Machine Learning-assisted Quantitative Mapping of Intracortical Axonal Plasticity Following a Focal Cortical Stroke in Rodents

Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.

Factors Affecting the Parental Stress of Children and Adolescents with Epilepsy / 정신신체의학

Objectives@#：The aim of this study was to investigate the impact of clinical and psychological factors on the parental stress of children and adolescents with epilepsy. @*Methods@#：Children and adolescents with epilepsy (n=90, age range=6-17 years) completed questionnaires on epilepsy-related variables, children’s depressive symptoms (Children’s Depression Inventory, CDI), children’s anxiety (Revised Children’s Manifest Anxiety Scale, RCMAS) and performed the scale for children’s intelligence (IQ). Parents who have children and adolescents with epilepsy completed questionnaires on parental stress (Questionnaire on Resources and stress, QRS), parental anxiety (State-Trait Anxiety Inventory, STAI), children’s attention problems (Abbreviated Conners Parent Rating Scale Revised, CPRS), and children’s behavioral problems (Korean Child Behavior Checklist, K-CBCL). Stepwise regression analysis was performed to determine the significant predictive variables that affect parental stress. @*Results@#：In the correlational analysis, duration of seizure treatment (r=0.253, p=0.016), children’s IQ (r= -0.544, p<0.001), children’s attention problems (r=0.602, p<0.001), children’s depressive symptoms (r=0.335, p=0.002), children’s anxiety (r=0.306, p=0.004), children’s behavioral problems (r=0.618, p<0.001), and parental anxiety (r=0.478, p<0.001), showed a significant correlation with parental stress. Children’s behavioral problem (β=0.241, p=0.010), children’s IQ (β=-0.472, p<0.001), and parental anxiety (β=0.426, p<0.001) were significantly related to the parental stress (Adjusted R2=0.619). @*Conclusions@#：Clinicians should pay attention to children’s intelligence and behavioral problems and parental anxiety, which affect parental stress with children and adolescents with epilepsy.

Neurologic Prognostication by QEEG in Post Cardiac Arrest Patients with Therapeutic Hypothermia

Background@#Post-cardiac arrest syndrome (PCAS) is one of the critical conditions which can result in a more serious brain injury. Early and accurate prognostication is crucial for deciding the patient’s therapeutic plan and setting the treatment goal. This study aimed to establish the prognostication values of quantitative electroencephalography (QEEG) in PCAS patients. @*Methods@#We recruited 183 PCAS patients treated with therapeutic hypothermia. Electroencephalography (EEG) data within 72 hours after cardiac arrest (CA) and clinical data were collected. QEEG analysis including power spectral density (PSD) and connectivity analysis of default mode network (DMN) with imaginary coherence were performed. @*Results@#There were significantly different patterns of PSD between neurologic good and poor outcome groups; absolute and relative power of the alpha 2 and beta 1 frequency (10-15 Hz) bands were increased in all brain regions of good outcome group. However, the relative power of the delta band and higher frequency bands over fast alpha (beta 3 and gamma bands over 20 Hz) were poor outcome markers. We found out that connectivity of DMN were significantly decreased in the poor outcome group compared with the good outcome group. @*Conclusions@#These findings suggest that QEEG analysis could quantify and automate the interpretation of EEG. Furthermore, they can improve the prognostic values for neurologic outcomes relatively accurately and objectively in PCAS patients treated with hypothermia compared with traditional visual grading.

A Study on the Factors Affecting Quality of Life in Children and Adolescents with Epilepsy and Their Families

OBJECTIVES: The aim of this study was to investigate the impact of clinical and psychological factors on the quality of life of children and adolescents with epilepsy and their families.METHODS: Children and adolescents with epilepsy and their families (n = 63, age range = 6–17 years) completed questionnaires on epilepsy-related variables, quality of life, children's depressive symptoms, children's anxiety, children's behavioral problems, children's attention problems, parental stress, and parental anxiety. Stepwise regression analysis was performed to determine the significant predictive variables that affect quality of life.RESULTS: In the correlational analysis, children's attention problems (r = 0.363, p = 0.004), parental anxiety (r = 0.377, p = 0.003), parental stress (r = 0.564, p < 0.001), and children's behavioral problems (r = 0.503, p < 0.001) showed a significant correlation with quality of life. Parental stress (β = 0.415, p = 0.001, adjusted R² = 0.345) and children's behavioral problems (β = 0.285, p = 0.02, adjusted R² = 0.345) were significantly related to the quality of life.CONCLUSIONS: Clinicians should pay attention to parental stress and children's behavioral problems, which affect quality of life in families with pediatric epilepsy.

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.

Neurological Complications Resulting from Non-Oral Occupational Methanol Poisoning

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.

A Study on the Factors Affecting Self-Concept of Children and Adolescents with Epilepsy

OBJECTIVES: The purpose of this study was to investigate the impact of clinical and psychological factors on the self-concept of children and adolescents with epilepsy. METHODS: Children and adolescents with epilepsy (n=60; age range=9–17 years) completed questionnaires about their epilepsy-related variables, self-concept, depressive symptoms, anxiety, family functions, and behavioral problems. The T-test and one-way analysis of variance were used to examine the variables affecting the total self-concept scores. To determine the independent variables by adjusting the significant variables, a stepwise regression analysis was performed. RESULTS: In the correlational analysis, age, depressive symptoms, anxiety, social problems, attention problems, and internalizing problems had significantly negative correlations with self-concept. On the other hand, IQ and family functions showed positive correlations with self-concept. Age (β=−0.177, p=0.015), depressive symptoms (β=−0.487, p<0.001), anxiety (β=−0.298, p=0.008), and attention problems (β= −0.138, p=0.048) were analyzed as independent factors to assess their impact on self-concept, and were found to account for 78.3% of the variance in self-concept by stepwise regression analysis. CONCLUSION: Parents and clinicians should pay attention to improving the self-concept of children and adolescents with epilepsy, especially if they have problems with depression, anxiety, or attention.

Structural and Functional Alterations at Pre-Epileptic Stage Are Closely Associated with Epileptogenesis in Pilocarpine-induced Epilepsy Model

Pilocarpine-induced rat epilepsy model is an established animal model that mimics medial temporal lobe epilepsy in humans. The purpose of this study was to investigate neuroimaging abnormalities in various stages of epileptogenesis and to correlate them with seizure severity in pilocarpine-induced rat epilepsy model. Fifty male Sprague-Dawley rats were subject to continuous video and electroencephalographic monitoring after inducing status epilepticus (SE) and seizure severity was estimated by frequency and total durations of class 3 to 5 spontaneous recurrent seizures (SRS) by modified Racine's classification. The 7.0 Tesla magnetic resonance imaging (MRI) with high resolution flurodeoxyglucose positron emission tomography (FDG-PET) was performed at 3 hours, 1, 3, 7 days and 4 weeks after the initial insult. The initial SRS was observed 9.7±1.3 days after the pilocarpine injection. MRI revealed an abnormal T2 signal change with swelling in both hippocampi and amygdala in acute (day 1 after injection) and latent phases (days 3 and 7), in association with PET hypometabolism in these areas. Interestingly, the mean frequency of class 3 to 5 SRS was positively correlated with abnormal T2 signals in hippocampal area at 3 days. SRS duration became longer with more decreased glucose metabolism in both hippocampi and amygdala at 7 days after pilocarpine injection. This study indicates that development and severity of SRS at chronic phase could be closely related with structural and functional changes in hippocampus during the latent period, a pre-epileptic stage.

Two cases of methyl alcohol intoxication by sub-chronic inhalation and dermal exposure during aluminum CNC cutting in a small-sized subcontracted factory

BACKGROUND: Methyl alcohol poisoning has been mainly reported in community. Two cases of methyl alcohol poisoning occurred in a small-sized subcontracted factory which manufactured smartphone parts in Korea. CASE PRESENTATION: One young female patient presented with dyspnea and visual disturbance. Another young male patient presented with visual disturbance and myalgia. They treated with sodium bicarbonate infusion and hemodialysis for metabolic acidosis. In addition, he received ethyl alcohol per oral treatment. Her and his urinary methyl alcohol concentration was detected as 7.632 mg/L, 46.8 mg/L, respectively, although they were treated hemodialysis. Results of the working environment measurement showed that the concentration of methyl alcohol (1030.1–2220.5 ppm) in the air exceeded the time weighted average (200 ppm). They were diagnosed with optic neuropathy due to methyl alcohol poisoning and still have visual impairment. CONCLUSIONS: Workers who hired as dispatched employees in a small-sized subcontracted factory were exposed to high concentrations of methyl alcohol. The workplace had poor ventilation system. In addition, workers did not wear proper personal protect equipment. Working environment measurement and annual chekups for workers were not performed. They were in a blind spot to occupational safety and health. More attention is needed to protect vulnerable workers’ health.

Social Behavioral Problems and the Health-Related Quality of Life in Children and Adolescents with Epilepsy

OBJECTIVE: The purpose of this study was to investigate the impact of specific behavioral problems on the health-related quality of life (HRQOL) in children and adolescents with epilepsy. METHODS: Children and adolescents with epilepsy (n=92; age range=6–17 years) and their mothers completed questionnaires about behavioral problems, HRQOL, socio-demographics, and epilepsy-related variables. To determine significant predictor variables of the HRQOL, the stepwise regression analyses and partial correlations were performed to adjust for other behavioral problems and covariates. RESULTS: The analyses revealed that an increase in social behavioral problems and delinquent behavior was associated with a decrease in the HRQOL. Lower levels of maternal education and the number of antiepileptic drugs were also associated with a decline in the HRQOL; the HRQOL and social behavioral problems remained significantly correlated after adjusting for maternal education level, number of antiepileptic drugs, and non-social behavioral problems. CONCLUSION: Parents and practitioners should provide intervention if behavioral problems, particularly social behavioral problems, are observed in children or adolescents with epilepsy.

Acute disseminated encephalomyelitis with tremor as the initial symptom

Multiple neurological deficits can occur in acute disseminated encephalomyelitis (ADEM) but rarely movement disorders. A 24-year-old female patient was admitted because of tremor in bothupper limbs. After admission, her mental status progressively declined into coma. Brain magnetic resonance imaging and cerebrospinal fluid analysis were compatible with ADEM. Tests for central nervous system infection and autoimmune diseases were all negative. She was given steroid and IVIG, and the patient fully improved. We report here the first case of adult ADEM, who presented with tremor as the initial neurological manifestation.

Cortico-Cortical Modulation Induced by 1-Hz Repetitive Transcranial Magnetic Stimulation of the Temporal Cortex

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has potential as a noninvasive neuromodulation treatment method for various neuropsychiatric disorders, and repeated sessions of rTMS are more likely to enhance the therapeutic efficacy. This study investigated neurophysiologic and spatiodynamic changes induced by repeated 1-Hz rTMS of the temporal cortex using transcranial magnetic stimulation (TMS) indices and fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twenty-seven healthy subjects underwent daily 1-Hz active or sham rTMS of the right temporal cortex for 5 consecutive days. TMS indices of motor cortical excitability were measured in both hemispheres daily before and after each rTMS session, and 2 weeks after the last stimulation. FDG-PET was performed at baseline and after the 5 days of rTMS sessions. RESULTS: All subjects tolerated all of the sessions well, with only three of them (11.1%) reporting mild transient side effects (i.e., headache, tinnitus, or local irritation). One-Hz rTMS decreased motor evoked potential amplitudes and delayed cortical silent periods in the stimulated hemisphere. Statistical parametric mapping of FDG-PET data revealed a focal reduction of glucose metabolism in the stimulated temporal area and an increase in the bilateral precentral, ipsilateral superior and middle frontal, prefrontal and cingulate gyri. CONCLUSIONS: Repeated rTMS sessions for 5 consecutive days were tolerated in all subjects, with only occasional minor side effects. Focal 1-Hz rTMS of the temporal cortex induces cortico-cortical modulation with widespread functional changes in brain neural networks via long-range neural connections.

Role of Sleep Center for Integrative Approach to Sleep Disorders / 이화의대지

The prevalence of sleep disorder is about 30% of the population. Common sleep disorders are insomnia, obstructive sleep apnea, narcolepsy, restless legs syndrome, rapid eye movement sleep behavior disorder and parasomnia. These sleep disorders lead various medical and mental complications. However, most sleep disorders are underdiagnosed and not treated appropriately. Sleep medicine is important for treating these sleep disorders and maintaining general healthy conditions. Specialized and comprehensive treatments for sleep disorder are important in sleep medicine.

The Effect of Ropinirole on the Quality of Life in Patients with Restless Legs Syndrome in Korea: An 8-Week, Multicenter, Prospective Study

BACKGROUND AND PURPOSE: Dopamine agonists are first-line drugs for treating the symptoms of restless legs syndrome (RLS). However, few studies have investigated the effect of dopamine agonists on the quality of life (QoL) in RLS patients. We conducted a study to determine whether ropinirole exerts positive effects on the QoL in RLS patients and to analyze the underlying factors. METHODS: Primary RLS patients from eight medical centers were recruited in the study. They were evaluated in the baseline phase using various questionnaires including the Korean versions of the International Restless Legs Scale (K-IRLS), RLS QoL questionnaire (K-RLSQoL), and the Short Form 36 Health Survey (SF-36). After taking ropinirole for 8 weeks the same questionnaires were again completed as a re-evaluation. We analyzed the statistical difference using a paired t-test, a Pearson's correlation, and a stepwise multiple regression in order to identify the factors associated with the QoL change. RESULTS: A total of 107 subjects, including 65 (60.7%) females, completed this study. They were aged 51.68+/-14.80 years (mean+/-SD) and had a symptom duration of 8.8+/-9.0 months. After treatment with ropinirole, there were significant improvements on the K-RLSQoL, SF-36, and K-IRLS. The Pearson's correlation analysis showed that the improvement of QoL in RLS patients was significantly correlated with the severity of RLS (r=0.236, p<0.014) at baseline. CONCLUSIONS: The results from this study suggest that treatment with ropinirole can improve the QoL in RLS patients. The improvement in the QoL is more related with the improvement of RLS symptoms.

Erratum: Cortico-Cortical Modulation Induced by 1-Hz rTMS of the Temporal Cortex

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Parasomnia Overlap Disorder Associated With Pontine Glioblastoma

Parasomnia overlap disorder is characterized by coexisting rapid eye movement (REM) sleep behavior disorder and non-REM parasomnia. We report herein an 8-year-old boy with REM sleep behavior disorder, sleep talking, and confusional arousal. Polysomnography revealed REM sleep without atonia, and arousal disorder. Neurological examination revealed bilateral ptosis, lateral gaze palsy, facial palsy, vertical nystagmus, and dysmetria. A pontine glioblastoma was found on brain magnetic resonance imaging, which could have been responsible for his neurologic deficit and sleep problem.

Correlation between Nocturia and Sleep: A Questionnaire Based Analysis

PURPOSE: This study evaluated the effectiveness and quality of sleep (QoS) in adult patients with nocturnal lower urinary tract symptoms (LUTS) including nocturia and nocturnal polyuria. MATERIALS AND METHODS: A total of 102 patients with nocturia and daytime LUTS were enrolled in this study. All patients completed a questionnaire that included the International Prostate Symptom Score (IPSS), quality of life score (QoL), overactive bladder questionnaire (OABq), and a sleepiness index. The sleepiness index was measured with the Korean Beck Depression Inventory (K-BDI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Berlin Questionnaire (BQ), and the International Restless Legs Syndrome Study Group (IRLSSG). Statistical analyses included the Student's t-test and chi-square test. Differences were considered significant at a p-value of less than 0.05. RESULTS: Nocturia during sleep was experienced by 68 (66.7%) out of 102 patients. There was no significant association between the nocturia- and the sleep-related scales, but with multiple regression analysis for sex and age, the K-BDI score (p=0.05), IPSS score (p=0.05), and OABq (p=0.02) were significantly higher in patients who woke up to void during sleep. A total of 57 (55.9%) patients diagnosed with overactive bladder with nocturia had severe daytime sleepiness on the ESS questionnaire (p=0.019) and more urgency symptoms on the IPSS questionnaire (p=0.007). CONCLUSIONS: Patients with nocturia had a greater risk of being depressive and felt sleepier during the daytime. LUTS including nocturia and sleep quality closely affected each other. Therefore, clinicians should consider patients' LUTS and sleep problems or QoS as well to provide more satisfying outcomes.

Peri-ictal Heart Rate Changes in Patients With Localization-Related Epilepsy

BACKGROUND: Epileptic seizures can be associated with changes in autonomic functions. This study evaluated heart rate (HR) changes at the transition from the preictal to the ictal state in patients with epileptic seizures, and investigated whether peri-ictal HR changes can help to predict electroencephalography (EEG) seizures prior to their onset. METHODS: We retrospectively studied 94 seizures in 33 patients who underwent video-EEG monitoring with scalp EEG and electrocardiography. The existence and initial timing of HR changes relative to the onset of EEG seizures were determined by analyzing consecutive RR-interval changes in 10-minute recordings. We evaluated the correlation between the peri-ictal HR changes and the type of localization-related epilepsy. RESULTS: Peri-ictal HR changes were documented in 70.2% (66/94) of all seizures, of which 62 were tachycardia (66.0%) and 4 were bradycardia (4.3%). Peri-ictal tachycardia occurred significantly with seizures as an ictal manifestation, more often in seizures with a right hemispheric onset than in those with a left hemispheric onset (77.4% vs. 50%, p=0.016). Peri-ictal HR changes were observed much earlier in seizures of mesial temporal lobe epilepsy (TLE) than in those of extratemporal lobe epilepsy (-54.4 s vs. -6.7 s, p<0.001). CONCLUSIONS: Peri-ictal HR changes were observed in 70.2% of seizures, 94% of which were tachycardia. These changes could be helpful in predicting seizure onset, especially in mesial TLE.

Predictive Factors of Neurologic Outcome in Patients With Hypoxic-Ischemic Encephalopathy After Cardiopulmonary Resuscitation

BACKGROUND: Cardiopulmonary resuscitation (CPR) can lead to various neurologic outcomes in patients with hypoxicischemic encephalopathy (HIE). This study investigated the usefulness of clinical markers and electroencephalography (EEG) in predicting the neurologic prognosis of HIE after CPR. METHODS: We reviewed the clinical findings of 51 patients with HIE, including the medical history, the duration from the onset of symptoms to the recovery of spontaneous circulation, Glasgow Coma Scale (GCS) and Full Outline of Unresponsiveness (FOUR) scores, and presence of seizure or status epilepticus. Patients were divided into three outcomes groups: death, persistent vegetative state, and recovering alertness and awareness. Digital EEG and visual and quantitative analyses were performed in each patient. For quantitative EEG (qEEG) analysis, we defined and compared the distance in the spatial band-power patterns and phase coherence patterns between healthy normal subjects and each patient. RESULTS: Patients with HIE showed a high mortality rate (54.9%, 28/51), and their neurologic prognosis was significantly related to the initial GCS and FOUR scores. In the qEEG analysis, patients' groups showed a prominent delta frequency band, and the healthy normal group presented a marked alpha predominance. As the severity decreased, the similarity in the spatial band-power pattern and functional connectivity pattern between normal subjects and patients increased. CONCLUSIONS: Low initial GCS and FOUR scores could be predictive of a poor neurologic prognosis in patients with HIE, and qEEG analysis might be a useful predictor of their neurologic outcomes.

A MELAS syndrome family harboring two mutations in mitochondrial genome

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a genetically heterogeneous mitochondrial disorder with variable clinical symptoms. Here, from the sequencing of the entire mitochondrial genome, we report a Korean MELAS family harboring two homoplasmic missense mutations, which were reported 9957T>C (Phe251Leu) transition mutation in the cytochrome c oxidase subunit 3 (COX3) gene and a novel 13849A>C (Asn505His) transversion mutation in the NADH dehydrogenase subunit 5 (ND5) gene. Neither of these mutations was found in 205 normal controls. Both mutations were identified from the proband and his mother, but not his father. The patients showed cataract symptom in addition to MELAS phenotype. We believe that the 9957T>C mutation is pathogenic, however, the 13849A>C mutation is of unclear significance. It is likely that the 13849A>C mutation might function as the secondary mutation which increase the expressivity of overlapping phenotypes of MELAS and cataract. This study also demonstrates the importance of full sequencing of mtDNA for the molecular genetic understanding of mitochondrial disorders.