Sung-Pa Park

Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up

The present study was conducted to evaluate the long-term effects of low-dose topiramate (TPM) monotherapy on the cognitive function of epilepsy patients. Forty-seven epilepsy patients received TPM, with target doses of 50, 75, and 100 mg/day. Cognitive tests were performed twice, at baseline and 1 year after starting medication. Thirty-six patients completed the follow-up neuropsychological tests. After a year of treatment, 16 patients (44%) complained of cognitive problems. Although it improved seizure frequency and EEG abnormalities, TPM had significantly negative effects on the digit span and verbal fluency tests. These cognitive effects were dose-related and significantly improved after withdrawal from TPM and substitution with older antiepileptic drugs. In conclusion, even at a low dose, TPM has long-term, negative effects on working memory and verbal fluency.

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 Nine patients were withdrawn prior to their follow-up tests.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.

Differential effects of seizure control and affective symptoms on quality of life in people with epilepsy

OBJECTIVE The purpose of the study was to delineate how affective symptoms (AS) influence quality of life (QOL) for individuals with drug-refractory epilepsy (DRE) and those with well-controlled epilepsy (WCE) independently. METHODS All subjects participating in the study were asked to complete reliable and validated self-report health questionnaires, including AS, measured with the Korean versions of the Beck Depression Inventory, Beck Anxiety Inventory, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). We examined predictors of QOLIE-31 scores among the various demographic and clinical factors. We compared the effects of AS on QOL between patients with DRE and those with WCE and investigated the differential effects of seizure control and AS on QOL. RESULTS Two hundred forty-nine patients with DRE or WCE were included in the study. The strongest predictor of QOL was AS, followed by seizure control and MRI abnormality. Affective symptoms had almost two times the effect of seizure control and six times the effect of MRI abnormality. Poorest QOL was noted in patients with DRE with AS, followed by those with WCE with AS, DRE without AS, and WCE without AS. CONCLUSION The major determinant of QOL in patients with epilepsy is AS rather than DRE or WCE status.

Electrophysiologic assessment of central auditory processing by auditory brainstem responses in children with autism spectrum disorders.

In addition to aberrant features in the speech, children with Autism Spectrum Disorder (ASD) may present unusual responses to sensory stimuli, especially to auditory stimuli. We investigated the auditory ability of children with ASD by using Auditory Brainstem Responses (ABR) as they can directly judge both hearing status and the integrity of auditory brainstem pathways. One hundred twenty-one children (71: ASD; M 58/F 13, mean age; 41.8 months, 50: control group; M 41/F 9, mean age; 38 months) were induded in the study. As compared with the values in the control group, the latency of wave V, wave I-V, and wave III-V inter-peak latencies were significantly prolonged (p<0.05) in the ASD group. The findings indicate that children with ASD have a dysfunction or immaturity of the central auditory nervous system. We suggest any children with prolonged III-V inter-peak latencies, especially high functioning children should be further evaluated for central auditory processing to set up a more appropriate treatment plan.

Validation of the generalized anxiety disorder-7 in people with epilepsy: a MEPSY study.

The Generalized Anxiety Disorder-7 (GAD-7) is a valuable instrument to screen for anxiety in primary care patients. However, it has not been validated in people with epilepsy (PWE). Therefore, we validated the GAD-7 and examined its differential effect from adverse effects of antiepileptic drugs (AEDs) on the detection of anxiety in Korean PWE. Eligible patients who visited outpatient clinics in 4 tertiary care hospitals and 1 secondary care hospital underwent several instruments including the Mini International Neuropsychiatric Interview-Plus Version 5.0.0 (MINI-Plus 5.0.0), the Korean version of the Neurological Disorders Depression Inventory for Epilepsy (K-NDDI-E), the Korean version of the Liverpool Adverse Event Profile (K-LAEP), and the Quality of Life in Epilepsy-10 (QOLIE-10). Two hundred forty-three patients were enrolled in the study, and 51 (21.0%) patients had GAD by the MINI-Plus 5.0.0. Cronbachs α coefficient for the GAD-7 was 0.924. At a cutoff score of 6, the GAD-7 had a sensitivity of 92.2%, a specificity of 89.1%, a positive predictive value of 69.1%, and a negative predictive value of 97.7%. The GAD-7 score was well correlated with the K-NDDI-E score, the K-LAEP score, and the QOLIE-10 overall and subscale scores. The impact of adverse effects of AEDs on the GAD-7 was less than that on the K-NDDI-E. In conclusion, the GAD-7 is a reliable and valid screening tool for detecting GAD in PWE.

Instant reocclusion following mechanical thrombectomy of in situ thromboocclusion and the role of low-dose intra-arterial tirofiban.

Background: An in situ thromboocclusion (IST) is defined as an infarct extensively involving all or most of a stenosed arterial territory, which is one major stroke mechanism related to intracranial atherosclerosis (ICAS). We focused on ISTs occurring in major cerebral arteries and analyzed their rate of instant reocclusion during mechanical thrombectomy (MT) compared with non-ISTs. Also, we introduced a treatment strategy of low-dose intra-arterial tirofiban administration to prevent such reocclusion following repeat recanalization, and evaluated its safety and efficacy. Methods: We analyzed 168 consecutive patients treated with MT over a 2-year period from May 2011 to April 2013. During MT, if angiography following a successful recanalization showed stenosis at the occlusion site, we performed additional angiographic runs every 10 min for 30 min after the recanalization. Then, if angiography revealed reocclusion, we performed a repeat recanalization, using the same MT technique but additionally followed by low-dose intra-arterial tirofiban infusion. Time-of-flight MR angiography or CT angiography was performed to confirm any underlying ICAS at the occlusion site 5-7 days after the procedure. The patients who had confirmed underlying ICAS were included in the IST cohort. Results: Of 168 enrolled patients, we excluded 36 who could not be checked for underlying ICAS at the occlusion site for one of the following reasons: recanalization failure (n = 11), rescue stenting after tirofiban failure (n = 5) and lack of follow-up vascular imaging (n = 20). The incidence of IST was 30.3% (40/132). All IST patients were confirmed to have underlying ICAS by follow-up vascular imaging. Instant reocclusion after successful recanalization was significantly more frequent in the IST cohort [26/40 (65%) vs. 3/92 (3.3%); p < 0.001]. Regarding the efficacy of low-dose intra-arterial tirofiban infusion, 85.7% of the reocclusion patients finally achieved a thrombolysis in cerebral infarction score 2/3 recanalization, but in the remaining 14.3% of the cases, the condition was refractory to the procedure and required rescue stenting. There were no cases of symptomatic intracranial hemorrhage following the procedure. Conclusions: In situ thromboocclusion was characterized by a significantly higher chance of instant reocclusion during MT. In such cases, low-dose intra-arterial tirofiban administration may be effective and safe. However, future confirmation by prospective multicenter trials seems necessary.

Frequency of affective symptoms and their psychosocial impact in Korean people with epilepsy: A survey at two tertiary care hospitals

We investigated the frequency of affective symptoms in Korean adults with epilepsy who visited epilepsy clinics at two tertiary care hospitals and in healthy adults. We also examined the psychosocial impact of affective symptoms on people with epilepsy (PWE). Participants were asked to complete self-report questionnaires to assess depression and anxiety symptoms, felt stigma, suicidal ideation, and quality of life (QOL). Of 568 PWE, 30.5% exhibited affective symptoms. The frequencies of depression and anxiety symptoms were 27.8% and 15.3%, respectively, significantly higher than those in healthy controls. Those with poor seizure control were more likely to endorse affective symptoms at the time of study. The frequencies of felt stigma and suicidal ideation were higher in PWE with affective symptoms than in those without. Quality of life was impacted by affective symptoms, especially when depression and anxiety coexisted. Reducing affective symptoms by appropriate seizure control may ameliorate psychosocial problems in PWE.

What is the role of depressive symptoms among other predictors of quality of life in people with well-controlled epilepsy on monotherapy?

The quality of life (QOL) of individuals with well-controlled epilepsy (WCE) is often not considered. We therefore investigated predictors determining QOL in patients who had been seizure free at least 1 year on stable antiepileptic drug (AED) monotherapy. They were asked to complete self-report health questionnaires, including the Beck Depression Inventory (BDI), Adverse Event Profile (AEP), and Quality of Life in Epilepsy Inventory-31 (QOLIE-31). We looked for predictors of QOLIE-31 scores among the various demographic, socioeconomic, and clinical factors and BDI, and AEP scores. Depression symptoms were manifested by 18.7% of patients. People with depression symptoms were more likely to report adverse events than those without depression symptoms. The strongest predictor of QOL was BDI score, followed by AEP total score, years of education, and income. BDI score had 3.37 times the effect of AEP total score. In conclusion, QOL of patients with WCE is determined mainly by depressive symptoms.

Psychiatric Symptoms and Quality of Life in Patients with Drug-Refractory Epilepsy Receiving Adjunctive Levetiracetam Therapy

Background and Purpose Levetiracetam (LEV) is a new antiepileptic drug that has been found to be effective as an adjunctive therapy for uncontrolled partial seizures. However, the results of several studies suggested that LEV has negative psychotropic effects, including irritability, aggressiveness, suicidality, and mood disorders. We investigated the impact of adjunctive LEV on psychiatric symptoms and quality of life (QOL) in patients with drug-refractory epilepsy (DRE) and determined the risk factors provoking psychiatric adverse events. Methods A 24-week, prospective, open-label study was conducted. At enrollment, we interviewed patients and reviewed their medical charts to collect demographic and clinical information. They were asked to complete self-report health questionnaires designed to measure various psychiatric symptoms and QOL at enrollment and 24 weeks later. Results Seventy-one patients were included in the study, 12 patients (16.9%) of whom discontinued LEV therapy due to serious adverse events including suicidality. The risk factor for premature withdrawal was a previous history of psychiatric diseases (odds ratio 4.59; 95% confidence interval, 1.22-17.32). LEV intake resulted in significant improvements in Beck Anxiety Inventory score (p<0.01) and some domains of the Symptom Checklist-90-Revised, such as somatization (p<0.05), obsessive-compulsiveness (p<0.05), depression (p<0.05), and anxiety (p<0.05). These improvements were not related to the occurrence of seizure freedom. The Quality of Life in Epilepsy Inventory-31 overall score and subscale scores, such as seizure worry (p<0.01), overall QOL (p<0.05), emotional well-being (p<0.05), energy-fatigue (p<0.05), and social function (p<0.05), also improved. Conclusions Adjunctive LEV in patients with DRE is likely to improve psychiatric symptoms and QOL. Clinicians should be well aware of the psychiatric histories of patients to prevent them from developing serious adverse events related to LEV.

Long-Term Efficacy and Safety of Zonisamide Monotherapy in Epilepsy Patients

Background and purpose Zonisamide (ZNS) is a useful antiepileptic drug with a broad therapeutic spectrum. However, there is limited information on the long-term use of ZNS as a monotherapy. This study investigated the long-term effects of ZNS as a monotherapy for the treatment of epilepsy. Methods We retrospectively analyzed the records of epilepsy patients treated with ZNS monotherapy at our clinic. We identified outcomes for patients treated with ZNS monotherapy for a minimum of 6 months. Efficacy was quantified as the percentage change in seizure frequency, and safety was assessed by the frequency and types of adverse events. Results Sixty patients who received ZNS for a minimum of 6 months were included. The mean duration of treatment was 19.8 months (range, 6-37 months), and the mean ZNS dosage was 255 mg/day (range, 100-500 mg/day). Twenty-seven patients (45%) were seizure-free, and an additional 20 patients (33%) had above 50% seizure frequency reduction at the last follow-up visit. Partial seizures with or without secondary generalization and generalized seizures were well controlled by ZNS, whereas complex partial seizures were not. Forty-eight patients (80%) reported mild-to-moderate adverse events, including memory loss (35%), attention deficit (27%), and weight loss (20%). Conclusions Long-term ZNS monotherapy is effective at treating a broad spectrum of seizure disorders, except complex partial seizures. However, a specific adverse event, such as cognitive impairment, is common and long-lasting.