Byung-In Lee

ILAE Official Report: A practical clinical definition of epilepsy

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >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 who either had an age‐dependent epilepsy syndrome but are now past the applicable age or who have remained seizure‐free for the last 10 years and off antiseizure medicines for at least the last 5 years. “Resolved” is not necessarily identical to the conventional view of “remission or “cure.” Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use.

Enhanced Detection of Right-to-Left Shunt Through Patent Foramen Ovale by Transthoracic Contrast Echocardiography Using Harmonic Imaging

When the results of transesophageal echocardiography was regarded as the gold standard for detecting a patent foramen ovale (PFO) in 136 consecutive patients referred for evaluation of cardiac source of embolism, transthoracic harmonic imaging using saline contrast was superior to fundamental imaging in accuracy for detecting a PFO (sensitivity, 22.5%; specificity [p < 0.05] and sensitivity, 100%; specificity 100%, respectively.)

Factors contributing to the stigma of epilepsy

PURPOSE To evaluate the factors, including personality and coping styles, likely to be influential in enhancing the social stigma of epilepsy. METHODS Data were collected from 400 adults with epilepsy recruited from 10 epilepsy centers in Korea. Clinical information about seizures was obtained by neurologists, and other information was collected from self-completed questionnaires, including those measuring stigma scales. RESULTS Thirty-one percent of people with epilepsy felt stigmatized by their condition and in 9% of these the stigma was severe. Multivariate analysis identified experiences of actual discrimination from society, introverted personality, problem solving controllability, and emotional subscale of QOLIE-31 as being independently associated with the social stigma of epilepsy. CONCLUSIONS Episodes of discrimination, coping strategies, and personality may be important in feeling the stigma of epilepsy. These findings may provide a basis for further studies to clarify the causative factors generating the stigma of epilepsy.

The prognosis for control of seizures with medications in patients with MRI evidence for mesial temporal sclerosis.

Summary: Purpose: Mesial temporal sclerosis (MTS) is the most common and important pathology in temporal lobe epilepsy (TLE), and its presence in magnetic resonance imaging (MRI) scans is strongly correlated with a successful surgical outcome. Despite the general assumption that patients with MTS respond poorly to medication, the long‐term prognosis for such patients has not yet been investigated. We studied the overall clinical prognosis of patients with MTS and analyzed the factors related to the degree of medical responsiveness.

Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients.

This study was a prospective, randomized, open-label investigation of the long-term effects of zonisamide (ZNS) monotherapy on cognition and mood of patients with epilepsy. Forty-three patients with epilepsy received ZNS, with final dose groups of 100, 200, 300, and 400mg/day. Cognitive and mood tests were done twice, at baseline and 1 year after starting medication. Nine patients were withdrawn prior to their follow-up tests. Three patients (33%) dropped out during the titration period because of cognitive and mood problems. Thirty-four patients completed follow-up neuropsychological tests. After 1 year of treatment, 16 patients (47%) complained of cognitive deficits. Only 5 patients (15%) experienced mood changes. Although ZNS decreased seizure frequency and EEG abnormalities and did not elicit significant mood changes, it had negative effects on several cognitive tests. Worse performance on delayed word recall, Trail Making Test Part B, and verbal fluency was related to dose. In conclusion, ZNS has adverse effects on cognition even after 1 year of treatment.

Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease

Huntingtons disease (HD) is characterized clinically by chorea, psychiatric disturbances, and dementia, while it is characterized pathologically by neuronal inclusions as well as striatal and cortical neurodegeneration. The neurodegeneration arises from the loss of long projection neurons in the cortex and striatum. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (Ask1) in the pathogenesis of HD. We analyzed the expression of Ask1 and huntingtin (htt) within the striatum and cortex and also examined the interaction of Ask1 with htt fragments in HD (R6/2) mice. Additionally, we inhibited Ask1 and analyzed the resulting changes in brain-derived neurotrophic factor (BDNF) expression, motor function, and striatal atrophy. Ask1 activity was blocked using an Ask1 antibody raised against the C-terminus of the Ask1 protein. The anti-Ask1 antibody was infused into the striatum of the HD mice for four weeks using a micro-osmotic pump. The levels of Ask1 protein and endoplasmic reticulum (ER) stress were increased in HD mice. Binding of inactivated Ask1 to htt fragments was more prevalent in the cytosol than the nucleus of cortical neurons. Binding of inactivated Ask1 to htt fragments prevented translocation of the htt fragments into the nucleus, resulting in an improvement in motor dysfunction and atrophy. In the normal state, active Ask1 may help htt fragments enter the nucleus, while inactivated Ask1 hinders this translocation by binding to but not releasing fragmented htt into the nucleus. We propose that Ask1 may interact with htt fragments and subsequently induce ER stress. BDNF depletion may be prevented by targeting Ask1; this would decrease ER stress and possibly ameliorate behavioral or anatomical abnormalities that accompany HD. Therefore, regulating the amounts and activity of the Ask1 protein is a novel strategy for treatment of HD.

Association of aortic plaque with intracranial atherosclerosis in patients with stroke

Objective: To determine whether there is a relationship between aortic plaques and intracranial (IC) atherosclerosis. Methods: We reviewed 922 patients with stroke who had both transesophageal echocardiography and cerebral angiography. The plaques of these patients were classified as either complex aortic plaques (CAP), which protruded ≥4 mm or were present as mobile lesions in the proximal aorta, or simple aortic plaques (SAP), which were <4 mm or present in the descending aorta. Cerebral artery atherosclerosis was classified as either an IC or extracranial (EC) atherosclerosis. Results: Among the 922 patients, we found aortic plaques in 237 patients (26%). There were 111 (47%) patients of SAP, 74 (31%) patients with CAP, and 52 (22%) patients that had both SAP and CAP. Angiography showed IC or EC atherosclerosis in 511 patients (55%). The presence of aortic plaques was significantly associated with IC or EC atherosclerosis. The significance appeared to be due to the strong association between the presence of SAP and IC atherosclerosis (51% SAP vs 35% no plaques; odds ratio = 1.94, 95% CI: 1.17 to 3.21). In the multiple logistic regression analysis, SAP were independent predictors of IC atherosclerosis Conclusions: The presence of simple aortic plaques may be a marker of advanced vascular disease. Detection of simple aortic plaques during transesophageal echocardiography may have clinical implications because patients with these plaques frequently had concomitant intracranial atherosclerosis, a risk factor for stroke.

Prolonged Ictal Amnesia with Transient Focal Abnormalities on Magnetic Resonance Imaging

Summary: A previously healthy woman had a prolonged amnestic state caused by complex partial status epilepticus with bilateral mesiotemporal lobe involvement confirmed by EEG with nasopharyngeal electrodes. A magnetic resonance imaging (MRI) scan obtained shortly after recovery from the amnesia showed reversible focal abnormalities consisting of increased signal intensity on T2‐weighted scan in the mesiotemporal lobe.

Thyrotoxic autoimmune encephalopathy: a repeat positron emission tomography study

Thyroid related autoantibodies have been related to the development of encephalopathy, known as Hashimoto’s encephalopathy. However, their relation with the encephalopathy occurring in patients with Graves’ disease has not been well established. The case is reported of a 51 year old woman presenting with subacute progressive dementia with evidence of hyperthyroidism. She had Graves’ disease associated with high titres of thyroid related autoantibodies. Her encephalopathy was not improved by antithyroid drugs, but promptly responded to corticosteroid treatment, and stabilised with a gradual reduction of thyroid related autoantibody titres. Brain positron emission tomography initially showed a diffuse and multifocal cerebral hypometabolism with subsequent normalisation on her clinical recovery, which was consistent with the acute and reversible cerebral inflammation probably mediated by autoimmune mechanisms.

Single photon emission computed tomography-EEG relations in temporal lobe epilepsy

addition to marked hyperperfusion at the focus, a relative decrease in perfusion around the hyperperfused region is a useful additional sign, again when compared with the interictal examination.5J2 This sign is clearly seen in their Cases 14 and 17 and should be incorporated in the interpretation. Thirdly, in seizures where there is bilateral ictal spread and early EEG termination on the side of the focus, ictal SPECT may show a corresponding “postictal” pattern with mesial hyperperfusion and lateral hypoperfusion on the side of the focus, while the contralateral side may show obvious hyperperfusion. We agree that cases with bilateral change can be difficult to interpret, as reflected by the fact that their two masked readers had initial discordant interpretations on three of the six mislateralized cases. Knowledge of the complex patterns of ictal perfusion will avoid incorrect lateralization of ictal SPECT. This emphasizes the need for comparison with the interictal examination and evaluation of the entire ictal scan, not just identifying the area of maximum perfusion. Finally, 16 of their 19 cases were studied with ethyl cysteinate dimer (ECD) (Neurolite) rather than hexamethyl-propylenamine oxime (HMPAO) (Ceretec), the ligand on which most experience has been accumulated to date. As Lee et al. note,’ there appear to be differences in the pharmacologic properties of these two tracers. Differences in uptake of ECD compared to HMPAO, particularly in the mesial temporal region, have been reported in healthy c ~ n t r o l s . ’ ~ J ~ Differences in uptake of these two isotopes in strokeI5 and brain tumors16 have also been reported. There has been no direct comparison of ECD and HMPAO in ictal SPECT, but our limited experience suggests that ECD images may be more diffcult to interpret and less definitive than HMPAO studies. Our long experience with HMPAO suggests that in approximately 95% of cases of temporal lobe epilepsy, ictal studies yield correct localization. Because of these concerns, we believe that further experience and comparative studies are required before ECD can be regarded as a substitute for HMPAO in ictal SPECT.