Clinical Spectrum of Myelin Oligodendrocyte Glycoprotein-Immunoglobulin G-Associated Disease in Korean Children

Background@#and Purpose: The myelin oligodendrocyte glycoprotein (MOG) antibody is detected at a high rate in childhood acquired demyelinating syndrome (ADS). This study aimed to determine the diagnostic value of the MOG antibody in ADS and the spectrum of MOGantibody-positive demyelinating diseases in children. @*Methods@#This study included 128 patients diagnosed with ADS (n=94) or unexplained encephalitis (n=34). The MOG antibody in serum was tested using an in-house live-cell-based immunofluorescence assay. @*Results@#The MOG antibody was detected in 48 patients (46 ADS patients and 2 encephalitis patients, comprising 23 males and 25 females). Acute disseminated encephalomyelitis (ADEM) (35.4%) was the most-common diagnosis, followed by the unclassified form (17.4%), isolated optic neuritis (ON) (15.2%), neuromyelitis optica spectrum disorder (13.0%), multiple sclerosis (MS) (10.8%), other clinically isolated syndromes [monophasic event except ADEM, isolated ON, or transverse myelitis (TM)] (8.7%), and unexplained encephalitis (4.3%). At the initial presentation, 35 out of the 46 patients with ADS had brain lesions detected in magnetic resonance imaging, and 54% of these 35 patients had encephalopathy. Nine of the 11 patients without brain lesions exhibited only ON. Thirty-nine percent of the patients experienced a multiphasic event during the mean follow-up period of 34.9 months (range 1.4–169.0 months). Encephalopathy at the initial presentation was frequently confirmed in the monophasic group (p= 0.011). @*Conclusions@#MOG antibodies were identified in all pediatric ADS phenotypes except for monophasic TM. Therefore, the MOG antibody test is recommended for all pediatric patients with ADS, especially before a diagnosis of MS and for patients without a clear diagnosis.

A familial case of limb-girdle muscular dystrophy with CAV3 mutation

Limb-girdle muscular dystrophy (LGMD) is a group of muscular dystrophies that has extremely heterogeneous clinical features and genetic background. The caveolin-3 gene (CAV3) is one of the causative genes. LGMD appears as a clinical continuum, from isolated skeletal muscle involvement to long QT syndrome. Here we report two patients without apparent muscle weakness in a family with CAV3 mutation.A 7-month-old Korean boy visited our muscle clinic because of an incidental finding of elevated serum creatine kinase (CK) concentration (680 IU/L, reference range, 20-270 IU/L) without clinical symptoms. The patient was born after an uneventful pregnancy and showed normal developmental milestones. He developed pseudohypertrophy of his calf muscle during the follow-up. We obtained a muscle biopsy at age 14 months, which showed size variations and degenerating/regenerating myofibers with endomysial fibrosis and immunohistochemical evidence of normal dystrophin. Under the impression of LGMD, we performed target panel sequencing and identified a heterozygous in-frame mutation of CAV3, c.307_312delGTGGTG (p.Val103_Val104del). Immunohistochemical staining of muscle indicated complete loss of caveolin-3 compared with normal control muscle, which supported the variant's pathogenicity. We performed segregation analysis and found that the patient's mother had the same variant with elevated serum CK level (972 IU/L).We report on autosomal dominant familial caveolinopathy caused by a pathogenic variant in CAV3, which was asymptomatic until the fourth decade. This case highlights the utility of next generation sequencing in the diagnosis of muscular dystrophies and the additive role of muscle biopsy to confirm the variants.

Clinical and Radiologic Features of Pediatric Cerebral Venous Thrombosis in Korea / 대한소아신경학회지

PURPOSE: Cerebral venous thrombosis (CVT) is a rare cause of pediatric stroke. Our goal was to describe the clinical CVT features among pediatric patients presenting at a tertiary referral center. METHODS: Patient data was retrospectively collected from the charts of all pediatric patients (newborn to 18 years old) who were diagnosed with CVT at Seoul National University Children's Hospital between 2000 and 2016. Magnetic resonance imaging or venography was conducted for diagnostic confirmation. Modified Rankin Scale (mRS) was used to evaluate neurologic outcome. RESULTS: Twenty patients were diagnosed with CVT during the study period (16 male, 4 female). Median age was 4 years. The most common risk factor was systemic infection (6/20, 30.0%). Twelve patients initially presented with headache or vomiting (12/20, 60.0%). Seizure was in only 3 patients within 48 hours of symptom onset; however, as the clinical course progressed, seizure was the symptom that most frequently led to brain imaging (12/20, 60.0%). Thrombosis in the superior sagittal sinus was frequently associated with intracranial hemorrhage (4/11, 36.4%) and clinical seizure (9/11, 81.8%). Anticoagulation and/or antiplatelet agents were used in 16 patients (16/20, 80%). At the 3-month follow-up, 14 patients (14/20, 70%) had an mRS of 0 or 1, showing that most of these patients had no neurologic impairment. CONCLUSION: Seizure and signs of increased intracranial pressure are the most common manifestation of pediatric CVT. However, clinical features are diverse and include age at symptom onset and underlying risk factors. Despite diagnostic delay, neurologic outcome is favorable in most patients.

Epstein-Barr Virus Infection associated Transverse Myelitis with Brain Involvement in an Immunosuppressed Patient: A Case Report / 대한소아신경학회지

A 19-year-old girl with immunosuppressive agents of tacrolimus and mychophenolate mofetil following liver transplantation due to glycogen storage disease visited hospital due to lower extremity motor weakness and blurred vision. Motor power was checked as grade II in the upper extremities and grade 0 in the lower extremities with absence of deep tendon reflexes and anal sphincter dysfunction. The magnetic resonance imaging (MRI) showed increased T2 high signal intensity lesions from C4 to L2 level of spinal cord, cerebral cortex, and the left optic nerve. The cerebrospinal fluid (CSF) analysis showed pleocytosis. Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) was detected as 5,954 copies/mL in CSF whereas all other microbiologic tests were negative. Anti-aquaporin 4 antibody and oligoclonal band were not detected. Intravenous immunoglobulin, methylprednisolone pulse therapy and 3-week course of acyclovir were administered. Although motor power in the upper extremities recovered to grade V, motor power in the lower extremities did not show any improvement. The EBV viral load was not detected in the follow-up CSF examination. EBV infection in an immune-compromised patient could cause extensive demyelinating diseases in central nervous system and result in severe disability.