•Epilepsy surgery is an effective and safe treatment for drug-resistant epilepsy.•It remains one of the most underutilized treatments in modern medicine.•Underutilization of epilepsy surgery may have ...patient and/or health system components.•Misconception about epilepsy surgery is prevalent among patients and providers.•Other barriers include inadequate access and complex presurgical evaluations.
One-third of persons with epilepsy have seizures despite appropriate medical therapy. Drug resistant epilepsy (DRE) is associated with neurocognitive and psychological decline, poor quality of life, increased risk of premature death, and greater economic burden. Epilepsy surgery is an effective and safe treatment for a subset of people with DRE but remains one of the most underutilized evidence-based treatments in modern medicine. The reasons for this quality gap are insufficiently understood. In this comprehensive review, we compile known significant barriers to epilepsy surgery, originating from both patient/family-related factors and physician/health system components. Important patient-related factors include individual and epilepsy characteristics which bias towards continued preferential use of poorly effective medications, as well as patient perspectives and misconceptions of surgical risks and benefits. Health system and physician-related barriers include demonstrable knowledge gaps among physicians, inadequate access to comprehensive epilepsy centers, complex presurgical evaluations, insufficient research, and socioeconomic bias when choosing appropriate surgical candidates
Despite a large number of available medical options, many individuals with epilepsy are refractory to existing therapies that mainly target neurotransmitter or ion channel activity. A growing body of ...preclinical data has uncovered a molecular pathway that appears crucial in many genetic and acquired epilepsy syndromes. The mammalian target of rapamycin (mTOR) pathway regulates a number of cellular processes required in the growth, metabolism, structure, and cell-cell interactions of neurons and glia. Rapamycin and similar compounds inhibit mTOR complex 1 and decrease seizures, delay seizure development, or prevent epileptogenesis in many animal models of mTOR hyperactivation. However, the exact mechanisms by which mTOR inhibition drives decreased seizure activity have not been completely determined. Nonetheless, these preclinical data have led to limited use in humans with epilepsy due to tuberous sclerosis complex and polyhydramnios, megalencephaly, and symptomatic epilepsy with promising results. Currently, larger controlled studies are underway using mTOR inhibitors in individuals with tuberous sclerosis complex and intractable epilepsy.
Adam P. Ostendorf , Satyanarayana Gedela Seminars in Pediatric Neurology Volume 24, Issue 4, November 2017, Pages 340-347 The effect of epilepsy extends beyond those with the diagnosis and impacts ...families, communities and society. Caregiver and sibling quality of life is often negatively affected by frequent seizures, comorbid behavioral and sleep disorders and stigma surrounding the diagnosis. Furthermore, the negative effects can be magnified by individual coping styles and resources available to families of those with epilepsy. Beyond the family and immediate caregivers, epilepsy affects local communities by drawing additional resources from education systems. The direct costs of caring for an individual with epilepsy and the indirect costs associated with decreased productivity place financial strain on individuals and health care systems throughout the world. This review details factors affecting family and caregiver quality of life and provides several approaches through which health care providers may address these concerns. Furthermore, we examine the financial effect of epilepsy on society and review emerging strategies to lessen health care use for individuals with epilepsy.
Deep brain stimulation of the centromedian nucleus of the thalamus (CMN) to treat drug-resistant epilepsy has been of interest for decades. However, little is known about the electrophysiological ...activity of the CMN during seizures. We describe a novel CMN EEG finding associated with seizure: post-ictal rhythmic thalamic activity.
Five patients with drug-resistant epilepsy of unknown etiology with focal onset seizures underwent stereoelectroencephalography monitoring as part of evaluation for potential resective surgery or neuromodulation. Two patients had previously undergone complete corpus callosotomy and vagus nerve stimulation. A standardized plan for implantation included targets in the bilateral CMN.
Each patient had frontal onset seizures, and two patients had additional insular, parietal, or mesial temporal onset seizures. Contacts of CMN were involved synchronously or rapidly after onset in most recorded seizures, particularly those with frontal onset. Focal onset hemiclonic and bilateral tonic-clonic seizures spread to involve cortical contacts with high-amplitude rhythmic spiking followed by abrupt offset with diffuse voltage attenuation. A post-ictal rhythmic 1.5 to 2.5 Hz delta frequency pattern, post-ictal rhythmic thalamic activity, emerged in CMN contacts amid the suppression of background activity in cortical contacts. In the two patients with corpus callosotomy, unilateral seizure spread and ipsilateral post-ictal rhythmic thalamic activity were observed.
We observed post-ictal rhythmic thalamic activity in five patients with stereoelectroencephalography monitoring of the CMN with convulsive seizures. This rhythm appears late in ictal evolution and may signal an important role of the CMN in seizure termination. Furthermore, this rhythm may help identify CMN involvement in the epileptic network.
•Prolonged seizures are associated with worse neurological outcomes.•As seizures continue, cellular changes may occur which drive treatment resistance.•Better data regarding medication optimization ...and novel therapies are needed.•Delayed treatment and use of incorrectly dosed medication are currently prevalent.•The time to treatment gap can be addressed with quality improvement methodologies.
Describe basic science, animal models and clinical data related to timing of treatment in status epilepticus (SE).
We summarized the results of 15 studies that reported time to treatment in SE, and reviewed basic and clinical literature.
SE is a life-threatening and time-sensitive emergency that requires immediate treatment. Current guidelines recommend escalation of anti-seizure medications (ASM) within specified time frames. Prolonged seizures may lead to changes in the composition and location of gamma-aminobutyric acid A receptors (GABAAR) and N-Methyl-d-aspartic acid receptors (NMDAR), leading to loss of inhibition and increased excitation. These biochemical changes are apparent in specific animal models having progressive resistance to benzodiazepines (BZD) with longer seizures.
Later treatments lead to decreased response to BZD, longer seizures, greater need of continuous infusions, potential brain injury and increased in-hospital mortality. Despite mounting evidence that early treatment of SE is more effective and safer, treatment and ASM escalation is often delayed compared to protocols. Literature review of 2212 patients with SE showed an average time to treatment of 42.4 min and time to hospital arrival of 56 min. Also, only 51.8% of patients received treatment by emergency medical services and 12.8% by their families, including patients with a previous diagnosis of epilepsy or with prior SE.
Morbidity and mortality may be avoided with rapid, effective treatment of SE. Treatment application and escalation remains delayed especially in outpatient settings, potentially leading to suboptimal outcomes. Implementation techniques and quality improvement methodologies may provide avenues for improving outcomes in SE.
Lennox-Gastaut syndrome is a severe, childhood-onset electroclinical syndrome comprised of multiple seizure types, intellectual and behavioral disturbances and characteristic findings on ...electroencephalogram of slow spike and wave complexes and paroxysmal fast frequency activity. Profound morbidity often accompanies a common and severe seizure type, the drop attack. Seizures often remain refractory, or initial treatment efficacy fades. Few individuals are seizure free despite the development of multiple generations of antiseizure medications over decades and high-level evidence on several choices. Approved medications such as lamotrigine, topiramate, rufinamide, felbamate and clobazam have demonstrated efficacy in reducing seizure burden. Cannabidiol has emerged as a promising investigational therapy with vast social interest yet lacks a standard, approved formulation. Palliative surgical procedures, such as vagal nerve stimulation and corpus callosotomy may provide reduction in total seizures and drop attacks. Emerging evidence suggests that complete callosotomy provides greater improvement in seizures without additional side effects. Etiologies such as dysplasia or hypothalamic hamartoma may be amenable for focal resection and thus offer potential to reverse this devastating epileptic encephalopathy.
To determine the clinical and electroencephalographic findings associated with prognosis in nonneonate children following cardiac arrest.
Retrospective observational study.
PICU and cardiac ICU.
...Nonneonate children with a history of cardiac arrest more than 2 minutes.
Electroencephalographic monitoring within 72 hours of return of spontaneous circulation.
Clinical and features, neurophysiologic data, and Pediatric Cerebral Performance Category scores were collected. Electroencephalographic traces were reviewed in a blinded manner, all seizures and electroencephalographic findings noted, and the electroencephalography was scored at 1 hour, 24 hours, and continuous electroencephalographic end. Discrete data regarding specific characteristics of the electroencephalographic background and seizures were studied. Univariate and multivariate analyses were performed to identify associations between clinical variables, electroencephalographic findings, and Pediatric Cerebral Performance Category score at hospital discharge. Multivariate analysis of 73 children revealed duration of cardiac arrest less than 20 minutes or continuous electroencephalographic background activity within 12 hours postreturn of spontaneous circulation were associated with good short term neurologic outcome. Change in electroencephalographic background score over time and electroencephalographic data collected after the initial hour were not associated with outcome.
Following pediatric cardiac arrest, an initially normal electroencephalography or generalized slowing of the electroencephalographic background was associated with good neurologic outcome at hospital discharge.
•This is the first study describing swallowing outcomes following corpus callosotomy surgery in young people.•Following corpus callosotomy surgery, swallowing issues were uncommon and ...transient.•Children and adolescents are likely to be advanced to a regular diet with thin liquids once post-surgery lethargy resolves.•A referral to the appropriate professional (e.g., speech pathologist) can assist the medical team in determining safe oral feeding strategies as needed.
Determine swallowing outcomes following corpus callosotomy (CC) surgery.
Retrospective chart review of patients undergoing CC between July 2016 and November 2018 at a large, urban children’s hospital.
Of the 18 patients without prior history of dysphagia who underwent CC, 15 received speech pathology consults for bedside swallowing evaluation (BSE). Four patients were referred for a videofluroscopic swallow study (VFSS), and 3 showed no signs of difficulty and were advanced to regular diets with thin liquids. One patient demonstrated swallowing difficulties during the VFSS and was placed on a regular diet with nectar thick liquids. Following a repeat swallow study 17 days post-surgery, the patient was advanced to thin liquids.
Postoperative dysphagia following CC is an uncommon and transient complication. Patients undergoing CC should have their swallowing evaluated prior to advancing their postoperative diet but are likely to return to normal diet and thin liquids by discharge.
Pediatric epilepsy surgery is underutilized. Only 1%-11% of children with drug resistant epilepsy (DRE) undergo surgical treatment, or less than half of those estimated to benefit. We conducted a ...systematic review of articles published in PubMed, EMBASE, and Web of Science in order to study the factors related to surgery underutilization as well as the impact on both the individual and the healthcare system. Our review demonstrates multiple factors leading to underutilization, including family misconceptions about epilepsy surgery, lack of provider knowledge, as well as systemic health disparities. While the upfront cost of epilepsy surgery is significant, the long-term financial benefits and reduced health resource utilization tilt the economic advantage in favor of surgery in children with DRE. Additionally, timely interventions improve seizure and cognitive outcomes with low risk of complications. Further interventions are needed at the levels of family, provider, and the healthcare system to increase access to pediatric epilepsy surgery.
Rapid, effective treatment for status epilepticus reduces associated morbidity and mortality, yet medication delivery remains slow in many hospitalized patients. We utilized quality improvement (QI) ...methodology to improve treatment times for hospitalized children with status epilepticus. We hypothesized rapid initial seizure treatment would decrease seizure morbidity.
We utilized QI and statistical process control analysis in a nonintensive care setting within a tertiary care pediatric hospital. We performed Plan-Do-Study-Act cycles including (1) revising the nursing process for responding to seizures, (2) emphasizing intranasal midazolam over intravenous lorazepam, (3) relocating medications and supplies, (4) developing documentation tools and reinforcing correct processes, (5) developing and disseminating an online education module for residents and nurse practitioners, and (6) completing standardization to intranasal midazolam.
Seventeen months after starting the project, 66 seizures had been treated with a benzodiazepine in a median (p25-p75) time of 7.5 minutes (5 to 10), decreased from a baseline of 14 minutes (8-30) (P = 0.01). The proportion of patients receiving a benzodiazepine in 10 minutes or less improved from 39% to 79%. The proportion of patients transferred to intensive care decreased from a baseline of 39% to 9% (P < 0.005), resulting in an estimated $2.1 million in mitigated hospital charges. Significant harm did not occur during the implementation of these interventions.
Children with status epilepticus were treated with benzodiazepines more rapidly and effectively following implementation of QI methodology. These interventions reduced utilization of critical care and mitigated hospital charges.
PDF
