Susan Koh

Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.

Purpose:  Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long‐term unmet mental health, social, and vocational needs. This cross‐sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE.

Behavioral Disorders in pediatric epilepsy: Unmet psychiatric need

Summary:  Purpose: This study examined the relation between psychiatric diagnosis and mental health services in children with epilepsy and the associated demographic, cognitive, linguistic, behavioral, and seizure‐related variables.

Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms

Children undergoing surgery with infant-onset epilepsy were classified into those with medically refractory infantile spasms (IS), successfully treated IS, and no IS history, and the groups were compared for pre- and postsurgery clinical and Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ). Children without an IS history were older at surgery and had longer epilepsy durations than those with IS despite similar substrates, surgeries, and seizure frequencies. In all groups, better postsurgery VABS-DQ scores were associated with early surgical intervention indicating that infant-onset epilepsy patients with or without IS are at risk for seizure-induced encephalopathy.

FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic tubers and cortex in patients with tuberous sclerosis complex : A preliminary report

Summary:  Purpose: Patients with tuberous sclerosis complex (TSC) are potential surgical candidates if the epileptogenic region(s) can be accurately identified. This retrospective study determined whether FDG‐PET/MRI coregistration and diffusion‐tensor imaging (DTI) showed better accuracy in the localization of epileptogenic cortex than structural MRI in TSC patients.

Children with ESES: Variability in the Syndrome

OBJECTIVE We undertook a retrospective study of children who present with significant activation of paroxysmal discharges during sleep to examine the clinical spectrum of disorders that present with such an EEG abnormality. BACKGROUND Electrical status epilepticus in sleep (ESES) is an electrographic pattern characterized by nearly continuous spike-wave discharges in slow wave sleep, usually with a frequency of 1.5-3 Hz and usually diffuse and bilateral in distribution. A variety of neurocognitive and behavioral problems have been associated with this EEG pattern. METHODS We conducted a retrospective review of 1497 EEG records of patients admitted to University of California, Los Angeles (UCLA) for overnight video-EEG monitoring during a 5 year interval. Demographic, clinical and electroencephalographic variables were evaluated. RESULTS EEG records for 102 patients meeting criteria were identified. Clinical information was available for 90 of those patients. Eighteen of these patients could be diagnosed with Landau-Kleffner syndrome (LKS). Key findings include: (1) neuroimaging abnormalities were uncommon in our LKS patients; (2) among children who do not fit the specific diagnostic criteria for LKS, a spike-wave index (SWI) >50% was more likely to be associated with global developmental disturbances than SWI < or =50% (p<0.05); (3) Children with generalized discharges were more likely to experience severe or global developmental disturbance than those with focal abnormalities, without reaching statistical significance (p=0.07). CONCLUSIONS Severity of ESES can vary over time between and within patients and clinical status does not always directly correlate with SWI. However, the prognosis of LKS is substantially better than CSWS and these two disorders could be classified in a dichotomous manner rather than be seen as two points along a continuum.

Magnetic source imaging localizes epileptogenic zone in children with tuberous sclerosis complex

The authors assessed whether magnetoencephalography/magnetic source imaging (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis complex (TSC). In six TSC children with focal seizures, ictal video-EEG predicted the region of resection with 56% sensitivity, 80% specificity, and 77% accuracy (p = 0.02), whereas interictal MEG/MSI fared better (100%, 94%, and 95%, respectively; p < 0.0001). Interictal MEG/MSI seems to identify epileptogenic zones more accurately in children with TSC and focal intractable epilepsy.

Pediatric Cortical Dysplasia: Correlations between Neuroimaging, Electrophysiology and Location of Cytomegalic Neurons and Balloon Cells and Glutamate/GABA Synaptic Circuits

Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic ‘pacemakers’, or abnormal neurotransmission. This study examined these hypotheses using in vitro electrophysiological techniques to determine intrinsic membrane properties and spontaneous glutamatergic and GABAergic synaptic activity for normal-pyramidal neurons, cytomegalic neurons and balloon cells from 67 neocortical sites originating from 43 CD patients (ages 0.2–14 years). Magnetic resonance imaging (MRI), 18fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and electrocorticography graded cortical sample sites from least to worst CD abnormality. Results found that cytomegalic neurons and balloon cells were observed more frequently in areas of severe CD compared with mild or normal CD regions as assessed by FDG-PET/MRI. Cytomegalic neurons (but not balloon cells) correlated with the worst electrocorticography scores. Electrophysiological recordings demonstrated that cytomegalic and normal-pyramidal neurons displayed similar firing properties without intrinsic bursting. By contrast, balloon cells were electrically silent. Normal-pyramidal and cytomegalic neurons displayed decreased spontaneous glutamatergic synaptic activity in areas of severe FDG-PET/MRI abnormalities compared with normal regions, while GABAergic activity was unaltered. In CD, these findings indicate that cytomegalic neurons (but not balloon cells) might contribute to epileptogenesis, but are not likely to be ‘pacemaker’ cells capable of spontaneous paroxysmal depolarizations. Furthermore, there was more GABA relative to glutamate synaptic neurotransmission in areas of severe CD. Thus, in CD tissue alternate mechanisms of epileptogenesis should be considered, and we suggest that GABAergic synaptic circuits interacting with cytomegalic and normal-pyramidal neurons with immature receptor properties might contribute to seizure generation.

Social competence in pediatric epilepsy: insights into underlying mechanisms

This study compared parent-based Child Behavior Checklist (CBCL) social competence scores of 90 children with complex partial seizures (CPS) and 62 with absence epilepsy (CAE) of average intelligence with scores of 91 healthy children. It also examined the role of seizure-related, cognitive, behavioral, linguistic, social communication, and demographic variables on these measures. When differences in cognitive, linguistic, and demographic variables were controlled for, the CPS and CAE groups had significantly lower scores in the school, but not in the social interaction and activities domains compared with the healthy control group. Among the patients, lower Full Scale IQ externalizing behaviors, disruptive disorders, minority status, and impaired social communication, but not seizure variables, predicted lower social competence scores. These findings demonstrate the importance of controlling for cognitive, behavioral, and demographic variables in social competence studies of children with CPS and CAE and the need to assess cognition and behavior when parents report school and social problems in these children.

Paroxysmal fast activity: an interictal scalp EEG marker of epileptogenesis in children.

PURPOSE High-frequency oscillations (>100Hz) have been proposed as localized markers of epileptic networks, but require intracranial electroencephalographic (EEG) recordings. This study explored if beta- and gamma-frequency paroxysmal fast activity (PFA), recorded interictally during non-REM sleep, could be used as a scalp EEG marker of epileptogenesis in children. METHODS The presence and scalp location of PFA was visually identified in 681 patients with overnight video-EEG (age 0-18 years), and compared with ictal onset sites. The clinical features of patients with PFA were compared with patients without PFA along with evidence of PFA evolution in 35 patients who had multiple video-EEG records. RESULTS PFA was present in 16% of all patients and in 28% of those with seizures. PFA was more frequently observed in EEGs from patients 3 years of age or younger (>40%), and children with infantile spasms (85%). When present, PFA predicted if the patient had epilepsy with 97% accuracy, and was not found in individuals with non-epileptic events. PFA localized with EEG-ictal onset sites with 91% sensitivity and 82% accuracy. Ictal scalp EEG events began with beta- and gamma-frequencies in 80% of patients with PFA, and they had increased seizure frequencies compared with non-PFA cases. In patients with multiple video-EEG studies, PFA showed progression over increased numbers of electrodes in 74%, improvement in 15%, and remained unchanged in 12% and correlated with seizure evolution. PFA was not associated with other seizure types, anatomic location, type of antiepileptic drug, etiology, or histopathology. CONCLUSIONS While relatively infrequent, interictal PFA was specific in identifying younger children with epilepsy, co-localized with the ictal onset sites on scalp video-EEG, and progressed and correlated with seizure severity. We propose that PFA is a scalp EEG marker of epileptic networks with the advantage of being recorded non-invasively during interictal non-REM sleep.

Infantile spasm-associated microencephaly in tuberous sclerosis complex and cortical dysplasia.

Objective: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD). Methods: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities. Results: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (−16%). In cases with a history of infantile spasms, both CD (−25%) and TSC (−35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (−16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (−36%), whereas CD patients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes. Conclusions: Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasia patients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosis patients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology.