Pivotal Role of Subcortical Structures as a Network Hub in Focal Epilepsy: Evidence from Graph Theoretical Analysis Based on Diffusion-Tensor Imaging

BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.

Ictal Epileptic Headache in an Elderly Patient with a Hippocampal Tumor

No abstract available.

Bilateral Optic Neuritis Mimicking Bilateral Optic Perineuritis

Optic perineuritis (OPN) is a rare form of orbital inflammatory disease of optic nerve sheath. The clinical presentation of OPN are known as distinct from demyelinating optic neuritis (ON). Recently, we have experienced a patient with bilateral idiopathic ON who had initial magnetic resonance imaging (MRI) feature of OPN. Serial MRI and funduscopic examination exhibited the bilateral ON findings. Serial MRI and funduscopic examination are needed in diagnosing OPN to differentiate to the temporal change of ON.

Vasculitis Findings for the Anterior Choroidal Artery in 3D-Time-of-Flight Magnetic Resonance Angiography

No abstract available.

Neurosyphilis Exhibiting Similar MRI Findings of Multiple Sclerosis

No abstract available.

A Practical Definition of Epilepsy

In 2005, the ILAE conceptually defined epilepsy as a disorder of the brain, characterized by an enduring predisposition to generate epileptic seizures and by its psychosocial consequences. In clinical practice, this definition of epilepsy is usually taken to mean at least two unprovoked seizures more than 24 h apart. The operational definition for special circumstances that do not meet the criteria of two unprovoked attacks has been recommended. In 2014, the ILAE refined the practical definition of epilepsy. With this definition, epilepsy is a disease of the brain with either: (1) at least two unprovoked (or reflex) seizures occurring more than 24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals past the applicable age of an age-dependent epilepsy syndrome or those who have remained seizure-free for the past 10 years, without seizure medicines for the past 5 years.

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.

Classifi cation of epileptic seizures and epilepsy syndromes

The efforts of ILAE for providing a standardized classifi cation and terminology of epileptic seizures and epilepsy syndrome; the international classifi cation of epileptic seizures in 1981 and international classifi cation of epilepsy syndromes and epilepsies in 1989, have provided outstanding achievement in promoting epilepsy care, research, and education over the past decades. However, further attempts of ILAE to improve and update the classifi cation systems have not been successful due to signifi cant heterogeneities and still incomplete knowledge on the fundamental pathophysiology of epilepsies. Despite these shortcomings, the Commission on Classifi cation and Terminology of ILAE recently published a new proposal, “Revised Terminology and Concepts for Organization of Epileptic seizures and Epilepsies”, which has generated lively discussions and debates throughout the international epilepsy communities. The basic concepts for the change seem to be rational and well taken but the proposal was not a classifi cation, which made the epilepsy communities somewhat confused and disappointed. A new proposal of classifi cation is urgently needed to replace the overdue ILAE-classifi cation.

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.

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.

A survey on the education, medical practice, research, and fringe benefits of Korean medical school faculty

In general, medical school faculty have to perform clinical practice in addition to their educational and research activities, unlike the professors of other departments, while simultaneously playing an important role within the medical profession. However, some organizational or environmental factors decrease the job satisfaction of medical professors. This study aimed to determine the current status of medical schools professors' job activities, satisfaction level, factors related to job satisfaction, and so on. A structured questionnaire was used in the survey and 936 valid responses (response rate, 79.1%) were analyzed using SAS version 9.1. Items included in the questionnaire were work tasks, satisfaction with work and environment, fringe benefits, and future plans. Our study found that the satisfaction of respondents with research activities was not high, and they had negative perceptions of their work environment. Also, it was found that job satisfaction was most affected by work environment. In the section on fringe benefits, a variety of fringe benefits were provided to respondents but their actual satisfaction was not high. To enhance the overall job satisfaction of medical school faculty, all the matters related to their work tasks and environmental factors have to be considered in the aspect of their own role in medical school. The limitations of this study were a low response rate to the early online survey and a long duration of the survey period. However, these limitations were resolved by an additional mail survey modality and statistical techniques. It is meaningful that this study was an extensive survey aimed at medical school faculty and dealt with a comprehensive range of issues.

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.

Ethical issues of using placebo in antiepileptic drugs trials in Asia

Any human trials should be designed and conducted within the ethical framework of the “Declaration of Helsinki” stating that any new agent must be tested against standard, proven therapies when available. In the clinical development of antiepileptic drugs, a double-blinded, placebo-controlled study is generally considered the gold standard for establishing their clinical effi cacy. However, placing patients with epilepsy on placebo is unethical because of negative impact of subsequent seizures resulting from “nontherapy”. The ethical concern is relatively small in an add-on trial but becomes problematic when a monotherapy is designed. Asia is expected to play a key role for future clinical development of new antiepileptic drugs. Timely action and collaborations of Asian epilepsy communities for advances in future clinical trials seems high in priority.

The Effect of Androsterone as the Metabolite of Testosterone to Seizure Suppression

BACKGROUND: Androsterone is one of the major metabolites from testosterone whose clinical importance remains unclear. This study evaluated the effects of androsterone on seizure susceptibility in mouse models of epilepsy. METHODS: The efficacy of androsterone (10~200 mg/kg, i.p.) against seizures induced by various GABA receptor antagonists and glutamate receptor agonists was evaluated. RESULTS: Androsterone protected mice against seizures induced by PTZ (pentylenetetrazol), PCX (picrotoxin), and DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate) in a dose-dependent manner. Androsterone did not protect against seizures induced by kainic acid, NMDA (N-methyl-D-aspartic acid), or 4-AP (4-aminopyridine) in mice. CONCLUSIONS: These results suggest that androsterone exhibits anticonvulsant activity that occurs largely via nongenomic mechanisms. Testosterone-derived androsterone might be an endogenous protective neuroactive steroid in the brain.

Anticonvulsant Effect of Flutamide in vitro Seizure Model / 대한간질학회지

PURPOSE: Flutamide (4-nitro-3-t-trifluoromethyl-isobutyranilide) is an androgen-receptor antagonist with typical antiandrogenic effect, used to treat androgen-dependent disorders such as prostate cancer. However, some reports noted that flutamide has direct effects to neuronal cells. It has been shown to retard the development of electrical kindling in rats. METHODS: We used the chemoconvulsant 4-aminopyridine (4-AP) and picrotoxin (PTX) in the in vitro hippocampal slice model to determine of flutamide for the suppression of epileptiform discharges. Extracellular field potential recordings were obtained from the CA3 pyramidal layer of hippocampus. RESULTS: The concentration of 30 and 100 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 57.8% and 66.8% each compared with the 4-AP only slices. In 100 micrometer PTX, 10 and 30 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 56.6% and 82.5% each. Intermixed with flumazenil, the anticonvulsant effect of flutamide was decreased. CONCLUSIONS: Flutamide suppressed epileptiform discharges induced by 4-AP and PTX in vitro seizure model. It suggests that flutamide influence to anti-epileptic activity by benzodiazepine site of the GABAA receptor.

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.

Treatment with MnTBAP Protects Against Early Nuclear Translocation of Endonuclease G and Reduces Cerebral Infarction after Focal Cerebral Ischemia/Reperfusion in Mice

BACKGROUND: Reactive Oxygen Species (ROS) have been implicated in the pathophysiology of brain injury after ischemia/reperfusion. Recently, it has been reported that endonuclease G (EndoG), a mitochondrial protein, is activated by neuronal excitotoxicity and translocated into nucleus inducing apoptosis. However, it is not elucidated whether ROS are involved in the nuclear translocation of EndoG in focal cerebral ischemia/reperfusion in mice. We investigated whether treatment of manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP) protects against early nuclear translocation of EndoG and reduces cerebral infarction after ischemia/reperfusion in mice METHODS: Adult male mice were subjected to middle cerebral artery occlusion (MCAO) for 60 min, followed by reperfusion. Immunohistochemistry and Western blot analysis for EndoG were performed at various time points after ischemia/reperfusion. Double staining with EndoG and Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling (TUNEL) was also performed. MnTBAP was used to determine whether the production of ROS could inhibit translocation of EndoG into the nucleus. RESULTS: Western blot analysis and Immunohistochemistry of EndoG showed that nuclear EndoG was detected as early as 4 hrs after reperfusion, and mitochondrial EndoG was significantly reduced at the same time. Double staining with EndoG and TUNEL showed a spatial relationship between EndoG expression and DNA fragmentation. MnTBAP-treated mice showed that the translocation of EndoG was attenuated in comparison with the vehicle- treated mice and decreased infarction volume after ischemia/reperfusion. CONCLUSIONS: MnTBAP reduced the generation of ROS, and inhibited the early translocation of EndoG, which was followed by the reduction of infarction volume in the ischemic brain after ischemia/reperfusion.