Jeffrey R. Tenney

Focal corticothalamic sources during generalized absence seizures: A MEG study

Magnetoencephalography (MEG) was used to determine cortical and subcortical contributions to the formation of spike and wave discharges in twelve newly diagnosed, drug naïve children during forty-four generalized absence seizures. Previous studies have implicated various cortical areas and thalamic nuclei in the generation of absence seizures, but the relative timing of their activity remains unclear. Beamformer analysis using synthetic aperture magnetometry (SAM) was used to confirm the presence of independent thalamic activity, and standardized Low Resolution Brain Electromagnetic Topography (sLORETA) was used to compute statistical maps indicating source locations during absence seizures. Sources detected in the 50ms prior to the start of the seizure were more likely to be localized to the frontal cortex or thalamus. At the time of the first spike on EEG, focal source localization was seen in the lateral frontal cortex with decreased thalamic localization. Following the spike, localization became more widespread throughout the cortex. Comparison of the earliest spike and wave discharge (SWD) (Ictal Onset) and a SWD occurring 3s into the seizure (mid-Ictal) revealed significant differences during the slow wave portion of the SWDs. This study of MEG recordings in childhood absence seizures provides additional evidence that there are focal brain areas responsible for these seizures which appear bilaterally symmetric and generalized with a conventional 10-20 placement scalp EEG.

The Current State of Absence Epilepsy: Can We Have Your Attention?

Absence seizures are common within many different epilepsies and span all the ages. Even though absence seizures were described more than three centuries ago advances associated with its classification, pathophysiology, genetics, treatment, prognosis, and associated co-morbidities continue to be made.

Cognitive and behavioral outcomes in benign childhood epilepsy with centrotemporal spikes

We review the evidence that BECTS may be associated with cognitive dysfunction and behavioral problems, the extent to which these problems may be associated with patterns of EEG abnormalities in BECTS, and the impact of antiepileptic medication on cognition and behavior in BECTS. A growing literature examining cognitive and behavioral outcomes suggests that children with BECTS perform below the level of their peers. Consistent with this, neuroimaging studies reveal that BECTS has an impact on structural and functional brain development, but the potential influence of frequency and lateralization of centrotemporal spikes (CTS) on cognition and behavior is not well understood. Treatment with AEDs is an option in BECTS, but existing studies have not clearly shown a clear relationship between elimination of CTS and improved cognitive or behavioral outcomes.

Low‐ and high‐frequency oscillations reveal distinct absence seizure networks

The aim of this study was to determine the frequency‐dependent, spatiotemporal involvement of corticothalamic networks to the generation of absence seizures.

Child Neurology: Alternating hemiplegia of childhood

Alternating hemiplegia of childhood (AHC) is a rare disorder characterized by recurrent attacks of hemiplegia affecting either side of the body, abnormalities of ocular movement, movement disorders, and progressive developmental delay. Children with AHC often have a delay in diagnosis or are misdiagnosed. A broad differential diagnosis is necessary when considering this condition. The clinical features of AHC were first described more than 3 decades ago but its cause remains largely unknown and there is little treatment evidence available. Early diagnosis and multicenter collaboration are necessary to better understand the prognosis of AHC and develop more effective treatments. A 12-month-old boy was sent for neurologic consultation after an episode of transient right-sided paralysis. His mother states that during the episode he was fully conscious but half of his body was paralyzed and he appeared to have a stroke. This episode lasted 6 hours and resolved when he slept. He was at his normal baseline upon waking. His mother states that the patient had a similar episode, although occurring on the left side, when he was 4 months old. There was a family history of migraines but no other neurologic disorders. He achieved normal developmental milestones during the first year of life and at 12 months of age was walking independently and had some words. Neurologic examination, done once symptoms had resolved, was normal. ### Differential diagnosis. Acute focal weakness in a child has many serious etiologies that must be investigated (table 1). The evaluation is focused on excluding serious or treatable causes. Evaluation should begin with MRI, magnetic resonance …

Child Neurology: Hemiconvulsion-hemiplegia-epilepsy syndrome

Hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome is an uncommon outcome of prolonged focal status epilepticus in childhood. The prolonged focal motor seizure usually occurs during the course of a febrile illness and is followed by hemiplegia ipsilateral to the side of convulsions. This is accompanied by radiologic evidence of acute cytotoxic edema in the affected hemisphere followed by chronic atrophy. Intractable epilepsy may develop at a time remote from the initial presentation. The clinical features of HHE syndrome were first described more than 5 decades ago but its pathophysiology remains poorly understood and the long-term cognitive outcomes are unclear. Early recognition of the syndrome may help provide patients and families with an accurate prognosis regarding the subsequent development of epilepsy. Neurology® 2012;79:e1–e4

Long-term outcomes of resective epilepsy surgery after invasive presurgical evaluation in children with tuberous sclerosis complex and bilateral multiple lesions.

OBJECT Tuberous sclerosis complex (TSC) with medically refractory epilepsy is characterized by multifocal brain abnormalities, traditionally indicating poor surgical candidacy. This single-center, retrospective study appraised seizurerelated, neuropsychological, and other outcomes of resective surgery in TSC patients with medically refractory epilepsy, and analyzed predictors for these outcomes. METHODS Patients with multilesional TSC who underwent epilepsy surgery between 2007 and 2012 were identified from an electronic database. All patients underwent multimodality noninvasive and subsequent invasive evaluation. Seizure outcomes were classified using the International League Against Epilepsy (ILAE) scale. The primary outcome measure was complete seizure remission (ILAE Class 1). Secondary outcome measures included 50% responder rate, change in full-scale IQ, electroencephalography improvement, and reduction in antiepileptic drug (AED) burden. RESULTS A total of 37 patients with TSC underwent resective surgery during the study period. After a mean follow-up of 5.68 ± 3.67 years, 56.8% achieved complete seizure freedom (ILAE Class 1) and 86.5% had ILAE Class 4 outcomes or better. The full-scale IQ on follow-up was significantly higher in patients with ILAE Class 1 outcome (66.70 ± 12.36) compared with those with ILAE Class 2 or worse outcomes (56.00 ± 1.41, p = 0.025). In 62.5% of the patients with ILAE Class 2 or worse outcomes, the number of AEDs were found to be significantly reduced (p = 0.004). CONCLUSIONS This study substantiates the evidence for efficacy of resective epilepsy surgery in patients with bilateral multilesional TSC. More than half of the patients were completely seizure free. Additionally, a high proportion achieved clinically meaningful reduction in seizure burden and the number of AEDs.

Deletion of 14-3-3ε and CRK: A Clinical Syndrome With Macrocephaly, Developmental Delay, and Generalized Epilepsy

Deletions of chromosome 17p13.3 result in neuronal migration defects such as isolated lissencephaly sequence and Miller-Dieker syndrome. LIS1 is the deleted gene within this region and is thought to directly cause isolated lissencephaly sequence and contribute to Miller-Dieker syndrome. Two additional genes (14-3-3ε and CRK) on the telomeric end of chromosome 17p reportedly contribute to the severe phenotype of Miller-Dieker syndrome. We report 2 patients with deletions of chromosome 17p13.3 involving the genes 14-3-3ε and CRK but not LIS1 with previously unreported, identical phenotypes of macrocephaly, small stature, dysmorphic features, generalized epilepsy, developmental delay, and nonspecific white matter changes. The findings in this report suggest that patients who have deletions of 14-3-3ε and/or CRK should be monitored closely for the development of seizures.

Cerebral glucose hypometabolism is associated with mitochondrial dysfunction in patients with intractable epilepsy and cortical dysplasia

Metabolic imaging studies, such as positron emission tomography (PET), allow for an assessment of physiologic functioning of the brain, and [18F]fluoro‐2‐deoxyglucose (FDG)–PET is now a commonly used technique in presurgical epilepsy evaluations. Focal interictal decreases in glucose consumption are often but inconsistently concordant with the ictal onset area, and the underlying mechanisms are poorly understood. The current study tests the hypothesis that areas of glucose hypometabolism, determined by FDG‐PET, are associated with mitochondrial dysfunction in patients with medically intractable epilepsy associated with isolated focal cortical dysplasia (FCD).

Comparison of magnetic source estimation to intracranial EEG, resection area, and seizure outcome

Magnetoencephalography (MEG) is used to guide intracranial electroencephalography (ICEEG) monitoring and determine areas for resection. The purpose of this retrospective cross‐sectional study was to report our experience using dipole modeling/dipole scanning, current density reconstructions, and beam‐forming methods in a large cohort of pediatric patients with intractable epilepsy.