Practical Drug Treatment Recommendations on the Drug Refractory Epilepsy Patients: 2021 Clinical Guideline Subcommittee for Epilepsy in the Korean Neurological Association

One third of the overall epilepsy population are estimated to be a drug refractory epilepsy (DRE), defined as the patients who failed to control seizure reduction, even tried two or more appropriate antiepileptic drugs (AEDs) trials. Those people need additional AEDs trials or other treatment options (resective surgery, neuromoulation, etc.). Here, we, clinical guideline committee of the Korean Neurological Association (KNA) introduce the recommendations of AEDs treatments including not only old and new AEDs currently available in Korea but also AEDs planned to be launched in the new future for DRE patients with literature review to help efficient decision of the clinician. The authors reviewed literatures and assessed efficacy and tolerability on 12 currently available and four newly introduced/or planned AEDs applied to DRE patients, published from November 2015 to July 2021. Brivaracetam, eslicarbazepine, canabidiol and cenobamate are the four AEDs that are newly introduced or planned to be launched soon. The reviewed articles are publications after November 2015, 2018 American Association of Neurology guideline, new AEDs which were introduced or planned to be launched as of 2021. All AEDs are classified based on the therapeutic rating scheme, generating recommendations. Overall 173 papers have been reviewed and analyzed for recommendation rationales. KNA introduce additional add-on treatment or conversional monotherapy guidelines on the drug refractory focal and generalized epilepsy. We hope these guidelines or recommendations to help clinical decision for the treatment of drug refractory epilepsy patients

Illness Experience of Married Korean Women with Epilepsy

PURPOSE: The purpose of this study was to understand and describe the illness experience of married Korean women with epilepsy. METHODS: Data were collected during 2015~2016 through individual in-depth interviews with 12 married women with epilepsy. Verbatim transcripts were analyzed using Giorgi's phenomenological analysis to uncover the meaning of the illness experience of the participants. RESULTS: The study results showed that the illness experience of married Korean women with epilepsy was clustered into a specific description of situated structure and a general description of situated structure. Six themes from 20 meaning units were identified: 1) Undermined self-esteem with stigma of being epileptic; 2) Limited social interaction; 3) Suffering sorrow as a ‘disqualified being’; 4) Shuttling back and forth across the boundary between healthy and epileptic; 5) Desperate struggle to meet the expectation of given role; 6) Self-empowering through self-restriction and realization. CONCLUSION: The findings from this study show that both the enacted and felt stigma of epilepsy impact on the life of married Korean women with epilepsy. Although the participants face social and interpersonal restriction and prejudices, they try their best to fulfill their role rather than to be cared for as patients. As the stigma and hardships of the participants are related to lack of knowledge, health professionals should focus not just on clinical intervention but also on providing targeted educational programs and counseling for these women to dispel the stigma of the disease and to increase their quality of life.

Essential Cryoglobulinemia Presenting as Polyneuropathy and Cerebral Infarction

Cryoglobulinemia is a rare medical condition defined by presence of cryoglobulins in serum and it may cause hyperviscosity syndrome or systemic vasculitis in variable organs including the skin, joints, liver, kidneys, lungs and nervous system. A vasculitic polyneuropathy or mononeuritis multiplex commonly occurs. However, central nervous system complications of cryoglobulinemia including stroke, encephalopathy and seizures are rarely reported. We represent a case of essential cryoglobulinemic vasculitis manifested as a sensorimotor polyneuropathy combined with an acute ischemic stroke attack.

The Prognostic Value of 20-minute Spot Electroencephalography within 72 hr after Resuscitation for Comatose Cardiac Arrest Survivors Treated with Therapeutic Hypothermia

PURPOSE: This study evaluated the utility of 20-minute spot electroencephalography (sEEG) for prognostication in patients treated with therapeutic hypothermia after cardiac arrest. METHODS: This was a retrospective, observational study using a prospectively collected hypothermia registry conducted at a single tertiary hospital over three years. We included patients who were monitored by sEEG within three days after resuscitation. We evaluated the prognostic value of continuous activity pattern (diffuse slowing or normal wave) for good outcome predictor and malignant pattern (epileptiform, burst suppression, and isoelectric pattern) for poor outcome predictors during hypothermia and normothermia period. RESULTS: Of 98 patients, continuous activity was displayed in 45 patients. Of these, 27 were included in the good outcome group, resulting in a positive predictive value (PPV) of 60.0% (sensitivity and specificity of 100.0 and 74.6%, respectively). Malignant patterns resulted in a PPV of 100.0% for poor outcomes (sensitivity and specificity of 35.2% and 100.0%, respectively). Continuous activity during hypothermia showed better prognostic performance for good outcome than those during normothermia (area under the curve (AUC)=0.900 (95% confidence interval (CI) 0.825-0.975) and AUC=0.827 (95% CI 0.692-0.962), respectively). For the poor outcome prediction, the AUC was 0.712 (95% CI 0.536-0.887) for malignant patterns during normothermia, and 0.656 (95% CI 0.522-0.789) for those during hypothermia. CONCLUSION: For patients treated with TH, continuous activity on sEEG, particularly during hypothermia, could contribute to the prediction of good outcomes with high specificity. Epileptiform discharge, burst suppression, and isoelectric patterns accurately predicted poor outcomes in this cohort.

Altered Consciousness After Acute Lacunar Infarction of the Corona Radiata in Patients With Severe White Matter Change

With an increasing proportion of the elderly, dementia due to severe cerebral white matter change is frequently observed. Because these patients cannot express their symptoms effectively, the recognition of stroke can be delayed. In addition, clinical characteristics of their stroke might be different. We reported on three patients with severe leukoaraiosis, who exhibited altered consciousness after acute lacunar infarction in the corona radiata. This clinico-radiological discrepancy may have resulted from different susceptibility to ischemia in patients with severe white matter change.

Coexisting Carotid Atherosclerosis in Patients with Intracranial Small- or Large-Vessel Disease

BACKGROUND AND PURPOSE: The coexistence of carotid atherosclerosis in ischemic stroke patients with small-vessel disease (SVD) or intracranial large-vessel disease (ICLVD) was investigated using carotid duplex ultrasonography, and whether its coexistence affected the clinical prognosis was determined. METHODS: Ischemic stroke patients with SVD or ICLVD were enrolled (n=103). Risk factors, demographic data, and National Institutes of Health Stroke Scale (NIHSS) scores were obtained for all of the subjects. Early neurological progression was defined by an increase in NIHSS score during the first 7 days. Carotid ultrasonography was performed to measure the intima-media thickness (IMT) and carotid plaques. RESULTS: Among the 103 patients who were retrospectively enrolled in this study (56 with SVD and 47 with ICLVD), 66 (64.1%) had an atherosclerotic plaque and 23 (22.3%) had increased IMT. Increased IMT was observed more frequently in ICLVD than in SVD [15/47 (31.9%) vs. 8/56 (14.3%), p=0.032]. An atherosclerotic plaque was observed on subsequent carotid ultrasonographic examination in 28 (50%) of the 56 patients whose computed tomography angiography scans of the neck vessels were interpreted as normal. There was no association between presence of atherosclerotic change and early neurologic progression (p=0.94). CONCLUSIONS: A coexisting atherosclerotic plaque or increased IMT was observed in 71.8% of patients with SVD or ICLVD. Whether the coexistence of carotid atherosclerotic change with either of these conditions affects the clinical prognosis remains to be elucidated.

A Unique Ultrasonographic Finding of Carotid Thrombus in a Patient with Acute Cardiogenic Cerebral Infarction / 대한뇌졸중학회지

In patients with acute ischemic stroke, carotid duplex ultrasonography has been used to assess atherosclerotic lesions at the extracranial carotid artery. We reported a unique sonographic finding of carotid artery thrombus in a patient with acute cardioembolic stroke and atrial fibrillation. An 81-year-old woman with atrial fibrillation was presented with dysarthria and left side hemiparesis. She had undergone surgical thrombectomy and angioplasty for her right brachial artery occlusion four days before the stroke onset. Diffusion-weighted MRI revealed multiple territorial infarctions suggestive of acute cardio-embolic stroke. CT angiography showed an occlusion of the right common carotid artery. On B-mode ultrasonography, longitudinal intraluminal tortuous cylinderic oscillating thrombus was observed on the right distal common carotid artery to the proximal internal carotid artery. This case illustrates a unique ultrasonographic finding of acute cardiogenic thrombus in the extracranial carotid artery.

Supra-Additive Neuroprotection by Renexin, a Mixed Compound of Ginkgo Biloba Extract and Cilostazol, Against Apoptotic White Matter Changes in Rat after Chronic Cerebral Hypoperfusion

BACKGROUND AND PURPOSE: White-matter (WM) lesions are known to potentiate cognitive impairment in poststroke patients. The present study was designed to assess whether Ginkgo biloba extract (GB) and cilostazol, which were evaluated alone and in a combination formula (Renexin), can attenuate the WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. METHODS: Animals were divided into five treatment groups: cilostazol (25 mg/kg/day), GB (20 mg/kg/day), Renexin (25 mg/kg/day cilostazol + 20 mg/kg/day GB), vehicle, and sham. The animals received the treatments orally 1 day after bilateral common carotid artery occlusion [two-vessel occlusion (2VO); except for the sham group, which underwent the surgery but the arteries were not occluded], and then the same dose every day for 21 days thereafter. Prior to sacrificing the rats, repetitive eight-arm radial maze testing was performed to examine their cognitive abilities. After drug administration and cognitive testing, brain tissues were isolated for Kluver-Barrera and terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end-labeling (TUNEL) staining, immunohistochemical assessment of glial fibrillary acidic protein (GFAP) and CD11b (OX-42), and to assay free-radical scavenging activity. RESULTS: We found that the significant WM lesions induced by 2VO was ameliorated significantly by treatment with cilostazol, GB, and Renexin, in association with increased TUNEL-positive cells. In addition, chronic cerebral hypoperfusion caused a large increase in the degree of GFAP and OX-42 immunoreactivity and free-radical activity in the optic tract. These abnormalities were significantly reversed by the three drugs, but most prominently by Renexin, suggesting a markedly enhanced or supra-additive effect of cilostazol and GB when administered together. CONCLUSIONS: Significant attenuation of cytoarchitectural damage and apoptotic cell death was found with GB and cilostazol, but a markedly enhanced effect was seen for treatment with their combination in the WM of rat brains after bilateral occlusion of the common carotid arteries. We suggest that combination therapy with GB and cilostazol provides enhanced neuroprotective effects and induces subsequent cognitive improvement in patients with chronic ischemic conditions.

Brain Abscess Associated with Pulmonary Arteriovenous Malformation

Pulmonary arteriovenous malformations (PAVMs) are induced right to left shunt and if untreated properly, those may cause severe neurological problems. A 35-year-old man who had a headache checked into an emergency room to define a brain abscess in his brain with CAT scan as well as to examine suspicious two PAVMs in his chest X-ray. Not long after the surgical management of the brain abscess, he suffered recurrent convulsive movements. We would proceed to operate his PAVMs to prevent recurrent critical neurologic complications such as brain abscess or meningitis.

Deep Brain Stimulation for the Treatment of Medically Intractable Epilepsy: a Review on Clinical Application

It has been suggested that epileptic seizures can be interrupted by deep brain stimulation (DBS) of various deep brain structures which may exert a therapeutic control on seizure generators or correspond to ictal onset zone themselves. Several groups have used DBS in drug-resistant epilepsy cases for which resective surgery cannot be applied. The promising subcortical brain structures are anterior and centromedian nucleus of the thalamus, subthalamic nucleus, and other nuclei to treat epilepsy in light of previous clinical and experimental data. Recently two randomized trials of neurostimulation for controlling refractory epilepsy employed the strategies to stimulate electrodes placed on both anterior thalamic nuclei or near seizure foci in response to electroencephalographically detected epileptiform activity. However, the more large-scale, long-term clinical trials which elucidates optimal stimulation parameters, ideal selection criteria for epilepsy DBS should be performed before long.

Brain Abscess Associated with Pulmonary Arteriovenous Malformation / 대한간질학회지

Pulmonary arteriovenous malformations (PAVMs) are induced right to left shunt and if untreated properly, those may cause severe neurological problems. A 35-year-old man who had a headache checked into an emergency room to define a brain abscess in his brain with CAT scan as well as to examine suspicious two PAVMs in his chest X-ray. Not long after the surgical management of the brain abscess, he suffered recurrent convulsive movements. We would proceed to operate his PAVMs to prevent recurrent critical neurologic complications such as brain abscess or meningitis.

Deep Brain Stimulation for the Treatment of Medically Intractable Epilepsy: a Review on Clinical Application / 대한간질학회지

It has been suggested that epileptic seizures can be interrupted by deep brain stimulation (DBS) of various deep brain structures which may exert a therapeutic control on seizure generators or correspond to ictal onset zone themselves. Several groups have used DBS in drug-resistant epilepsy cases for which resective surgery cannot be applied. The promising subcortical brain structures are anterior and centromedian nucleus of the thalamus, subthalamic nucleus, and other nuclei to treat epilepsy in light of previous clinical and experimental data. Recently two randomized trials of neurostimulation for controlling refractory epilepsy employed the strategies to stimulate electrodes placed on both anterior thalamic nuclei or near seizure foci in response to electroencephalographically detected epileptiform activity. However, the more large-scale, long-term clinical trials which elucidates optimal stimulation parameters, ideal selection criteria for epilepsy DBS should be performed before long.

Crossed Cerebellar Diaschisis in Complex Partial Status Epilepticus

Crossed cerebellar diaschisis has been described mostly in hemispheric stroke and supratentorial tumors with positron-emission tomography (PET) and single photon emission computed tomography (SPECT). Rarely it has been described with brain diffusion-weighted MRI of status epilepticus. We report a patient with status epilepticus, who developed MRI abnormalities in the cerebral cortex and contralateral cerebellum. EEG abnormalities correlated anatomically with the cerebral cortex of image change. An aggressive medication resulted in seizure control, reversal of neurologic deficit, and improvement or resolution of the MRI and EEG abnormalities in 3 weeks. We concluded that both localization and resolution of lesions may be explained by reversible excitotoxic cell damage due to seizure-related excessive synaptic activity.

Crossed Cerebellar Diaschisis in Complex Partial Status Epilepticus / 대한간질학회지

Crossed cerebellar diaschisis has been described mostly in hemispheric stroke and supratentorial tumors with positron-emission tomography (PET) and single photon emission computed tomography (SPECT). Rarely it has been described with brain diffusion-weighted MRI of status epilepticus. We report a patient with status epilepticus, who developed MRI abnormalities in the cerebral cortex and contralateral cerebellum. EEG abnormalities correlated anatomically with the cerebral cortex of image change. An aggressive medication resulted in seizure control, reversal of neurologic deficit, and improvement or resolution of the MRI and EEG abnormalities in 3 weeks. We concluded that both localization and resolution of lesions may be explained by reversible excitotoxic cell damage due to seizure-related excessive synaptic activity.

Quality of Life Assessment in Epilepsy Patients With Topiramate

BACKGROUND: Quality of life is important in epilepsy treatment. We evaluated the effect of topiramate on the quality of life in epilepsy patients and on the characteristics of the clinical features in patients with improved scores on the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). METHODS: We included 631 adult epilepsy patients, who were followed for 16 weeks. We analyzed the effect of topiramate on QOLIE-10 score. The patients were classified into those with improved scores (IG) and those whose scores did not improve (NG). We compared each QOLIE-10 item and their clinical features between the IG and NG groups. RESULTS: All item scores, as well as the total score, improved after topiramate treatment. Comparison of the scores for each item showed that working and social factor differences of both the IG (>0.72) and NG groups (>0.80) were higher than for the other items. Age, gender, seizure onset, topiramate dose, adverse event, education level, employment, and migraine did not differ significantly between the IG and NG groups. The effect on seizure reduction was the most significant among the clinical features (P<0.001). The epilepsy syndrome, etiology, previous antiepileptic drugs (AEDs), and weight changes did not differ significantly between the two groups (P<0.05). CONCLUSIONS: Topiramate treatment can influence the quality of life in adult epilepsy patients, and especially work and social factors. Seizure reduction, epilepsy syndrome, etiology, previous AEDs, and weight change may be the most affected clinical factors in patients who have improved quality of life with topiramate.

Headache Related to Secondary Hemochromatosis After Frequent Blood Transfusions

No abstract available.

Contralateral MCA Infarction Mimicking Post-stroke Seizure in a Patient With Previous Right MCA Infarct

No abstract available.

Abnormal Integrity of Corticocortical Tracts in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.

Diffusion Tensor Imaging in Acute Ischemic Stroke: Usefulness of Fractional Anisotropy

BACKGROUND: Progressing stroke (PS) variably develops from initially the same size and severity, and is most frequently observed in lacunar infarctions. We investigated fractional anisotrophy (FA), mean diffusivity (MD) and infarct volume by using diffusion tensor imaging during the acute phase of ischemic stroke to determine whether these parameters are useful in characterizing and predicting PS. METHODS: In this study, 55 consecutive patients admitted within 24 hours of the onset of their first ischemic stroke were included. NIH stroke scale (NIHSS) and Canadian Neurological scale (CNS) were performed upon admission, twice a day, and at discharge. Modified Rankin scale and Barthel index were also evaluated. PS was defined as a 2-point drop in NIHSS and a 1-point drop in CNS from admission to day 3. A correlation analysis was performed between clinical scale scores and imaging parameters, and the distribution of those values was compared between the two groups with and without PS. RESULTS: Significant correlations were observed between clinical scale scores and infarct volumes. The FA ratio in 14 patients with PS was lower than the patients without PS (p=0.004). Other characteristics including infarct volume and MD ratio were not different. The FA ratio remained as an independent predictor of PS (OR, 1.055; p=0.011). CONCLUSIONS: In acute ischemic stroke within the first 24 hours, only infarct volume was correlated with clinical status. However, patients with PS showed lower FA values, which accounts for rapid and severe vasogenic edema involving the disruption of the cell membrane and axonal fibers. Moreover, FA may be a predictor of PS.

Analysis of SPECT in Two Sub-types of Subcortical Ischemic Vascular Dementia

BACKGROUND: The brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Eurkinjuntti, incorporates the two familiar entities, "the lacunar state" and "Binswanger's disease". However, it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of the regional cerebral blood flow (rCBF) in the two subsets of SIVD. METHODS: 12 SIVD patients with predominant white matter lesions, 13 patients with predominant multiple lacunar infarctions and 17 controls were evaluated. The general cognitive function and the severity of dementia were measured by using the K-MMSE and the clinical dementia rating scale. The patients simultaneously met both the NINDS-AIREN criteria for probable or possible vascular dementia (VaD) and the Eurkinjuntti's brain imaging criteria for SIVD. 99mTc-ethyl cysteinate dimmer (ECD)-SPECT was performed to measure the rCBF, and statistical parametric mapping (SPM) was applied to the objective analysis of the SPECT data. RESULTS: SPM analysis of the SPECT images revealed that decreased rCBF in the bilateral thalami, anterior cingulated gyri, superior temporal gyri, caudate heads and left parahippocampal gyrus was significant in the patients with SVaD compared to the controls (uncorrected P=0.001). This pattern of rCBF reduction was the same in both the SIVD patients with predominant white matter lesions and with predominant lacunar infarctions. CONCLUSIONS: Our study suggests that the two subsets of SIVD proposed by Eurkinjuntti may have a common functional abnormality, and the Eurkinjuntti's criteria offers a solution for researchers to identify the more homogeneous group of VaD patients.