Chung-Kyu Suh

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 Nine patients were withdrawn prior to their follow-up tests.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

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.

Comparison of Cognitive Effects of Lamotrigine and Oxcarbazepine in Epilepsy Patients

Background and Purpose This study compared the cognitive effects of 1 year of treatment with lamotrigine (LTG) and oxcarbazepine (OXC) in epilepsy patients. Methods This retrospective study investigated 60 epilepsy patients undergoing neuropsychological tests who were either newly diagnosed or untreated in the preceding 6 months. The cognitive function in 30 patients receiving LTG monotherapy and 30 age-matched patients receiving OXC monotherapy was compared after 1 year. The neuropsychological scores at baseline and all of the epilepsy-relevant variables except seizure type did not differ between the groups. The mean daily dosages of LTG and OXC at 1 year were 93 mg and 825 mg, respectively. Results The posttreatment list-learning performance was better in the LTG group than in the OXC group (p<0.05). The incidence of cognitive complaints did not differ between the two groups. The list-learning performance and Trail Making Test scores were better in each group after treatment. Conclusions LTG and OXC monotherapies have similar, slightly beneficial effects on cognitive function, and are probably not harmful.

Cognitive Impairment in Juvenile Myoclonic Epilepsy

Background and purpose Cognitive impairments are frequent consequences of epilepsy, with intellectual ability reportedly being lower in patients with idiopathic generalized epilepsies than in the general population. However, neuropsychological investigations have been rarely performed in patients with juvenile myoclonic epilepsy (JME). We aimed to quantify the cognitive function in JME patients using various neuropsychological tests. Methods We compared cognitive function in 27 JME patients with that in 27 healthy volunteers using tests examining cognitive performance, such as the verbal and visual memory, frontal function, attention, IQ score, and mood. In the JME group, we examined risk factors for cognitive function such as age, sex, family history, education level, age at seizure onset, seizure frequency, EEG abnormality, disease duration, and previous intake of antiepileptic drugs. Results Verbal learning was significantly lower in JME patients than in controls, and attention and verbal fluency were impaired in JME patients compared with controls. However, general intellectual ability and mood did not differ between the groups. Early onset of seizure and long duration of disease were closely related to impaired cognitive function. Conclusions JME patients may exhibit impaired cognitive function, in terms of memory and execution, despite having normal intelligence and mood.

Cognitive Effects of Low-dose Topiramate Compared with Oxcarbazepine in Epilepsy Patients

Background and Purpose Low-dose topiramate (TPM) monotherapy has recently been found effective for seizure control in newly diagnosed epilepsy. In higher dosages, TPM has been associated with relatively high rates of adverse cognitive effects; similar side effects have been seen after rapid titration or polytherapy. However, its cognitive effects during low-dose monotherapy have not been established. We evaluated the cognitive effects of low-dose TPM compared with oxcarbazepine (OXC), a drug that does not appear to affect cognitive function. Methods Cognitive tests and subjective complaints of 30 patients with low-dose TPM monotherapy (50-200 mg/day) were retrospectively compared with those of 30 patients with OXC monotherapy at 1 year of medication. The two groups did not differ with respect to epilepsy-relevant variables, nor on baseline neuropsychological tests. Results The TPM group showed a significant difference in the performance of delayed word recall (P<0.05), backward digit span (P<0.01), and verbal fluency (P<0.05) compared with the OXC group. The TPM group showed worse performances of digit span and verbal fluency. The OXC group showed better performances of delayed word recall. The incidence of cognitive complaints was higher in the TPM group (50%) than in the OXC group (20%) (P<0.05). These cognitive effects shown in the TPM group were dose-related. The cognitive dysfunction was trivial with patients taking 50 mg/day TPM. Conclusions Even at low-dose, TPM has a negative effect on working memory and verbal fluency compared with OXC. It can be demonstrated at 1 year of treatment.

Outcome of forced-suction thrombectomy in acute intracranial internal carotid occlusion

Objectives Ischemic stroke from acute intracranial distal internal carotid artery (ICA) occlusion usually carries a poor prognosis. Despite the intra-arterial revascularization therapies, the results are still unsatisfactory. The aim of this study was to compare the outcomes between two endovascular techniques, the modified Penumbra System (mPS) and mechanical clot disruption (MCD), and to confirm the influence of recanalization on the outcomes. Methods In a retrospective review of 39 consecutive cases of acute distal ICA occlusion, the recanalization rates and functional outcomes at 3 months of the two intra-arterial techniques during two consecutive periods (May 2006 to February 2009: MCD technique (n=19) vs March 2009 to August 2010: mPS technique (n=20)) were compared. Univariate and multivariate analyses were performed to determine the predictors of a favorable functional outcome. Results The rate of successful recanalization (Thrombolysis In Cerebral Infarction score 2 or 3) was significantly higher in the mPS group than in the MCD group (85% (17/20) vs 32% (6/19); p=0.001). Favorable outcomes at 3 months (modified Rankin Scale score 0–2) were achieved in 9/20 and 3/19 in the mPS and MCD groups, respectively (45% vs 16%; p=0.048). Binary logistic regression analysis showed that younger age and successful recanalization were independent predictors of a favorable functional outcome. Conclusions Forced-suction thrombectomy using the mPS technique may be a viable option for acute distal ICA occlusion and could result in more successful recanalization and a more positive clinical outcome.

Subacute Neurological Deterioration with Selective Axonal Injury in Patients with Acute Ischemic Stroke following Reperfusion of Middle Cerebral Artery Occlusion.

To date, the long-term effects of reperfusion on the salvaged brain tissues have not been addressed in the literature. We report 4 cases presenting subacute neurological deteriorations with selective axonal injury following reperfusion therapies for acute ischemic stroke. Our case series based on 4 patients showed common features distinct from those of early reperfusion injury in that (1) the neurological symptoms developed after 1–2 months of reperfusion therapies, (2) these symptoms were accompanied by the subcortical white matter changes on brain MRI, and (3) these findings were mostly reversible with time. This suggests that axons in the reperfused brain may be vulnerable to further neurological injury.