James J. Riviello

Outcome of Severe Refractory Status Epilepticus in Children

Summary:  Purpose: Refractory status epilepticus (RSE) is the persistence of seizure activity despite appropriate therapy; it is treated with high‐dose suppressive anesthetic agents. We report here the outcome of RSE in a large series of children.

Behavioral side effects of gabapentin in children

Summary: We report 7 children who received gabapentin (GBP) as adjunctive medication and subsequently developed behavioral side effects. These behavioral changes consisted of intensification of baseline behaviors as well as new behavioral problems. Behaviors that parents considered most troublesome were tantrums, aggression directed toward others, hyperactivity, and defiance. All behavioral changes were reversible and were managed by dose reduction or discontinuation of GBP. All children had baseline attention deficit hyperactivity disorder and developmental delays.

Vagus nerve stimulation in pediatric epilepsy: a review

Therapeutic options for intractable epilepsy include new and investigational antiepileptic drugs, ketogenic diet, epilepsy surgery, and, now, vagus nerve stimulation, which is approved by the U.S. Food and Drug Administration for the treatment of refractory partial seizures in adolescents and adults. The exact mechanisms of action are unknown. Although the use of vagus nerve stimulation in children has increased, including those younger than 12 years of age or those with generalized epilepsy, there has been no large controlled pediatric study to date. The identification of favorable prognostic indicators, especially in children, would be useful. Preliminary results suggest that children with Lennox-Gastaut syndrome may have a favorable response, with improvement in both seizure control and global evaluation scores. Improved global evaluation scores have occurred even without an associated improvement in seizure control.

Bilateral volume reduction of the superior temporal areas in Landau-Kleffner syndrome.

No specific anatomic abnormalities have been detected in typical Landau–Kleffner syndrome (LKS), an acquired epileptic aphasia with language regression in children. In four children with typical LKS without obvious anatomic abnormalities, the authors performed MRI volumetric analysis of various neocortical regions and subcortical substructures. Volume reduction was detected in bilateral superior temporal areas (26 to 51%), specifically in planum temporale (25 to 63%) and superior temporal gyrus (25 to 57%), where receptive language is localized.

Early thalamic lesions in patients with sleep-potentiated epileptiform activity

Objective: To compare the prevalence and type of early developmental lesions in patients with a clinical presentation consistent with electrical status epilepticus in sleep either with or without prominent sleep-potentiated epileptiform activity (PSPEA). Methods: We performed a case-control study and enrolled patients with 1) clinical features consistent with electrical status epilepticus in sleep, 2) ≥1 brain MRI scan, and 3) ≥1 overnight EEG recording. We quantified epileptiform activity using spike percentage, the percentage of 1-second bins in the EEG tracing containing at least 1 spike. PSPEA was present when spike percentage during non-REM sleep was ≥50% than spike percentage during wakefulness. Results: One hundred patients with PSPEA (cases) and 47 patients without PSPEA (controls) met the inclusion criteria during a 14-year period. Both groups were comparable in terms of clinical and epidemiologic features. Early developmental lesions were more frequent in cases (48% vs 19.2%, p = 0.002). Thalamic lesions were more frequent in cases (14% vs 2.1%, p = 0.037). The main types of early developmental lesions found in cases were vascular lesions (14%), periventricular leukomalacia (9%), and malformation of cortical development (5%). Vascular lesions were the only type of early developmental lesions that were more frequent in cases (14% vs 0%, p = 0.005). Conclusions: Patients with PSPEA have a higher frequency of early developmental lesions and thalamic lesions than a comparable population of patients without PSPEA. Vascular lesions were the type of early developmental lesions most related to PSPEA.

Intraoperative monitoring of motor evoked potentials in very young children.

OBJECT Neurophysiological monitoring of motor evoked potentials (MEPs) during complex spine procedures may reduce the risk of injury by providing feedback to the operating surgeon. While this tool is a well-established surgical adjunct in adults, clinical data in children are sparse. The purpose of this study was to determine the reliability and safety of MEP monitoring in a group of children younger than 3 years of age undergoing neurosurgical spine procedures. METHODS A total of 10 consecutive spinal procedures in 10 children younger than 3 years of age (range 5-31 months, mean 16.8 months) were analyzed between January 1, 2008, and May 1, 2010. Motor evoked potentials were elicited by transcranial electric stimulation. A standardized anesthesia protocol for monitoring consisted of a titrated propofol drip combined with bolus dosing of fentanyl or sufentanil. RESULTS Motor evoked potentials were documented at the beginning and end of the procedure in all 10 patients. A mean baseline stimulation threshold of 533 ± 124 V (range 321-746 V) was used. Six patients maintained MEP signals ≥ 50% of baseline amplitude throughout the surgery. There was a greater than 50% decrease in intraoperative MEP amplitude in at least 1 extremity in 4 patients. Two of these patients returned to baseline status by the end of the case. Two patients had a persistent decrement or variability in MEP signals at the end of the procedure; this correlated with postoperative weakness. There were no complications related to the technique of monitoring MEPs. CONCLUSIONS A transcranial electric stimulation protocol monitoring corticospinal motor pathways during neurosurgical procedures in children younger than 3 years of age was reliably and safely implemented. A persistent intraoperative decrease of greater than 50% in this small series of 10 pediatric patients younger than 3 years of age predicted a postoperative neurological deficit. The authors advocate routine monitoring of MEPs in this pediatric age group undergoing neurosurgical spine procedures.

Focal Cortical Malformations Can Show Asymmetrically Higher Uptake on Interictal Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography (PET)

Interictal fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is a component of the presurgical evaluation of patients with medically intractable epilepsy, including patients with malformations of cortical development. The authors describe 3 cases of focal cortical malformations that displayed asymmetrically higher uptake on FDG-PET performed in the interictal state in patients undergoing evaluation for possible focal resection for refractory localization-related epilepsy. The evaluation included routine and prolonged video electroencephalography (EEG), magnetic resonance imaging (MRI), interictal FDG-PET with concurrent EEG, and single-photon emission computed tomography (SPECT). All 3 patients had focal cortical malformations on MRI corresponding to regions of asymmetrically higher uptake on FDG-PET. EEG confirmed that the FDG-PET studies were performed in the interictal state. The lesions included a large region of subcortical heterotopia in the right frontal lobe, a left temporal lobe dysplasia, and a region of subcortical heterotopia in the right occipital lobe. In both patients with subcortical heterotopia, there were other focal regions of cortical malformation that were not associated with abnormal or asymmetric uptake on FDG-PET. Previous reports describe decreased uptake on interictal PET in most cases of focal cortical malformations. Normal to increased uptake has been reported with band heterotopia. The authors demonstrate that other types of focal malformations of cortical development, including focal subcortical heterotopia and lobar dysplasia, can be associated with asymmetrically higher uptake on interictal FDG-PET.

Treatment of Childhood Idiopathic Language Deterioration with Valproate

Childhood idiopathic language deterioration is a rare condition in which children lose previously gained language skills. In some children this language deterioration occurs in association with behavioral seizures or EEG epileptiform activity. The effectiveness of antiepileptic drugs in this patient population is not known. Here we retrospectively reviewed records of 57 children with childhood idiopathic language deterioration associated with seizures or epileptiform activity on their EEG who received valproate for the purpose of treating their language impairment. In 22 of the children improvement in language skills was observed. In two children language returned to normal while in the other 20 the improvement was modest. Children who responded to valproate had an earlier age of onset of the aphasia than children who were nonresponders. Seizure type, EEG findings, developmental status, and presence or absence of a frequency-modulated auditory evoked potential were not related to response. This study demonstrates that valproate can be helpful in improving language function in some children with idiopathic language deterioration associated with seizures or epileptiform activity on the EEG.

Long-term response to high-dose diazepam treatment in continuous spikes and waves during sleep.

BACKGROUND This study evaluated whether the reduction in epileptiform activity after treatment with high-dose diazepam in continuous spikes and waves during sleep persists over time. PATIENTS Patients aged 1 to 21 years with continuous spikes and waves during sleep who received high-dose nocturnal diazepam and who had electroencephalogram follow-up were included. Twenty-nine patients met the inclusion criteria and underwent a total of 48 high-dose diazepam treatment cycles. RESULTS An overnight reduction of the spike wave percentage of at least 25% (i.e., 75-50%) occurred in 29 cycles (20 patients), and persisted within 6 months in 16 of 29 cycles (12 patients), but returned to baseline in three of 29 cycles (three patients). An overnight reduction of at least 50% (i.e., 75-25%) occurred in 15 cycles (13 patients), and persisted within 6 months in eight of 15 cycles (eight patients), but returned to baseline in three cycles (three patients). Twenty of 29 cycles that responded in the short term had persistent response on follow-up. Thirteen cycles of treatment were associated with mild side effects that did not recur with repeated treatment cycles. CONCLUSIONS Treatment with high-dose diazepam reduced epileptiform activity in continuous spikes and waves during sleep in the short term, and improvement persisted for several months in most cycles. Short-term response predicted persistence of this effect on subsequent follow-up.

Factors associated with treatment delays in pediatric refractory convulsive status epilepticus

Objective To identify factors associated with treatment delays in pediatric patients with convulsive refractory status epilepticus (rSE). Methods This prospective, observational study was performed from June 2011 to March 2017 on pediatric patients (1 month to 21 years of age) with rSE. We evaluated potential factors associated with increased treatment delays in a Cox proportional hazards model. Results We studied 219 patients (53% males) with a median (25th–75th percentiles [p25–p75]) age of 3.9 (1.2–9.5) years in whom rSE started out of hospital (141 [64.4%]) or in hospital (78 [35.6%]). The median (p25–p75) time from seizure onset to treatment was 16 (5–45) minutes to first benzodiazepine (BZD), 63 (33–146) minutes to first non-BZD antiepileptic drug (AED), and 170 (107–539) minutes to first continuous infusion. Factors associated with more delays to administration of the first BZD were intermittent rSE (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.14–2.09; p = 0.0467) and out-of-hospital rSE onset (HR 1.5, 95% CI 1.11–2.04; p = 0.0467). Factors associated with more delays to administration of the first non-BZD AED were intermittent rSE (HR 1.78, 95% CI 1.32–2.4; p = 0.001) and out-of-hospital rSE onset (HR 2.25, 95% CI 1.67–3.02; p < 0.0001). None of the studied factors were associated with a delayed administration of continuous infusion. Conclusion Intermittent rSE and out-of-hospital rSE onset are independently associated with longer delays to administration of the first BZD and the first non-BZD AED in pediatric rSE. These factors identify potential targets for intervention to reduce time to treatment.