51.3 +/- 10.4; 145 men) underwent brain magnetic resonance imaging (MRI) at the Center for Health Promotion at Kangnam St. Mary Hospital and cardiovascular risk factors were assessed by interview and physical examination. We performed chi-square test and 2-sample t-test for univariate analysis and multiple logistic regressions for multivariate analysis to evaluate the prevalence and risk factors of SCI. RESULTS: SCI lesions were observed in 84 subjects (29.8%). Univariate analysis showed that old age, hypertension and abnormal pulmonary function tests were associated with SCI. Old age (over 55) (OR 4.521; 95%CI, 2.631~7.768), and an abnormal pulmonary function test (OR, 3.100; 95%CI, 1.267~7.587) were demonstrated to be independent risk factors for SCI on multivariate analysis. CONCLUSIONS: Silent brain infarcts commonly affect the elderly, especially those over 55. Old age, hypertension, and abnormal pulmonary function tests are associated with SCI.

Reliability and Validity of the Korean Version of Revised form of Hasegawa Dementia Scale (K-HDS)

BACKGROUND: The revised version of the Hasegawa Dementia Scale (HDS-R) is a useful dementia screening tool with a test for frontal lobe function and is relatively less influenced by education level and linguistic ability. We developed a Korean version of HDS-R (K-HDS) by translating the HDS-R to screen dementia patients in the Korean elderly. METHODS: The basic structure of the HDS-R was preserved but some questions were modified for lingual and cultural difference. It was administrated along with the Korean version of the MMSE, Korean Dementia Screening Questionnaire, Short form Samsung Dementia Questionnaire and Clinical Dementia Rating (CDR) scales, to 151 patients (55 Alzheimer's disease, 73 vascular dementia, 23 others) with mild to moderate dementia and to 225 elderly control subjects. To screen dementia, the optimal cut-off score was estimated by receiver operating characteristic (ROC) curve analysis. By comparing the Area Under the Curve, the diagnostic efficiency of K-HDS was compared with that of K-MMSE. RESULTS: The K-HDS had good internal consistency (Crohnbach's alpha coefficient=0.66), inter-rater reliability (r=0.95), and test-retest reliability (r=0.92). K-HDS was well correlated with the K-MMSE (r=0.84) and CDR (r=-0.67), which confirms the validity of this test. The optimal cut-off score was different according to educational level. In patients with an educational level less than 10 years, the cut-off score was 20 with the sensitivity of 87.0% and the specificity of 83%. With an educational level of 10 years or more, the cut-off score was 22 with the sensitivity of 93.0% and the specificity of 89.6%. The overall diagnostic efficiency of K-HDS was superior to that of K-MMSE especially in patients with an educational level of less than 10 years. CONCLUSIONS: The K-HDS is a reliable, valid and useful tool to screen dementia in the Korean elderly.

An Autopsy Case of Pick's Disease

Pick's disease is a rare neurodegenerative disorder presenting cortical type of dementia. Pick's disease shows unique clinical and pathological features, that are due to a degeneration of fronto-temporal lobes of the cerebrum. The authors experienced a case of Pick's disease in a 58-year-old male patient who had dementia symptoms for five years. The patient showed compulsive behavior since five years ago. Memory decline started from four years ago and progressed. Brain CT disclosed lobar atrophy of the cerebral gyri in frontal and temporal lobes. He died of septicemia associated with aspiration pneumonia. At autopsy, both cerebral hemispheres showed marked encephalomalacia. The gyral atrophy was moderately severe in prefrontal and anterior temporal lobes. Coronal section disclosed moderate dilatation of the lateral ventricles. Microscopically, there were marked neuronal loss in prefrontal and anterior temporal cortices. Also noted were Pick's cells and Pick's body in occasional pyramidal cells preserved.