Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Frontal Lobe Disfunction In Children And Adolescents With Temporal Lobe Epilepsy And Possible Correlation With Psychiatric Disorders [a Disfunção Do Lobo Frontal Em Crianças E Adolescentes Com Epilepsia De Lobo Temporal E Sua Possível Correlação Com A Ocorrência De Transtornos Psiquiátricos]

Introduction: There is evidence that individuals with certain types of epilepsy may present cognitive disorders, and that these disorders can be more debilitating than seizures proper. Frontal lobe disorders are reported in adults with temporal lobe epilepsy, carachterized by executive disfunction. Rationale: Literary revision of work concerning the occurence of frontal lobe dysfunction in children and adolescents with temporal lobe epilepsy. Methods: Systematic revision of published literature in PUBMED. Results: Frontal lobe dysfunction has been poorly studied in children with epilepsy, especially in temporal lobe epilepsy. In the only study on the subject, executive deficit was demonstrated. Moreover, children with mesial sclerosis had more deficit in execution/planning than those with frontal or temporal neocortical lesions. Presence of frontal lobe dysfunction, in patients with partial and generalized epilepsy, may corroborate evidence that epilepsy and psychiatric disorders are epiphenomena and not cause-effect related phenomena. Conclusion: There are few articles on frontal lobe dysfunction in children with temporal lobe epilepsy. It would be interesting to find out if, and how much this occurs, and if patients with distinct etiologies present different levels of functional disability.113131136ILAE - Diagnosis. Clinical Neuropsychology: Cognitive Function in Epilepsy. Epilepsia 200344(6):29-30Blume, W.T., Diagnosis and management of epilepsy (2003) CMAJ, 168 (4), pp. 441-448Akanuma, N., Lateralising Value of Neuropsychological Protocols for Presurgical Assessment of Temporal Lobe Epilepsy (2003) Epilepsia, 44 (3), pp. 408-418Kim, H., Material- Specific Memory in Temporal Lobe Epilepsy: Effects of seizure Laterality and Language Dominance (2003) Neuropsychology, 17 (1), pp. 59-68Kim, H., Differential Effects of left versus right mesial temporal lobe epilepsy on Wechsler Intelligence Factors (2003) Neuropsychology, 17 (4), pp. 556-565Hermann, B.P., Seidenberg, M., Schoenfeld, J., Davis, K., Neuropsychological characteristics of the syndrome of Mesial Temporal Lobe Epilepsy (1997) Arch Neurol, 54 (4), pp. 369-376Riva, D., (2001) Memory disturbance in early hippocampal pathology, pp. 167-174. , Avanzini G et al. Limbic seizures in Children. Milão: John Libbey;Cheung, M., Chang, A.S., Memory impairment in humans after bilateral damage to lateral temporal neocortex (2003) Neuroreport, 14 (3), pp. 371-374Lezak MD. Neuropsychological Assessment. 3a ed. Nova Iorque: Oxford University Press1995. p.42621-5Doval, O., Gaviria, M., Kanner, A.M., (2001) Frontal lobe dysfunction in epilepsy, pp. 261-271. , editors. Psychiatric Issues in epilepsy, a practical guide to diagnosis and treatment. Filadélfia: Lippincott Williams & Wilkins;Hermann, B.P., Seidenberg, M., Executive system dysfunction in temporal lobe epilepsy: Effects of nociferous cortex versus hippocampal pathology (1995) J Clin Exp Neuropsychol, 7, pp. 809-819Trenery, M., Jack Jr, C.R., Wisconsin Card Sorting Test performance before and after temporal loberctomy (1994) J Epilepsy, 7, pp. 313-317Corcoran, R., Upton, D., A role for the hippocampus in card sorting? (1993) Cortex, 29, pp. 293-304Hermann, B.P., Wyler, A.R., Ritchie, E.T., Wisconsin Card Sorting Test performance in patients with complex partial seizures of temporal lobe origin (1988) J Clin Neuropsychol, 10, pp. 467-476Horner, M.D., Flashman, L.A., Freides, D., Focal epilepsy and the Wisconsin Card Sorting Test (1989) J Clin Exp Neuropsychol, 11, p. 74Adams, C.B.T., Temporal lobectomy in 44 children: Outcome and neuropsychological follow-up (1990) J. Epilepsy, 3 (1), pp. 157-168Jambaque, I., Verbal and visual memory impairment in children with epilepsy (1993) Neuropsychologia, 314, pp. 1321-1337Lendt, M., Helmstaedter, C., Elger, C.E., Pre-and postoperative neuropsychological profiles in children and adolescents with temporal lobe epilepsy (1999) Epilepsia, 40 (11), p. 1543Szabó, C.A., Neuropsychological effect of temporal lobe resection in preadolescent children with epilepsy (1998) Epilepsia, 39 (8), pp. 814-819Igarashi, K., Oguni, H., Osawa, M., Yutaka, A., Wisconsin Card Sorting Test in children with Temporal Lobe Epilepsy (2002) Brain & Devel, 24 (3), pp. 174-178Bortz, J.J., Neuropsychiatry and memory issues in epilepsy (2003) Epilepsy, 78 (6), pp. 781-787Ott, D., Behavioral Disorders in Pediatric Epilepsy: Unmet Psychiatric Need (2003) Epilepsia, 44 (4), pp. 591-597Thome-Souza, S., Kuczynski, E., Assumpcao Jr, F., Rzezak, P., Fuentes, D., Fiore, L., Valente, K.D., Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy? (2004) Epilepsy Behav, 5 (6), pp. 988-994. , Dec;Kanner, A.M., Balabanov, A., Depression and epilepsy: How closely related are they? (2002) Neurology, 58 (8 SUPPL. 5), pp. S27-S39. , Apr 23;Gadian, D.G., Isaacs, E.B., Cross, J.H., Connelly, A., Jackson, G.D., King, M.D., Neville, B.G.R., Vargha-Khadem, F., Lateralization of brain fuction in childhood revealed by magnetic resonance spectroscopy (1996) Neurology, 46, pp. 974-977Hermann, B., Seidenberg, M., Bell, B., Rutecki, P., Sheth, R., Ruggles, K., Wendt, G., Magnotta, V., The neurodevelopmental impact of childhood onset temporal lobe epilepsy on brain structure and fuction (2002) Epilepsia, 43 (9), pp. 1062-1071Gilliam, F., Maton, B., Martin, R.C., Extent of 1H spectroscopy abnormalities independently predicts mood status and quality of life in temporal lobe epilepsy (2000) Epilepsia, 41 (SUPPL. 7), p. 54Schildkraut, J.J., The catecolamine hypothesis of affective disorders: A review of supporting evidence (1965) Am J Psychiatry, 122, pp. 509-522Jobe, P.C., Dailey, J.W., Wernick, J.F., A noradrenergic and serotonergic hypothesis of the linkage between epilepsy and affective disorders (1999) Crit Rev Neurobiol, 13, pp. 317-356Jobe, P.C., Mishra, P.K., Adams-Curtis, L.E., The genetically epilepsy-prone rat (GEPR) (1995) Ital J Neurol Sci, 16, pp. 91-99Lehmann, A., Audiogenic seizures data in mice supporting new theories of biogenic amines mechanisms in the central nervous system (1967) Life Sci, 6, pp. 1423-1431Meldrum, B.S., Anlezark, G.M., Adam, H.K., Greenwod, D.T., Anticonvulsivant and proconvulsant properties of viloxazine hydrochloride: Pharmacological and pharmacokinetic studies in rodents and epileptic baboon (1982) Psychopharmacology (Berl), 76, pp. 212-217Polc, P., Scheeberg, J., Haefely, W., Effects of several centrally active drugs on the sleep-wakefulness cycle of cats (1979) Neuropharmacology, 18, pp. 259-267Piette, Y., Delaunois, A.L., De Shaepdryver, A.F., Heymans, C., Imipramine and electroshock threshold (1963) Arch Int Pharmacodyn Ther, 144, p. 293Yanagita, T., Wakasa, Y., Kiyohara, H., Drug dependence potential of viloxazine hydrochloride tested in rhesus monkeys (1980) Pharmacol Biochem Behav, 12, pp. 155-161Fromm, G.H., Rosen, J.A., Amores, C.Y., Clinical and experimental investigation of the effect of imipramine on epilepsy (1971) Epilepsia, 12, p. 282Fromm, G.H., Wessel, H.B., Glass, J.D., Alvin, J.D., Van Horn, G., Imipramine in absence and myoclonic-astatic seizures (1978) Neurology, 28, pp. 953-957Fromm, G.H., Amores, C.Y., Thies, W., Imipramine in epilepsy (1972) Arch Neurol, 27, pp. 198-20

Distinct Domains Of Impulsivity Are Impaired In Juvenile Myoclonic Epilepsy But Not In Temporal Lobe Epilepsy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Objective: The Barratt Impulsiveness Scale (BIS-11) is the most widely used questionnaire to study impulsivity in persons with psychiatric disorders, but it has rarely been applied to persons with epilepsy. The present study aimed to evaluate the usefulness of BIS-11 as a tool to explore impulsivity in two distinct epilepsy syndromes. Method: The BIS-11 was applied to 20 patients with juvenile myoclonic epilepsy (JME) (32.5 +/- 8.95 years old), 20 patients with temporal lobe epilepsy (TLE) (37.7 +/- 13.25 years old), and 26 healthy controls (31.86 +/- 11.25 years old). The scores in motor, attentional, and lack of planning impulsivity were compared between groups. Results: Patients with JME showed higher scores than patients with TLE and controls in all domains: motor (JME vs TLE: 28.60 vs 13.25 (mean score), p < 0.001 and JME vs controls: 28.60 vs 14.12, p < 0.001), attentional (JME vs TLE: 21.55 vs 13.45, p < 0.001 and JME vs controls: 21.55 vs 14.88, p < 0.001) and nonplanning (JME vs TLE: 28.05 vs 13.10, p < 0.001 and JME vs controls: 28.05 vs 16.15, p < 0.001). Conclusion: Higher BIS-11 scores in all domains of impulsivity [i.e., motor, attentional, and lack of planning] corroborated previous findings described in patients with JME. On the other hand, BIS-11 could not demonstrate problem solving and inhibitory control deficits related to impulsive behavior, which were described in patients with TLE. Other behavioral measures may be more sensitive to some aspects of impulsivity in TLE. Our results reinforce the concept that distinct epileptic syndromes require different neuropsychological approaches, especially considering a complex construct such as impulsivity. (C) 2015 Elsevier Inc. All rights reserved.454448Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [12/09025-3, 13/11361-4]CNPq [307262/2011-1

Delineating behavioral and cognitive phenotypes in juvenile myoclonic epilepsy: are we missing the forest for the trees?

Patients with juvenile myoclonic epilepsy (JME) have executive dysfunction and impulsive traits. There are lines of evidence that JME is a heterogeneous epilepsy syndrome considering outcome. In this study, we aimed to analyze this heterogeneity beyond seizure control. The objective was to identify whether the pattern of cognitive dysfunction and impulse control is also heterogeneous, in an attempt to establish possible differences in patients with easy-and hard-to-control epilepsies. Essentially, 57 patients with JME were compared with 44 controls. Patients and controls were assessed with a neuropsychological battery for executive, attention, and memory functions. The expression of impulsive traits was evaluated with the Temperament and Character Inventory - novelty seeking domain. Then, patients were categorized according to seizure control as having easy-and hard-to-control JME. Patients with hard-to-control JME showed worse performance in 12 out of 25 neuropsychological tests than those with easy-to-control JME. Patients with hard-to-control JME also demonstrated significantly higher scores in novelty seeking -subfactor impulsiveness (p=0.002). Our study demonstrated the existence of distinct or more severe cognitive and psychiatric profiles in a subset of patients with JME. Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits. These findings suggest that patients with JME are not equally compromised by executive and memory deficits or dysfunction, neither by their impulsive traits. Thus, there is a need for a better characterization of patients with JME to include diverse phenotypes since our results suggest a possible existence of distinct groups of patients with JME549599CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP307262/2011-105/56464-9; 07/52110-