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Background@#and Purpose Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy, and necessitates a multimodal evaluation to ensure optimal surgical treatment. This study aimed to determine the supportive value of the morphometric analysis program (MAP) in detecting FCD using data from a single institution in Korea. @*Methods@#To develop a standard reference for the MAP, normal-looking MRIs by two scanners that are frequently used in this center were chosen. Patients with drug-resistant epilepsy and FCD after surgery were candidates for the analysis. The three-dimensional T1-weighted MRI scans of the patients were analyzed as test cases using the MAP. @*Results@#The MRI scans of 87 patients were included in the analysis. The radiologist detected abnormal findings correlated with FCD (RAD positive [RAD(+)]) in 34 cases (39.1%), while the MAP could detect FCD in 25.3% of cases. A combination of the MAP (MAP[+] cases) with interpretations by the radiologist increased the detection to 42.5% (37 cases). The lesion detection rate was not different according to the type of reference scanners except in one case. MAP(+)/RAD(-) presented in three cases, all of which had FCD type IIa. The detection rate was slightly higher using the same kind of scanner as a reference, but not significantly (35.0% vs. 22.4% p=0.26). @*Conclusions@#The results of postprocessing in the MAP for detecting FCD did not depend on the type of reference scanner, and the MAP was the strongest in detecting FCD IIa. We suggested that the MAP could be widely utilized without developing institutional standards and could become an effective tool for detecting FCD lesions.
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Background@#and Purpose Perampanel (PER) is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist used to treat focal and generalized epilepsy. Comprehensive data from real-world settings with long-term follow-ups are still scarce. This study aimed to determine the factors related to PER retention and the polytherapy pattern with PER. @*Methods@#We reviewed all patients with epilepsy with a history of PER prescription during 2008–2017 and over a follow-up of >3 years. PER usage patterns and associated factors were analyzed. @*Results@#Among the 2,655 patients in the cohort, 328 (150 females, 178 males) were enrolled.The ages at onset and diagnosis were 21.1±14.7 years and 25.6±16.1 years (mean±standard deviation), respectively. The age at the first visit to our center was 31.8±13.8 years. Seizure types were focal, generalized, and unknown onset in 83.8%, 15.9%, and 0.3% of patients, respectively. The most common etiology was structural (n=109, 33.2%). The maintenance duration of PER was 22.6±19.2 months (range=1–66 months). The initial number of concomitant antiseizure medications was 2.4±1.4 (range=0–9). The most common regimen was PER plus levetiracetam (n=41, 12.5%). The median number of 1-year seizures before PER usage was 8 (range=0–1,400). A seizure reduction of >50% was recorded in 34.7% of patients (52.0% and 29.2% in generalized and focal seizures, respectively). The 1-, 2-, 3-, 4-, and 5-year retention rates for PER were 65.3%, 50.4%, 40.4%, 35.3%, and 21.5%, respectively. A multivariate analysis indicated that lower age at onset was associated with longer retention (p=0.01). @*Conclusions@#PER was safely used in patients with diverse characteristics and was maintained for a long time in a real-world setting, especially in patients with a lower age at onset.
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Background@#and Purpose Japanese encephalitis (JE) is caused by the JE virus of the Flaviviridae family and is spread by mosquito bites, and no specific antiviral treatment for it exists. Here we describe the clinical presentations, laboratory findings, clinical outcomes, and adverse events after combination treatment of immunoglobulin, ribavirin, and interferon-α2b administered to patients with JE. @*Methods@#Data were collected and reviewed from a prospective cohort of encephalitis patients admitted to Seoul National University Hospital between August 1, 2010 and October 31, 2019.We reviewed the medical records of the patients diagnosed with JE and treated either with supportive care only or with combination treatment of intravenous immunoglobulin, oral ribavirin, and subcutaneous interferon-α2b. @*Results@#Eleven patients were diagnosed with laboratory-confirmed JE based on the diagnosis criteria of JE. The median age was 61 years, and five patients were male. Eight patients were treated with the combination therapy, while three patients received supportive management only. Four of the eight patients (50%) treated with the combination therapy showed partial recovery, while one patient (12.5%) showed complete recovery. Two patients experienced hemolytic anemia related to ribavirin and febrile reaction to immunoglobulin, respectively. Among the three patients who received supportive management only, one (33.3%) showed partial recovery and the other two (67.7%) did not show improvement. @*Conclusions@#Combination treatment of immunoglobulin, ribavirin, and interferon-α2b was found to be tolerable in JE in this study. Further studies of appropriate designs and involving larger numbers of patients are warranted to explore the efficacy of this combination therapy.
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Background@#and Purpose Japanese encephalitis (JE) is caused by the JE virus of the Flaviviridae family and is spread by mosquito bites, and no specific antiviral treatment for it exists. Here we describe the clinical presentations, laboratory findings, clinical outcomes, and adverse events after combination treatment of immunoglobulin, ribavirin, and interferon-α2b administered to patients with JE. @*Methods@#Data were collected and reviewed from a prospective cohort of encephalitis patients admitted to Seoul National University Hospital between August 1, 2010 and October 31, 2019.We reviewed the medical records of the patients diagnosed with JE and treated either with supportive care only or with combination treatment of intravenous immunoglobulin, oral ribavirin, and subcutaneous interferon-α2b. @*Results@#Eleven patients were diagnosed with laboratory-confirmed JE based on the diagnosis criteria of JE. The median age was 61 years, and five patients were male. Eight patients were treated with the combination therapy, while three patients received supportive management only. Four of the eight patients (50%) treated with the combination therapy showed partial recovery, while one patient (12.5%) showed complete recovery. Two patients experienced hemolytic anemia related to ribavirin and febrile reaction to immunoglobulin, respectively. Among the three patients who received supportive management only, one (33.3%) showed partial recovery and the other two (67.7%) did not show improvement. @*Conclusions@#Combination treatment of immunoglobulin, ribavirin, and interferon-α2b was found to be tolerable in JE in this study. Further studies of appropriate designs and involving larger numbers of patients are warranted to explore the efficacy of this combination therapy.
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Background@#and PurposeThe first-line medications for the symptomatic treatment of rapid eye movement sleep behavior disorder (RBD) are clonazepam and melatonin taken at bedtime. We aimed to identify the association between depression and treatment response in patients with idiopathic RBD (iRBD). @*Methods@#We reviewed the medical records of 123 consecutive patients (76 males; age, 66.0±7.7 years; and symptom duration, 4.1±4.0 years) with iRBD who were treated with clonazepam and/or melatonin. Clonazepam and melatonin were initially administered at 0.25–0.50 and 2 mg/day, respectively, at bedtime, and the doses were subsequently titrated according to the response of individual patients. Treatment response was defined according to the presence or absence of any improvement in dream-enacting behaviors or unpleasant dreams after treatment. @*Results@#Forty (32.5%) patients were treated with clonazepam, 56 (45.5%) with melatonin, and 27 (22.0%) with combination therapy. The doses of clonazepam and melatonin at followup were 0.5±0.3 and 2.3±0.7 mg, respectively. Ninety-six (78.0%) patients reported improvement in their RBD symptoms during a mean follow-up period of 17.7 months. After adjusting for potential confounders, depression was significantly associated with a negative treatment response (odds ratio=3.76, 95% confidence interval=1.15–12.32, p=0.029). @*Conclusions@#We found that comorbid depression is significantly associated with a negative response to clonazepam and/or melatonin in patients with iRBD. Further research with larger numbers of patients is needed to verify our observations and to determine the clinical implications of comorbid depression in the pathophysiology of iRBD.
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Murine typhus is one of the most prevalent rickettsial infections in the world, caused by the bacterial genus Rickettsia. Though the disease manifests a relatively benign clinical course with fever, rash, and headache being the 3 classic symptoms, neurological complications may arise in patients that could become permanent. In this case study, a patient with a brain abscess caused by R typhi infection is described. Based upon the recent reemergence of arthropod-borne disease, the findings in this case are significant; R typhi can cause a brain abscess that mimics a brain tumor, which delays the diagnosis and appropriate management of the disease. Murine typhus should always be considered when performing the differential diagnosis of brain abscesses in South Korea.
Subject(s)
Humans , Brain Abscess , Brain Neoplasms , Brain , Diagnosis , Diagnosis, Differential , Exanthema , Fever , Headache , Korea , Rickettsia , Typhus, Endemic Flea-BorneABSTRACT
OBJECTIVE: Huntington's disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect. METHODS: We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line. Exosomes were then harvested from these cells using an optimized protocol. The exosomes (Exo-124) exhibited a high level of miR-124 expression and were taken up by recipient cells. RESULTS: When Exo-124 was injected into the striatum of R6/2 transgenic HD mice, expression of the target gene, RE1-Silencing Transcription Factor, was reduced. However, Exo-124 treatment did not produce significant behavioral improvement. CONCLUSION: This study serves as a proof of concept for exosome-based delivery of miRNA in neurodegenerative diseases.
Subject(s)
Animals , Mice , Cell Line , Exosomes , Huntington Disease , Methods , MicroRNAs , Neurodegenerative Diseases , Transcription FactorsABSTRACT
Tryptophan metabolites regulate a variety of physiological processes, and their downstream metabolites enter the kynurenine pathway. Age-related changes of metabolites and activities of associated enzymes in this pathway are suggestable and would be potential intervention targets. Blood levels of serum tryptophan metabolites in C57BL/6 mice of different ages, ranging from 6 weeks to 10 months, were assessed using high-performance liquid chromatography, and the enzyme activities for each metabolic step were estimated using the ratio of appropriate metabolite levels. Mice were subjected to voluntary chronic aerobic exercise or high-fat diet to assess their ability to rescue age-related alterations in the kynurenine pathway. The ratio of serum kynurenic acid (KYNA) to 3-hydroxylkynurenine (3-HK) decreased with advancing age. Voluntary chronic aerobic exercise and high-fat diet rescued the decreased KYNA/3-HK ratio in the 6-month-old and 8-month-old mice groups. Tryptophan metabolites and their associated enzyme activities were significantly altered during aging, and the KYNA/3-HK ratio was a meaningful indicator of aging. Exercise and high-fat diet could potentially recover the reduction of the KYNA/3-HK ratio in the elderly.
Subject(s)
Aged , Animals , Humans , Infant , Mice , Aging , Chromatography, Liquid , Diet, High-Fat , Exercise , Kynurenic Acid , Kynurenine , Physiological Phenomena , TryptophanABSTRACT
BACKGROUND AND PURPOSE: Hypertrophic pachymeningitis (HP) is a rare disease caused by autoimmunity in the meninx that causes various neurologic symptoms, including headache, seizures, weakness, paresthesia, and cranial nerve palsies. Although the first-line therapy for HP is steroids, many HP cases are refractory to steroids or recur when the steroids are tapered. Here we report three HP cases that were successfully treated with rituximab (RTX). METHODS: From an institutional cohort recruited from April 2012 to July 2016, three HP cases that were identified to be steroid-refractory were treated with RTX (four weekly doses of 375 mg/m²). Clinical improvement was assessed by the number of relapses of any neurologic symptom and the largest dural thickness in MRI. RESULTS: All three patients were recurrence-free of neurologic symptoms and exhibited prominent decreases in the dural thickness after RTX treatment. No adverse events were observed in the patients. CONCLUSIONS: We suggest RTX as a second-line therapy for steroid-refractory HP. Further studies are warranted to confirm this observation in a larger population and to consider RTX as a first-line therapy.
Subject(s)
Humans , Autoimmunity , Cohort Studies , Cranial Nerve Diseases , Headache , Magnetic Resonance Imaging , Meningitis , Neurologic Manifestations , Paresthesia , Rare Diseases , Recurrence , Rituximab , Seizures , SteroidsABSTRACT
BACKGROUND AND PURPOSE: Herpes simplex encephalitis (HSE) is the most common type of sporadic encephalitis worldwide, and it remains fatal even when optimal antiviral therapy is applied. There is only a weak consensus on the clinical outcomes and prognostic factors in patients with HSE. This study examined whether the radiological and electrophysiological findings have a prognostic value in patients with HSE. METHODS: We retrospectively analyzed patients who were diagnosed with HSE by applying the polymerase chain reaction to cerebrospinal fluid and who received intravenous acyclovir at our hospital from 2000 to 2014. We evaluated the clinical outcomes at 6 months after onset and their correlations with initial and clinical findings, including the volume of lesions on MRI, the severity of EEG findings, and the presence of epileptic seizures at the initial presentation. RESULTS: Twenty-nine patients were enrolled (18 men and 11 women). Univariate analysis revealed that the presence of severe EEG abnormality and epileptic seizures at the initial presentation were significant correlated with a poor clinical outcome at 6 months (p=0.005 and p=0.009, respectively). In multivariate analysis, the presence of severe EEG abnormality was the only independent predictor of a poor outcome at 6 months (p=0.006). CONCLUSIONS: In cases of HSE, the initial EEG severity and seizure presentation may be useful predictive factors for the outcome at 6 months after acyclovir treatment.
Subject(s)
Humans , Male , Acyclovir , Cerebrospinal Fluid , Consensus , Electroencephalography , Encephalitis , Encephalitis, Herpes Simplex , Epilepsy , Herpes Simplex , Magnetic Resonance Imaging , Multivariate Analysis , Polymerase Chain Reaction , Retrospective Studies , Seizures , SimplexvirusABSTRACT
BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is the most common type of autoimmune synaptic encephalitis and it often responds to treatment. We analyzed the clinical characteristics of anti-NMDAR encephalitis in Korea. METHODS: Serum and/or cerebrospinal fluid (CSF) of adult patients (aged > or =18 years) with encephalitis of undetermined cause were screened for anti-NMDAR antibodies using a cell-based indirect immunofluorescence assay. The patients came from 41 university hospitals. RESULTS: Of the 721 patients screened, 40 were identified with anti-NMDAR antibodies and clinical details of 32 patients were obtained (median age, 41.5 years; 15 females). Twenty-two patients (68.8%) presented with psychiatric symptoms, 16 (50%) with seizures, 13 (40.6%) with movement disorders, 15 (46.9%) with dysautonomia, 11 (34.4%) with memory disturbance, and 11 (34.4%) with speech disturbance. Magnetic resonance imaging, electroencephalography, and CSF examinations yielded nonspecific findings. Tumor information was only available for 22 patients: 5 patients had tumors, and 2 of these patients had ovarian teratomas. Twenty-two patients received immunotherapy and/or surgery, and therapeutic responses were analyzed in 21 patients, of which 14 (66.7%) achieved favorable functional outcomes (score on the modified Rankin Scale of 0-2). CONCLUSIONS: This study investigated the clinical characteristics of adult anti-NMDAR encephalitis in Korea. Currently, elderly patients who do not have tumors are commonly diagnosed with this condition. Understanding the detailed clinical characteristics of this disease will improve the early detection of anti-NMDAR encephalitis in patients both young and old.
Subject(s)
Adult , Aged , Humans , Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Antibodies , Cerebrospinal Fluid , Electroencephalography , Encephalitis , Fluorescent Antibody Technique, Indirect , Hospitals, University , Immunotherapy , Korea , Magnetic Resonance Imaging , Memory , Movement Disorders , Primary Dysautonomias , Seizures , TeratomaABSTRACT
Oxcarbazepine (OXC) is generally assumed to be safe with regard to the risk for adverse hematopoietic effects. Recently, pancytopenia and leukopenia associated with the treatment of OXC have been reported. However, that serious adverse effect has never been reported in Korea. We describe a case of 47-year-old woman with temporal lobe epilepsy who developed reversible leukopenia following OXC monotherapy. She stopped to take OXC and WBC count was normalized completely.
Subject(s)
Female , Humans , Carbamazepine , Epilepsy, Temporal Lobe , Korea , Leukopenia , PancytopeniaABSTRACT
Oxcarbazepine (OXC) is generally assumed to be safe with regard to the risk for adverse hematopoietic effects. Recently, pancytopenia and leukopenia associated with the treatment of OXC have been reported. However, that serious adverse effect has never been reported in Korea. We describe a case of 47-year-old woman with temporal lobe epilepsy who developed reversible leukopenia following OXC monotherapy. She stopped to take OXC and WBC count was normalized completely.
Subject(s)
Female , Humans , Carbamazepine , Epilepsy, Temporal Lobe , Korea , Leukopenia , PancytopeniaABSTRACT
Anti-leucine-rich glioma inactivated-1 (LGI1) limbic encephalitis (LE) is a rare neurological disorder that has a subacute course of progressive encephalopathy and fasciobrachial dystonic seizures. We report a patient with anti-LGI1 LE that presented with atypical manifestations that complicated the diagnosis. A 62-year-old woman presented with a chronic course of memory disturbance and a subsequent relapse with an altered mental status after 10 months. The patient reported frequent chest pain of squeezing and dull nature, typically lasting 10-30 seconds. The chest pain was related to partial seizures, which were confirmed by video-EEG monitoring. Anti-LGI1 antibody was identified in serum and CSF. The patient's symptoms improved by immune modulation treatment. Patients with anti-LGI1 LE can experience atypical partial seizures, and a chronic relapsing course. Clinical suspicions and video-EEG monitoring are helpful for the early diagnosis and effective immune modulation.
Subject(s)
Female , Humans , Middle Aged , Chest Pain , Diagnosis , Early Diagnosis , Glioma , Limbic Encephalitis , Memory , Nervous System Diseases , Recurrence , SeizuresABSTRACT
The neurological manifestations caused by Epstein-Barr virus (EBV) occur only rarely in association with its primary infection or reactivation. The mechanism by which EBV produces neurological disease is unknown. This article describes two cases of polymerase-chain-reaction-proven EBV brainstem encephalitis. The sera of both patients contained autoantibodies against N-methyl-D-aspartate receptor (NMDAR), suggesting the presence of a secondary immunological mechanism. Prospective studies are needed to reveal whether the subgroup of patients with EBV encephalitis and anti-NMDAR antibodies have different clinical presentations and would benefit from immunotherapy.
Subject(s)
Humans , Antibodies , Autoantibodies , Brain Stem , Encephalitis , Herpesvirus 4, Human , Immunotherapy , N-Methylaspartate , Neurologic ManifestationsABSTRACT
The neurological manifestations caused by Epstein-Barr virus (EBV) occur only rarely in association with its primary infection or reactivation. The mechanism by which EBV produces neurological disease is unknown. This article describes two cases of polymerase-chain-reaction-proven EBV brainstem encephalitis. The sera of both patients contained autoantibodies against N-methyl-D-aspartate receptor (NMDAR), suggesting the presence of a secondary immunological mechanism. Prospective studies are needed to reveal whether the subgroup of patients with EBV encephalitis and anti-NMDAR antibodies have different clinical presentations and would benefit from immunotherapy.
Subject(s)
Humans , Antibodies , Autoantibodies , Brain Stem , Encephalitis , Herpesvirus 4, Human , Immunotherapy , N-Methylaspartate , Neurologic ManifestationsABSTRACT
Autoimmune encephalitis is a group of disorders that predominantly affects the limbic system, with or without an associated neoplasm. Recently GABAB receptor antibody has been identified in a subset of encephalitides. We report a case of anti-GABAB receptor antibody encephalitis in a 64-year-old woman, who presented with transient, recurrent abnormal behavior and complex partial seizures. She had a history of breast cancer, which was in complete remission and her workup, including blood, imaging and routine cerebrospinal fluid studies was unremarkable. Indirect immunofluorescence assays with patient's serum revealed the presence of autoantibodies against GABAB receptor. She showed significant improvement after initiating immunotherapy. This case illustrates the importance of autoantibody testing in the diagnosis of encephalitis.
Subject(s)
Female , Humans , Autoantibodies , Brain Diseases , Breast Neoplasms , Encephalitis , Fluorescent Antibody Technique, Indirect , Hashimoto Disease , Immunotherapy , Limbic Encephalitis , Limbic System , SeizuresABSTRACT
Autoimmune encephalitis is a group of disorders that predominantly affects the limbic system, with or without an associated neoplasm. Recently GABAB receptor antibody has been identified in a subset of encephalitides. We report a case of anti-GABAB receptor antibody encephalitis in a 64-year-old woman, who presented with transient, recurrent abnormal behavior and complex partial seizures. She had a history of breast cancer, which was in complete remission and her workup, including blood, imaging and routine cerebrospinal fluid studies was unremarkable. Indirect immunofluorescence assays with patient's serum revealed the presence of autoantibodies against GABAB receptor. She showed significant improvement after initiating immunotherapy. This case illustrates the importance of autoantibody testing in the diagnosis of encephalitis.