Age at onset of epilepsy, pharmacoresistance, and cognitive outcomes

Abstract

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

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

“…An estimated 75% of all MLC patients experiences at least one seizure and 63% of patients older than 6 years has been diagnosed with epilepsy, which is in line with previous reports,12, 35 and confirms that epilepsy is common in MLC. Epilepsy in MLC patients is mostly well controlled with medication compared to the general epilepsy population (only 14% had moderately to poorly controlled epilepsy versus 20–30% of general epilepsy patients) 36, 37. However, occurrence of status epilepticus is high (∼17%) compared to the overall occurrence reported for children and adults with epilepsy during follow‐up (∼10%),38, 39 indicating that once seizures are initiated, restoring neuronal network activity to its normal state is hampered in MLC.…”

Emerging surgical therapies in the treatment of pediatric epilepsy

“…In a 2009 statement, the International League Against Epilepsy defined DRE as the "failure of adequate trials of two tolerated, appropriately chosen and used antiepileptic drug schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom" (1). DRE represents a major therapeutic challenge and can be associated with significant comorbidities, including cognitive impairment, depression, anxiety, developmental delay, and impaired activities of daily living (3,4). Although it was initially perceived as a therapeutic option only after all other options were exhausted, surgical treatment of properly selected patients can provide long-term seizure control rates of 50-70% (5).…”

Surgical strategies for pediatric epilepsy

“…Although myriad benefits, including fewer medications and improvements in neurocognitive and behavioral measures (7), may be realized from any significant reduction in seizure frequency, the ultimate goal of surgical intervention is complete seizure remission whenever possible. Patients with DRE may be particularly vulnerable to the debilitating developmental effects of intractable seizures, especially those with an early age of onset (8), implying that early surgical evaluation may be associated with significant cognitive and developmental gains. The ability to achieve a surgical cure is influenced by a wide variety of factors, including demographic, pathologic, and surgical considerations (9).…”