Objective: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal-to-bilateral tonic-clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally.
View Article and Find Full Text PDFNeuromodulation has taken a foothold in the landscape of surgical treatment for medically refractory epilepsies and offers additional surgical treatment options for patients who are not candidates for resective/ablative surgery. Approximately one third of patients with epilepsy suffer with medication-refractory epilepsy. A persistent underuse of epilepsy surgery exists.
View Article and Find Full Text PDFObjective: Impairment in consciousness is a debilitating symptom during and after seizures; however, its mechanism remains unclear. Limbic seizures have been shown to spread to arousal circuitry to result in a "network inhibition" phenomenon. However, prior animal model studies did not relate physiological network changes to behavioral responses during or following seizures.
View Article and Find Full Text PDFFocal limbic seizures can cause loss of consciousness. Previous work suggests that hippocampal seizures can increase activity in the lateral septum (LS) and decrease cholinergic output from the basal forebrain (BF), leading to deficits in conscious arousal. The mechanism by which LS and BF interact is unclear.
View Article and Find Full Text PDFThe postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation.
View Article and Find Full Text PDFGigantism (early-onset acromegaly) is a rare pediatric disorder caused by a growth hormone (GH)-secreting pituitary adenoma. Approximately 50% patients of gigantism have a germline mutation, most commonly an inactivating mutation in the aryl-hydrocarbon interacting receptor protein (AIP) gene on chromosome 11q13.2.
View Article and Find Full Text PDFImportance: Seizures recur in as many as half of patients who undergo surgery for drug-resistant temporal lobe epilepsy (TLE). Understanding why TLE is resistant to surgery in some patients may reveal insights into epileptogenic networks and direct new therapies to improve outcomes.
Objective: To characterize features of surgically refractory TLE.
Seizures have traditionally been considered hypersynchronous excitatory events and epilepsy has been separated into focal and generalized epilepsy based largely on the spatial distribution of brain regions involved at seizure onset. Epilepsy, however, is increasingly recognized as a complex network disorder that may be distributed and dynamic. Responsive neurostimulation (RNS) is a recent technology that utilizes intracranial electroencephalography (EEG) to detect seizures and delivers stimulation to cortical and subcortical brain structures for seizure control.
View Article and Find Full Text PDFImpaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals.
View Article and Find Full Text PDFUnlabelled: Impaired breathing, cardiac function, and arousal during and after seizures are important causes of morbidity and mortality. Previous work suggests that these changes are associated with depressed brainstem function in the ictal and post-ictal periods. Lower brainstem serotonergic systems are postulated to play an important role in cardiorespiratory changes during and after seizures, whereas upper brainstem serotonergic and other systems regulate arousal.
View Article and Find Full Text PDFWe report a 41-year-old woman with a history of an uncomplicated spinal hemangioma resection, who developed acute onset sensory-motor polyneuropathy following influenza vaccine administration. With extensive workup she was diagnosed with POEMS syndrome with progressive headaches, visual loss with papilledema, and repeated elevated lumbar puncture opening pressures despite treatment with acetazolamide and immunosuppressive therapy. Her symptoms dramatically improved following ventriculoperitoneal shunt placement.
View Article and Find Full Text PDFWhen drug-resistant epilepsy is poorly localized or surgical resection is contraindicated, current neurostimulation strategies such as deep brain stimulation and vagal nerve stimulation can palliate the frequency or severity of seizures. However, despite medical and neuromodulatory therapy, a significant proportion of patients continue to experience disabling seizures that impair awareness, causing disability and risking injury or sudden unexplained death. We propose a novel strategy in which neuromodulation is used not only to reduce seizures but also to ameliorate impaired consciousness when the patient is in the ictal and postictal states.
View Article and Find Full Text PDFImpaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity.
View Article and Find Full Text PDFObjective: Understanding the neural mechanisms that support human consciousness is an important frontier in neuroscience and medicine. We previously developed a rodent model of temporal lobe seizures that recapitulates the human electroencephalography (EEG) signature of ictal and postictal neocortical slow waves associated with behavioral impairments in level of consciousness. The mechanism of slow-wave production in epilepsy may involve suppression of the subcortical arousal systems including the brainstem and intralaminar thalamic nuclei.
View Article and Find Full Text PDFA 64-year-old right-handed woman presented to an outside hospital with a 1-week history of weakness noted while walking. She reported bilateral weakness greater on the right, and several falls. She denied lower extremity numbness.
View Article and Find Full Text PDFHigh-frequency oscillations in the brain open a new window for studies of language development in humans. The objective of this study is to determine the spatiotemporal and frequency signatures of word processing in healthy children. Sixty healthy children aged 6-17 years were studied with a whole-cortex magnetoencephalography (MEG) system using a word recognition paradigm optimized for children.
View Article and Find Full Text PDFPeriventricular leukomalacia, PVL, is the leading cause of cerebral palsy in prematurely born infants, and therefore more effective interventions are required. The objective of this study was to develop an ischemic injury model of PVL in mice and to determine the feasibility of in vivo magnetization transfer (MT) magnetic resonance imaging (MRI) as a potential monitoring tool for the evaluation of disease severity and experimental therapeutics. Neonatal CD-1 mice underwent unilateral carotid artery ligation on postnatal day 5 (P5); at P60, in vivo T2-weighted (T2w) and MT-MRI were performed and correlated with postmortem histopathology.
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