The Grey Zone in Multiple Sleep Latency Test for Diagnosis of Narcolepsy: A Survey of Korean Neurologist

Objectives@#Clinicians often depend on the results of the the multiple sleep latency test (MSLT) for diagnosing narcolepsy, but the diagnosis can be confusing when there is a co-existence of obstructive sleep apnea (OSA). This study is aimed to address the diagnostic tendency and the strategies of treatment for narcolepsy and other hypersomnia in the grey zone. @*Methods@#We performed a web-based survey of Korean neurologists who were interested in narcolepsy and had experience with sleep studies. @*Results@#The results of this survey present their concerns according to the severity of comorbid OSA in analyzing the results of the MSLT. @*Conclusions@#This study also might help by providing the opinions of experienced Korean neurologists for the assessment and management of excessive daytime sleepiness.

Consideration for Coronavirus Disease 2019 Drug Treatment in Patients with Epilepsy on Antiepileptic Drugs

Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

Clinical Outcomes of Japanese Encephalitis after Combination Treatment of Immunoglobulin, Ribavirin, and Interferon-α2b

Background@#and Purpose Japanese encephalitis (JE) is caused by the JE virus of the Flaviviridae family and is spread by mosquito bites, and no specific antiviral treatment for it exists. Here we describe the clinical presentations, laboratory findings, clinical outcomes, and adverse events after combination treatment of immunoglobulin, ribavirin, and interferon-α2b administered to patients with JE. @*Methods@#Data were collected and reviewed from a prospective cohort of encephalitis patients admitted to Seoul National University Hospital between August 1, 2010 and October 31, 2019.We reviewed the medical records of the patients diagnosed with JE and treated either with supportive care only or with combination treatment of intravenous immunoglobulin, oral ribavirin, and subcutaneous interferon-α2b. @*Results@#Eleven patients were diagnosed with laboratory-confirmed JE based on the diagnosis criteria of JE. The median age was 61 years, and five patients were male. Eight patients were treated with the combination therapy, while three patients received supportive management only. Four of the eight patients (50%) treated with the combination therapy showed partial recovery, while one patient (12.5%) showed complete recovery. Two patients experienced hemolytic anemia related to ribavirin and febrile reaction to immunoglobulin, respectively. Among the three patients who received supportive management only, one (33.3%) showed partial recovery and the other two (67.7%) did not show improvement. @*Conclusions@#Combination treatment of immunoglobulin, ribavirin, and interferon-α2b was found to be tolerable in JE in this study. Further studies of appropriate designs and involving larger numbers of patients are warranted to explore the efficacy of this combination therapy.

Sleep Disorders and Risk of Motor Vehicle Accident

Driving is a complicated process that demands coordination between a range of neurocognitive functions, including attention, visuo-perception, and appropriate judgment, as well as sensory and motor responses. Therefore, several factors may reduce the driving performance of an individual, such as sleepiness, distraction, overspeeding, alcohol consumption, and sedative drugs, all of which increase the hazard of motor vehicle accidents. Among them, drowsy driving is a major cause of traffic accidents, leading to more serious injuries as compared to other causes of major traffic accidents. Although sleep disorders have been highly associated among drowsy drivers, they are often untreated and unrecognized as a disease. In particular, obstructive sleep apnea and narcolepsy are some sleep disorders that are highly related to traffic accidents. Insomnia, which can cause inadequate sleep duration and promote sedative effects from sleeping pills, may also cause traffic accidents. These conditions are especially applicable to commercial bus or truck drivers, nocturnal workers, and shift workers, who are highly vulnerable to drowsy driving. Therefore, assertive screening and management of sleep disorders are necessary in general private drivers and relevant occupational drivers.

Reduced Flicker Lighting Enhances Theta-Band Phase Synchrony during Working Memory Tasks

Objectives@#We analyzed theta-band phase synchrony (TBPS) under reduced and ordinary flicker lighting to determine the effect of light flickers on neurocognitive processes. @*Methods@#Nineteen healthy participants (mean age, 30.4±4.5 years; male, 63.2%) performed the Sternberg working memory tasks with event-related potential recording under reduced and control flicker conditions, respectively. We measured the P300 amplitude during memory retrieval, and for TBPS analysis, we calculated the weighted phase lag index within the P300 time window. Furthermore, we used standardized low-resolution brain electromagnetic tomography (sLORETA) to determine differences in functional cortical source connectivity between the two flicker conditions. @*Results@#The hit rate (F1,18=0.862, p=0.365), reaction time (F1,18=0.021, p=0.887), and P300 amplitude (F1,18=3.992, p=0.061) did not differ between the two flicker conditions. However, connectivity analysis at the scalp level showed that TBPS under reduced flicker lighting was significantly higher than that under control flicker lighting at higher memory loads (p=0.002). Cortical source imaging with sLORETA confirmed that reduced flicker lighting significantly increased TBPS between the left prefrontal cortex and right hippocampus compared with control flicker lighting (false discovery rate<0.1). @*Conclusions@#Reduced flicker lighting enhanced TBPS during the working memory task compared with control flicker lighting. Reduced flicker light may improve cognitive functioning by facilitating information transfer within the brain network. Flicker conditions should be considered when optimizing lighting, especially in environments demanding high-level cognitive performance.

Proposal for Prevention of Drowsy Driving-Related Motor Vehicle Accidents in Patients With Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is known to be associated with various health concerns, including sleepiness, fatigue, cognitive dysfunction, diminished quality of life, hypertension, cardiovascular diseases, and stroke. OSA-induced sleepiness at the wheel reduces vigilance and driving performance, which significantly increase the risk of motor vehicle accidents. Sleepiness-induced motor vehicle accidents are characterized by high morbidity and mortality. OSA is a well-established significant risk factor for drowsy driving-related motor vehicle accidents, which can be prevented through appropriate treatment. However, currently no clinical guidelines or regulations are available for evaluation or management of the risk of motor vehicle accidents in patients with OSA in Korea. In this review, we discuss the risk of motor vehicle accidents in patients with OSA, the effects of positive airway pressure therapy as a preventive measure to reduce this risk, and the published recommendations for OSA in other countries with regard to fitness to drive. We propose recommendations for screening, evaluation, and treatment of OSA with regard to the risk of motor vehicle accidents, which would serve as useful practical guidelines for sleep specialists in clinical practice. Further research is warranted to establish optimal strategies for effective improvements in OSA-related traffic safety.

Proposal for Preventing Motor Vehicle Accident Related to Drowsy Driving in Patients With Narcolepsy

Narcolepsy is a chronic sleep disorder characterized by irresistible sleep attacks, hypersomnolence, cataplexy (sudden loss of muscle tone provoked by emotion), and sleep paralysis. Individuals with narcolepsy are at a high risk of experiencing sleepiness while driving leading to road traffic accidents. To prevent such accidents, some countries have regulations for commercial and noncommercial drivers with narcolepsy. Evaluating sleepiness is essential. Therefore, several subjective reports and objective tests were used to predict the possibility of car crashes or near-misses. Brain stimulants are effective in treating narcolepsy and can reduce daytime sleepiness in these patients. However, no guideline has been established for the driving safety of patients with narcolepsy in Korea. The Korean Sleep Research Society has prepared this proposal for preventing motor vehicle accidents caused by drowsy driving in patients with narcolepsy.

Sleep Disorders and Risk of Motor Vehicle Accident

Driving is a complicated process that demands coordination between a range of neurocognitive functions, including attention, visuo-perception, and appropriate judgment, as well as sensory and motor responses. Therefore, several factors may reduce the driving performance of an individual, such as sleepiness, distraction, overspeeding, alcohol consumption, and sedative drugs, all of which increase the hazard of motor vehicle accidents. Among them, drowsy driving is a major cause of traffic accidents, leading to more serious injuries as compared to other causes of major traffic accidents. Although sleep disorders have been highly associated among drowsy drivers, they are often untreated and unrecognized as a disease. In particular, obstructive sleep apnea and narcolepsy are some sleep disorders that are highly related to traffic accidents. Insomnia, which can cause inadequate sleep duration and promote sedative effects from sleeping pills, may also cause traffic accidents. These conditions are especially applicable to commercial bus or truck drivers, nocturnal workers, and shift workers, who are highly vulnerable to drowsy driving. Therefore, assertive screening and management of sleep disorders are necessary in general private drivers and relevant occupational drivers.

Reduced Flicker Lighting Enhances Theta-Band Phase Synchrony during Working Memory Tasks

Objectives@#We analyzed theta-band phase synchrony (TBPS) under reduced and ordinary flicker lighting to determine the effect of light flickers on neurocognitive processes. @*Methods@#Nineteen healthy participants (mean age, 30.4±4.5 years; male, 63.2%) performed the Sternberg working memory tasks with event-related potential recording under reduced and control flicker conditions, respectively. We measured the P300 amplitude during memory retrieval, and for TBPS analysis, we calculated the weighted phase lag index within the P300 time window. Furthermore, we used standardized low-resolution brain electromagnetic tomography (sLORETA) to determine differences in functional cortical source connectivity between the two flicker conditions. @*Results@#The hit rate (F1,18=0.862, p=0.365), reaction time (F1,18=0.021, p=0.887), and P300 amplitude (F1,18=3.992, p=0.061) did not differ between the two flicker conditions. However, connectivity analysis at the scalp level showed that TBPS under reduced flicker lighting was significantly higher than that under control flicker lighting at higher memory loads (p=0.002). Cortical source imaging with sLORETA confirmed that reduced flicker lighting significantly increased TBPS between the left prefrontal cortex and right hippocampus compared with control flicker lighting (false discovery rate<0.1). @*Conclusions@#Reduced flicker lighting enhanced TBPS during the working memory task compared with control flicker lighting. Reduced flicker light may improve cognitive functioning by facilitating information transfer within the brain network. Flicker conditions should be considered when optimizing lighting, especially in environments demanding high-level cognitive performance.

Clinical Outcomes of Japanese Encephalitis after Combination Treatment of Immunoglobulin, Ribavirin, and Interferon-α2b

Background@#and Purpose Japanese encephalitis (JE) is caused by the JE virus of the Flaviviridae family and is spread by mosquito bites, and no specific antiviral treatment for it exists. Here we describe the clinical presentations, laboratory findings, clinical outcomes, and adverse events after combination treatment of immunoglobulin, ribavirin, and interferon-α2b administered to patients with JE. @*Methods@#Data were collected and reviewed from a prospective cohort of encephalitis patients admitted to Seoul National University Hospital between August 1, 2010 and October 31, 2019.We reviewed the medical records of the patients diagnosed with JE and treated either with supportive care only or with combination treatment of intravenous immunoglobulin, oral ribavirin, and subcutaneous interferon-α2b. @*Results@#Eleven patients were diagnosed with laboratory-confirmed JE based on the diagnosis criteria of JE. The median age was 61 years, and five patients were male. Eight patients were treated with the combination therapy, while three patients received supportive management only. Four of the eight patients (50%) treated with the combination therapy showed partial recovery, while one patient (12.5%) showed complete recovery. Two patients experienced hemolytic anemia related to ribavirin and febrile reaction to immunoglobulin, respectively. Among the three patients who received supportive management only, one (33.3%) showed partial recovery and the other two (67.7%) did not show improvement. @*Conclusions@#Combination treatment of immunoglobulin, ribavirin, and interferon-α2b was found to be tolerable in JE in this study. Further studies of appropriate designs and involving larger numbers of patients are warranted to explore the efficacy of this combination therapy.

Comorbid Depression Is Associated with a Negative Treatment Response in Idiopathic REM Sleep Behavior Disorder

Background@#and PurposeThe first-line medications for the symptomatic treatment of rapid eye movement sleep behavior disorder (RBD) are clonazepam and melatonin taken at bedtime. We aimed to identify the association between depression and treatment response in patients with idiopathic RBD (iRBD). @*Methods@#We reviewed the medical records of 123 consecutive patients (76 males; age, 66.0±7.7 years; and symptom duration, 4.1±4.0 years) with iRBD who were treated with clonazepam and/or melatonin. Clonazepam and melatonin were initially administered at 0.25–0.50 and 2 mg/day, respectively, at bedtime, and the doses were subsequently titrated according to the response of individual patients. Treatment response was defined according to the presence or absence of any improvement in dream-enacting behaviors or unpleasant dreams after treatment. @*Results@#Forty (32.5%) patients were treated with clonazepam, 56 (45.5%) with melatonin, and 27 (22.0%) with combination therapy. The doses of clonazepam and melatonin at followup were 0.5±0.3 and 2.3±0.7 mg, respectively. Ninety-six (78.0%) patients reported improvement in their RBD symptoms during a mean follow-up period of 17.7 months. After adjusting for potential confounders, depression was significantly associated with a negative treatment response (odds ratio=3.76, 95% confidence interval=1.15–12.32, p=0.029). @*Conclusions@#We found that comorbid depression is significantly associated with a negative response to clonazepam and/or melatonin in patients with iRBD. Further research with larger numbers of patients is needed to verify our observations and to determine the clinical implications of comorbid depression in the pathophysiology of iRBD.

Postherpetic Pseudohernia: Lesion Localization using Thoracic Spine Magnetic Resonance Imaging

No abstract available.

Association between Restless Legs Syndrome Symptoms and Self-Reported Hypertension: a Nationwide Questionnaire Study in Korea

BACKGROUND: The association between restless legs syndrome (RLS) and hypertension remains controversial. We investigated the relationship between RLS and hypertension in a nationwide sample of the Korean adult population. METHODS: This was a cross-sectional questionnaire-based study including 2,740 adults aged 19 years or more. Subjects who met the four essential International RLS Study Group criteria and reported symptoms occurring at least once a week were defined as the RLS group. The presence of hypertension was defined as a self-reported history of physician-diagnosed hypertension. We conducted multiple logistic regression analysis to determine the independent association between RLS symptoms and self-reported hypertension after adjusting for potential confounding factors. RESULTS: Among the 2,740 subjects, 68 (2.5%; 95% confidence interval [CI], 1.9%–3.1%) were found to have RLS with a symptom frequency of at least once a week. The prevalence of self-reported hypertension was 30.9% (95% CI, 20.5%–42.0%) in the RLS group, which was significantly higher than that in controls (12.4%; 95% CI, 11.2%–13.6%; P < 0.001). Multiple logistic regression analysis showed that the adjusted odds ratio for self-reported hypertension in the RLS group was 2.10 (95% CI, 1.12–3.93) compared to controls. In addition to RLS symptoms, old age, being overweight, low education level, diabetes mellitus, and short sleep duration were significantly associated with self-reported hypertension. CONCLUSION: RLS symptoms occurring at least once a week is independently associated with a higher prevalence of self-reported hypertension in the adult Korean population. Further research will confirm the clinical implication of the present results and the causal relationship between RLS and hypertension.

Two Cases of Radiologically Isolated Syndrome: First Case Report in Korea

With increasing sensitivity, availability, and use of magnetic resonance imaging (MRI) in the past three decades, there is also an increase in incidental abnormal findings. The most common findings of these incidental abnormalities are white matter lesions that are interpreted as demyelinating based on radiological criteria. MRI findings suggestive of multiple sclerosis (MS) in patients without typical MS symptoms and with normal neurologic findings are now defined as a radiologically isolated syndrome (RIS) which reported relatively low incidence, especially hard to find case report in Korea. The natural history and pathophysiologic processes of RIS remain largely unknown. The nature, prevalence, and long-term prognosis of RIS, as well as the role of disease-modifying therapy should be established in the future.

Japanese Encephalitis Presenting with Unilateral Medial Temporal Lobe Lesion

No abstract available.

Effects of Transcranial Direct-Current Stimulation Therapy on Primary Chronic Insomnia: A Proof-of Concept Clinical Trial

OBJECTIVES: To assess the effect and safety of transcranial direct-current stimulation (tDCS) in primary chronic insomnia. METHODS: A one-month, double-blind, randomized, sham-controlled trial was performed. A total of 7 patients with primary chronic insomnia received tDCS using anodal (n=3), cathodal (n=2), or sham stimulation (n=2). They were followed up at 1 week and 1 month after treatment. The primary outcome measures included improvement in total sleep time (TST), sleep latency (SL), and sleep efficiency (SE) at 1 month follow-up. RESULTS: TST and SE were improved with tDCS at 1 month follow-up in all patients (100%) of the anodal group, one (50%) of the cathodal group, and one (50%) of the sham group. tDCS improved SL at 1 month follow-up in two patients (67%) of the anodal group, one (50%) of the cathodal group, and none (0%) of the sham group. With respect to adverse events, transient itching sensation occurred in one patient of the anodal group. None of the other groups reported adverse events. CONCLUSIONS: Our results suggest that tDCS may be effective and safe for treatment of primary chronic insomnia. A larger controlled study needs to be further investigated.

Left Ventricular Ejection Fraction Predicts Poststroke Cardiovascular Events and Mortality in Patients without Atrial Fibrillation and Coronary Heart Disease

BACKGROUND AND OBJECTIVES: It is controversial that decreased left ventricular function could predict poststroke outcomes. The purpose of this study is to elucidate whether left ventricular ejection fraction (LVEF) can predict cardiovascular events and mortality in acute ischemic stroke (AIS) without atrial fibrillation (AF) and coronary heart disease (CHD). METHODS: Transthoracic echocardiography was conducted consecutively in patients with AIS or transient ischemic attack at Soonchunhyang University Hospital between January 2008 and July 2016. The clinical data and echocardiographic LVEF of 1,465 patients were reviewed after excluding AF and CHD. Poststroke disability, major adverse cardiac events (MACE; nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) and all-cause mortality during 1 year after index stroke were prospectively captured. Cox proportional hazards regressions analysis were applied adjusting traditional risk factors and potential determinants. RESULTS: The mean follow-up time was 259.9±148.8 days with a total of 29 non-fatal strokes, 3 myocardial infarctions, 33 cardiovascular deaths, and 53 all-cause mortality. The cumulative incidence of MACE and all-cause mortality were significantly higher in the lowest LVEF ( < 55) group compared with the others (p=0.022 and 0.009). In prediction models, LVEF (per 10%) had hazards ratios of 0.54 (95% confidence interval [CI], 0.36–0.80, p=0.002) for MACE and 0.61 (95% CI, 0.39–0.97, p=0.037) for all-cause mortality. CONCLUSIONS: LVEF could be an independent predictor of cardiovascular events and mortality after AIS in the absence of AF and CHD.

Left Ventricular Ejection Fraction Predicts Poststroke Cardiovascular Events and Mortality in Patients without Atrial Fibrillation and Coronary Heart Disease

BACKGROUND AND OBJECTIVES@#It is controversial that decreased left ventricular function could predict poststroke outcomes. The purpose of this study is to elucidate whether left ventricular ejection fraction (LVEF) can predict cardiovascular events and mortality in acute ischemic stroke (AIS) without atrial fibrillation (AF) and coronary heart disease (CHD).@*METHODS@#Transthoracic echocardiography was conducted consecutively in patients with AIS or transient ischemic attack at Soonchunhyang University Hospital between January 2008 and July 2016. The clinical data and echocardiographic LVEF of 1,465 patients were reviewed after excluding AF and CHD. Poststroke disability, major adverse cardiac events (MACE; nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) and all-cause mortality during 1 year after index stroke were prospectively captured. Cox proportional hazards regressions analysis were applied adjusting traditional risk factors and potential determinants.@*RESULTS@#The mean follow-up time was 259.9±148.8 days with a total of 29 non-fatal strokes, 3 myocardial infarctions, 33 cardiovascular deaths, and 53 all-cause mortality. The cumulative incidence of MACE and all-cause mortality were significantly higher in the lowest LVEF ( < 55) group compared with the others (p=0.022 and 0.009). In prediction models, LVEF (per 10%) had hazards ratios of 0.54 (95% confidence interval [CI], 0.36–0.80, p=0.002) for MACE and 0.61 (95% CI, 0.39–0.97, p=0.037) for all-cause mortality.@*CONCLUSIONS@#LVEF could be an independent predictor of cardiovascular events and mortality after AIS in the absence of AF and CHD.

Differential Effect of Light Emitting Diode Light on Electroencephalographic Oscillations in Young and Old Healthy Subjects

OBJECTIVES: To investigate brain oscillatory characteristics according to brightness and color temperature of light emitting diode (LED) light in young and elderly subjects. METHODS: We analyzed 22 young (age, 29.0±5.2 years) and 23 elderly (age, 64.8±4.5 years) healthy subjects. A LED light source was used with a combination of two color temperature (6,500 K vs. 3,000 K) and two brightness (700 lx vs. 300 lx) conditions. Participants were exposed to each light condition in relaxed wakefulness. Then, we analyzed power spectral density and functional connectivity from eye-open electroencephalography. RESULTS: A main effect of brightness on delta (p=0.044) and theta (p=0.038) power was significant in the elderly subjects. Bright light enhanced delta and theta power in the frontal region. By contrast, power spectral density of young subjects was affected by color temperature; high color temperature significantly increased beta-band power of the central region (p=0.034). Regarding functional connectivity, a significant effect of color temperature was observed in delta (p=0.006) and beta (p=0.046) frequencies. High color temperature light enhanced beta connectivity of young subjects (p=0.007), while not affecting that of elderly subjects (p=0.979). CONCLUSIONS: The present study demonstrated that spectral power and functional connectivity as well as subjective feelings are affected by the brightness and color temperature of LED light. These results might help us to understand the neurophysiological effects of light and identify the optimal indoor lighting conditions for an individual's environment.

Hyponatremia during Acyclovir Treatment of Bell's Palsy

A 61-year-old woman with chronic kidney disease presented with general weakness and a confused mentality. Two days before admission she had been diagnosed as Bell's palsy at an outpatient clinic, and started to take oral prednisolone and acyclovir. A blood test at admission revealed hyponatremia (128 mmol/L). After withdrawing acyclovir, her plasma sodium levels began to increase, returning to normal 2 weeks later. This case could provide further evidence for a causal relationship between acyclovir and hyponatremia.