Yang-Ha Hwang

Direct thrombus retrieval using the reperfusion catheter of the penumbra system: forced-suction thrombectomy in acute ischemic stroke.

BACKGROUND AND PURPOSE: Although the PS has been the most promising mechanical thrombectomy device in terms of recanalization rates, even the PS cannot recanalize all cases of occlusion. Under such circumstances, we simply modified the PS, identified certain advantages, and applied this modification as a primary technique for recanalization. Here we describe and discuss the technical details and results of our preliminary experience. MATERIALS AND METHODS: This study included 22 consecutive patients with acute ischemic stroke secondary to large-artery occlusion who underwent modified thrombectomy by using the PS for recanalization. Direct wedging between the tip of the reperfusion catheter and the proximal part of the clot followed by forceful suction by using a 20- or 50-mL syringe is a unique feature of this technique. What is distinctive is that this does not require use of a separator or aspiration pump. RESULTS: All treated vessels (100%) were successfully recanalized. A TICI scale of 2b or 3 was achieved in 81.9% of patients. A 3-month favorable functional outcome (mRS score, 0–2) was achieved in 45.5% of patients. The only procedural complication was a transient dissection of the proximal ICA, which developed while advancing the guide catheter. CONCLUSIONS: Forced-suction thrombectomy is a simple modification of the PS. On the basis of our data, this technique allows safe and effective revascularization in acute large-vessel occlusion. Thus, for achieving the best outcome, the modified PS technique is proposed as a viable option for acute stroke management, either by itself or in conjunction with other devices or drugs.

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 Nine patients were withdrawn prior to their follow-up tests.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

Reperfusion Therapy in Unclear-Onset Stroke Based on MRI Evaluation (RESTORE) A Prospective Multicenter Study

Background and Purpose— Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke. Methods— This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch >20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries. Results— Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5 ± 10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14–4.49). Conclusions— In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.

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.

Impact of Time-to-Reperfusion on Outcome in Patients with Poor Collaterals

More than 200 patients with MCA +/- ICA occlusions who successfully reperfused with endovascular techniques were assessed. The probability of good outcome was not significantly influenced by onset-to-reperfusion and puncture-to-reperfusion periods in patients with good collaterals but dropped significantly in patients with poor collaterals. BACKGROUND AND PURPOSE: The relationship between reperfusion and clinical outcome is time-dependent, and the effect of reperfusion on outcome can vary on the basis of the extent of collateral flow. We aimed to identify the impact of time-to-reperfusion on outcome relative to baseline angiographic collateral grade in patients successfully treated with endovascular revascularization for acute large-vessel anterior circulation stroke. MATERIALS AND METHODS: Two hundred seven patients were selected for analysis from our prospectively maintained registry. Inclusion criteria were M1 MCA ± ICA occlusions, onset-to-puncture time within 8 hours, and successful endovascular reperfusion. Baseline angiographic collateral grades were independently evaluated and dichotomized into poor (0–1) versus good (2–4). Multivariable analyses were performed to identify the effect of collateral-flow adequacy on favorable outcome on the basis of onset-to-reperfusion time and puncture-to-reperfusion time. RESULTS: In the poor collateral group, the odds of favorable outcome significantly dropped for patients with onset-to-reperfusion time of >300 minutes or puncture-to-reperfusion time of >60 minutes (onset-to-puncture time: ≤300, 59% versus >300, 32%; OR, 0.24; P = .011; puncture-to-reperfusion time: ≤60, 73% versus >60, 32%; OR, 0.21, P = .011), whereas the probability of favorable outcome in the good collateral group was not significantly influenced by onset-to-reperfusion time or puncture-to-reperfusion time. In the subgroup lesion-volume growth analysis by using DWI, the effect of puncture-to-reperfusion time of >60 minutes was significantly greater compared with the effect of puncture-to-reperfusion time of <60 minutes in the poor collateral group (β = 41.6 cm3, P = .001). CONCLUSIONS: Time-to-reperfusion including onset-to-reperfusion time and puncture-to-reperfusion time in patients with poor collaterals is an important limiting factor for favorable outcome in a time-dependent fashion. Future trials may benefit from a noninvasive imaging technique to detect poor collaterals along with a strategy for rapid reperfusion.

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.