MEG predicts epileptic zone in lesional extrahippocampal epilepsy: 12 pediatric surgery cases

PURPOSE: To discover whether the spatial distribution of spike sources determined by magnetoencephalography (MEG) provides reliable information for planning surgery and predicting outcomes in pediatric patients with lesional extrahippocampal epilepsy. METHODS: We retrospectively studied 12 children with extrahippocampal epilepsy secondary to cortical dysplasia (CD), tumor, or porencephalic cyst. We compared interictal MEG spike source locations and somatosensory evoked fields derived from equivalent-current dipole modeling with intraoperative or extraoperative electrocorticography (ECoG). RESULTS: MEG spike sources were found in proximity to the lesion in all patients and extended from lesions in five patients with CD. Marginal spike sources were noted in three patients with tumors, one patient with a cyst, and one with CD, and extramarginal sources in three patients with tumors. Three patients with tumors underwent lesionectomy only; two had further cortical excisions. One patient with CD underwent lesionectomy only, three had lesionectomy and cortical excisions, and two had lesionectomy and multiple subpial transection. Asymmetric MEG spike sources correlated with ECoG findings in all patients. Residual epileptiform discharges on postexcisional ECoG corresponded to spike sources in three patients with tumors and one patient with a cyst. Eleven patients have been seizure free for 1-6 years (mean, 4 years). One patient had residual seizures after incomplete excision of right temporal CD. CONCLUSIONS: MEG delineated asymmetric epileptogenicity surrounding lesions and the eloquent cortex. Complete tumor resection produced favorable outcomes despite residual postexcisional ECoG spikes and extramarginal MEG spike sources. CD characterized by clusters of MEG spike sources within and extending from lesions seen on magnetic resonance imaging (MRI) should be removed to prevent seizures.     

Treatment of interictal epileptiform discharges in cerebral palsy patients without clinical epilepsy: hope for a better outcome in prognosis

Cerebral palsy (CP) is a motor disorder due to cerebral damage. It is commonly associated with neuro-psychological retardation and also with epilepsy; hence, its management warrants a multi-dimensional approach. In a significant number of CP patients, interictal epileptiform discharges (IEDs) are obtained in their EEG even in absence of clinical epilepsy. Epileptiform discharge-firing cortical neurons are found to be associated with elevated intracellular Ca(2+) levels and exhibition of abnormal response on exposure to excitotoxic glutamate; both these features have been found to lead to subsequent death of these neurons. This further damage is likely to aggravate the already existing cortical damage in CP patients thereby worsening their prognosis. IEDs are also known to be associated with other neuro-psychological disorders like cognitive impairment and behavioral problems even in absence of clinical epilepsy. Thus, the IEDs cannot be viewed as benign events and their occurrence even in absence of clinical epilepsy cannot be ignored. A few trials aimed at treating IEDs in autistic patients without epilepsy and in children with behavior problems have yielded favorable results. Based on these studies, the author proposes inclusion of EEG investigation in the management protocol of CP patients and treatment of IEDs (when detected even in absence of clinical epilepsy) for a better outcome in their prognosis.     

Significance of the EEG in the decision to initiate antiepileptic treatment in patients with epilepsy: A perspective on recent evidence

The significance of electroencephalography in the prediction of seizure recurrence after a first unprovoked seizure remains a topic of debate. Opinion on the initiation of antiepileptic treatment after a first seizure also remains divided. However, in view of recent evidence, this article is intended to highlight the significance of a properly performed EEG in the decision to initiate antiepileptic drug treatment as early as possible to prevent further morbidity and other consequences.     

Lacosamide as an adjunctive therapy in pediatric patients with refractory focal epilepsy

Purpose: To evaluate the efficacy and safety of lacosamide in pediatric patients with refractory focal epilepsy. Methods: We reviewed retrospectively the medical records of children younger than 18 years of age treated at Seoul National University Bundang Hospital, in whom oral lacosamide was used as an adjunctive treatment for refractory focal epilepsy. Clinical information regarding the patients’ epilepsy and the outcome of lacosamide treatment was gathered and analyzed. Results: Twenty-one patients (16 boys, 5 girls) were included, with a median age of 13.9 (range, 1.2–17.9) years. The mean number of concomitant antiepileptic drugs was 3.0 (range, 1–6) and the mean duration of follow-up was 10.1 (range, 6.1–13.0) months. The mean maintenance dose of lacosamide was 5.4 (range, 1.4–9.8) mg/kg/day. Fourteen patients (67%) were responders; four of these were seizure free at the last follow-up. Seven patients (33%) were nonresponders: two of these presented with <50% seizure reduction and five showed no change in seizure frequency. Two patients (10%) discontinued oral lacosamide because of adverse events (aggressive behavior and depression). Mild transient treatment-related adverse events were observed in eight of the 21 patients (38%). Conclusions: Lacosamide represents a useful drug that is effective for a wide range of pediatric refractory focal epilepsy and is well tolerated.     

Efficacy and tolerability of oral lacosamide as adjunctive therapy in pediatric patients with pharmacoresistant focal epilepsy

The results of adjunctive lacosamide treatment in 18 pediatric patients with pharmacoresistant focal epilepsy are reported. All had severe forms of focal epilepsy with or without secondary generalization and were concurrently receiving one to three other antiepileptic drugs. Lacosamide was administered orally, and final dose, after slow titration, ranged between 1.7 and 10 mg/kg. Mean treatment duration was 8 months (range=3 weeks-17 months). Treatment efficacy was assessed at two time points with a 1-year interval. The reported greater than 50% reduction in seizure frequency was 36% in the initial short-term and 20% in the following long-term assessment. Side effects, mostly somnolence and irritability, were reported by 39% of patients in both evaluations. Our data suggest that lacosamide treatment in pediatric patients is safe at doses up to 10 mg/kg/day without any major side effects, but studies in larger series are needed to validate and extend these findings.     

Postoperative seizure control and antiepileptic drug use in pediatric epilepsy surgery patients: the UCLA experience, 1986-1997

PURPOSE: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control. METHODS: This study determined pre- and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures. RESULTS: Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = 0.0001). CONCLUSIONS: This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.     

Effect of corpus callosotomy on attention deficit and behavioral problems in pediatric patients with intractable epilepsy

To evaluate the effect of corpus callosotomy (CC) on attention deficit and behavioral problems in pediatric patients with intractable epilepsy, we retrospectively investigated sequential patients who had undergone CC to control seizures. Between August 2005 and April 2010, a total of 15 patients aged between 3.1 and 17.9 years underwent CC at our institute. All the patients experienced either drop attacks or head nodding, which were considered to be therapeutic targets of CC. A standardized instrument, the Child Behavior Checklist (CBCL), was used to assess behavioral and emotional problems before and after surgery. On postoperative EEGs, 8 (53%) showed improvement and 7 (47%) showed no change in epileptiform discharges. The Attention Problems scale and total score on the CBCL significantly improved in patients whose postoperative EEGs showed improvement. In addition to amelioration of target seizures, CC can improve attention impairments in association with improvement in the postoperative EEG.     

The changes in the topological properties of brain structural network based on diffusion tensor imaging in pediatric epilepsy patients with vagus nerve stimulators: A graph theoretical analysis

PurposeThis study aimed to analyze the topological characteristics of brain structural network in pediatric epilepsy patients with vagus nerve stimulation (VNS) by applying graph theoretical approaches.MethodsNine patients with generalized seizures and eight normal controls (NC) were enrolled. Based on diffusion tensor imaging, graph theory analysis was used to characterize the topological properties in preoperative patients (EP-pre), postoperative patients (EP-post) and NC. The global properties included clustering coefficient (Cp), shortest path length (Lp), small-worldness (γ, λ, δ), global network efficiency (Eg) and local network efficiency (Eloc). The regional properties included degree centrality (DC), nodal efficiency (NE), nodal local efficiency (NLE) and nodal shortest path length (Np). Two sample t-test and paired sample t-test were utilized to compare properties difference.ResultsAll three groups followed small-world characteristics. There was no significant difference in small-worldness, Cp, Lp, Eg or Eloc between EP-pre and EP-post. Compared with EP-pre: DC in EP-post decreased in the right cuneus and right temporal gyri, while increased in the right paracentral lobule; NE in EP-post decreased in the left dorsolateral superior frontal gyrus, right cuneus, right supramarginal gyrus, and right rolandic operculum, while increased in the right paracentral lobule; NLE in EP-post decreased in the left posterior cingulate gyrus and right supramarginal gyrus, while increased in the left parahippocampal gyrus; NP in EP-post decreased in the right paracentral lobule, while increased in the right cuneus.ConclusionVNS causes topological characteristics changes in pediatric patients with generalized seizures through regulating regional properties in some brain structures.