Lesion Detection Through MRI Postprocessing in Pathology-Proven Focal Cortical Dysplasia:Experience at a Single Institution in the Republic of Korea

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.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1

Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1

Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Adult Diffuse Midline Glioma: Version 2021.1

Background@#There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. @*Results@#The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. @*Conclusion@#The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

The Korean Society for Neuro-Oncology (KSNO) Guideline for Antiepileptic Drug Usage of Brain Tumor: Version 2021.1

Background@#To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. @*Methods@#The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. @*Results@#The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. @*Conclusion@#The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

A National Consensus Survey for Current Practicein Brain Tumor Management I: Antiepileptic Drug andSteroid Usage

Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors.As part I of the survey, the aim of this study is to evaluate national patterns of clinical practiceabout antiepileptic drug (AED) and steroid usage for management of brain tumors. @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questionswere developed by consensus of the Guideline Working Group. @*Results@#: The overall response rate was 12.8% (54/423). Regarding AED usage, the majority ofrespondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperativeperiod. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naïvepatients, and others prescribed AED as the case may be. The duration of AED prophylaxis showedwide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) wasthe most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents usesteroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoraledema (90.9%) was considered as the most important factor determining steroid usage followed bydegree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue thesteroids within a week after surgery if there are no specific medical conditions, while 7.3% preferredslow tapering up to a month after surgery. @*Conclusion@#: The survey demonstrated the prevailing practice patterns on AED and steroid usagein neuro-oncologic field among members of the KSNO. This information provides a point of referencefor establishing a practical guideline in the management of brain tumor patients.

A National Consensus Survey for Current Practicein Brain Tumor Management II:Diffuse Midline Glioma and Meningioma

Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors.As part II of the survey, the aim of this study is to evaluate the national patterns of clinical practicefor patients with diffuse midline glioma and meningioma. @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included4 questions of diffuse midline glioma and 6 questions of meningioma (including 2 case scenarios).All questions were developed by consensus of the Guideline Working Group. @*Results@#: In the survey about diffuse midline glioma, 76% respondents performed histologicconfirmation to identify H3K27M mutation on immunohistochemical staining or sequencing methods.For treatment of diffuse midline glioma, respondents preferred concurrent chemoradiotherapy withtemozolomide (TMZ) and adjuvant TMZ (63.8%) than radiotherapy alone (34.0%). In the surveyabout meningioma, respondents prefer wait-and-see policy for the asymptomatic small meningiomawithout peritumoral edema. However, a greater number of respondents had chosen surgical resectionas the first choice for all large size meningiomas without exception, and small size meningiomaswith either peritumoral edema or eloquent location. There was no single opinion with major consensuson long-term follow-up plans for asymptomatic meningioma with observation policy. As many as68.1% of respondents answered that they would not add any adjuvant therapies for World Health Organizationgrade II meningiomas if the tumor was totally resected including dura. @*Conclusion@#: The survey demonstrates the prevailing clinical practice patterns for patients with diffusemidline glioma and meningioma among members of the KSNO. This information provides a pointof reference for establishing a practical guideline in the management of diffuse midline glioma andmeningioma.

A National Consensus Survey for Current Practicein Brain Tumor Management III: Brain Metastasis andPrimary Central Nervous System Lymphoma

Background@#: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO)conducted the nationwide questionnaire survey for diverse queries facing to treat patients with braintumor. As part III of the survey, the aim of this study is to evaluate the national patterns of clinical practicefor patients with brain metastasis and primary central nervous system lymphoma (PCNSL). @*Methods@#: A web-based survey was sent to all members of the KSNO by email. The survey included7 questions of brain metastasis and 5 questions of PCNSL, focused on the management strategiesin specific situations. All questions were developed by consensus of the Guideline WorkingGroup. @*Results@#" In the survey about brain metastasis, respondents preferred surgical resection withadjuvant treatment for patients with a surgically accessible single brain metastatic lesion less than 3cm in size without extracranial systemic lesions. However, most respondents considered radiosurgeryfor surgically inaccessible lesions. As the preferred treatment of multiple brain metastases according tothe number of brain lesions, respondents tended to choose radiotherapy with increasing number of lesions.Radiosurgery was mostly chosen for the brain metastases of less than or equal to 4. In the surveyabout PCNSL, a half of respondents choose high-dose methotrexate-based polychemotherapy asthe first-line induction therapy for PCNSL. The consolidation and salvage therapy showed a little variationamong respondents. For PCNSL patients with cerebrospinal fluid dissemination, intrathecal chemotherapywas most preferred. @*Conclusion@#: The survey demonstrates the prevailing clinical practice patterns for patients withbrain metastasis and PCNSL among members of the KSNO. This information provides a point of referencefor establishing a practical guideline in the management of brain metastasis and PCNSL.

Sympathetic Overactivity Based on Heart-Rate Variability in Patients with Obstructive Sleep Apnea and Cerebral Small-Vessel Disease

BACKGROUND AND PURPOSE: Obstructive sleep apnea (OSA) is associated with cerebral white-matter changes (WMC), but the underlying mechanisms are not completely understood. Our aim was to identify the cardiovascular autonomic characteristics during sleep that are associated with cerebral WMC in OSA patients. METHODS: We recruited subjects from our sleep-center database who underwent both polysomnography and brain MRI within a 1-year period. Sixty patients who had OSA with WMC (OSA+WMC), 44 patients who had OSA without WMC (OSA−WMC), and 31 control subjects who had neither OSA nor WMC were analyzed. Linear and nonlinear indices of heart-rate variability (HRV) were analyzed in each group according to different sleep stages and also over the entire sleeping period. RESULTS: Among the nonlinear HRV indices, the Poincaré ratio (SD12) during the entire sleep period was significantly increased in the OSA+WMC group, even after age adjustment. Meanwhile, detrended fluctuation analysis 1 during non-rapid-eye-movement sleep tended to be lowest in the OSA+WMC group. These indices were altered regardless of the presence of hypertension or diabetes. In the subgroup analysis of middle-aged OSA patients, approximate entropy during rapid-eye-movement sleep was significantly lower in OSA+WMC patients than in OSA−WMC patients. Overall, the nonlinear HRV indices suggest that sympathetic activity was higher in the OSA+WMC group than in the OSA−WMC and control groups. CONCLUSIONS: Our findings suggest that dysregulation of HRV, especially overactivation of sympathetic tone, could be a pathophysiologic mechanism underlying the development of WMC in OSA patients.

Case of Rickettsia typhi-induced Brain Abscess Mimicking Brain Tumor

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.

Prognostic Value of Initial Standard EEG and MRI in Patients with Herpes Simplex Encephalitis

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.

Applications of CRISPR/Cas9 for Gene Editing in Hereditary Movement Disorders

Gene therapy is a potential therapeutic strategy for treating hereditary movement disorders, including hereditary ataxia, dystonia, Huntington's disease, and Parkinson's disease. Genome editing is a type of genetic engineering in which DNA is inserted, deleted or replaced in the genome using modified nucleases. Recently, clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9 (CRISPR/Cas9) has been used as an essential tool in biotechnology. Cas9 is an RNA-guided DNA endonuclease enzyme that was originally associated with the adaptive immune system of Streptococcus pyogenes and is now being utilized as a genome editing tool to induce double strand breaks in DNA. CRISPR/Cas9 has advantages in terms of clinical applicability over other genome editing technologies such as zinc-finger nucleases and transcription activator-like effector nucleases because of easy in vivo delivery. Here, we review and discuss the applicability of CRISPR/Cas9 to preclinical studies or gene therapy in hereditary movement disorders.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis in Korea: Clinical Features, Treatment, and Outcome

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.

Association of 3 Stigmas of Cerebral Microangiopathy With Early Neurological Deterioration in Lacunar Infarction

BACKGROUND: Neurological deterioration following acute lacunar infarction is not uncommon. Its association with poor clinical outcome is well-known, but little is known about what causes it. This study aimed to elucidate whether 3 stigmas of cerebral microangiopathy, a pathogenesis of lacunar infarction, are associated with neurological deterioration in patients with acute lacunar infarction. METHODS: Patients with acute lacunar infarction who were admitted within 24 hours of onset were identified using a prospective stroke registry. Patients who presented neurological deterioration within 7 days of hospitalization (progressive lacune group) were matched to 4 controls (non-progressive lacune group) for 'onset to arrival time'. Three stigmas of cerebral microangiopathy (leukoaraiosis, cerebral microbleeds, and silent lacunes) were measured using initial brain MRI, and their associations with neurological deterioration were analyzed. RESULTS: During 45 months, a total of 23 patients were identified and matched to 80 controls. Simple comparison of 2 groups showed that those 3 stigmas of cerebral microangiopathy were not significantly associated with neurological deterioration. Hyperlipidemia (p=0.18), history of transient ischemic attack or stroke (p=0.01), initial NIH stroke scale (p=0.07), white blood cell counts (p=0.16), and lesion volume (p=0.03) were possibly different (p's0.5). CONCLUSIONS: This study did not find a relationship between cerebral microangiopathy and neurological deterioration following acute lacunar infarction. The possibility of inadequate power should be noted.

Etiologies and Vascular Risk Factors in Patients With Central Retinal Artery Occlusion Treated by Intra-Arterial Thrombolysis

No abstract available.