Neuronal activity is critical for synaptogenesis and the development of neuronal networks. In the immature brain excitation predominates over inhibition facilitating the development of normal brain circuits, but also rendering it more susceptible to seizures. In this paper, we review the evolution of the subunit composition of neurotransmitter receptors during development, how it promotes excitation in the immature brain, and how this subunit composition of neurotransmission receptors may be also present in the epileptic brain. During normal brain development, excitatory glutamate receptors peak in function and gamma-aminobutiric acid (GABA) receptors are mainly excitatory rather than inhibitory. A growing body of evidence from animal models of epilepsy and status epilepticus has demonstrated that the brain exposed to repeated seizures presents a subunit composition of neurotransmitter receptors that mirrors that of the immature brain and promotes further seizures and epileptogenesis. Studies performed in samples from the epileptic human brain have also found a subunit composition pattern of neurotransmitter receptors similar to the one found in the immature brain. These findings provide a solid rationale for tailoring antiepileptic treatments to the specific subunit composition of neurotransmitter receptors and they provide potential targets for the development of antiepileptogenic treatments.
ABSTRACT PURPOSE T2‐hyperintense signal changes in corpus callosum (CC) have been described in epilepsy and encephalitis/encephalopathy. Little is known about their pathophysiology. The aim of this study was to examine the clinical presentation and evolution of CC lesions and relationship to seizures. METHODS We identified 12 children among 29,634 patients from Radiology Database. We evaluated following characteristics: seizures and accompanying medical history, antiepileptic drug usage, presenting symptoms, and radiological evolution of lesions. RESULTS CC lesions were seen in patients with prior diagnosis of epilepsy ( n = 5) or in those with new onset seizures ( n = 3), or with encephalitis/encephalopathy without history of seizures ( n = 4). Seizure clustering or disturbances of consciousness were the main presenting symptoms. No relationship was observed between CC lesion and AEDs. On imaging, ovoid lesions at presentation resolved on follow up imaging and linear lesions persisted. DTI showed that the fibers passing through splenial lesions originated from the posterior parietal cortex and occipital cortex bilaterally. CONCLUSION In patients with seizures, no clear relationship was demonstrated between seizure characteristics or AED use with CC lesions. Ovoid lesions resolved and may have different pathophysiologic mechanism when compared to linear lesions that persisted.
To describe the time elapsed from onset of pediatric convulsive status epilepticus (SE) to administration of antiepileptic drug (AED).This was a prospective observational cohort study performed from June 2011 to June 2013. Pediatric patients (1 month-21 years) with convulsive SE were enrolled. In order to study timing of AED administration during all stages of SE, we restricted our study population to patients who failed 2 or more AED classes or needed continuous infusions to terminate convulsive SE.We enrolled 81 patients (44 male) with a median age of 3.6 years. The first, second, and third AED doses were administered at a median (p25-p75) time of 28 (6-67) minutes, 40 (20-85) minutes, and 59 (30-120) minutes after SE onset. Considering AED classes, the initial AED was a benzodiazepine in 78 (96.3%) patients and 2 (2-3) doses of benzodiazepines were administered before switching to nonbenzodiazepine AEDs. The first and second doses of nonbenzodiazepine AEDs were administered at 69 (40-120) minutes and 120 (75-296) minutes. In the 64 patients with out-of-hospital SE onset, 40 (62.5%) patients did not receive any AED before hospital arrival. In the hospital setting, the first and second in-hospital AED doses were given at 8 (5-15) minutes and 16 (10-40) minutes after SE onset (for patients with in-hospital SE onset) or after hospital arrival (for patients with out-of-hospital SE onset).The time elapsed from SE onset to AED administration and escalation from one class of AED to another is delayed, both in the prehospital and in-hospital settings.
Abstract Objective Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic‐clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection. Methods During electroencephalographic (EEG) long‐term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals. We analyzed PPG signals during three time periods, which were defined with respect to seizures detected on EEG: (1) baseline (>30 minutes prior to seizure), (2) preseizure period, and (3) postseizure period. Furthermore, we selected five random control segments during seizure‐free periods. PPG features, including frequency, amplitude, duration, slope, smoothness, and area under the curve, were automatically calculated. We used a linear mixed‐effect model to evaluate changes in PPG features between different time periods in an attempt to identify signal changes that detect seizures. Results We prospectively enrolled 174 patients from the epilepsy monitoring unit at Boston Children's Hospital. Twenty‐five GTCSs were recorded from 13 patients. Data from the first recorded GTCS of each patient were included in the analysis. We observed an increase in PPG frequency during pre‐ and postseizure periods that was higher than the changes during seizure‐free periods (frequency increase: preseizure = 0.22 Hz, postseizure = 0.58 Hz vs changes during seizure‐free period = 0.05 Hz). The PPG slope decreased significantly by 56.71 nW/s during preseizure periods compared to seizure‐free periods. Additionally, the smoothness increased significantly by 0.22 nW/s during the postseizure period compared to seizure‐free periods. Significance Monitoring of PPG signals may assist in the detection of GTCSs in patients with epilepsy. PPG may serve as a promising biomarker for future seizure detection systems and may contribute to future seizure prediction systems.
