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Nabatîyé et Tahta, Lebanon

Kulandaivel K.,Neuroscience Center at Dartmouth | Holmes G.L.,Neuroscience Center at Dartmouth
Epilepsy and Behavior

There is increasing evidence that there is a strong relationship between brain oscillations and neurocognitive function. We used EEG power spectral analysis to determine if frequency and power provide an independent measure of developmental impairment in infants. We examined the spectral power of EEGs in 200 infants between 6 and 24. months of age who were evaluated for seizures. Infants were stratified into three age groups 6-12, 12-18, and 18-24. months, and development assessments were coded as normal, moderately delayed, and severely delayed. Compared with the normal infants, children with developmental delay had lower mean frequencies and greater delta and less theta and alpha power. Delta/theta and theta/alpha ratios were highly significant indicators of developmental status. This study demonstrates that frequency and power of brain oscillations during wakefulness is a strong predictor of development in infants. The findings support the concept that normal oscillatory activity is critical for normal cognitive function during development. © 2011 Elsevier Inc. Source

de Leo J.A.,Neuroscience Center at Dartmouth | de Leo J.A.,Dartmouth Hitchcock Medical Center
ASN Neuro

GBM (glioblastoma multiforme) is a highly aggressive brain tumour with very poor prognosis despite multi-modalities of treatment. Furthermore, recent failure of targeted therapy for these tumours highlights the need of appropriate rodent models for preclinical studies. In this review, we highlight the most commonly used rodent models (U251, U86, GL261, C6, 9L and CNS-1) with a focus on the pathological and genetic similarities to the human disease. We end with a comprehensive review of the CNS-1 rodent model. © 2011 The Author(s). Source

Bender A.C.,Neuroscience Center at Dartmouth | Morse R.P.,Neuroscience Center at Dartmouth | Scott R.C.,Neuroscience Center at Dartmouth | Scott R.C.,University College London | And 2 more authors.
Epilepsy and Behavior

Dravet syndrome (DS) is a childhood disorder associated with loss-of-function mutations in SCN1A and is characterized by frequent seizures and severe cognitive impairment. Animal studies have revealed new insights into the mechanisms by which mutations in this gene, encoding the type I voltage-gated sodium channel (Na v1.1), may lead to seizure activity and cognitive dysfunction. In this review, we further consider the function of fast-spiking GABAergic neurons, one cell type particularly affected by these mutations, in the context of the temporal coordination of neural activity subserving cognitive functions. We hypothesize that disruptions in GABAergic firing may directly contribute to the poor cognitive outcomes in children with DS, and discuss the therapeutic implications of this possibility. © 2011 Elsevier Inc. Source

Kleen J.K.,Neuroscience Center at Dartmouth | Scott R.C.,Neuroscience Center at Dartmouth | Scott R.C.,University College London | Holmes G.L.,Neuroscience Center at Dartmouth | Lenck-Santini P.P.,Neuroscience Center at Dartmouth
Annals of Neurology

Objective: Cognitive impairment is common in epilepsy, particularly in memory function. Interictal spikes (IISs) are thought to disrupt cognition, but it is difficult to delineate their contribution from general impairments in memory produced by etiology and seizures. We investigated the transient impact of focal IISs on the hippocampus, a structure crucial for learning and memory and yet highly prone to IISs in temporal lobe epilepsy (TLE). Methods: Bilateral hippocampal depth electrodes were implanted into 14 Sprague-Dawley rats, followed by intrahippocampal pilocarpine or saline infusion unilaterally. Rats that developed chronic spikes were trained in a hippocampal-dependent operant behavior task, delayed-match-to-sample. Depth-electroencephalogram (EEG) was recorded during 5,562 trials among five rats, and within-subject analyses evaluated the impact of hippocampal spikes on short-term memory operations. Results: Hippocampal spikes that occurred during memory retrieval strongly impaired performance (p < 0.001). However, spikes that occurred during memory encoding or memory maintenance did not affect performance in those trials. Hippocampal spikes also affected response latency, adding approximately 0.48 seconds to the time taken to respond (p < 0.001). Interpretation: We found that focal IIS-related interference in cognition extends to structures in the limbic system, which required intrahippocampal recordings. Hippocampal spikes seem most harmful if they occur when hippocampal function is critical, extending human studies showing that cortical spikes are most disruptive during active cortical functioning. The cumulative effects of spikes could therefore impact general cognitive functioning. These results strengthen the argument that suppression of IISs may improve memory and cognitive performance in patients with epilepsy. © 2010 American Neurological Association. Source

Lazow S.P.,Dartmouth Hitchcock Medical Center | Thadani V.M.,Dartmouth Hitchcock Medical Center | Gilbert K.L.,Dartmouth Hitchcock Medical Center | Morse R.P.,Dartmouth Hitchcock Medical Center | And 7 more authors.

Purpose: There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well-established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. Methods: Fifty-eight patients underwent resective FLE surgery with a mean follow-up period of 79.3 months (range 12-208 months). Patient demographics, clinical seizure characteristics, seizure-onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow-up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. Key Findings: Thirty-three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0-208). Only 14 patients (24%) were completely seizure-free without auras (Engel IA) throughout the entire follow-up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. Significance: Findings indicate that that long-term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI-negative patients. © Wiley Periodicals, Inc. © 2012 International League Against Epilepsy. Source

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