Predominant Myofibrillar Pathology with Preserved Sarcolemmal Aquaporin 4 Immunoreactivity in a Patient with Neuromyelitis Optica-Associated HyperCKemia / 고신대학교의과대학학술지

A 49-year-old man developed recurrent myalgia and hyperCKemia during acute attacks of neuromyelitis optica. Muscle biopsy was performed, and the pathological findings were analyzed. Predominant myofibrillar pathology was observed, which constitutes a unique finding that has not been reported before. This case result shows that neuromyelitis optica-associated hyperCKemia can produce variable pathologic phenotypes. Further studies are needed to elucidate the relationship between myofibril destruction and aquaporin 4 autoimmunity.

Comparison of Neuropathic Pain in Neuromyelitis Optica Spectrum Disorder and Multiple Sclerosis

3) of the pain in domains of tingling/prickling sensation (p=0.024), mechanical allodynia (p=0.027), sudden pain attacks (p=0.018), and thermal hyperalgesia (p=0.002) were significantly more frequent in NMOSD compared to MS patients. Among the patients experiencing pain with a neuropathic component, total pain-related interference (p=0.045) scores were significantly higher in NMOSD patients than in MS patients. In daily life, pain interfered with normal work (p=0.045) and relationships with other people (p=0.039) more often in NMOSD patients than in MS patients. Although pain medication was prescribed more frequently in NMOSD patients, the percentage of patients experiencing medication-related pain relief was lower in those patients.CONCLUSIONS: The severity of neuropathic pain and the pain-related interference in daily life were greater in NMOSD patients than in MS patients. Individualized analgesic management should be considered based on a comprehensive understanding of neuropathic pain in these patients.

Validation of the Korean Version of the 12-Item Multiple Sclerosis Walking Scale and Application to Neuromyelitis Optica Spectrum Disorder

Background@#and PurposeGait problems are a primary complaint in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported measure assessing the impact of MS on the walking ability. We aimed to adapt and validate the Korean version of the MSWS-12 for the Korean population with MS and NMOSD. @*Methods@#Thirty-four MS and 35 NMOSD patients were recruited. The MSWS-12 questionnaire was translated into the Korean language and evaluated for its validity and reliability in these patients. @*Results@#The MS and NMOSD patients had mean ages of 35.9 and 42.1 years, respectively, median disease durations of 5.6 and 7.2 years, median Expanded Disability Status Scale (EDSS) scores of 2.75 (range, 0–6.5) and 3.5 (range, 0–7.5), and median baseline MSWS-12 total scores of 25 [interquartile range (IQR), 2.60–53.65] and 25 (IQR, 7.29–50.00). The baseline MSWS-12 total score in the patients with MS showed strong correlations with scores for the EDSS, timed 25-foot walk (T25FW), Multiple Sclerosis Impact Scale-29 (MSIS-29) physical dimension, and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS), with Spearman's correlation coefficients (ρ) of 0.922, 0.756, 0.933, and −0.874, respectively. In patients with NMOSD, the baseline MSWS-12 total score showed strong correlations with scores for the EDSS, MSIS-29 physical dimension, and SF-36 PCS (ρ=0.769, 0.910, and −0.852, respectively), and moderate correlations with scores for the T25FW and Fatigue Severity Scale-9 (ρ=0.597 and 0.630, respectively). @*Conclusions@#The Korean version of the MSWS-12 appears to be a valid and reliable scale that can be used for Korean patients with MS. The MSWS-12 can also be applied to patients with NMOSD.

Real-World Effectiveness of Disease-Modifying Therapies in Korean Patients with Relapsing Multiple Sclerosis

BACKGROUND AND PURPOSE: This study assessed the long-term outcomes of disease-modifying therapies (DMTs) in Korean multiple sclerosis (MS) patients treated in real-world clinical settings in Korea. METHODS: We retrospectively evaluated the medical records of 160 patients with an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS who were treated for at least 2 years. A status of 3 for no evidence of disease activity (NEDA3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging (MRI) evaluations. RESULTS: Patients who were initially treated with interferon β (n=152), glatiramer acetate (n=6), or teriflunomide (n=2) were included. The mean disease duration was 8.2 years. Compared to pretreatment, annualized relapse rates were significantly reduced after treatment [from 1.0±0.8 to 0.2±0.4 (mean±standard deviation), p < 0.001]. At the follow-up, 79 patients (49%) had changed their treatment regimen due to lack of efficacy (33%), side effects (14%), or other reasons (2%). Disability progression was observed in 18% of the patients over a mean treatment duration of 5.7 years. After 2 years, NEDA3 was observed in 38% of the patients. Loss of NEDA3 at 2 years was associated with long-term disability progression [odds ratio (OR)=17.975, p=0.003]. Poor response to first-line treatment was independently associated with a delay in treatment from disease onset (OR=1.238, p=0.049) and 10 or more brain lesions in the initial MRI (OR=3.648, p=0.047). CONCLUSIONS: This study has provided real-world evidence that DMTs are effective in reducing disease activity and disability progression in Korean MS patients.

A Variant Guillain-Barré Syndrome with Anti-Ganglioside Complex Antibody

BACKGROUND: Recently, anti-ganglioside complex (GSC) antibodies were discovered among the various subtypes of Guillain-Barré syndrome. GSC is the novel glycoepitopes formed by two individual ganglioside molecules. CASE REPORT: We present a 36-year-old man with overlap Miller Fisher syndrome and acute bulbar palsy who had anti-GSC antibody that provided diagnostic robustness. CONCLUSION: Anti-GSC testing could be considered important in patients who show atypical manifestation with negative antibody reaction against each constituent ganglioside.

Emergence of Myasthenia Gravis with Myositis in a Patient Treated with Pembrolizumab for Thymic Cancer

No abstract available.

Neutralizing Antibodies Against Interferon-Beta in Korean Patients with Multiple Sclerosis

BACKGROUND AND PURPOSE: Patients treated with interferon-beta (IFN-β) can develop neutralizing antibodies (NAbs) against IFN-β that can negatively affect the therapeutic response. This study assessed the prevalence of NAbs and the impact of NAb positivity on the therapeutic response to IFN-β in Korean patients with multiple sclerosis (MS). METHODS: This was a multicenter study involving 150 MS patients from 9 Korean medical centers who were treated with IFN-β for at least 6 months. Sera that had not been influenced by acute treatment were assessed for NAbs using a luciferase reporter gene assay. To evaluate the association between persistent positivity for NAbs and disease activity, NAbs were tested at 2 different time points in 75 of the 150 patients. Disease activity was defined as the presence of clinical exacerbations and/or active MRI lesions during a 1-year follow-up after NAb positivity was confirmed. RESULTS: NAbs were found in 39 of the 150 (26%) MS patients: 30 of the 85 (35%) who were treated with subcutaneous IFN-β-1b, 9 of the 60 (15%) who were treated with subcutaneous IFN-β-1a, and 0 of the 5 (0%) who were treated with intramuscular IFN-β-1a. Thirty of the 39 patients exhibiting NAb positivity were tested at different time points, and 20 of them exhibited persistent NAb positivity. Disease activity was observed more frequently in patients with persistent NAb positivity than in those with transient positivity or persistent negativity [16/20 (80%) vs. 4/55 (7%), respectively; p < 0.001]. When disease activity was compared between patients with persistent and transient NAb positivity, the difference was unchanged and remained statistically significant [16/20 (80%) vs. 2/10 (20%), p=0.004]. CONCLUSIONS: These results further support that persistent NAb positivity is associated with disease activity in MS patients treated with IFN-β.

The early diagnosis and treatments in multiple sclerosis / 고신대학교의과대학학술지

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system that leads to neurological disability. The diagnosis of MS relies on the MRI criteria, which can demonstrate dissemination in space and time. Exclusion of other demyelinating mimics is essential because there are no specific biomarker for MS and MRI criteria are still have imperfect. There is incremental improvements in MS treatment option that have contributed to the delay of disease progression. The early initiation of DMT may ameliorate the neurological disability. In this review, we discusses the new diagnostic MS criteria and summarize the evidences supporting the early treatment in the course of MS.

Acute Myeloradiculitis Associated with Herpes Simplex Virus Type 2 Presenting with Acute Flaccid Paralysis

We describe two patients with acute myeloradiculitis associated with herpes simplex virus type 2 (HSV-2). They were previously healthy and immunocompetent and had no history of herpes infection or rash. Myeloradiculitis manifested as an acute flaccid paralysis that primarily involved the conus medullaris and cauda equina. laccid paralysis can be caused by HSV-2 myeloradiculitis, and so early antiviral treatment should be considered.

Cerebral Cortex Involvement in Neuromyelitis Optica Spectrum Disorder

BACKGROUND AND PURPOSE: Brain lesions involving the cerebral cortex are rarely described in patients with neuromyelitis optica spectrum disorder (NMOSD), in contrast to multiple sclerosis. We investigated cerebral cortex involvement using conventional brain magnetic resonance imaging (MRI) in anti-aquaporin-4 (AQP4)-antibody-positive NMOSD patients. METHODS: The study enrolled 215 NMOSD patients who were seropositive for the anti-AQP4 antibody from 5 referral hospitals, and retrospectively analyzed their demographic, clinical, and MRI findings. Abnormal cerebral cortex lesions on brain MRI were identified by a neuroradiologist and two neurologists using consensus. RESULTS: Most of the 215 enrolled patients (87%) were female. The median age at onset was 22.5 years (range: 15-36 years) and the mean follow-up duration was 123 months. Brain lesions were found in 143 of 194 patients (74%) in whom MRI was performed during follow-up. Brain lesions involving the cerebral cortex were identified in 6 of these 194 patients (3.1%). Five of the patients were female, and the six patients together had a median age of 29 years (range: 15-36 years) at the time of lesion presentation. Three of them showed leptomeningeal enhancement in the lesions. At presentation of the cortex-involving lesions, five of these patients were not being treated at the time of presentation, while the sixth was being treated with interferon-beta. CONCLUSIONS: Although rare, cortical involvement occurs in NMOSD and is commonly combined with leptomeningeal enhancement. We speculate that this occurs only in patients who are not treated appropriately with immunosuppressant drugs.

Serial MRI of Hypoxic Brain Damage after Hydrogen Sulfide Exposure

Hydrogen sulfide is a colorless gas and frequently lethal occupational hazard that causes tissue hypoxia with prominent neurological signs. Depending on the amount of exposure, many neurotoxic effects such as headache, disequilibrium, and loss of consciousness have been reported. However, a few address the brain MRI findings in hydrogen sulfide poisoning. We report serial brain MRI findings in a patient with hydrogen sulfide intoxication.

Meningoencephalitis associated with Parvovirus B19 Infection in an Immunocompetent Patient / 고신대학교의과대학학술지

Parvovirus B19 (PVB19) infection is a rare cause of meningoencephalitis. A 53-year-old previously healthy woman presented with fever, headache, and multiple erythema on the both legs. Cerebrospinal fluid study revealed pleocytosis and elevated opening pressure and protein level. Brain MRI showed multiple, asymmetric, hyperintensity in the brain stem, basal ganglia, white matter, and gray matter. Anti-B19 IgM antibody and PCR for PVB19 were positive in serum. Clinician should consider PVB19 infection in any case of acute febrile illness with erythema and meningoencephalitis.

Prevalence of Anti-Ganglioside Antibodies and Their Clinical Correlates with Guillain-Barre Syndrome in Korea: A Nationwide Multicenter Study

BACKGROUND AND PURPOSE: No previous studies have investigated the relationship between various anti-ganglioside antibodies and the clinical characteristics of Guillain-Barre syndrome (GBS) in Korea. The aim of this study was to determine the prevalence and types of anti-ganglioside antibodies in Korean GBS patients, and to identify their clinical significance. METHODS: Serum was collected from patients during the acute phase of GBS at 20 university-based hospitals in Korea. The clinical and laboratory findings were reviewed and compared with the detected types of anti-ganglioside antibody. RESULTS: Among 119 patients, 60 were positive for immunoglobulin G (IgG) or immunoglobulin M antibodies against any type of ganglioside (50%). The most frequent type was IgG anti-GM1 antibody (47%), followed by IgG anti-GT1a (38%), IgG anti-GD1a (25%), and IgG anti-GQ1b (8%) antibodies. Anti-GM1-antibody positivity was strongly correlated with the presence of preceding gastrointestinal infection, absence of sensory symptoms or signs, and absence of cranial nerve involvement. Patients with anti-GD1a antibody were younger, predominantly male, and had more facial nerve involvement than the antibody-negative group. Anti-GT1a-antibody positivity was more frequently associated with bulbar weakness and was highly associated with ophthalmoplegia when coupled with the coexisting anti-GQ1b antibody. Despite the presence of clinical features of acute motor axonal neuropathy (AMAN), 68% of anti-GM1- or anti-GD1a-antibody-positive cases of GBS were diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (AIDP) by a single electrophysiological study. CONCLUSIONS: Anti-ganglioside antibodies were frequently found in the serum of Korean GBS patients, and each antibody was correlated strongly with the various clinical manifestations. Nevertheless, without an anti-ganglioside antibody assay, in Korea AMAN is frequently misdiagnosed as AIDP by single electrophysiological studies.

Validity of Korean Versions of the Multiple Sclerosis Impact Scale and the Multiple Sclerosis International Quality of Life Questionnaire

BACKGROUND AND PURPOSE: Assessment of the health-related quality of life (HRQoL) is important in clinical evaluations of multiple sclerosis (MS) patients for quantifying the impact of illness and treatment on their daily lives. Although MS-specific HRQoL instruments have been used internationally, there are no data regarding HRQoL instruments specifically designed for patients with MS in Korea. The objective of this study was to determine the reliability and validity of the Korean Multiple Sclerosis Impact Scale (MSIS-29) and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire. METHODS: Fifty-six patients with MS were recruited from June 2009 to February 2010 at the National Cancer Center in Korea. The original English versions of the MSIS-29 scale and the MusiQoL questionnaire were translated into Korean and evaluated for their acceptability, reliability, and validity. RESULTS: The patients wereaged 36.5+/-8.6 years (mean+/-SD; range, 20-56 years). Their score on the Expanded Disability Status Scale was 2.0+/-1.9 (mean; range, 0-7.5), and their disease duration was 5.2+/-4.7 years (mean+/-SD; range, 1-24 years). The Korean versions of the MSIS-29 and MusiQoL questionnaires showed satisfactory psychometric properties, including construct validity (item-internal consistencies of 0.59-0.95 and 0.59-0.92, respectively; item-discriminant validities of 95-100% and 93.8-100%), internal consistency (Cronbach's alpha coefficients of 0.96-0.97 and 0.77-0.96), reliability (intraclass correlation coefficients of 0.78-0.90 and 0.50-0.93), unidimensionality (Loevinger scalability coefficients of 0.70-0.78 and 0.63-0.90), and acceptability. External validity testing indicated the presence of significant correlations between similar aspects of the two questionnaires. CONCLUSIONS: The Korean translated versions of the MSIS-29 and MusiQoL questionnaires demonstrated reliability and validity for measuring HRQoL in Korean patients with MS.

Molar Tooth Sign in Joubert Syndrome

No abstract available.

Clinical and Pathological Features of Clevudine Induced Myopathy

BACKGROUND: Clevudine (Revovir(R)) is a recently introduced antiviral drug, and clinical trials have demonstrated its potent, sustained antiviral activity without specific adverse events. However, several studies have found severe myopathy during clevudine therapy. Our study aimed to summarize the clinical and pathological features of clevudine-induced myopathy. METHODS: We analyzed the demographic data, clinical features, and pathologic findings of 18 consecutive hepatitis-B patients who developed skeletal myopathy during clevudine therapy. RESULTS: The 18 patients comprised 11 women and 7 men aged 48.2+/-14.0 years (mean+/-standard deviation; range 28-74 years). Each of the 18 patients was treated with clevudine for at least 5 months (range 5-20 months) before the development of symptoms. In all patients the main symptom was proximal muscular weakness that progressed slowly over several months. Elevated creatine kinase and myopathic patterns on electromyography were found. Muscle biopsies revealed severe myonecrosis associated with numerous ragged red fibers and cytochrome-c-oxidase-negative fibers, mitochondrial proliferation, and predominant type-II fiber atrophy. The muscle weakness gradually improved within 20 weeks after discontinuation of clevudine. CONCLUSIONS: Clevudine therapy can induce myopathy associated with mitochondrial toxicity. Careful clinical and laboratory monitoring of the skeletal muscle dysfunction is required in patients receiving clevudine therapy.

Clinical Efficacy of Plasmapheresis in Patients with Neuromyelitis Optica Spectrum Disorder and Effects on Circulating Anti-Aquaporin-4 Antibody Levels

BACKGROUND AND PURPOSE: Although plasmapheresis is becoming standard practice as a rescue therapy for neuromyelitis optica (NMO), evidence for the therapeutic efficacy of plasmapheresis is limited, and the effect of plasmapheresis on anti-aquaporin-4 (AQP4) levels in patients with NMO has not been reported. Here, our objective was to evaluate the clinical efficacy of therapeutic plasmapheresis and its effect on anti-AQP4 antibody levels in patients with NMO spectrum disorder (NMOSD). METHODS: We retrospectively reviewed the medical records of 15 patients with NMOSD who had 18 acute attacks and received plasmapheresis because they did not respond to high-dose intravenous methylprednisolone (IVMP) therapy. Anti-AQP4 antibodies were measured before and after plasmapheresis. The primary outcomes were functional improvements immediately and 6 months after plasmapheresis, and the secondary outcome was the change in anti-AQP4 antibody serum levels following plasmapheresis. RESULTS: Plasmapheresis following IVMP therapy led to significant improvement in 50% of the 18 attacks in 15 patients immediately after the procedure was completed, and in 78% (14 attacks) after 6 months. Plasmapheresis was generally well tolerated in all patients. Anti-AQP4 antibody serum levels declined significantly following plasmapheresis, to a mean of 15% of the preplasmapheresis levels. Lower scores on the visual outcome scale recorded before an attack were associated with significant immediate improvement upon the completion of plasmapheresis (p=0.03). CONCLUSIONS: Plasmapheresis following IVMP therapy effectively removed anti-AQP4 antibodies and was accompanied by a substantial improvement in the neurological disability of patients with NMOSD. Lower levels of pre-existing neurological damage may be associated with an improved acute response to plasmapheresis.

Diagnostic Value of Cerebrospinal Fluid Level of Carcinoembryonic Antigen in Patients with Leptomeningeal Carcinomatous Metastasis

BACKGROUND AND PURPOSE: Multifocal seeding of the leptomeninges by malignant cells, which is usually referred to as leptomeningeal carcinomatous metastasis, produces substantial morbidity and mortality. The diagnosis of leptomeningeal metastasis is usually established by cerebrospinal fluid (CSF) investigation, including cytology, cell counts, protein, glucose, and a tumor marker such as carcinoembryonic antigen (CEA). This study examined the diagnostic value of CEA in the CSF. METHODS: We measured the CSF CEA level in 32 patients with leptomeningeal metastasis. The control group consisted of 19 cancer patients without leptomeningeal metastasis. CEA was measured by the chemiluminescent emission method. RESULTS: The CEA level was significantly higher in patients with leptomeningeal metastasis than in the control group (p<0.005). The level of CSF protein was higher and that of CSF glucose was lower in patients with leptomeningeal metastasis than in the control group (p<0.005). CONCLUSIONS: The CSF CEA level is useful for diagnosing leptomeningeal carcinomatous metastasis. The CSF levels of protein and glucose are also useful in the diagnosis.

A Case of Dopamine Dysregulation Syndrome and Repetitive Behavior Caused by Levodopa in Parkinson's Disease

Levodopa treatment in Parkinson's disease (PD) can cause a wide range of non-motor manifestations including poor impulse control and stereotyped behaviors. Punding is a term used to describe complex prolonged, purposeless and repetitive behavior in patients under dopamine replacement therapy. We report a 64-year-old PD patient who, concomitantly with self-increment of levodopa, developed punding behaviors in association with dopamine dysregulation syndrome. Gradual reduction of dopaminergic medication partially alleviated repetitive behavior over time.

Reversible Encephalopathy Induced by Metronidazole

We describe a patient with metronidazole-induced reversible encephalopathy characterized by dizziness, dysar- thria and ataxia. Brain T2 weighted magnetic resonance images(MRI) show increased signal intensities of the dentate nucleus of the cerebellum. Both neurological signs and abnormalities on MRI resolved dramatically with discontinuation of metronidazole.