High-resolution pediatric age–specific 18F-FDG PET template: a pilot study in epileptogenic focus localization

Background PET imaging has been widely used in diagnosis of neurological disorders; however, its application to pediatric population is limited due to lacking pediatric age–specific PET template. This study aims to develop a pediatric age–specific PET template (PAPT) and conduct a pilot study of epileptogenic focus localization in pediatric epilepsy. Methods We recruited 130 pediatric patients with epilepsy and 102 age-matched controls who underwent 18F-FDG PET examination. High-resolution PAPT was developed by an iterative nonlinear registration-averaging optimization approach for two age ranges: 6–10 years (n = 17) and 11–18 years (n = 50), respectively. Spatial normalization to the PAPT was evaluated by registration similarities of 35 validation controls, followed by estimation of potential registration biases. In a pilot study, epileptogenic focus was localized by PAPT-based voxel-wise statistical analysis, compared with multi-disciplinary team (MDT) diagnosis, and validated by follow-up of patients who underwent epilepsy surgery. Furthermore, epileptogenic focus localization results were compared among three templates (PAPT, conventional adult template, and a previously reported pediatric linear template). Results Spatial normalization to the PAPT significantly improved registration similarities (P < 0.001), and nearly eliminated regions of potential biases (< 2% of whole brain volume). The PAPT-based epileptogenic focus localization achieved a substantial agreement with MDT diagnosis (Kappa = 0.757), significantly outperforming localization based on the adult template (Kappa = 0.496) and linear template (Kappa = 0.569) (P < 0.05). The PAPT-based localization achieved the highest detection rate (89.2%) and accuracy (80.0%). In postsurgical seizure-free patients (n = 40), the PAPT-based localization also achieved a substantial agreement with resection areas (Kappa = 0.743), and the highest detection rate (95%) and accuracy (80.0%). Conclusion The PAPT can significantly improve spatial normalization and epileptogenic focus localization in pediatric epilepsy. Future pediatric neuroimaging studies can also benefit from the unbiased spatial normalization by PAPT. Trial registration. NCT04725162: https://clinicaltrials.gov/ct2/show/NCT04725162

Anticonvulsant vs. Proconvulsant Effect of in situ Deep Brain Stimulation at the Epileptogenic Focus

Since deep brain stimulation (DBS) at the epileptogenic focus (in situ) denotes long-term repetitive stimulation of the potentially epileptogenic structures, such as the amygdala, the hippocampus, and the cerebral cortex, a kindling effect and aggravation of seizures may happen and complicate the clinical condition. It is, thus, highly desirable to work out a protocol with an evident quenching (anticonvulsant) effect but free of concomitant proconvulsant side effects. We found that in the basolateral amygdala (BLA), an extremely wide range of pulsatile stimulation protocols eventually leads to the kindling effect. Only protocols with a pulse frequency of ≤1 Hz or a direct current (DC), with all of the other parameters unchanged, could never kindle the animal. On the other hand, the aforementioned DC stimulation (DCS), even a pulse as short as 10 s given 5 min before the kindling stimuli or a pulse given even to the contralateral BLA, is very effective against epileptogenicity and ictogenicity. Behavioral, electrophysiological, and histological findings consistently demonstrate success in seizure quenching or suppression as well as in the safety of the specific DBS protocol (e.g., no apparent brain damage by repeated sessions of stimulation applied to the BLA for 1 month). We conclude that in situ DCS, with a novel and rational design of the stimulation protocol composed of a very low (∼3% or 10 s/5 min) duty cycle and assuredly devoid of the potential of kindling, may make a successful antiepileptic therapy with adequate safety in terms of little epileptogenic adverse events and tissue damage.

Large-Scale Desynchronization During Interictal Epileptic Discharges Recorded With Intracranial EEG

It is increasingly recognized that deep understanding of epileptic seizures requires both localizing and characterizing the functional network of the region where they are initiated, i. e., the epileptic focus. Previous investigations of the epileptogenic focus' functional connectivity have yielded contrasting results, reporting both pathological increases and decreases during resting periods and seizures. In this study, we shifted paradigm to investigate the time course of connectivity in relation to interictal epileptiform discharges. We recruited 35 epileptic patients undergoing intracranial EEG (iEEG) investigation as part of their presurgical evaluation. For each patient, 50 interictal epileptic discharges (IEDs) were marked and iEEG signals were epoched around those markers. Signals were narrow-band filtered and time resolved phase-locking values were computed to track the dynamics of functional connectivity during IEDs. Results show that IEDs are associated with a transient decrease in global functional connectivity, time-locked to the peak of the discharge and specific to the high range of the gamma frequency band. Disruption of the long-range connectivity between the epileptic focus and other brain areas might be an important process for the generation of epileptic activity. Transient desynchronization could be a potential biomarker of the epileptogenic focus since 1) the functional connectivity involving the focus decreases significantly more than the connectivity outside the focus and 2) patients with good surgical outcome appear to have a significantly more disconnected focus than patients with bad outcomes.

Unilateral prefrontal lobotomy for epilepsy: technique and surgical anatomy

OBJECTIVESurgery for frontal lobe epilepsy remains a challenge because of the variable seizure outcomes after surgery. Disconnective procedures are increasingly applied to isolate the epileptogenic focus and avoid complications related to extensive brain resection. Previously, the authors described the anterior quadrant disconnection procedure to treat large frontal lobe lesions extending up to but not involving the primary motor cortex. In this article, they describe a surgical technique for unilateral disconnection of the prefrontal cortex, while providing an accurate description of the surgical and functional anatomy of this disconnective procedure.METHODSThe authors report the surgical treatment of a 5-month-old boy who presented with refractory epilepsy due to extensive cortical dysplasia of the left prefrontal lobe. In addition, with the aim of both describing the subcortical intrinsic anatomy and illustrating the different connections between the prefrontal lobe and the rest of the brain, the authors dissected six human cadaveric brain hemispheres. These dissections were performed from lateral to medial and from medial to lateral to reveal the various tracts sectioned during the three different steps in the surgery, namely the intrafrontal disconnection, anterior callosotomy, and frontobasal disconnection.RESULTSThe first step of the dissection involves cutting the U-fibers. During the anterior intrafrontal disconnection, the superior longitudinal fasciculus in the depth of the middle frontal gyrus, the uncinate fasciculus, and the inferior frontooccipital fasciculus in the depth of the inferior frontal gyrus at the level of the anterior insular point are visualized and sectioned, followed by sectioning of the anterior limb of the internal capsule. Once the frontal horn is reached, the anterior callosotomy can be performed to disconnect the genu and the rostrum of the corpus callosum. The intrafrontal disconnection is deepened toward the falx, and at the medial surface, the cingulum is sectioned. The frontobasal disconnection involves cutting the anterior limb of the anterior commissure.CONCLUSIONSThis technique allows selective isolation of the epileptogenic focus located in the prefrontal lobe to avoid secondary propagation. Understanding the surface and white matter fiber anatomy is essential to safely perform the procedure and obtain a favorable seizure outcome.

Language Processing and Reorganization in the Brain in Patients with Temporal Lobe Epilepsy

This paper explores language comprehension and production in patients with temporal lobe epilepsy, a neurological disorder characterized by an epileptogenic focus near language areas or their homologues in the brain. Behavioral studies have shown that language processing in patients with temporal lobe epilepsy could be impaired across language domains — from single words to discourse. Neuroimaging data suggest that temporal lobe epilepsy may lead to changes in the lateralization and localization of language functions, reorganization of functional connections, and alterations in cortical structure and white matter tracts. The severity of language impairments and the degree of functional and structural reorganization in the brain correlate with clinical factors, including lateralization of the epileptogenic focus, age at seizure onset, disease duration, and frequency of epileptiform activity