An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies

In addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.

Management of Alcohol Withdrawal Syndrome and Alcohol Withdrawal Seizure

Alcohol withdrawal syndrome (AWS) is a common condition occurring after intentional or unintentional abrupt cessation of alcohol in an alcohol-dependent individual. AWS represents a major problem in our society and alcohol withdrawal seizure is the major cause of seizures encountered by neurology residents in the emergency department. Patients with AWS present with mild symptoms of tremulousness and agitation or more severe symptoms including withdrawal seizures and delirium tremens. Particularly, severe AWS can produce significant rates of the morbidity (complications) and mortality. When diagnosed and managed insufficiently, the morbidity and mortality rates increase. Nevertheless, patients with AWS may be neglected and are often marginalized and the teaching about AWS to neurology residents is usually minimal. Also, attending neurologists are often poorly informed on the topic. Although there is insufficient consensus about the optimal investigation and management, the purpose of this review is to serve as a summary of the appropriate identification and management of this important condition in a neurological setting.

Two Cases of Sleep-Related Painful Erection

Sleep-related painful erection (SRPE) is characterized by deep penile pain accompanied with erection occurring rapid eye movement (REM) movement period. Two (47-year-old and 40-year-old, respectively) male visited with the complaint of painful penile erection occurring during sleep. They had no problems with erection during daytime sexual activities except for mild premature ejaculation in one patient. Urologic inspections revealed no focal abnormalities. Polysomnography with simultaneous penile erection monitoring showed several episodes of awakening with painful erection which are time-locked to onset of REM sleep periods. According to the diagnostic criteria in international classification of sleep disorders, each patient was diagnosed to have chronic, severe SRPE. Despite of a low prevalence of SRPE, this condition should be considered in a patient who presents with nocturnal penile. A polysomnography accompanied with penile erection recording may help confirm diagnosis.

Guidelines for the prevention and management of cardiovascular disease associated with fine dust/Asian dust exposure

Epidemiological studies have demonstrated an increased risk for cardiovascular events in relation to both short- and long-term exposure to ambient particulate matter (PM). Several plausible mechanistic pathways have been described, including an enhanced propensity for arrhythmias, systemic inflammatory responses, and the chronic promotion of atherosclerosis. On the basis of this review, several new findings were reached, including the following: exposure to PM including PM <2.5 microm in diameter can trigger cardiovascular disease-related mortality; longer-term exposure (e.g., a few years) increases the risk for cardiovascular mortality; reductions in PM levels are associated with decreases in cardiovascular mortality within a period as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM exposure and cardiovascular morbidity and mortality. Finally, PM exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality. The purpose of this statement is to develop evidence-based practical guidelines for healthcare professionals and regulatory agencies with a comprehensive review of the literature on air pollution and cardiovascular disease and a specific focus on the clinical implications.

Atypical Unilateral Posterior Reversible Encephalopathy Syndrome Mimicking a Middle Cerebral Artery Infarction

Posterior reversible encephalopathy syndrome (PRES) is usually a reversible clinical and radiological entity associated with typical features on brain MR or CT imaging. However, the not-so-uncommon atypical radiological presentations of the condition are also present and they may go unrecognised as they are confused with other conditions. Here, we report a very rare case of atypical, unilateral PRES in a 49-year-old uremic, post-transplant female patient who presented with seizures. Initial MRI showed high-grade occlusion of the left middle cerebral artery (MCA) and lesions suggestive of subacute infarction in the ipsilateral frontotemporoparietal lobe. Patient symptoms had resolved a day after the onset without any specific treatment but early follow-up CT findings suggested hemorrhagic transformation. Follow-up MRI performed 2 years later showed complete disappearence of the lesions and persisting MCA occlusion.

Clinical Features of Obstructive Sleep Apnea That Determine Its High Prevalence in Resistant Hypertension

PURPOSE: Resistant hypertension (HTN) occurs in 15-20% of treated hypertensive patients, and 70-80% of resistant hypertensive patients have obstructive sleep apnea (OSA). The characteristics of resistant HTN that predispose patients to OSA have not been reported. Therefore, we aimed to determine the clinical, laboratory, and polysomnographic features of resistant HTN that are significantly associated with OSA. MATERIALS AND METHODS: Hypertensive patients (n=475) who underwent portable polysomnography were enrolled. The patients were categorized into controlled (n=410) and resistant HTN (n=65) groups. The risk factors for the occurrence of OSA in controlled and resistant hypertensive patients were compared, and independent risk factors that are associated with OSA were analyzed. RESULTS: Out of 475 patients, 359 (75.6%) were diagnosed with OSA. The prevalence of OSA in resistant HTN was 87.7%, which was significantly higher than that in controlled HTN (73.7%). Age, body mass index, neck circumference, waist circumference, and hip circumference were significantly higher in OSA. However, stepwise multivariate analyses revealed that resistant HTN was not an independent risk factor of OSA. CONCLUSION: The higher prevalence and severity of OSA in resistant HTN may be due to the association of risk factors that are common to both conditions.

Current status of human papillomavirus vaccines

Cervical cancer is a malignant neoplasm arising from cells that originate in the cervix uteri. It is the second most prevalent cancer among women. It can have several causes; an infection with some type of human papillomavirus (HPV) is the greatest risk factor for cervical cancer. Over 100 types of HPVs have been identified, and more than 40 types of HPVs are typically transmitted through sexual contact and infect the anogenital region. Among these, a number of HPVs types, containing types 16 and 18, are classified as "high-risk" HPVs that can cause cervical cancer. The HPVs vaccine prevents infection with certain species of HPVs associated with the development of cervical cancer, genital warts, and some less common cancers. Two HPVs vaccines are currently on the global market: quadrivalent HPVs vaccine and bivalent HPV vaccine that use virus-like particles as a vaccine antigen. This review discusses the current status of HPVs vaccines on the global market, clinical trials, and the future of HPVs vaccine development.

Efficacy of Phenytoin for Nocturnal Muscle Cramps: A Preliminary Study

BACKGROUND: Nocturnal muscle cramps are sudden, involuntary, painful muscle contractions that occur in the night and are accompanied by hardening of the muscles. Many symptomatic treatments have been introduced for nocturnal muscle cramps, such as quinine, magnesium, and phenytoin. However, the efficacy and safety of these drugs have not been adequately evaluated. To demonstrate the efficacy and safety of phenytoin treatment for nocturnal muscle cramps, we conducted a retrospective study of 16 patients with nocturnal muscle cramps. METHODS: We reviewed 16 patients (6 men, 10 women) who suffered frequent nocturnal muscle cramps and were treated with phenytoin. The patients' clinical information (age, sex, disease duration, and locations of cramps), treatment dosage, and frequency of cramps were obtained by reviewing their medical records. RESULTS: The patients were aged 63.1+/-14.7 years (mean+/-SD; age range, 30-80 years; median age, 68 years). Twelve and four patients received phenytoin doses of 100 and 200 mg/day, respectively. The median duration of medication was 51 days (range, 14-378 days). Phenytoin treatment was effective in all patients; 13 patients (81.3%) experienced a total remission of their symptoms, and a significant reduction (66.7-85.7%) in the frequency of cramps was found in the remaining 3 patients. No adverse effects were reported by any of the patients. CONCLUSIONS: While this retrospective study was conducted with only a small number of patients, the clinical results suggest that phenytoin is a safe and helpful therapy for the treatment of nocturnal muscle cramps.

Glossopharyngeal Neuralgia Secondary to Tongue Squamous Cell Carcinoma

No abstract available.

Genetic Variations of ABCC2 Gene Associated with Adverse Drug Reactions to Valproic Acid in Korean Epileptic Patients

The multidrug resistance protein 2 (MRP2, ABCC2) gene may determine individual susceptibility to adverse drug reactions (ADRs) in the central nervous system (CNS) by limiting brain access of antiepileptic drugs, especially valproic acid (VPA). Our objective was to investigate the effect of ABCC2 polymorphisms on ADRs caused by VPA in Korean epileptic patients. We examined the association of ABCC2 single-nucleotide polymorphisms and haplotype frequencies with VPA related to adverse reactions. In addition, the association of the polymorphisms with the risk of VPA related to adverse reactions was estimated by logistic regression analysis. A total of 41 (24.4%) patients had shown VPA-related adverse reactions in CNS, and the most frequent symptom was tremor (78.0%). The patients with CNS ADRs were more likely to have the G allele (79.3% vs. 62.7%, p = 0.0057) and the GG genotype (61.0% vs. 39.7%, p = 0.019) at the g.-1774delG locus. The frequency of the haplotype containing g.-1774Gdel was significantly lower in the patients with CNS ADRs than without CNS ADRs (15.8% vs. 32.3%, p = 0.0039). Lastly, in the multivariate logistic regression analysis, the presence of the GG genotype at the g.-1774delG locus was identified as a stronger risk factor for VPA related to ADRs (odds ratio, 8.53; 95% confidence interval, 1.04 to 70.17). We demonstrated that ABCC2 polymorphisms may influence VPA-related ADRs. The results above suggest the possible usefulness of ABCC2 gene polymorphisms as a marker for predicting response to VPA-related ADRs.

Insulinoma Presenting as Hypersomnia and Unconscious Wandering

Insulinoma is a rare endocrine tumor that frequently causes neurologic symptoms. We report a case of a 17-year-old man with hypersomnia and abnormal behavior lasting for 10 months. He had recurrent attacks of hypersomnia that lasted for up to 36 hours and of unconscious wandering mimicking an ictal or postictal state. Hypoglycemia was documented (30 mg/dL) and insulinoma was found at the most-recent episode. Clinicians should be aware that hypersomnia and unconscious wandering can present in association with hypoglycemia.

The Localizing and Lateralizing Value of Auras in Lesional Partial Epilepsy Patients

PURPOSE: We investigated the localizing and lateralizing values of auras in patients with lesional partial epilepsy on an outpatient basis. MATERIALS AND METHODS: A total of 276 subjects were retrospectively selected for this study if they had a unilateral single lobar lesion based on magnetic resonance image (MRI) results, and their scalp electroencephalography (EEG) findings were not discordant with the MRI-defined lobar localization and lateralization. According to the lesion locations, subjects were considered as having mesial temporal (MTLE), lateral temporal (LTLE), frontal (FLE), parietal (PLE), or occipital (OLE) lobe epilepsies. Auras were classified into 13 categories. RESULTS: A hundred and seventy-six subjects (63.8%) had experienced at least one aura. FLE subjects had the fewest number of auras. Epigastric and psychic auras were frequent among MTLE subjects, while visual auras were common in those with PLE and OLE. Somatosensory auras and whole body sensations were more frequent in the subjects with PLE than those without. Autonomic auras were more common in MTLE subjects than in LTLE subjects. Dysphasic auras were more frequently found in left-sided epilepsies. Five pairs of aura categories showed concurrent tendencies, which were the epigastric and autonomic auras, autonomic and emotional auras, visual and vestibular auras, auditory and vestibular auras, and whole-body sensation and auditory auras. Autonomic and emotional auras had a concurrent tendency in left-sided epilepsies, but not in right-sided epilepsies. CONCLUSION: Our results support the previously known localizing value of auras, and suggest that dysphasic auras and the association of emotional and autonomic auras may have a lateralizing value.

Rheumatoid Meningitis: Neurologic Manifestation and Pathologic Findings

Rheumatoid meningitis, one of the most severe complications of rheumatoid arthritis, presents various symptoms such as headache, confusion, loss of consciousness, seizure, fever, and focal neurological deficits. A 63-year-old man with the history of rheumatoid arthritis presented with intermittent left leg weakness, seizures and later developed fever and confusion. Brain MRI demonstrated leptomeningeal enhancement in right fronto-parietal area. Brain biopsy revealed multifocal suppurative inflammation. After aggressive immunosuppressive treatment, he had gradually recovered and the lesion was reduced on a follow-up MRI.

Clinical Evaluation of Sleep Disorders in Childhood and Adolescence

PURPOSE: Sleep disorders cause serious complications to growth and development in children given that sleep plays an important role in maintaining physical and psychological health. In this study, we investigated the clinical characteristics of sleep disorders in childhood and adolescence, their polysomnographs (PSG), as well as other related diseases. METHODS: Forty-two patients who took PSG in Severance Children's Hospital from September 2006 to April 2010 were involved in this study. Their medical records were retrospectively reviewed. RESULTS: Among 42 patients, there were 29 boys and 13 girls; their mean age was 9 years 10 months. Twenty-three (55%) patients reported headache as their chief complaint. Symptoms associated with headache were insomnia, snoring and mouth breathing, daytime sleepiness, abnormal behavior during sleep, and hyperactivity. Among the 23 patients with headaches, nine (39%) had abnormal PSG. Among 21 patients with snoring and mouth breathing, only five (24%) were diagnosed as obstructive sleep apnea and others had primary snoring. In the analysis of sleep disorders according to age, obstructive sleep apnea was evenly distributed across all ages. CONCLUSION: In this study, various clinical symptoms related to childhood and adolescence sleep disorder with headache being the most common symptom. Although sleep disorders are harmful to children and adolescence, they are frequently overlooked. Therefore, careful attention related to the diagnosis and treatment of sleep disorders is required.

Neurocutaneous Melanosis Presenting as Chronic Partial Epilepsy

BACKGROUND: Neurocutaneous melanosis (NCM) is a rare neurocutaneous syndrome characterized by the presence of multiple congenital melanocytic nevi (CMN) and the proliferation of melanocytes in the central nervous system, usually involving the leptomeninges. Chronic partial epilepsy as a sole manifestation is rare in NCM. CASE REPORT: A 32-year-old man suffering from chronic partial epilepsy presented with multiple CMN on his trunk and scalp. Brain MRI demonstrated a focal lesion in the right amygdala that was consistent with interictal epileptiform discharges in the right temporal region on electroencephalography (EEG). An anterior temporal lobectomy was performed, and the pathology investigation revealed numerous melanophages in the amygdala. The patient was seizure-free after surgery. CONCLUSIONS: We report a patient with NCM presenting as chronic partial epilepsy who was successfully treated by anterior temporal lobectomy.

A Case of Long-term Follow-up Rasmussen's Encephalitis / 대한간질학회지

Rasmussen encephalitis (RE) is a rare, severe, and progressive disorder characterized by focal motor seizures, epilepsia partialis continua, hemiparesis, and intellectual decline. Although clinical features of RE are heterogenous, the progression of the disease is generally divided into three stages which are prodromal, acute, residual stages. We report a 29-year-old woman who had shown typical progression of the disease but preserved cognitive function during a longterm follow-up.

Intramedullary Spinal Cord Cavernous Hemangiomas Presented With Radiculopathy

Cavernous hemangioma may exist in the spinal cord as well as intracranium. Intramedullary spinal cord cavernous hemangioma usually manifests with myelopathy. We report a case of intramedullary cavernous hemangiomas having presented with isolated radicular pain.

Chronic Recurrent Cholangitis Induced by Carbamazepine / 대한간질학회지

Carbamazepine (CBZ) is one of the most commonly used antiepileptic agents. With its potent effects against seizure or neuropathic pain, it also has several undesirable adverse events. CBZ has been known to induce hepatotoxicity because the drug is mainly metabolized through hepatic system, and asymptomatic liver enzyme elevation occurs in 5~10% of patients receiving CBZ. There are several cases of symptomatic hepatitis or hepatic necrosis by CBZ, however, reports of chronic cholangitis associated with CBZ medication are rare. Here, we present a case of chronic recurrent cholangitis by CBZ with pathological evidence.

Ictal Nose Wiping in a Patient with Mesial Temporal Lobe Epilepsy / 대한간질학회지

Seizure-associated nose wiping occurs usually during postictal period and is more frequent in temporal than extratemporal lobe epilepsy. The hand used to wipe the nose is highly suggestive of ipsilateral partial seizure onset. We describe a patient with the left mesial temporal lobe epilepsy, who showed ictal nose wiping by the left hand. The hypothetical mechanism remains unknown but may be a response to olfactory aura or increased ictal nasal secretions. In this patient, subtraction ictal SPECT coregistered to MRI (SISCOM) study revealed hyperperfusion mainly in the left temporal lobe, especially amygdala. Our patient may support an important role of amygdala concerned with olfactory system or autonomic activity in provoking nose wiping.

Long-Term Dysfunction of Frontal Lobe in a Patient with Isolated Reversible Splenial Lesion after Status Epilepticus / 대한간질학회지

Reversible splenial edema has been often reported in epilepsy patients. Clinical presentation is reported to be silent in general. We experienced a patient with splenial lesion and cognitive dysfunction. A 21-year-old man underwent video-EEG monitoring for preoperative evaluation. He had suffered from viral encephalitis eight years ago and developed chronic drug-resistant epilepsy. After antiepileptic drugs withdrawal, he developed eight episodes of secondarily generalized tonic-clonic seizures for several hours and some seizures were repeated without recovery of consciousness. Majority of ictal EEG onset presumed to originate from the left frontal region. After seizures he had shown disorientation and irritability with gradual recovery. Brain MRI demonstrated a splenial lesion. Though splenial lesion disappeared on follow-up MRI, neuropsychological test demonstrated frontal lobe dysfunction 6 months later compared with that performed just before the video-EEG monitoring. We report a patient with isolated reversible splenial lesion associated with long term dysfunction of frontal lobe.