Dae Lim Koo

Resection of individually identified high‐rate high‐frequency oscillations region is associated with favorable outcome in neocortical epilepsy

High‐frequency oscillations (HFOs) represent a novel electrophysiologic marker of endogenous epileptogenicity. Clinically, this propensity can be utilized to more accurately delineate the resection margin before epilepsy surgery. Currently, prospective application of HFOs is limited because of a lack of an exact quantitative measure to reliably identify HFO‐generating areas necessary to include in the resection. Here, we evaluated the potential of a patient‐individualized approach of identifying high‐rate HFO regions to plan the neocortical resection.

Let there be no light: the effect of bedside light on sleep quality and background electroencephalographic rhythms

OBJECTIVES Artificial lighting has been beneficial to society, but unnecessary light exposure at night may cause various health problems. We aimed to investigate how whole-night bedside light can affect sleep quality and brain activity. PATIENTS AND METHODS Ten healthy sleepers underwent two polysomnography (PSG) sessions, one with the lights off and one with the lights on. PSG variables related to sleep quality were extracted and compared between lights-off and lights-on sleep. Spectral analysis was performed to rapid eye movement (REM) sleep and non-REM (NREM) sleep epochs to reveal any light-induced differences in background brain rhythms. RESULTS Lights-on sleep was associated with increased stage 1 sleep (N1), decreased slow-wave sleep (SWS), and increased arousal index. Spectral analysis revealed that theta power (4-8Hz) during REM sleep and slow oscillation (0.5-1Hz), delta (1-4Hz), and spindle (10-16Hz) power during NREM sleep were decreased in lights-on sleep conditions. CONCLUSIONS Sleeping with the light on not only causes shallow sleep and frequent arousals but also has a persistent effect on brain oscillations, especially those implicated in sleep depth and stability. Our study demonstrates additional hazardous effect of light pollution on health.

Effect of oxcarbazepine on bone mineral density and biochemical markers of bone metabolism in patients with epilepsy

PURPOSE Antiepileptic drugs (AEDs) may cause adverse effects on bone metabolism and bone mineral density (BMD). The aim of this study is to determine the effect of oxcarbazepine (OXC) monotherapy on biochemical markers of bone metabolism and BMD in epilepsy patients. METHODS Forty-one new onset drug naïve epilepsy patients were recruited (19 females, 22 males; mean age: 28.2±8.4 years). We measured biochemical markers of bone metabolism (serum calcium, phosphate, bone alkaline phosphatase, parathyroid hormone, osteocalcin, insulin-like growth factor (IGF)-1, C-telopeptide, Vitamin D3 levels) and BMD by DEXA (dual energy X-ray absorptiometry) method in all patients before and after a long-term OXC monotherapy. RESULTS Most of biochemical markers were not changed significantly, but serum calcium (p=0.0087) and bone specific ALP was reduced (p=0.0499) significantly after OXC monotherapy in epilepsy patients. BMD at the lumbar spine (L2 to L4) was significantly increased after OXC monotherapy (p=0.0001), revealed by repeated measures ANOVA with Bonferronis correction of confounders including sex, age, average dose, and treatment duration. However, BMD at the lumbar spine (L2 to L4) was significantly increased (p=0.012) only in female patients in each gender analysis. CONCLUSIONS This study demonstrates that a long-term OXC monotherapy does not appear to have harmful effect on bone health in drug naïve epilepsy patients.

Cerebral Microbleeds on MRI in Patients with Obstructive Sleep Apnea

STUDY OBJECTIVES Obstructive sleep apnea (OSA) is known to increase the risk of stroke. Cerebral microbleeds (CMBs) are considered one of the precursors to symptomatic stroke. We aimed to clarify the relationship between OSA and CMBs. METHODS We recruited patients who visited our clinic for the evaluation of sleep-disordered breathing. All patients underwent both overnight polysomnography and brain magnetic resonance imaging, which included T2*-weighted gradient-recalled echo images. We applied multivariate logistic regression and partial correlation analysis to estimate the relationship between OSA and CMBs. RESULTS A total of 75 (45 male, 30 female) patients were enrolled. Their mean age was 60.5 years. Patients with CMBs had a significantly higher apneahypopnea index (AHI) compared with those without CMBs. AHI equal to or greater than 15 was a significant independent predictor of CMBs (adjusted odds ratio, 4.51; 95% CI, 1.40-14.58; p = 0.012) in the multivariate regression analysis. In addition, a partial correlation analysis adjusted for age, hypertension, diabetes, and cardiovascular disease revealed a positive relationship between AHI and the number of CMBs (r = 0.585, p = 0.028). CONCLUSIONS Moderate-to-severe OSA can be one of the independent predictors of CMBs which are considered a surrogate marker of overt stroke.

Stress and sleep quality in doctors working on-call shifts are associated with functional gastrointestinal disorders

AIM To investigate the role of sleep quality and psychosocial problems as predictors of functional gastrointestinal disorders (FGIDs) in doctors that work 24 hour-on-call shifts. METHODS In this cross-sectional observation study, using the Rome III Questionnaire and Pittsburgh Sleep Quality Index (PSQI), we analyzed 170 doctors with 24 hour-on-call shifts. RESULTS Among the participants that had experienced a 24 hour-on-call shift within the last 6 mo, 48 (28.2%) had FGIDs. Overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 16.5% and 17.1%, respectively, with 5.3% exhibiting both. Sleep scores (PSQI) (8.79 ± 2.71 vs 7.30 ± 3.43, P = 0.008), the presence of serious psychosocial alarm (83.3% vs 56.6%, P = 0.004), and the proportion of doctors who experienced over two months of recent on-call work (81.2% vs 68.9%, P = 0.044) were significantly different between individuals with or without FGIDs. Multivariate analysis revealed that presenting serious psychosocial alarm was an independent risk factor for prevalence of FD (OR = 5.47, 95%CI: 1.06-28.15, P = 0.042) and poor sleep quality (PSQI ≥ 6) was a predictor of IBS (OR = 4.17, 95%CI: 1.92-19.02, P = 0.016). CONCLUSION Physicians should recognize the role of sleep impairment and psychological stress in the development of FGIDs and a comprehensive approach should be considered to manage patients with FGIDs.

Acoustic Characteristics of Stridor in Multiple System Atrophy.

Nocturnal stridor is a breathing disorder prevalent in patients with multiple system atrophy (MSA). An improved understanding of this breathing disorder is essential since nocturnal stridor carries a poor prognosis (an increased risk of sudden death). In this study, we aimed to classify types of stridor by sound analysis and to reveal their clinical significance. Patients who met the criteria for probable MSA and had undergone polysomnography (PSG) were recruited. Patients were then assessed clinically with sleep questionnaires, including the Pittsburgh Sleep Quality Index, and the Hoehn and Yahr scale. Nocturnal stridor and snoring were analyzed with the Multi-Dimensional Voice Program. Nocturnal stridor was recorded in 22 patients and snoring in 18 patients using the PSG. Waveforms of stridors were classified into rhythmic or semirhythmic after analysis of the oscillogram. Formants and harmonics were observed in both types of stridor, but not in snoring. Of the 22 patients diagnosed with stridor during the present study, fifteen have subsequently died, with the time to death after the PSG study being 1.9 ± 1.4 years (range 0.8 to 5.0 years). The rhythmic waveform group presented higher scores on the Hoehn and Yahr scale and the survival outcome of this group was lower compared to the semirhythmic waveform group (p = 0.030, p = 0.014). In the Kaplan Meier’s survival curve, the outcome of patients with rhythmic waveform was significantly less favorable than the outcome of patients with semirhythmic waveform (log-rank test, p < 0.001). Stridor in MSA can be classified into rhythmic and semirhythmic types and the rhythmic component signifies a poorer outcome.

Asymmetric Gray Matter Volume Changes Associated with Epilepsy Duration and Seizure Frequency in Temporal-Lobe-Epilepsy Patients with Favorable Surgical Outcome

Background and Purpose This study aimed to estimate the changes in gray matter volume (GMV) and their hemispheric difference in patients with mesial temporal lobe epilepsy (MTLE) using a voxel-based morphometry (VBM) methodology, and to determine whether GMV changes are correlated with clinical features. Methods VBM analysis of brain MRI using statistical parametric mapping 8 (SPM8) was performed for 30 left MTLE (LMTLE) and 30 right MTLE (RMTLE) patients and 30 age- and sex-matched healthy controls. We also analyzed the correlations between GMV changes and clinical features of MTLE patients. Results In SPM8-based analyses, MTLE patients showed significant GMV reductions in the hippocampus ipsilateral to the epileptic focus, bilateral thalamus, and contralateral putamen in LMTLE patients. The GMV reductions were more extensive in the ipsilateral hippocampus, thalamus, caudate, putamen, uncus, insula, inferior temporal gyrus, middle occipital gyrus, cerebellum, and paracentral lobule in RMTLE patients. These patients also exhibited notable reductions of GMV in the contralateral hippocampus, thalamus, caudate, putamen, and inferior frontal gyrus. We observed that GMV reduction was positively correlated with several clinical features (epilepsy duration and seizure frequency in RMTLE, and history of febrile seizure in LMTLE) and negatively correlated with seizure onset age in both the RMTLE and LMTLE groups. Conclusions Our study revealed GMV decreases in the hippocampus and extrahippocampal regions. Furthermore, the GMV reduction was more extensive in the RMTLE group than in the LMTLE group, since it included the contralateral hemisphere in the former. This difference in the GMV reduction patterns between LMTLE and RMTLE may be related to a longer epilepsy duration and higher seizure frequency in the latter.

Clinical Considerations of Obstructive Sleep Apnea with Little REM Sleep

Background and Purpose Obstructive sleep apnea (OSA) is more severe during rapid eye movement (REM) sleep than during non-REM sleep. We aimed to determine the features of patients with OSA who experience little REM sleep. Methods Patients with a chief complaint of sleep-disordered breathing were enrolled. All subjects underwent overnight polysomnography (PSG) and completed questionnaires on sleep quality. Patients were divided into the following three groups according to the proportion of REM sleep detected in overnight PSG: little REM sleep [REM sleep <20% of total sleep time (TST)], normal REM sleep (20–25% of TST), and excessive REM sleep (>25% of TST). Multiple logistic regression analyses were applied to the data. The success rate of continuous positive airway pressure (CPAP) titration was estimated in these groups. Results The age and body mass index of the patients were 47.9±15.9 years (mean±SD) and 25.2±4.1 kg/m2, respectively. The 902 patients comprised 684 (76%) men and 218 (24%) women. The apnea-hypopnea index (AHI) in the little-REM-sleep group was 22.1±24.4 events/hour, which was significantly higher than those in the other two groups (p<0.05). Multiple logistic regression showed that a higher AHI (p<0.001; odds ratio, 1.512; 95% confidence interval, 1.020–1.812) was independently predictive of little REM sleep. The titration success rate was lower in the little-REM-sleep group than in the normal-REM-sleep group (p=0.038). Conclusions The AHI is higher and the success rate of CPAP titration is lower in OSA patients with little REM sleep than those with normal REM sleep.

Giant Cell Arteritis Associated Arteritic Anterior Ischemic Optic Neuropathy: Sudden Vision Loss on the Contralateral Side of Headache

Dear Editor, Giant-cell arteritis (GCA), also known as temporal arteritis, is a primary systemic autoimmune disease characterized by infiltration of moderate-size and large blood vessels.1 GCA is the most common primary vasculitis in adults older than 50 years, and GCA patients commonly experience cranial or systemic symptoms, including unilateral or bilateral headache, scalp tenderness, weight loss, fatigue, and fever.2 An abrupt-onset headache is the main symptom in more than two-thirds of GCA patients.3 Severe headache often occurs on the side of the affected artery. Irreversible vision loss occurs in up to 20% of GCA patients, and this is considered a medical emergency.4 Arteritic anterior ischemic optic neuropathy (AAION) is the most serious ophthalmological complication of GCA.2 Here we report the case of a patient with unilateral headache attributed to GCA and contralateral AAION. A 74-year-old man was referred with new-onset headache with a 1-month history in the right temporal area, with systemic manifestations including right jaw claudication, malaise, scalp tenderness, and loss of appetite. Laboratory findings revealed a white blood cell count of 11.67×103/μL with a slight elevation of neutrophils and platelets at 320×103/μL. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) had increased to 49 mm/hr and 3.85 mg/dL, respectively. Ultrasonography showed thickening of the right superficial temporal artery, but brain MRI and angiography revealed no significant abnormalities. On the second day after the daily administration of 60 mg of oral prednisone, his left eye visual acuity deteriorated rapidly, although the headache was significantly improved. An ophthalmological examination indicated intact right eye visual acuity but significant impairments in the left eye, with only finger counting possible. A relative afferent pupillary defect was detected in the left eye. The intraocular pressure was 11 mm Hg in the right eye and 15 mm Hg in the left eye. A fundus examination confirmed the presence of papilledema (Frisen grade 2) in the left eye (Fig. 1A and B). Fluorescein angiography showed that the choroidal blood flow in the left eye was decreased. Intravenous methylprednisolone was administered at 1,000 mg daily for 5 days and both temporal arteries were biopsied. Intimal thickening and perivascular lymphohistiocytic inflammatory infiltration were evident in both superficial temporal arteries (Fig. 1C–F). After administering 500 mg of cyclophosphamide intravenously, the optic disc swelling was reduced and the left eye visual acuity was slightly improved. Inflammatory markers including ESR and CRP returned to normal levels. The pathophysiology of GCA involves inflammation, myointimal thickening, and stenosis of moderate-size to large vessels. Stenosis may result in complete occlusion or turbulent flow that leads to thrombosis. GCA is, in essence, a form of systemic arteritis, and biopsy studies of bilateral temporal arteries have had a reported concordance rate of 96% (93–99%).5 Bilateral simultaneous biopsy of the temporal arteries has been considered a safe gold stanEung-joon Lee Kyung Ah Woo Dae Lim Koo

Repetitive Questioning and Writing in a Patient with Transient Global Amnesia

Dear Editor, Transient global amnesia (TGA) is a syndrome involving temporary memory loss. TGA mainly occurs in middle-aged to elderly individuals and can last up to 24 hours.1 During a TGA episode, patients typically ask repetitive questions, and this characteristic behavior has been considered as an important diagnostic feature for TGA.2 We report on a patient with TGA who presented with repetitive questioning as well as repetitive writing during the TGA episode. A 52-year-old woman visited our emergency room with her husband, who described her condition as asking repetitive questions despite repeatedly being given correct answers. He had observed that she appeared agitated and cried during the early phase of the episode. Even after her husband had adequately answered her questions, the patient repeatedly asked questions like “Why am I here?” and “What is the date today?” Her husband also presented papers with writings that the patient had made during the period of the TGA episode. In these writings, the patient repetitively asked and wrote about the date of symptom onset, her worries regarding the marital state of her younger sister, and the name of the school and the grades her children were in (Fig. 1A). She had completely recovered to her baseline status after about 6 hours of memory loss and altered behavior. On the day after the TGA episode, we asked the patient to rewrite the same content to allow us to compare the text with that produced during the episode (Fig. 1B). The patient’s style of writing during the TGA episode was more cursive than at baseline, but no grammatical or spelling errors were observed (Fig. 1A). During the episode, the patient showed no signs of neurological deficits, and the findings of physical and neurological examinations were normal. She had no medical history of vascular risk factors or drug use. The results of the laboratory tests were within normal limits. Brain computed tomography showed no abnormalities, and diffusion-weighted imaging revealed no specific dot lesions. Electroencephalography performed three times did not reveal any epileptiform discharges. No further episodes developed during the 2-month follow-up period. A diagnosis of TGA depends on the patient’s history. Characteristic repetitive questioning is a common symptom that accompanies an episode and needs to be witnessed by an observer to fulfill the criteria for TGA.1-3 Cognitive impairment is typically restricted to memory loss with no aphasia or apraxia. While there has been one case report of grammatical and spelling errors during text messaging on a cellular phone, and without repetitive writing,4 our patient showed repetitiveness in handwritten text on paper without any grammatical or spelling errors. Abnormal venous drainage from the temporal lobes has been considered a feasible hypothesis for the pathogenesis of TGA, although the precise cause and mechanisms of TGA remain unclear.5 The authors suggested that repetitive questioning and writing is related to an altered state of the temporal lobe, which is involved in memory impairment and automatic behaviors. In the absence of witnessed amnesia or repetitive questioning, reDae Lim Koo Jin-Ah Kim Hyunwoo Nam