Publications by authors named "Aaron E L Warren"

Objectives: A supraclavicular insertion approach for vagus nerve stimulation (VNS) may permit a wider range of VNS settings compared to traditional insertion techniques due to increased anatomic distance between VNS leads and the recurrent laryngeal nerve. Beyond potential technical advantages, this approach could offer greater cosmetic satisfaction for patients. However, the safety and efficacy of the supraclavicular approach is uncertain.

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Background: Deep brain stimulation (DBS) is a standard treatment for movement disorders, epilepsy, and others, yet its influence on postprocedural sleep quality remains an under-researched topic.

Study Objectives: We performed a systematic review and meta-analysis of all DBS effects on sleep.

Methods: The use of preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) was utilized.

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Article Synopsis
  • Disorders of consciousness (DoC) refer to conditions where a person has reduced awareness or ability to respond, and deep brain stimulation (DBS) is being explored as a treatment, with varying effectiveness based on patient specifics and stimulation methods.
  • In a study of 40 DoC patients receiving DBS, improved consciousness was linked to better gray matter preservation, particularly in the striatum, and effective stimulation targeted specific brain areas, particularly the thalamic centromedian-parafascicular complex.
  • The research highlights the need for precise electrode placement and suggests a connection between successful DBS treatment for DoC and mechanisms involved in other conditions that impair consciousness, such as absence seizures and brain lesions
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Objective: Lennox-Gastaut syndrome (LGS) is a severe, childhood-onset epilepsy that is typically refractory to treatment. We surveyed the current landscape of LGS treatment, aiming to identify challenges to the development of efficacious therapies, and to articulate corresponding priorities toward clinical trials that improve outcomes.

Methods: The LGS Special Interest Group of the Pediatric Epilepsy Research Consortium integrated evidence from the literature and expert opinion, into a narrative review.

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Article Synopsis
  • * It finds that while more implanted contacts may increase the chances of treatment progression, they do not correlate with better SOZ localization or improved seizure outcomes, with specific brain regions more frequently linked to seizure onset.
  • * Overall, SEEG is effective for localizing SOZ in various types of epilepsy, helping guide treatment decisions despite variability in electrode placement across institutions.
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  • Developmental and epileptic encephalopathies (DEEs) are serious childhood epilepsy syndromes with frequent seizures and significant cognitive impairments, often not responding to standard treatments.
  • Recent advancements in neuromodulation techniques like deep brain stimulation (DBS) and responsive neurostimulation (RNS) show promise in managing these conditions by targeting specific brain networks involved in seizures.
  • Initial findings, particularly with DBS for Lennox-Gastaut syndrome (LGS), indicate some effectiveness, but mixed results across various DEEs highlight the need for a better understanding of brain networks to guide optimal treatment strategies.
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Article Synopsis
  • ! Drug-resistant temporal lobe epilepsy (TLE) is linked with damage in the hippocampus, but research is starting to view it as a wider network issue rather than just localized pathology. * ! A study involving 94 patients assessed the relationship between the brain's functional networks and areas of hippocampal atrophy, revealing two distinct brain networks connected to those atrophied areas. * ! The findings highlight that one network correlates positively with certain brain regions (temporolimbic, medial prefrontal, parietal), while another shows negative correlations with frontoparietal regions, suggesting complex interactions in TLE beyond the hippocampus. *
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Objective: Deep brain stimulation (DBS) of the centromedian nucleus (CM) is used to treat diverse brain diseases including epilepsy, Tourette syndrome, and disorders of consciousness. However, the CM is challenging to visualize on routine MRI. Many surgeons use an indirect targeting method based on established stereotactic coordinates.

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Objectives: Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI.

Methods: Data were acquired from two independent datasets which included 156 older adult veterans (69.

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The centromedian (CM) nucleus of the thalamus is a promising target for a range of brain diseases including drug-resistant generalized and multifocal epilepsy. CM is highly connected to cortical and subcortical regions including frontoparietal/sensorimotor cortex, striatum, brainstem, and cerebellum, which are involved in some generalized epilepsy syndromes like Lennox-Gastaut syndrome (LGS). In this video, the authors describe their methodology for targeting CM for deep brain stimulation (DBS).

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Introduction: Infantile epileptic spasms syndrome (IESS) is a common developmental and epileptic encephalopathy with poor long-term outcomes. A substantial proportion of patients with IESS have a potentially surgically remediable etiology. Despite this, epilepsy surgery is underutilized in this patient group.

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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.

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Objective: Patients with focal, lesional epilepsy present with seizures at variable ages. Larger lesion size and overlap with sensorimotor or default mode network (DMN) have been associated with younger age at seizure onset in cohorts with mixed types of focal cortical dysplasia (FCD). Here, we studied determinants of age at seizure onset in patients with bottom-of-sulcus dysplasia (BOSD), a discrete type of FCD with highly localized epileptogenicity.

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Status Epilepticus (SE), unresponsive to medical management, is associated with high morbidity and mortality. Surgical management is typically considered in these refractory cases. The best surgical approach for affected patients remains unclear; however, given the lack of controlled trials exploring the role of surgery.

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Current applications of neurostimulation for generalized epilepsy use a one-target-fits-all approach that is agnostic to the specific epilepsy syndrome and seizure type being treated. The authors describe similarities and differences between the 2 "archetypes" of generalized epilepsy-Lennox-Gastaut syndrome and Idiopathic Generalized Epilepsy-and review recent neuroimaging evidence for syndrome-specific brain networks underlying seizures. Implications for stimulation targeting and programming are discussed using 5 clinical questions: What epilepsy syndrome does the patient have? What brain networks are involved? What is the optimal stimulation target? What is the optimal stimulation paradigm? What is the plan for adjusting stimulation over time?

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Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics of BOSD, with the aims of improving management and understanding pathogenesis. We studied 85 patients with BOSD diagnosed between 2005-2022.

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Introduction: Prompt dissemination of clinical trial results is essential for ensuring the safety and efficacy of intracranial neurostimulation treatments, including deep brain stimulation (DBS) and responsive neurostimulation (RNS). However, the frequency and completeness of results publication, and reasons for reporting delays, are unknown. Moreover, the patient populations, targeted anatomical locations, and stimulation parameters should be clearly reported for both reproducibility and to identify lacunae in trial design.

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Objective: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking.

Methods: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software.

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Functional magnetic resonance images (fMRI) acquired using echo planar sequences typically suffer from spatial distortions due to susceptibility induced off-resonance fields, which may cause geometric mismatch with structural images and affect subsequent quantification and localization of brain function. State-of-the art distortion correction methods (for example, using FSL's topup or AFNI's 3dQwarp algorithms) require the collection of additional scans - either field maps or images with reverse phase encoding directions (i.e.

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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.

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Objective: Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach.

Methods: We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median = 5.

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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]).

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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.

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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.

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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.

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