Effects of Continuous Positive Airway Pressure on Sleep State Misperception in Patients With Obstructive Sleep Apnea

Background@#Little is known regarding the effects of continuous positive airway pressure (CPAP) on sleep misperception in obstructive sleep apnea (OSA). @*Methods@#Sleep state perception was measured by subtracting the objective total sleep time from the subjective sleep duration. Sleep underestimation and overestimation were defined as ± 60 minutes sleep perception. Insomnia and depressive symptoms were assessed using questionnaires. Finally, nonparametric statistical analyses were performed. @*Results@#Of the 339 patients with OSA included in the study, 90 (26.5%) and 45 (13.3%) showed sleep underestimation and overestimation, respectively. Overall, a significant underestimation of sleep was noted during CPAP titration comparing to a diagnostic PSG (P < 0.001). OSA patients with insomnia or depressive symptoms did not show any changes in sleep perception between diagnostic and CPAP titration studies, whereas those without insomnia or depressed mood showed significantly underestimated sleep duration during CPAP titration. Patients with OSA and either underestimated or overestimated misperception showed perceptual improvements during CPAP titration regardless of the presence of insomnia or depressive symptoms. However, of 204 patients with normal sleep perception, 138 (67.6%) and 10 (4.9%) had underestimation and overestimation of sleep during CPAP titration. @*Conclusion@#CPAP titration may improve sleep perception with moderate to severe OSA who have sleep misperception. However, CPAP titration may result in sleep misperception especially underestimation of sleep in those who have normal sleep perception.

Characterization of a Peptide Antibody Specific to the Adenylyl Cyclase-Associated Protein of Acanthamoeba castellanii

Acanthamoeba keratitis (AK) is a rare infectious disease and accurate diagnosis has remained arduous as clinical manifestations of AK were similar to keratitis of viral, bacterial, or fungal origins. In this study, we described the production of a polyclonal peptide antibody against the adenylyl cyclase-associated protein (ACAP) of A. castellanii, and evaluated its differential diagnostic potential. Enzyme-linked immunosorbent assay revealed high titers of A. castellanii-specific IgG and IgA antibodies being present in low dilutions of immunized rabbit serum. Western blot analysis revealed that the ACAP antibody specifically interacted with A. castellanii, while not interacting with human corneal epithelial (HCE) cells and other causes of keratitis such as Fusarium solani, Pseudomonas aeruginosa, and Staphylococcus aureus. Immunocytochemistry (ICC) results confirmed the specific detection of trophozoites and cysts of A. castellanii co-cultured with HCE cells. The ACAP antibody also specifically interacted with the trophozoites and cysts of 5 other Acanthamoeba species. These results indicate that the ACAP antibody of A. castellanii can specifically detect multiple AK-causing members belonging to the genus Acanthamoeba and may be useful for differentially diagnosing Acanthamoeba infections.

Sex Differences in Excessive Daytime Sleepiness Among Patients With Obstructive Sleep Apnea

Background@#and Purpose To identify sex differences in daytime sleepiness associated with apnea severity and periodic limb movements during sleep (PLMS) in subjects with obstructive sleep apnea (OSA). @*Methods@#This study used the Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), and Sleep Hygiene Index (SHI) in logistic regression analyses with interaction terms. Severe OSA, excessive daytime sleepiness (EDS), and PLMS were defined as an apnea-hypopnea index of ≥30, an ESS score of ≥11, and a periodic limb movements index of >15, respectively. @*Results@#The 1,624 subjects with OSA (males, 79.1%) comprised 45.3%, 38.2%, and 16.4% with severe OSA, EDS, and PLMS, respectively. Multiple logistic regression without interaction terms showed that sex, severe OSA, and PLMS were not significantly associated with EDS. However, significant interactions were noted between sex and severe OSA and PLMS in EDS in both crude and adjusted models (all p values<0.05). In the adjusted model, severe OSA was associated with EDS in males (p=0.009) but not in females. PLMS were more likely to be associated with EDS in females (p=0.013), whereas PLMS were less likely to be associated with EDS in males (p=0.041). The models were adjusted by the BDI score, SHI, and presence of medical comorbidities. @*Conclusions@#There are significant sex differences in subjective daytime sleepiness in subjects with severe OSA and PLMS. Severe OSA and PLMS may influence daytime sleepiness more in males and females, respectively.

Validation of the Uniform Case Definition Criteria for Differentiating Tuberculous Meningitis, Viral Meningitis, and Bacterial Meningitis in Adults / 감염과화학요법

We validated the uniform case definition for differentiating tuberculous meningitis (TBM) from both viral meningitis (VM) and bacterial meningitis (BM) in adults from South Korea, a country with an intermediate TB-burden. ‘Probable’ TBM differentiated ‘definite’ TBM with a sensitivity of 81% and specificity of 98%. ‘Possible TBM’ criteria identified ‘definite’ TBM with a sensitivity of 100% and specificity of 60%. Despite the usefulness of the uniform case definition criteria, there was substantial overlaps among VM, BM, and ‘possible’ TBM, especially in severe cases of VM and indolent cases of BM.

Does Rapid Eye Movement Sleep Aggravate Obstructive Sleep Apnea?

OBJECTIVES.: To investigate the apnea-hypopnea index (AHI) according to the sleep stage in more detail after control of posture. METHODS.: Patients who underwent nocturnal polysomnography between December 2007 and July 2018 were retrospectively evaluated. Inclusion criteria were as follows: age >18 years, sleep efficacy >80%, and patients who underwent polysomnography only in the supine position (100% of the time). Patients were classified into different groups according to the methods: the first, rapid eye movement (REM)-dominant group (AHIREM/AHINREM >2), non-rapid eye movement (NREM)-dominant group (AHINREM/AHIREM >2), and non-dominant group; and the second, light sleep group (AHIN1N2>AHISWS) and slow wave sleep (SWS) group (AHISWS>AHIN1N2). RESULTS.: A total of 234 patients (mean age, 47.4±13.9 years) were included in the study. There were 108 patients (46.2%) in the REM-dominant group, 88 (37.6%) in the non-dominant group, and 38 (16.2%) in the NREM-dominant group. The AHI was significantly higher in the NREM-dominant group than in the REM-dominant group (32.9±22.9 events/hr vs. 18.3±9.5 events/hr, respectively). There were improvements in the AHI from stage 1 to SWS in NREM sleep with the highest level in REM sleep. A higher AHISWS than AHIN1N2 was found in 16 of 234 patients (6.8%); however, there were no significant predictors of these unexpected results except AHI. CONCLUSION.: Our results demonstrated the highest AHI during REM sleep stage in total participants after control of posture. However, there were 16.2% of patients showed NREM-dominant pattern (AHINREM/AHIREM >2) and 6.8% of patients showed higher AHISWS than AHIN1N2. Therefore, each group might have a different pathophysiology of obstructive sleep apnea (OSA), and we need to consider this point when we treat the patients with OSA.

Effects of Appointing a Full-Time Neurointensivist to Run a Closed-Type Neurological Intensive Care Unit

BACKGROUND AND PURPOSE: To investigate whether appointing a full-time neurointensivist to manage a closed-type neurological intensive care unit (NRICU) improves the quality of critical care and patient outcomes. METHODS: This study included patients admitted to the NRICU at a university hospital in Seoul, Korea. Two time periods were defined according to the presence of a neurointensivist in the preexisting open-type NRICU: the before and after periods. Hospital medical records were queried and compared between these two time periods, as were the biannual satisfaction survey results for the families of patients. RESULTS: Of the 15,210 patients in the neurology department, 2,199 were admitted to the NRICU (n=995 and 1,204 during the before and after periods, respectively; p<0.001). The length of stay was shorter during the after than during the before period in both the NRICU (3 vs. 4 days; p<0.001) and the hospital overall (12.5 vs. 14.0 days; p<0.001). Neurological consultations (2,070 vs. 3,097; p<0.001) and intrahospital transfers from general intensive care units to the NRICU (21 vs. 40; p=0.111) increased from the before to after the period. The mean satisfaction scores of the families of the patients also increased, from 78.3 to 89.7. In a Cox proportional hazards model, appointing a neurointensivist did not result in a statistically significant change in 6-month mortality (hazard ratio, 0.82; 95% confidence interval, 0.652–1.031; p=0.089). CONCLUSIONS: Appointing a full-time neurointensivist to manage a closed-type NRICU had beneficial effects on quality indicators and patient outcomes.

Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing's syndrome

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis hrough GR acetylation in experimental CS.

Epilepsy and Driving Regulation in Korea

In Korea, current status of epilepsy and driving are challenging and there are lack of formal legal guidelines about driving in patients with epilepsy. According to the default standards in Korean Road Traffic law, patients with epilepsy are restricted or prohibited from driving except who are conditionally allowed to drive by the Aptitude Judgement Committee (AJC). Though the AJC consist of medical doctors and traffic officials, new regulation and guidelines are required for various type of seizure and characteristics of patients with epilepsy. This review outlines the current applicable legislation about epilepsy and driving in Korea as well as that of the overseas country calling for new laws to establish a consistent assessment.

Tuberculous Meningitis-Mimicking Varicella-Zoster Meningitis / 감염과화학요법

BACKGROUND: Varicella-zoster virus (VZV) is one of the most common etiologies of aseptic meningitis. The severest manifestation of VZV meningitis is occasionally confused with tuberculous meningitis (TBM). Thus, we investigated the clinical manifestations of VZV meningitis as compared with those of TBM. MATERIALS AND METHODS: All adult patients who were diagnosed with VZV meningitis or TBM were enrolled at a tertiary hospital in Seoul, South Korea, during an 8-year period. The clinical characteristics and cerebrospinal fluid (CSF) profile of patients were analyzed. RESULTS: Seventy-nine patients with VZV meningitis and 24 patients with TBM were enrolled in this study. Of the 79 patients with VZV meningitis, 63 (80%) did not received empirical anti-tuberculous therapy (Group 1) and the remaining 16 (20%) received empirical anti-tuberculous therapy (Group 2), compared with 24 patients with TBM (Group 3). Altered mental status, intensive care unit (ICU) admission, neurologic sequelae, CSF protein levels, and CSF adenosine deaminase levels revealed a trend of being higher in Group 3 than Group 2, which was higher than Group 1. However, the CSF/serum glucose ratio was significantly lower in Group 3 than in Group 1 or Group 2. CONCLUSION: About one fifth of VZV meningitis cases presented as severe manifestations, mimicking TBM. The CSF/serum glucose ratio might be useful to differentiate VZV meningitis from TBM until definite diagnostic tests are available. Physicians should keep in mind that a differential diagnosis between severe VZV meningitis and TBM is needed.

Identification and Characterization of Protein Arginine Methyltransferase 1 in Acanthamoeba castellanii

Protein arginine methyltransferase (PRMT) is an important epigenetic regulator in eukaryotic cells. During encystation, an essential process for Acanthamoeba survival, the expression of a lot of genes involved in the encystation process has to be regulated in order to be induced or inhibited. However, the regulation mechanism of these genes is yet unknown. In this study, the full-length 1,059 bp cDNA sequence of Acanthamoeba castellanii PRMT1 (AcPRMT1) was cloned for the first time. The AcPRMT1 protein comprised of 352 amino acids with a SAM-dependent methyltransferase PRMT-type domain. The expression level of AcPRMT1 was highly increased during encystation of A. castellanii. The EGFP-AcPRMT1 fusion protein was distributed over the cytoplasm, but it was mainly localized in the nucleus of Acanthamoeba. Knock down of AcPRMT1 by synthetic siRNA with a complementary sequence failed to form mature cysts. These findings suggested that AcPRMT1 plays a critical role in the regulation of encystation of A. castellanii. The target gene of AcPRMT1 regulation and the detailed mechanisms need to be investigated by further studies.

DNA Methylation of Gene Expression in Acanthamoeba castellanii Encystation

Encystation mediating cyst specific cysteine proteinase (CSCP) of Acanthamoeba castellanii is expressed remarkably during encystation. However, the molecular mechanism involved in the regulation of CSCP gene expression remains unclear. In this study, we focused on epigenetic regulation of gene expression during encystation of Acanthamoeba. To evaluate methylation as a potential mechanism involved in the regulation of CSCP expression, we first investigated the correlation between promoter methylation status of CSCP gene and its expression. A 2,878 bp of promoter sequence of CSCP gene was amplified by PCR. Three CpG islands (island 1–3) were detected in this sequence using bioinformatics tools. Methylation of CpG island in trophozoites and cysts was measured by bisulfite sequence PCR. CSCP promoter methylation of CpG island 1 (1,633 bp) was found in 8.2% of trophozoites and 7.3% of cysts. Methylation of CpG island 2 (625 bp) was observed in 4.2% of trophozoites and 5.8% of cysts. Methylation of CpG island 3 (367 bp) in trophozoites and cysts was both 3.6%. These results suggest that DNA methylation system is present in CSCP gene expression of Acanthamoeba. In addition, the expression of encystation mediating CSCP is correlated with promoter CpG island 1 hypomethylation.

Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

Development of Spinal Epidural Abscess during Treatment of Pneumococcal Meningitis / 대한내과학회지

There have been a few reports of pneumococcal meningitis complicated by spinal epidural abscess. A 58-year-old female with Streptococcus pneumoniae meningitis underwent a recurrent pleocytosis without apparent clinical deterioration after appropriate antibiotic treatment. Subsequently, she developed a spinal epidural abscess. Spinal epidural abscess is a rare complication of pneumococcal meningitis, and subclinical deterioration of neutrophil-dominant pleocytosis may precede development of a spinal epidural abscess in individuals with bacterial meningitis.

Seizure Frequencies and Number of Anti-epileptic Drugs as Risk Factors for Sudden Unexpected Death in Epilepsy

The purpose of this study was to investigate the association between clinical variables and sudden unexpected death in epilepsy (SUDEP) and identify risk factors for SUDEP. SUDEP is one of the most frequent causes of death in patients with epilepsy. Previous studies have reported possible risk factors associated with SUDEP, but there need to be elucidated yet. The cases were 26 patients with SUDEP and three control patients were included for each case, matched for age, sex, and date of initial clinical visit. All demographic and clinical characteristics, including age, sex, disease duration, classification of epilepsy, age at seizure onset, kind and number of antiepileptic drugs, were compared between cases and controls. Seizure frequency was higher in SUDEP cases than in controls (P=0.035). Univariate analysis using conditional logistic regression showed that higher seizure frequency (odds ratio [OR]=3.1, P=0.021) and the number of antiepileptic drugs (AEDs) (OR=2.0, P=0.009) were significantly associated with SUDEP. Only the number of AEDs remained significant in multivariate analysis (OR=1.8, P=0.026). Frequent seizures and multi-drug therapy were associated with SUDEP. This may suggest that the severity of epilepsy is associated with SUDEP, regardless of the type of AED used.

Paraneoplastic Extralimbic Encephalitis Presenting with Partial Motor Clonic Seizure in a Patient with Invasive Thymoma

Paraneoplastic encephalitis presenting with partial clonic seizure is rare. We report a 57-year-old man with clonic seizure in his left arm. He had past medical history of recurrent thymoma and thymomectomy. Magnetic resonance imaging showed multiple brain lesions, but none of them were congruent with the partial seizure. His symptoms and brain lesions resolved after steroid therapy. This is the first reported case extralimbic encephalitis presenting as partial seizure with invasive thymoma in Korea.

Paraneoplastic Extralimbic Encephalitis Presenting with Partial Motor Clonic Seizure in a Patient with Invasive Thymoma

Paraneoplastic encephalitis presenting with partial clonic seizure is rare. We report a 57-year-old man with clonic seizure in his left arm. He had past medical history of recurrent thymoma and thymomectomy. Magnetic resonance imaging showed multiple brain lesions, but none of them were congruent with the partial seizure. His symptoms and brain lesions resolved after steroid therapy. This is the first reported case extralimbic encephalitis presenting as partial seizure with invasive thymoma in Korea.

The First Reported Case of West Nile Encephalitis in Korea

West Nile encephalitis was first identified in 1937, but until now, it was never diagnosed in Korea. A 58-yr-old Korean man was admitted with headache and cognitive dysfunction. The patient had been on a business trip in Guinea. Cerebrospinal fluid (CSF) showed pleocytosis. The patient complained of both leg weakness,and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging (MRI). A specific neutralizing antibody for West Nile virus was positive in serum. After a treatment with interferon-alpha 3mu, follow up CSF findings recovered completely after 3 months later. The first case of West Nile encephalitis in Korea was imported from Guinea, and was cured successfully.

The First Reported Case of West Nile Encephalitis in Korea

West Nile encephalitis was first identified in 1937, but until now, it was never diagnosed in Korea. A 58-yr-old Korean man was admitted with headache and cognitive dysfunction. The patient had been on a business trip in Guinea. Cerebrospinal fluid (CSF) showed pleocytosis. The patient complained of both leg weakness,and arachnoiditis and myelitis were observed on lumbar magnetic resonance imaging (MRI). A specific neutralizing antibody for West Nile virus was positive in serum. After a treatment with interferon-alpha 3mu, follow up CSF findings recovered completely after 3 months later. The first case of West Nile encephalitis in Korea was imported from Guinea, and was cured successfully.

The Utility of Three Screening Questionnaires for Obstructive Sleep Apnea in a Sleep Clinic Setting

PURPOSE: The aim of this study was to determine the diagnostic value of three screening questionnaires in identifying Korean patients at high risk for obstructive sleep apnea (OSA) in a sleep clinic setting in Korea. MATERIALS AND METHODS: Data were collected from 592 adult patients with suspected OSA who visited a sleep center. All patients completed the Sleep Apnea of Sleep Disorder Questionnaire (SA-SDQ), the Berlin questionnaire, and the STOP-Bang questionnaire. Estimated OSA risk was compared to a diagnosis of OSA. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each questionnaire. RESULTS: The prevalence of OSA was 83.6% using an apnea-hypopnea index (AHI) > or =5/h and 58.4% for an AHI > or =15/h. The STOP-Bang questionnaire had a high sensitivity (97% for AHI > or =5/h, 98% for AHI > or =15/h), but the specificity was low (19% and 11%, respectively). In contrast, the sensitivity of the SA-SDQ was not high enough (68% for AHI > or =5/h, 74% for AHI > or =15/h) to be useful in a clinical setting, whereas the specificity was relatively good (66% and 61%, respectively). The sensitivity and specificity values of the Berlin questionnaire fell between those of the STOP-Bang questionnaire and the SA-SDQ. CONCLUSION: The STOP-Bang questionnaire may be useful for screening OSA in a sleep clinic setting, but its specificity is lower than the acceptable level for this purpose. A new screening questionnaire with a high sensitivity and acceptable specificity is therefore needed in a sleep clinic setting.

Idiopathic REM Sleep Behavior Disorder in Young Adults and Quantitative Analysis of Polysomnography

Rapid eye movement sleep behavior disorder (RBD) is a sleep disorder characterized by loss of muscle atonia during REM sleep associated with dream enactment, which usually start at the age of older than 50. RBD in elders are known to be developing symptoms of neurodegenerative disorders in the course of disease. However, the pathophysiology and prognosis of "early-onset" idiopathic RBD is unclear. Several existing standard value about REM sleep without atonia (RSWA) of RBD patients was established with "late-onset" RBD for those diagnosed at age 50 and greater, RSWA metrics in "early-onset" RBD patients diagnosed prior to age 50 years have not been previously described. Therefore, we report here two patients who were diagnosed as "early-onset" idiopathic RBD, and performed quantitative RSWA scoring. We suggested that "early-onset" idiopathic RBD has different etiologies the various characteristics of RSWA than adults with RBD.