Publications by authors named "James Gugger"

Background: The piriform cortex has been implicated in the initiation, spread and termination of epileptic seizures. This understanding has extended to surgical management of epilepsy, where it has been shown that resection or ablation of the piriform cortex can result in better outcomes. How and why the piriform cortex may play such a crucial role in seizure networks is not well understood.

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Traumatic brain injury (TBI) remains a pervasive clinical problem associated with significant morbidity and mortality. However, TBI remains clinically and biophysically ill-defined, and prognosis remains difficult even with the standardization of clinical guidelines and advent of multimodality monitoring. Here we leverage a unique data set from TBI patients implanted with either intracranial strip electrodes during craniotomy or quad-lumen intracranial bolts with depth electrodes as part of routine clinical practice.

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  • Temporal encephaloceles (TE) are a lesser-known cause of epilepsy that can be surgically treated, and this systematic review compiles data on their clinical characteristics and treatment outcomes.
  • The analysis included 24 studies with a total of 423 patients, finding that TE patients typically have later seizure onset, different seizure patterns, and a greater incidence of idiopathic intracranial hypertension (IIH) compared to those without TE.
  • Surgical interventions show promising outcomes, with a 75-85% success rate for different surgical techniques, indicating that better recognition and understanding of TE could improve epilepsy management.
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  • Positron Emission Tomography (FDG-PET) is commonly used to pinpoint seizure onset zones in temporal lobe epilepsy, but it’s expensive and uses a radioactive substance; an alternative, Arterial Spin Labeling (ASL), quantifies brain blood flow via MRI but isn't as effective for the same purpose.
  • This study involved 68 epilepsy patients, comparing FDG-PET with ASL to evaluate their coupling and effectiveness in localizing seizure onset zones, while also developing a deep learning tool called FlowGAN to create PET-like images from ASL data.
  • Results showed that while FDG-PET and ASL demonstrated varying levels of correlation in different brain regions, FDG-PET
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Importance: Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes.

Objective: To investigate associations of PTE with dementia risk.

Design, Setting, And Participants: The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years.

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Objective: To determine the association between brain MRI abnormalities and incident epilepsy in older adults.

Methods: Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI.

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Rationale: Seizure induction techniques are used in the epilepsy monitoring unit (EMU) to increase diagnostic yield and reduce length of stay. There are insufficient data on the efficacy of alcohol as an induction technique.

Methods: We performed a retrospective cohort study using six years of EMU data at our institution.

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  • Traumatic brain injury (TBI) leads to ongoing brain degeneration, with noticeable atrophy occurring months to years after the initial injury.
  • A study involving 37 individuals with moderate-severe TBI showed initial cortical thinning and volume loss in brain regions by 3 months post-injury, with selective continued atrophy in certain areas over the first year.
  • Despite significant brain atrophy, neurocognitive functioning improved during this period, revealing complex patterns of degeneration that vary by brain region and injury severity, suggesting future research could use early atrophy as a biomarker for TBI outcomes.
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Objective: Veterans are at elevated risk of epilepsy due to higher rates of traumatic brain injury (TBI). However, little work has examined the extent to which quality of care is associated with key outcomes for Veterans with epilepsy (VWE). This study aimed to examine the impact of quality of care on three outcomes: patients' knowledge of epilepsy self-care, proactive epilepsy self-management, and satisfaction with care.

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Background And Motivation: Functional gradients have been used to study differences in connectivity between healthy and diseased brain states, however this work has largely focused on the cortex. Because the subcortex plays a key role in seizure initiation in temporal lobe epilepsy (TLE), subcortical functional-connectivity gradients may help further elucidate differences between healthy brains and TLE, as well as differences between left (L)-TLE and right (R)-TLE.

Methods: In this work, we calculated subcortical functional-connectivity gradients (SFGs) from resting-state functional MRI (rs-fMRI) by measuring the similarity in connectivity profiles of subcortical voxels to cortical gray matter voxels.

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Objective: Traumatic brain injury results in diffuse axonal injury and the ensuing maladaptive alterations in network function are associated with incomplete recovery and persistent disability. Despite the importance of axonal injury as an endophenotype in TBI, there is no biomarker that can measure the aggregate and region-specific burden of axonal injury. Normative modeling is an emerging quantitative case-control technique that can capture region-specific and aggregate deviations in brain networks at the individual patient level.

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Objective: Evaluating patients with drug-resistant epilepsy often requires inducing seizures by tapering antiseizure medications (ASMs) in the epilepsy monitoring unit (EMU). The relationship between ASM taper strategy, seizure timing, and severity remains unclear. In this study, we developed and validated a pharmacokinetic model of total ASM load and tested its association with seizure occurrence and severity in the EMU.

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Background And Motivation: Functional gradients have been used to study differences in connectivity between healthy and diseased brain states, however this work has largely focused on the cortex. Because the subcortex plays a key role in seizure initiation in temporal lobe epilepsy (TLE), subcortical functional-connectivity gradients may help further elucidate differences between healthy brains and TLE, as well as differences between left (L)-TLE and right (R)-TLE.

Methods: In this work, we calculated subcortical functional-connectivity gradients (SFGs) from resting-state functional MRI (rs-fMRI) by measuring the similarity in connectivity profiles of subcortical voxels to cortical gray matter voxels.

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To determine the effect of implanting electrodes on electrographic features of nearby and connected brain regions in patients with drug-resistant epilepsy, we analyzed intracranial EEG recordings from 10 patients with drug-resistant epilepsy who underwent implant revision (placement of additional electrodes) during their hospitalization. We performed automated spike detection and measured EEG functional networks. We analyzed the original electrodes that remained in place throughout the full EEG recording, and we measured the change in spike rates and network connectivity in these original electrodes in response to implanting new electrodes.

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  • Researchers wanted to learn how sleep and seizures affect spikes in the brain to help plan surgery for people with epilepsy who don't respond to medicine.
  • They looked at data from 101 patients with epilepsy and found that spikes happen more often during sleep than when people are awake or after a seizure.
  • The study showed that using sleep-related changes in spike activity can help find where seizures start in the brain, which is important for doctors when planning surgery.
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Traumatic brain injury is a global public health problem associated with chronic neurological complications and long-term disability. Biomarkers that map onto the underlying brain pathology driving these complications are urgently needed to identify individuals at risk for poor recovery and to inform design of clinical trials of neuroprotective therapies. Neuroinflammation and neurodegeneration are two endophenotypes potentially associated with increases in brain extracellular water content, but the nature of extracellular free water abnormalities after neurotrauma and its relationship to measures typically thought to reflect traumatic axonal injury are not well characterized.

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Background And Purpose: Dysfunction of the blood-brain-barrier (BBB) is a recognized pathological consequence of traumatic brain injury (TBI) which may play an important role in chronic TBI pathophysiology. We hypothesized that BBB disruption can be detected with dynamic contrast-enhanced (DCE) MRI not only in association with focal traumatic lesions but also in normal-appearing brain tissue of TBI patients, reflecting microscopic microvascular injury. We further hypothesized that BBB integrity would improve but not completely normalize months after TBI.

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Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation.

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Background And Objectives: Epilepsy is defined by the occurrence of multiple unprovoked seizures, but quality of life (QOL) in people with epilepsy is determined by multiple factors, in which psychiatric comorbid conditions play a pivotal role. Therefore, understanding the interplay between comorbid conditions and QOL across epilepsy phenotypes is an important step toward improved outcomes. Here, we report the impact of QOL across distinct epilepsy phenotypes in a cohort of post-9/11 veterans with high rates of traumatic brain injury (TBI).

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Importance: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known.

Objective: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort.

Design, Setting, And Participants: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018.

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Background And Objectives: Late-onset epilepsy (LOE; i.e., epilepsy starting in later adulthood) affects a significant number of individuals.

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Understanding risk for epilepsy among persons who sustain a mild (mTBI) traumatic brain injury (TBI) is crucial for effective intervention and prevention. However, mTBI is frequently undocumented or poorly documented in health records. Further, health records are non-continuous, such as when persons move through health systems (e.

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