Association of Cerebral and Systemic Physiology With Quantitative Electroencephalographic Characteristics of Early Posttraumatic Seizures.

PURPOSE: Early posttraumatic seizures (EPTS) occur after pediatric traumatic brain injury and have been associated with unfavorable outcomes. We aimed to characterize the relationship among quantitative EEG characteristics of early posttraumatic seizures, cerebral and somatic physiologic measures. METHODS: Differences in baseline physiologic, neuroimaging, and demographic characteristics between those with and without early posttraumatic seizures were investigated using Mann-Whitney U test or Fisher exact test. Multivariable dynamic structural equations modeling was used to investigate time series associations between ictal quantitative EEG characteristics with intracranial pressure, arterial blood pressure, heart rate (HR), and cerebral regional oximetry. Quantitative EEG characteristics included amplitude, total power, spectral edge frequency, peak value frequency, complexity, and periodicity. RESULTS: Among 72 children, 146 seizures were identified from 19 patients. Early posttraumatic seizures were associated with younger age (P = 0.0034), increased HR (P = 0.0018), and increased Glasgow Outcome Scale-Extended scores (P = 0.0377). Group dynamic structural equations modeling analysis of the first seizure for patients demonstrated that intracranial pressure is negatively associated with spectral edge frequency (standardized regression coefficient -0.12, 99% credible interval [-0.21 to -0.04]), and HR is positively associated with peak value frequency (standardized regression coefficient 0.16, [0.00-0.31]). Among nine patients with seizures arising over the frontal lobe regions, HR was positively associated with peak value frequency (standardized regression coefficient 0.26 [0.02-0.50]) and complexity (standardized regression coefficient 0.14 [0.03-0.26]). Variation in strength and direction of associations was observed between subjects for relationships that were significant during group analysis. CONCLUSIONS: Quantitative EEG characteristics of pediatric early posttraumatic seizures are associated with variable changes in cerebral and systemic physiology, with spectral edge frequency negatively associated with intracranial pressure and peak value frequency positively associated with HR.

Treatment Timing, EEG, Neuroimaging, and Outcomes After Acute Necrotizing Encephalopathy in Children.

BACKGROUND: Acute necrotizing encephalopathy (ANE) is a rare condition associated with rapid progression to coma and high incidence of morbidity and mortality. METHODS: Clinical, electroencephalographic (EEG), and brain magnetic resonance imaging (MRI) characteristics and immunomodulatory therapy timing were retrospectively analyzed in children with ANE. ANE severity scores (ANE-SS) and MRI scores were also assessed. The associations of patient characteristics with 6-month modified Rankin scale (mRS) and length of hospitalization were determined using either univariate linear regression or one-way analysis of variance. RESULTS: 7 children were retrospectively evaluated. Normal EEG sleep spindles (P = .024) and early treatment (R2 = .57, P = .030) were associated with improved outcomes (ie, decreased mRS). Higher ANE-SS (R2 = .79, P = .011), higher age (R2 = .62, P = .038), and presence of brainstem lesions (P = .015) were associated with longer length of hospitalization. Other patient characteristics were not significantly associated with mRS or length of hospitalization. CONCLUSION: Early immunomodulatory therapy and normal sleep spindles are associated with better functional outcome in children with ANE.

Nicotine: A Targeted Therapy for Epilepsy Due to nAChR Gene Variants.

OBJECTIVE: Genetic variants of the neuronal nicotinic acetylcholine receptor (nAChR) cause autosomal dominant sleep-related hypermotor epilepsy. Approximately 30% of autosomal dominant sleep-related hypermotor epilepsy patients are medically intractable. In preclinical models, pathogenic nAChR variants cause a gain of function mutation with sensitivity to acetylcholine antagonists and agonists. Nicotine modifies the activity of nAChRs and can be used as targeted therapy. METHODS: We reviewed next-generation sequencing epilepsy panels from a single laboratory (GeneDx) from patients at Children's Medical Center Dallas between 2011 and 2015 and identified patients with nAChR variants. Retrospective review of records included variant details, medical history, neuroimaging findings, and treatment history. RESULTS: Twenty-one patients were identified. Four patients were prescribed nicotine patches for intractable seizures. Three of 4 patients had a clinical response, with >50% seizure reduction. CONCLUSIONS: Treatment with a nicotine patch can be an effective therapy in epilepsy patients with nAChR gene variants. We propose consideration of transdermal nicotine treatment in intractable epilepsy with known nAChR variants as an experimental therapy. Further clinical trials are needed to fully define therapeutic effects.

EEG is A Predictor of Neuroimaging Abnormalities in Pediatric Extracorporeal Membrane Oxygenation.

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity; this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis.

Outcomes among patients with infantile spasms treated with hormonal therapy and adjuvant topiramate versus hormonal therapy alone.

Hormonal therapy is the first-line treatment for infantile spasms and is sometimes used in combination with topiramate for better seizure control and potentially improved developmental outcomes. Retrospective review of pediatric patients with infantile spasms, with data compiled on patient sex, age at onset, etiology, electroencephalographic and imaging findings, topiramate use, spasm resolution (at one, six, and 12 months), and developmental outcome (at 12 months). Of 105 patients screened, 55 (28 female) met inclusion criteria (28 [51%] had spasms with known etiology and 27 [49%] had spasms with unknown etiology). Forty-six patients were followed for 12 months or longer to determine seizure outcome; a 12-month developmental assessment was documented for 49 patients. Thirty-seven patients (67%) received combination therapy; 18 (33%) received hormonal therapy alone. Resolution of spasms was comparable among treatment groups, with no difference relative to spasm etiology (p>0.18 for all). No difference was found in developmental outcomes with and without adjunct topiramate (p=0.38). Combination therapy was the most common treatment at our institution. However, combination therapy was not found to be beneficial for the treatment of spasms or developmental outcomes when compared to hormonal therapy alone.

De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias.

Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed CaV2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.

Hypothalamic Hamartoma With Infantile Spasms: Case Report With Surgical Treatment.

We report a 10-month-old boy with treatment-resistant infantile spasms associated with hypothalamic hamartoma (HH). Electroencephalography before surgical treatment showed modified hypsarrhythmia. Transventricular endoscopic resection and disconnection resulted in immediate and enduring disappearance of the epileptic spasms and improvement in the postoperative electroencephalography. After 8 years of treatment, the patient has nondisabling gelastic seizures associated with a small amount of residual HH but no other seizure types. He is not taking any antiepilepsy drugs. He is academically and socially successful. We are not aware of any prior reports of surgical treatment of HH with concurrent infantile spasms as an uncontrolled seizure type. The immediate disappearance of infantile spasms demonstrates that the HH lesion itself is an active and necessary component within the epileptic network responsible for spasms in this particular condition. This case contributes to the recognition that focal pathologies can be responsible for infantile spasms with hypsarrhythmia and respond successfully to surgical intervention.

Seizures Induced by Exiting Water: A Unique Form of Reflex Epilepsy.

INTRODUCTION: Reflex epilepsies represent a form of epilepsy in which unique modes of seizure precipitation are characterized by endogenous or exogenous stimuli. Hot water epilepsy represents a subtype of reflex epilepsy in which seizure precipitation arises from the act of immersing the head with hot water. Bathing epilepsy represents another subtype of reflex epilepsy in which seizure precipitation arises from the immersion with water at lukewarm temperatures. CASE SERIES: We report on 2 boys with a unique form of bathing epilepsy characterized by the act of exiting out of water. The first patient had a family history significant for a brother with frontal lobe epilepsy. He underwent an evaluation in the epilepsy monitoring unit in which a reflex seizure was recorded while exiting the shower. This seizure was characterized by an ictal onset in the left frontal lobe and subsequent secondary generalization. The second patient initially had nonreflex seizures arising from the left temporal lobe and went on to develop reflex seizures upon exiting water. For both patients, the precipitation of seizures was independent of water or environmental temperature, exposure of specific body parts, or duration of water immersion. Both children experienced a sensation of coldness, followed by convulsive or atonic activity. CONCLUSIONS: Our cases represent a unique form of bathing epilepsy in which seizure precipitation is dependent upon exiting water.