Discerning Seizure-Onset v. Propagation Zone: Pre-and-Post-Operative Resting-State fMRI Directionality and Boerwinkle Neuroplasticity Index.

The goal of this study was to determine resting state fMRI (rs-fMRI) effective connectivity (RSEC) capacity, agnostic of epileptogenic events, in distinguishing seizure onset zones (SOZ) from propagation zones (pZ). Consecutive patients (2.1-18.2 years old), with epilepsy and hypothalamic hamartoma, pre-operative rs-fMRI-directed surgery, post-operative imaging, and Engel class I outcomes were collected. Cross-spectral dynamic causal modelling (DCM) was used to estimate RSEC between the ablated rs-fMRI-SOZ to its region of highest connectivity outside the HH, defined as the propagation zone (pZ). Pre-operatively, RSEC from the SOZ and PZ was expected to be positive (excitatory), and pZ to SOZ negative (inhibitory), and post-operatively to be either diminished or non-existent. Sensitivity, accuracy, positive predictive value were determined for node-to-node connections. A Parametric Empirical Bayes (PEB) group analysis on pre-operative data was performed to identify group effects and effects of Engel class outcome and age. Pre-operative RSEC strength was also evaluated for correlation with percent seizure frequency improvement, sex, and region of interest size. Of the SOZ's RSEC, only 3.6% had no connection of significance to the pZ when patient models were individually reduced. Among remaining, 96% were in expected (excitatory signal found from SOZ â†’ pZ and inhibitory signal found from pZ â†’ SOZ) versus 3.6% reversed polarities. Both pre-operative polarity signals were equivalently as expected, with one false signal direction out of 26 each (3.7% total). Sensitivity of 95%, specificity 73%, accuracy of 88%, negative predictive value 88%, and positive predictive value of 88% in identifying and differentiating the SOZ and pZ. Groupwise PEB analysis confirmed SOZ â†’ pZ EC was excitatory, and pZ â†’ SOZ EC was inhibitory. Patients with better outcomes (Engel Ia vs. Ib) showed stronger inhibitory signal (pZ â†’ SOZ). Age was negatively associated with absolute RSEC bidirectionally but had no relationship with Directionality SOZ identification performance. In an additional hierarchical PEB analysis identifying changes from pre-to-post surgery, SOZ â†’ pZ modulation became less excitatory and pZ â†’ SOZ modulation became less inhibitory. This study demonstrates the accuracy of Directionality to identify the origin of excitatory and inhibitory signal between the surgically confirmed SOZ and the region of hypothesized propagation zone in children with DRE due to a HH. Thus, this method validation study in a homogenous DRE population may have potential in narrowing the SOZ-candidates for epileptogenicity in other DRE populations and utility in other neurological disorders.

Temporal encephalocele: a novel indication for magnetic resonance-guided laser interstitial thermal therapy for medically intractable epilepsy.

Temporal encephalocele (TE) is a rare but surgically treatable/curable cause of temporal lobe epilepsy (TLE). The surgical intervention varies from local disconnection to extensive anterior temporal lobectomy and amygdalohippocampectomy (ATL/AH). Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has evolved as a minimally invasive alternative for intractable epilepsy with good results, however, application of MRgLITT for intractable pediatric epilepsy secondary to TE has not been reported. We present a detailed technical report and clinical experience of MRgLITT in two adolescent children with medically intractable TLE secondary to TE. Pre-surgical evaluation revealed anterior inferior TE with concordant clinico-electrophysiological data. Both the patients underwent MRgLITT after review with the institutional multidisciplinary epilepsy team and discussion with the patient and the family. Both the patients were discharged on post-operative day one and have been seizure-free since the procedure at the last follow-up visit at 18 months and 6 months, respectively. The present series demonstrates first-ever clinical and technical experience of MRgLITT for TE with intractable pediatric epilepsy. The excellent post-operative seizure outcome and favorable postoperative course support MRgLITT as the first line of surgical intervention for TE with intractable TLE and broadens the application of MRgLITT.

Challenges Enrolling Children Into Traumatic Brain Injury Trials: An Observational Study.

OBJECTIVES: In preparation for a clinical trial of therapeutic agents for children with moderate-to-severe blunt traumatic brain injuries (TBIs) in emergency departments (EDs), we conducted this feasibility study to (1) determine the number and clinical characteristics of eligible children, (2) determine the timing of patient and guardian arrival to the ED, and (3) describe the heterogeneity of TBIs on computed tomography (CT) scans. METHODS: We conducted a prospective observational study at 16 EDs of children ≤ 18 years of age presenting with blunt head trauma and Glasgow Coma Scale scores of 3-12. We documented the number of potentially eligible patients, timing of patient and guardian arrival, patient demographics and clinical characteristics, severity of injuries, and cranial CT findings. RESULTS: We enrolled 295 eligible children at the 16 sites over 6 consecutive months. Cardiac arrest and nonsurvivable injuries were the most common characteristics that would exclude patients from a future trial. Most children arrived within 2 hours of injury, but most guardians did not arrive until 2-3 hours after the injury. There was a substantial range in types of TBIs, with subdural hemorrhages being the most common. CONCLUSION: Enrolling children with moderate-to-severe TBI into time-sensitive clinical trials will require large numbers of sites and meticulous preparation and coordination and will prove challenging to obtain informed consent given the timing of patient and guardian arrival. The Federal Exception from Informed Consent for Emergency Research will be an important consideration for enrolling these children.

Damage control of civilian penetrating brain injuries in environments of low neuro-monitoring resources.

INTRODUCTION: Gunshot wounds to the head are more common in military settings. Recently, a damage control (DC) approach for the management of these lesions has been used in combat areas. The aim of this study was to evaluate the results of civilian patients with penetrating gunshot wounds to the head, managed with a strategy of early cranial decompression (ECD) as a DC procedure in a university hospital with few resources for intensive care unit (ICU) neuro-monitoring in Colombia. MATERIALS AND METHODS: Fifty-four patients were operated according to the DC strategy (<12 h after injury), over a 4-year period. Variables were analysed and results were evaluated according to the Glasgow Outcome Scale (GOS) at 12 months post injury; a dichotomous variable was established as 'favourable' (GOS 4-5) or 'unfavourable' (GOS 1-3). A univariate analysis was performed using a χ(2) test. RESULTS: Forty (74.1%) of the patients survived and 36 (90%) of them had favourable GOS. Factors associated with adverse outcomes were: Injury Severity Score (ISS) greater than 25, bi-hemispheric involvement, intra-cerebral haematoma on the first CT, closed basal cisterns and non-reactive pupils in the emergency room. CONCLUSION: DC for neurotrauma with ECD is an option to improve survival and favourable neurological outcomes 12 months after injury in patients with penetrating traumatic brain injury treated in a university hospital with few resources for ICU neuro-monitoring.

Commentary on Kamper et. al., juvenile traumatic brain injury evolves into a chronic brain disorder: The challenges in longitudinal studies of juvenile traumatic brain injury.

Juvenile traumatic brain injury (TBI) leaves survivors facing a potential lifetime of cognitive, somatic and emotional symptoms. A recent study published in Experimental Neurology (Kamper et al., 2013) explored the chronic consequences of focal brain injury induced in the juvenile animal, extending their previous observations out to 6months post-injury. The results demonstrate transient, persistent, and late onset behavioral dysfunction, which are associated with subtle evidence for enduring histopathology. In line with investigations about chronic traumatic encephalopathy from brain injury initiated in the adult, juvenile TBI establishes signs of a chronic brain disorder, with unique considerations relative to ongoing developmental processes. This commentary discusses the challenges in evaluating aging with injury in the juvenile population, the current methods of juvenile TBI, and what can be anticipated for the future of the field.