Long-term intellectual outcome after temporal lobe surgery in childhood

Skirrow, Caroline; Cross, J. Helen; Cormack, Francesca; Harkness, William; Vargha‐Khadem, Faraneh; Baldeweg, Torsten

doi:10.1212/wnl.0b013e31821527f0

Cited by 213 publications

(243 citation statements)

References 40 publications

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“…AEDs can have an impact on cognitive function with certain ones having an especially high risk. 28,29 Phenobarbital has residual effects even after discontinuation in young children treated for febrile seizures. 30 In utero exposure to certain AEDs, most notably sodium valproate, is associated with substantial decrements in cognitive function in early childhood.…”

Section: Discussionmentioning

confidence: 99%

“…Further, surgical series also report some improvement in cognitive scores after surgery, suggesting that the seizures themselves negatively affect cognition and that the earlier the surgery is done, the better the postsurgical ability to acquire developmental and cognitive skills. 2,20,28,32 The hazards associated with seizures-injuries, mortality, and loss of autonomy-are all extremely important. Our data add to a building body of literature that highlights the cognitive consequences of poorly controlled seizures in the developing brain and provides more support for emerging recommendations and guidelines regarding early identification of pharmacoresistance 11 and referral to specialty care, particularly for children, 21 although similar considerations also occur in adults.…”

Section: Discussionmentioning

confidence: 99%

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Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes

et al. 2012

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Objectives: Increasing evidence suggests that uncontrolled seizures have deleterious effects on cognition and behavior, particularly in the developing brain. Methods:In a community-based cohort, 198 children, aged Ͻ8 years with new-onset epilepsy were followed prospectively and reassessed with the Wechsler Intelligence Scales for Children, Third Edition (WISC-III) 8-9 years later. Linear regression analyses with interactions between age at onset (age) and pharmacoresistance (PR) were used to test whether earlier onset conveyed greater vulnerability to the effects of uncontrolled seizures. Full-scale IQ (FSIQ) and the 4 subdomain scores were examined. Adjustment for adaptive behavior scores in a subset was performed. A dichotomous indicator for IQ Ͻ80 or Ն80 was used to permit inclusion of children who were not tested, particularly those who were untestable.Results: FSIQ was not correlated with age. PR was associated with an 11.4 point lower FSIQ (p ϭ 0.002) and similar decrements in each WISC-III domain. There were substantial age-PR interactions for FSIQ (p ϭ 0.003) and 3 domain scores, indicating a lessening impact of PR with increasing age. The dichotomous IQ indicator was strongly correlated with age at onset in the pharmacoresistant group (p Ͻ 0.0001) and not in the non-pharmacoresistant group (p ϭ 0.61). Adjustment for adaptive behavior measured near onset did not alter the conclusions. Conclusions:Uncontrolled seizures impair cognitive function with effects being most severe in infancy and lessening with increasing age at onset. These findings further emphasize the need for early aggressive treatment and seizure control in infants and young children. Seizures and epilepsy are increasingly being recognized to have moderate to profound effects on cognitive function. There is an increasing body of literature demonstrating that, in children with refractory epilepsy who are evaluated for epilepsy surgery, earlier age at onset is associated with lower IQ or developmental scores, 1-5 and longer duration of epilepsy before surgery is negatively correlated with IQ and ability to rebound after surgery 2,4,6 . A drug treatment trial for infantile spasms reported a striking correlation between both age at onset and delay to treatment with developmental scores assessed later at age 4 years.7 These studies focused on severe epilepsy (spasms) or pharmacoresistant surgical epilepsy and by design do not allow comparisons with cognitive outcomes in well-controlled epilepsy. Consequently, they cannot directly address the separate roles of onset age vs seizures in the developing brain.In a prospective community-based study of children with epilepsy, we examined the association of cognitive scores assessed 8 -9 years after initial diagnosis and age at onset of epilepsy, pharmacoresistance, and the interaction between the two. We specifically hypothesized that the

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes

et al. 2012

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“…Age range samples include patients less than 6 or 7 years at surgery, 19,28 3 to 7 years, 6 8 to 159 months, 34 less than 3 years, 20,26 or 3 to 36 months. 3 A number of studies 7,21,22,29,32,37 have focused on temporal lobectomies and have provided important information regarding outcome following this procedure, with some variable findings. Yet, these studies, so far, have wide surgical age ranges, crossing developmental stages, as well as lengthy presurgical seizure durations, lasting many years, and do not differentiate between outcome following short versus long presurgical seizure duration.…”

mentioning

confidence: 99%

Impact of epilepsy surgery on development of preschool children: identification of a cohort likely to benefit from early intervention

Shurtleff

Barry

Firman

et al. 2015

PED

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OBJECT Outcomes of focal resection in young children with early-onset epilepsy are varied in the literature due to study differences. In this paper, the authors sought to define the effect of focal resection in a small homogeneous sample of children who were otherwise cognitively intact, but who required early surgical treatment. Preservation of and age-appropriate development of intelligence following focal resection was hypothesized. METHODS Cognitive outcome after focal resection was retrospectively reviewed for 15 cognitively intact children who were operated on at the ages of 2–6 years for lesion-related, early-onset epilepsy. Intelligence was tested prior to and after surgery. Effect sizes and confidence intervals for means and standard deviations were used to infer changes and differences in intelligence between 1) groups (pre vs post), 2) left versus right hemisphere resections, and 3) short versus long duration of seizures prior to resection. RESULTS No group changes from baseline occurred in Full Scale, verbal, or nonverbal IQ. No change from baseline intelligence occurred in children who underwent left or right hemisphere surgery, including no group effect on verbal scores following surgery in the dominant hemisphere. Patients with seizure durations of less than 6 months prior to resection showed improvement from their presurgical baseline in contrast to those with seizure duration of greater than 6 months prior to surgery, particularly in Wechsler Full Scale IQ and nonverbal intelligence. CONCLUSIONS This study suggests that surgical treatment of focal seizures in cognitively intact preschool children is likely to result in seizure remediation, antiepileptic drug discontinuation, and no significant decrement in intelligence. The latter finding is particularly significant in light of the longstanding concern associated with performing resections in the language-dominant hemisphere. Importantly, shorter seizure duration prior to resection can result in improved cognitive outcome, suggesting that surgery for this population should occur sooner to help improve intelligence outcomes.

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“…56 Studies in epilepsy surgery patients have demonstrated that AED withdrawal achieves incremental IQ gains. [58][59][60] In a recent, randomised, placebo-controlled, phase II, double-blind study in adolescents with uncontrolled focal-onset seizures (n=133), no statistically significant difference was reported for add-on perampanel versus placebo in Cognitive Drug Research global cognition score. 61 In this study, perampanel was increased weekly in 2-mg increments to 8-12 mg/day during 6-week titration and the maintenance phase lasted 13 weeks.…”

Section: Impact On Behavioural Change In Epilepsymentioning

confidence: 99%

Reflections on the Use of Perampanel in Epilepsy – Lessons from the Clinic and Real-world Evidence

Trinka¹,

Carreño²

2017

European Neurological Review

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O ptimal epilepsy management includes five important elements: rational treatment selection, efficacy, off-target effects, adherence and interactions and dosing issues. Perampanel (2-[2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl]benzonitrile; E2007) is the first potent, selective, orally-active non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist approved for the treatment of patients with epilepsy. Results from randomised controlled trials and real-world studies of refractory epilepsy populations treated with perampanel showed effective frequency reduction for both focal-onset seizures (without and with secondary generalisation) and for primary generalised tonic-clonic seizures. Perampanel therapeutic doses have been calculated to only inhibit a fraction of AMPA receptors, thereby to enable sufficient seizure control without substantial impairment of neurological function. Further investigation in special subpopulations of people with epilepsy, including the elderly and people with learning disability or psychiatric comorbidities, is warranted. With an average long half-life of 105 hours, perampanel may be more forgiving in circumstances of suboptimal adherence. Perampanel is not a strong inducer or inhibitor of cytochrome P450 enzymes, and dose adjustment is not always required for the elderly or for those with mild renal impairment.

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Long-term intellectual outcome after temporal lobe surgery in childhood

Cited by 213 publications

References 40 publications

Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes

Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes

Impact of epilepsy surgery on development of preschool children: identification of a cohort likely to benefit from early intervention

Reflections on the Use of Perampanel in Epilepsy – Lessons from the Clinic and Real-world Evidence

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