Stereoelectroencephalography for Epilepsy Presurgical Assessment: A Nationwide Survey of Evolution of Practice in Australia.

Background And Objectives: Stereoelectroencephalography (SEEG) is increasingly used worldwide for epilepsy presurgical evaluation. A data-driven view of SEEG practice evolution is lacking for any world region. We aimed to perform a nationwide survey of SEEG use in Australian adult epilepsy centers.

Pearls & Oy-Sters: Tiny Frontal Lesion Presenting With Generalized Epilepsy.

A 19-year-old woman presented with drug-refractory epilepsy since age 7 years. She had bilateral tonic seizures, generalized paroxysmal fast activity, and trains of anteriorly predominant <2.5 Hz generalized spike-wave discharges, but no intellectual disability.

A generalized epilepsy network derived from brain abnormalities and deep brain stimulation.

Idiopathic generalized epilepsy (IGE) is a brain network disease, but the location of this network and its relevance for treatment remain unclear. We combine the locations of brain abnormalities in IGE (131 coordinates from 21 studies) with the human connectome to identify an IGE network. We validate this network by showing alignment with structural brain abnormalities previously identified in IGE and brain areas activated by generalized epileptiform discharges in simultaneous electroencephalogram-functional magnetic resonance imaging.

Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome.

This paper outlines the therapeutic rationale and neurosurgical targeting technique for bilateral, closed-loop, thalamocortical stimulation in Lennox-Gastaut syndrome, a severe form of childhood-onset epilepsy. Thalamic stimulation can be an effective treatment for Lennox-Gastaut syndrome, but complete seizure control is rarely achieved. Outcomes may be improved by stimulating areas beyond the thalamus, including cortex, but the optimal targets are unknown.

Frontoparietal F-FDG-PET hypo-metabolism in Lennox-Gastaut syndrome: Further evidence highlighting the key network.

Introduction: Lennox Gastaut syndrome (LGS) can be conceptualised as a "secondary network epilepsy", in which the shared electroclinical manifestations reflect epileptic recruitment of a common brain network, despite a range of underlying aetiologies. We aimed to identify the key networks recruited by the epileptic process of LGS using interictal 2-deoxy-2-(F)fluoro-D-glucose positron emission tomography (F-FDG-PET).

Methods: Group analysis of cerebral F-FDG-PET, comparing 21 patients with LGS (mean age = 15 years) and 18 pseudo-controls (mean age = 19 years), studied at Austin Health Melbourne, between 2004 and 2015.

Paroxysmal fast activity is a biomarker of treatment response in deep brain stimulation for Lennox-Gastaut syndrome.

Objective: Epilepsy treatment trials typically rely on seizure diaries to determine seizure frequency, but these are time-consuming and difficult to maintain accurately. Fast, reliable, and objective biomarkers of treatment response are needed, particularly in Lennox-Gastaut syndrome (LGS), where high seizure frequency and comorbid cognitive and behavioral issues are additional obstacles to accurate diary-keeping. Here, we measured generalized paroxysmal fast activity (GPFA), a key interictal electrographic feature of LGS, and correlated GPFA burden with seizure diaries during a thalamic deep brain stimulation (DBS) treatment trial (Electrical Stimulation of the Thalamus in Epilepsy of Lennox-Gastaut Phenotype [ESTEL]).

Cognition, adaptive skills and epilepsy disability/severity in patients with Lennox-Gastaut syndrome undergoing deep brain stimulation for epilepsy in the ESTEL trial.

Purpose: We previously reported seizure and EEG outcomes of the ESTEL study (Electrical Stimulation of Thalamus for Epilepsy of Lennox-Gastaut phenotype). To assess potential cognitive and behavioral changes during chronic, duty-cycle stimulation of bilateral thalamic centromedian nucleus, we compared standardized cognitive and behavioral measurements, as well as caregiver assessments of disability/severity, before implantation and after 3-months stimulation.

Methods: Twenty patients with LGS (17-37 years;13 females) were studied; one participant was not randomized due to DBS device removal, with outcomes of 19 remaining participants reported here.

The Optimal Target and Connectivity for Deep Brain Stimulation in Lennox-Gastaut Syndrome.

Objective: Deep brain stimulation (DBS) can reduce seizures in Lennox-Gastaut syndrome (LGS). However, little is known about the optimal target and whether efficacy depends on connectivity of the stimulation site. Using outcome data from the ESTEL trial, we aimed to determine the optimal target and connectivity for DBS in LGS.

DBS of Thalamic Centromedian Nucleus for Lennox-Gastaut Syndrome (ESTEL Trial).

Objective: Prior uncontrolled studies have reported seizure reductions following deep brain stimulation (DBS) in patients with Lennox-Gastaut syndrome (LGS), but evidence from randomized controlled studies is lacking. We aimed to formally assess the efficacy and safety of DBS to the centromedian thalamic nucleus (CM) for the treatment of LGS.

Methods: We conducted a prospective, double-blind, randomized study of continuous, cycling stimulation of CM-DBS, in patients with LGS.

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome.

Objective: We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial.

Methods: Twelve LGS patients (mean age = 26.8 years) underwent bilateral CM-DBS implantation.

The epileptic network of Lennox-Gastaut syndrome: Cortically driven and reproducible across age.

Objective: To identify brain regions underlying interictal generalized paroxysmal fast activity (GPFA), and their causal interactions, in children and adults with Lennox-Gastaut syndrome (LGS).

Methods: Concurrent scalp EEG-fMRI was performed in 2 separately analyzed patient groups with LGS: 10 children (mean age 8.9 years) scanned under isoflurane-remifentanil anesthesia and 15 older patients (mean age 31.

Hemiconvulsion-hemiplegia-epilepsy evolving to contralateral hemi-Lennox-Gastaut-like phenotype.

Background: Hemiconvulsion-hemiplegia-epilepsy (HHE) involves infantile-onset acute hemiconvulsive febrile status epilepticus with subsequent unilateral cerebral atrophy and hemiparesis. Chronic epilepsy later develops, typically involving refractory focal seizures; however, the underlying pathophysiology of this epilepsy is not well understood.

Patient: We present a boy who had a typical acute presentation of HHE at 23 months, but an unusual evolution to chronic epilepsy in which the initially unaffected hemisphere was significantly abnormal.

Intraoperative definition of bottom-of-sulcus dysplasia using intraoperative ultrasound and single depth electrode recording - A technical note.

Bottom of sulcus dysplasias (BOSDs) are localized focal cortical dysplasias (FCDs) centred on the bottom of a sulcus that can be highly epileptogenic, but difficult to delineate intraoperatively. We report on a patient with refractory epilepsy due to a BOSD, successfully resected with the aid of a multimodal surgical approach using neuronavigation based on MRI and PET, intraoperative ultrasound (iUS) and electrocorticography (ECoG) using depth electrodes. The lesion could be visualized on iUS showing an increase in echogenicity at the grey-white matter junction.

Thalamocortical functional connectivity in Lennox-Gastaut syndrome is abnormally enhanced in executive-control and default-mode networks.

Objective: To identify abnormal thalamocortical circuits in the severe epilepsy of Lennox-Gastaut syndrome (LGS) that may explain the shared electroclinical phenotype and provide potential treatment targets.

Methods: Twenty patients with a diagnosis of LGS (mean age = 28.5 years) and 26 healthy controls (mean age = 27.

Refractory focal motor seizures controlled with intramuscular botulinum toxin.

Patients with recurrent focal motor seizures present a management dilemma, as anti-convulsants are often ineffective, and resective surgery poses a high risk of motor deficit. We describe three patients with recurrent focal motor seizures that remained refractory despite numerous anti-convulsant trials. All patients showed either hyperperfusion on Single-Photon Emission Computerised Tomography (SPECT) or hypermetabolism on Positron Emission Tomography (PET) in primary motor cortex during periods of sustained jerking, although EEG abnormalities were uncommon.

Cognitive network reorganization following surgical control of seizures in Lennox-Gastaut syndrome.

We previously observed that adults with Lennox-Gastaut syndrome (LGS) show abnormal functional connectivity among cognitive networks, suggesting that this may contribute to impaired cognition. Herein we report network reorganization following seizure remission in a child with LGS who underwent functional magnetic resonance imaging (fMRI) before and after resection of a cortical dysplasia. Concurrent electroencephalography (EEG) was acquired during presurgical fMRI.

Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

Background: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested.

Methods: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg).

Abnormal cognitive network interactions in Lennox-Gastaut syndrome: A potential mechanism of epileptic encephalopathy.

Objective: In patients with Lennox-Gastaut syndrome (LGS), recurrent epileptic activity is thought to contribute to impaired cognition (epileptic encephalopathy). Using concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI), we recently showed that epileptiform discharges in LGS recruit large-scale networks that normally support key cognitive processes. In LGS, given that epileptic activity engages cognitive networks, and cognition is pervasively impaired, we hypothesized that cognitive network interactions in LGS are persistently abnormal.

Pontine and cerebral atrophy in Lennox-Gastaut syndrome.

Objectives: Lennox-Gastaut syndrome (LGS) is a severe epilepsy of childhood onset associated with intellectual disability and multiple seizure types. Characteristic interictal electrographic discharges include generalized paroxysmal fast activity and slow spike and wave, which we have previously shown recruit widespread areas of association cortex. We wished to determine whether patients with Lennox-Gastaut syndrome (LGS) have changes in cerebral volumes that match this pattern of cortical recruitment.

Epileptic encephalopathy: Use and misuse of a clinically and conceptually important concept.

The term epileptic encephalopathy (EE) denotes a process by which epileptic activity adversely affects brain function over and above the underlying etiology. Underlying mechanisms are poorly understood, but recent studies demonstrate that seizures and interictal epileptiform discharges can disrupt distributed neural networks that underpin cognitive functions, both temporarily and permanently. EE is just one of a number of factors that can affect development in epilepsy.