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Objective To determine the nature of staring spells and factors distinguishing epileptic from nonepileptic staring spells, we studied the clinical and demographic features of children with staring spells referred to a regional new-onset seizure clinic. Study design Our retrospective chart review encompassed 2818 consecutive patients evaluated in the new-onset seizure clinic between September 22, 2015, and March 19, 2018. We identified 121 patients with newly presenting staring spells. Results Sixty-two of 121 (51%) children were diagnosed with nonepileptic staring spells and 59 (49%) with epileptic seizures (24 with absence epilepsy, 35 with focal epilepsy). Patients with nonepileptic staring spells were younger (4.8 vs 7.1 years, P = .001) and more likely to have developmental delay ( P = .005) than the seizure group. There was an 8.9-month delay on average from the onset of staring spells to the new-onset seizure clinic visit. The emergency department was a referral source for 80% (28/35) of focal seizures. In children with focal seizures, the staring spells typically lasted >1minute (29/35, 83%), whereas only 19 of 62 (31%) of children with nonepileptic staring spells had events lasting this long ( P = .04). All children had a routine electroencephalography (EEG) on the day of new-onset seizure clinic visit. EEG was diagnostic in 100% (24/24) of absence seizures and 51% (18/35) of focal seizures. Conclusions In children presenting with staring spells, the differential diagnosis of epileptic staring spells vs nonepileptic staring spells can be made by history and routine EEG. Staring was as likely to be epileptic as nonepileptic spells. Younger children with developmental delay were more likely to have nonepileptic events. Our simple approach based on event duration, postictal symptoms, and EEG allowed identification of epileptic staring on first visit to new-onset seizure clinic but requires validation in future prospective studies including long-term video EEG monitoring and follow-up.

The creatine transporter (CrT) maintains brain creatine (Cr) levels, but the effects of its deficiency on energetics adaptation under stress remain unclear. There are also no effective treatments for CrT deficiency, the second most common cause of X-linked intellectual disabilities. Herein, we examined the consequences of CrT deficiency in brain energetics and stress-adaptation responses plus the effects of intranasal Cr supplementation. We found that CrT-deficient (CrT–/y) mice harbored dendritic spine and synaptic dysgenesis. Nurtured newborn CrT–/y mice maintained baseline brain ATP levels, with a trend toward signaling imbalance between the p-AMPK/autophagy and mTOR pathways. Starvation elevated the signaling imbalance and reduced brain ATP levels in P3 CrT–/y mice. Similarly, CrT–/y neurons and P10 CrT–/y mice showed an imbalance between autophagy and mTOR signaling pathways and greater susceptibility to cerebral hypoxia-ischemia and ischemic insults. Notably, intranasal administration of Cr after cerebral ischemia increased the brain Cr/N-acetylaspartate ratio, partially averted the signaling imbalance, and reduced infarct size more potently than intraperitoneal Cr injection. These findings suggest important functions for CrT and Cr in preserving the homeostasis of brain energetics in stress conditions. Moreover, intranasal Cr supplementation may be an effective treatment for congenital CrT deficiency and acute brain injury.

Aim We evaluated the clinical and demographic features of children presenting with unprovoked seizures at a regional new-onset seizure clinic (NOSc). Methods We retrospectively reviewed charts of 492 consecutive patients evaluated in the NOSc at the Childrne’s Healthcare of Atlanta Results Nonepileptic events (NEE) were diagnosed in 102 (24%) and epileptic seizures in the remaining 326 (76%). Patients with NEE were younger than patients with epileptic seizure (5.0 vs. 7.4 years). Except for headache which occurred more frequently in NEE (14% vs. 6%), frequencies of comorbidities were similar in groups with NEE and epileptic seizure. Electroencephalogram (EEG) was performed in 98%, and finding was abnormal in 51%. Brain magnetic resonance imaging (MRI) was performed in 55%, and finding was abnormal in 15%. An electroclinical epilepsy syndrome was diagnosed in 42%. Antiseizure medication was started in 25% with first seizure and in 77% with recurrent seizures. Interpretation For children with newly-presenting seizures, a regional NOSc provided efficient, timely diagnosis and appropriate evaluations and treatment. Timely recognition of NEE resulted in fewer unnecessary evaluations and treatment for a quarter of referred patients whereas identification of the specific types of seizures and epilepsy allowed appropriate use, including deferral, of neuroimaging and guided treatment selection.

The purpose of this study was to evaluate relationships between subsarcolemmal mitochondrial aggregates and electron transport chain deficiencies in skeletal muscle with the objective of establishing an association between mitochondrial accumulation and electron transport chain complex deficiency. We conducted a large-scale, retrospective study to evaluate factors associated with subsarcolemmal mitochondrial aggregates (percent) in pediatric patients who received muscle biopsies for suspected respiratory chain disorders. Patients were included if they had histochemical stains for assessment of mitochondrial pathology and had biochemical testing for muscle electron transport chain complex activities. Significant positive bivariate correlations (n = 337) were found between subsarcolemmal mitochondrial aggregate percentage and electron transport chain complexes II, IV, I + III, and II + III activities. Evaluation showed that a cutoff value of2% subsarcolemmal mitochondrial aggregates had poor overall diagnostic accuracy (mean, 32%), compared with a5% cutoff (mean, 60%). To better evaluate the effects of subsarcolemmal mitochondrial aggregates percentages, patients were stratified according to lower one-third (group 1, n = 120 plus ties) and upper one-third (group 2, n = 115 plus ties) of subsarcolemmal mitochondrial aggregates values. Although only minor clinical and pathologic differences were observed, group 1 participants had significantly lower electron transport chain complex activities than group 2 for all enzymes except complex III. Logistic regression showed over 2-fold greater odds of deficiency for electron transport chain complexes I + III (P = .01) and II + III (P = .03) for group 1 participants compared with group 2. We conclude that, contrary to the previous2.0% subsarcolemmal mitochondrial aggregates cutoff for respiratory chain disorder, patients with a low subsarcolemmal mitochondrial aggregates percentage (≤4%) are significantly more likely to have electron transport chain complex deficiency than patients with increased subsarcolemmal mitochondrial aggregates percentage (≥10%). This morphological approach for assessment of mitochondrial proliferation may assist clinicians to select further testing to rule out an electron transport chain complex deficiency in children by other methods, including direct biochemical testing of electron transport chain complex activities, measurement of muscle coenzyme Q10 content, or evaluation for a mitochondrial DNA depletion syndrome.

Individuals with epilepsy have difficulties with social function that are not adequately accounted for by seizure severity or frequency. This study examined the relationship between language ability and social functioning in 193 children with epilepsy over a period of 36 months following their first recognized seizure. The findings show that children with persistent seizures have poorer language function, even at the onset of their seizures, than do their healthy siblings, children with no recurrent seizures, and children with recurrent but not persistent seizures. They continue to demonstrate poorer language function 36 months later. This poor language function is associated with declining social competence. Intervention aimed at improving social competence should include consideration of potential language deficits that accompany epilepsy and social difficulty.

Recent reports suggest that high-frequency epileptic activity is highly localized to epileptogenic zones. The goal of the present study was to investigate the potential usefulness of noninvasive localization of high-frequency epileptic activity for epilepsy surgery.Data obtained in 4 patients, who had seizures during routine magnetoencephalography (MEG) tests, were retrospectively studied. The MEG data were digitized at 4000 Hz, and 3D MR images were obtained. The magnetic sources were volumetrically localized with wavelet-based beamformer. The MEG results were subsequently compared with clinical data.The 4 patients had 1-4 high-frequency neuromagnetic components (110-910 Hz) in ictal and interictal activities. The loci of high-frequency activities were concordant with intracranial recordings therein 3 patients, who underwent presurgical evaluation. The loci of high-frequency ictal activities were in line with semiology and neuroimaging in all 4 of the patients. High-frequency epileptic activity was highly localized to the epileptogenic zones.High-frequency epileptic activity can be volumetrically localized with MEG. Source analysis of high-frequency neuromagnetic signals has the potential to determine epileptogenic zones noninvasively and preoperatively for epilepsy surgery.