Modeling the Interictal Epileptic State for Therapeutic Development with Tetanus Toxin.

Focal forms of epilepsy can result from a wide range of insults and can vary from focal symptoms to generalized convulsions. Most drugs that have been developed for epilepsy focus on the prevention of seizures. On Electroencephalography (EEG), seizures are characterized by a repetitive buildup of epileptic waveforms that can spread across the brain. Brain regions that produce seizures generate far more frequent 'interictal' spikes seen between seizures, and in animal models, these spikes occur prior to the development of seizures. Interictal spiking by itself has been shown to have significant adverse clinical effects on cognition and behavior in both patients and animal models. While the exact relationships between interictal spiking and seizures are not well defined, interictal spikes serve as an important biomarker that, for some forms of epilepsy, can serve as a surrogate biomarker and as a druggable target. While there are many animal models of seizures for drug development, here we review models of interictal spiking, focusing on tetanus toxin, to study the relationship between interictal spiking, seizures, cognition, and behavior. Studies on human cortical regions with frequent interictal spiking have identified potential therapeutic targets; therefore, having a highly consistent model of spiking will be invaluable not only for unraveling the initial stages of the pathological cascade leading to seizure development but also for testing novel therapeutics. This review offers a succinct overview of the use of tetanus toxin animal models for studying and therapeutic development for interictal spiking.

Diffuse microglial responses and persistent EEG changes correlate with poor neurological outcome in a model of subarachnoid hemorrhage.

The mechanism by which subarachnoid hemorrhage (SAH) leads to chronic neurologic deficits is unclear. One possibility is that blood activates microglia to drive inflammation that leads to synaptic loss and impaired brain function. Using the endovascular perforation model of SAH in rats, we investigated short-term effects on microglia together with long-term effects on EEG and neurologic function for up to 3 months. Within the first week, microglia were increased both at the site of injury and diffusely across the cortex (2.5-fold increase in SAH compared to controls, p = 0.012). Concomitantly, EEGs from SAH animals showed focal increases in slow wave activity and diffuse reduction in fast activity. When expressed as a fast-slow spectral ratio, there were significant interactions between group and time (p < 0.001) with less ipsilateral recovery over time. EEG changes were most pronounced during the first week and correlated with neurobehavioral impairment. In vitro, the blood product hemin was sufficient to increase microglia phagocytosis nearly six-fold (p = 0.032). Immunomodulatory treatment with fingolimod after SAH reduced microglia, improved neurological function, and increased survival. These findings, which parallel many of the EEG changes seen in patients, suggest that targeting neuroinflammation could reduce long-term neurologic dysfunction following SAH.

Automated segmentation of ventricular volumes and subarachnoid hemorrhage from computed tomography images: Evaluation of a rule-based pipeline approach.

Changes in ventricular size, related to brain edema and hydrocephalus, as well as the extent of hemorrhage are associated with adverse outcomes in patients with subarachnoid hemorrhage (SAH). Frequently, these are measured manually using consecutive non-contrast computed tomography scans. Here, we developed a rule-based approach which incorporates both intensity and spatial normalization and utilizes user-defined thresholds and anatomical templates to segment both lateral ventricle (LV) and SAH blood volumes automatically from CT images. The algorithmic segmentations were evaluated against two expert neuroradiologists on representative slices from 20 admission scans from aneurysmal SAH patients. Previous methods have been developed to automate this time-consuming task, but they lack user feedback and are hard to implement due to large-scale data and complex design processes. Our results using automatic ventricular segmentation aligned well with expert reviewers with a median Dice coefficient of 0.81, AUC of 0.91, sensitivity of 81%, and precision of 84%. Automatic segmentation of SAH blood was most reliable near the base of the brain with a median Dice coefficient of 0.51, an AUC of 0.75, precision of 68%, and sensitivity of 50%. Ultimately, we developed a rule-based method that is easily adaptable through user feedback, generates spatially normalized segmentations that are comparable regardless of brain morphology or acquisition conditions, and automatically segments LV with good overall reliability and basal SAH blood with good precision. Our approach could benefit longitudinal studies in patients with SAH by streamlining assessment of edema and hydrocephalus progression, as well as blood resorption.

Spike-induced cytoarchitectonic changes in epileptic human cortex are reduced via MAP2K inhibition.

Interictal spikes are electroencephalographic discharges that occur at or near brain regions that produce epileptic seizures. While their role in generating seizures is not well understood, spikes have profound effects on cognition and behaviour, depending on where and when they occur. We previously demonstrated that spiking areas of human neocortex show sustained MAPK activation in superficial cortical Layers I-III and are associated with microlesions in deeper cortical areas characterized by reduced neuronal nuclear protein staining and increased microglial infiltration. Based on these findings, we chose to investigate additional neuronal populations within microlesions, specifically inhibitory interneurons. Additionally, we hypothesized that spiking would be sufficient to induce similar cytoarchitectonic changes within the rat cortex and that inhibition of MAPK signalling, using a MAP2K inhibitor, would not only inhibit spike formation but also reduce these cytoarchitectonic changes and improve behavioural outcomes. To test these hypotheses, we analysed tissue samples from 16 patients with intractable epilepsy who required cortical resections. We also utilized a tetanus toxin-induced animal model of interictal spiking, designed to produce spikes without seizures in male Sprague-Dawley rats. Rats were fitted with epidural electrodes, to permit EEG recording for the duration of the study, and automated algorithms were implemented to quantify spikes. After 6 months, animals were sacrificed to assess the effects of chronic spiking on cortical cytoarchitecture. Here, we show that microlesions may promote excitability due to a significant reduction of inhibitory neurons that could be responsible for promoting interictal spikes in superficial layers. Similarly, we found that the induction of epileptic spikes in the rat model produced analogous changes, including reduced neuronal nuclear protein, calbindin and parvalbumin-positive neurons and increased microglia, suggesting that spikes are sufficient for inducing these cytoarchitectonic changes in humans. Finally, we implicated MAPK signalling as a driving force producing these pathological changes. Using CI-1040 to inhibit MAP2K, both acutely and after spikes developed, resulting in fewer interictal spikes, reduced microglial activation and less inhibitory neuron loss. Treated animals had significantly fewer high-amplitude, short-duration spikes, which correlated with improved spatial memory performance on the Barnes maze. Together, our results provide evidence for a cytoarchitectonic pathogenesis underlying epileptic cortex, which can be ameliorated through both early and delayed MAP2K inhibition. These findings highlight the potential role for CI-1040 as a pharmacological treatment that could prevent the development of epileptic activity and reduce cognitive impairment in both patients with epilepsy and those with non-epileptic spike-associated neurobehavioural disorders.

Emerging roles of long non-coding RNAs in human epilepsy.

Genome-scale biological studies conducted in the post-genomic era have revealed that two-thirds of human genes do not encode proteins. Most functional non-coding RNA transcripts in humans are products of long non-coding RNA (lncRNA) genes, an abundant but still poorly understood class of human genes. As a result of their fundamental and multitasking regulatory roles, lncRNAs are associated with a wide range of human diseases, including neurological disorders. Approximately 40% of lncRNAs are specifically expressed in the brain, and many of them exhibit distinct spatiotemporal patterns of expression. Comparative genomics approaches have determined that 65%-75% of human lncRNA genes are primate-specific and hence can be posited as a contributing potential cause of the higher-order complexity of primates, including human, brains relative to those of other mammals. Although lncRNAs present important mechanistic examples of epileptogenic functions, the human/primate specificity of lncRNAs questions their relevance in rodent models. Here, we present an in-depth review that supports the contention that human lncRNAs are direct contributors to the etiology and pathogenesis of human epilepsy, as a means to accelerate the integration of lncRNAs into clinical practice as potential diagnostic biomarkers and therapeutic targets. Meta-analytically, the major finding of our review is the commonality of lncRNAs in epilepsy and cancer pathogenesis through mitogen-activated protein kinase (MAPK)-related pathways. In addition, neuroinflammation may be a relevant part of the common pathophysiology of cancer and epilepsy. LncRNAs affect neuroinflammation-related signaling pathways such as nuclear factor kappa- light- chain- enhancer of activated B cells (NF-κB), Notch, and phosphatidylinositol 3- kinase/ protein kinase B (Akt) (PI3K/AKT), with the NF-κB pathway being the most common. Besides the controversy over lncRNA research in non-primate models, whether neuroinflammation is triggered by injury and/or central nervous system (CNS) toxicity during epilepsy modeling in animals or is a direct consequence of epilepsy pathophysiology needs to be considered meticulously in future studies.

Prevention of Alzheimer Pathology by Blocking Neuregulin Signaling on Microglia.

Plaque formation, microglial activation, and synaptic loss are pathologic hallmarks of Alzheimer's disease; however, removing plaques has had little clinical benefit. Here, we show that neuregulin-1, a glial growth factor, induces inflammatory cytokines and promotes phagocytic activity in vitro and augments microglial activation and plaque formation in 5XFAD Alzheimer's mice. Brain-specific targeting of neuregulin-1 by intraventricular delivery of a novel neuregulin-1 fusion protein antagonist, GlyB4, significantly alters microglial morphology and function to a nonpathogenic morphology in early-stage 5XFAD mice and prevents plaques from forming. Once plaques have already formed, GlyB4 reduces new plaque formation and prevents synaptic loss. Selective, targeted disruption of neuregulin-1 signaling on brain microglia with GlyB4 could be a novel "upstream" approach to slow or stop disease progression in Alzheimer's disease.

INTUITION: a data platform to integrate human epilepsy clinical care and support for discovery.

To make appropriate clinical decisions, clinicians consider many types of data from multiple sources to arrive at a diagnosis and plan. However, the current health systems have siloed data, making it challenging to develop information platforms that integrate this process into a single place for comprehensive clinical evaluation and research. INTUITION is a human brain integrative data system that facilitates multimodal data integration, unified storage, cohort selection, and analysis of multidisciplinary datasets. In this article, we describe the use of INTUITION to include electronic health records together with co-registered neuroimaging and EEG from patients who undergo invasive brain surgery for epilepsy. In addition to providing clinically useful visualizations and analytics to help guide surgical planning, INTUITION also links a bank of human brain epileptic tissues from specific brain locations to quantitative EEG, imaging, histology, and omics studies in a unique, completely integrated informatics platform. Having a clinically useful platform for integrating multimodal datasets can not only aid in clinical management decisions but also in creating a unique resource for research and discovery when linked to spatially mapped tissue samples.

Lipidomics, Acute Ischemic Stroke, Symptoms, and Outcomes: Observational Study Protocol.

BACKGROUND: Acute ischemic stroke is one of the leading causes of death and disability globally. Recent advances in omics methodology enable lipidomic profiling, which may provide knowledge of the underlying pathology of acute ischemic stroke and its associated outcomes. OBJECTIVE: This study aims to examine the longer-term relationships between symptoms and outcomes following acute ischemic stroke and the underlying lipidomic signatures over 6 months during recovery between acute ischemic stroke patients who received reperfusion therapies and those who did not. METHODS: This prospective cohort study will enroll 104 participants post-acute ischemic stroke in two groups based on their receipt of reperfusion therapy (Group 1) or not (Group 2; n = 52/group). Peripheral plasma samples will be collected from both groups for lipidomic analysis over 6 months. Arterial blood samples will be collected during the procedure for those receiving reperfusion. Self-reported symptoms and outcome data will be collected from both groups. DISCUSSION: We will compare and examine the associations among plasma lipidomic biomarkers and symptoms and cognitive, functional, and health-related quality of life outcomes over 6 months between acute ischemic stroke patients who did and did not receive reperfusion intervention.

Activity-Dependent Non-Coding RNA MAPK Interactome of the Human Epileptic Brain.

The human brain has evolved to have extraordinary capabilities, enabling complex behaviors. The uniqueness of the human brain is increasingly posited to be due in part to the functions of primate-specific, including human-specific, long non-coding RNA (lncRNA) genes, systemically less conserved than protein-coding genes in evolution. Patients who have surgery for drug-resistant epilepsy are subjected to extensive electrical recordings of the brain tissue that is subsequently removed in order to treat their epilepsy. Precise localization of brain tissues with distinct electrical properties offers a rare opportunity to explore the effects of brain activity on gene expression. Here, we identified 231 co-regulated, activity-dependent lncRNAs within the human MAPK signaling cascade. Six lncRNAs, four of which were antisense to known protein-coding genes, were further examined because of their high expression and potential impact on the disease phenotype. Using a model of repeated depolarizations in human neuronal-like cells (Sh-SY5Y), we show that five out of six lncRNAs were electrical activity-dependent, with three of four antisense lncRNAs having reciprocal expression patterns relative to their protein-coding gene partners. Some were directly regulated by MAPK signaling, while others effectively downregulated the expression of the protein-coding genes encoded on the opposite strands of their genomic loci. These lncRNAs, therefore, likely contribute to highly evolved and primate-specific human brain regulatory functions that could be therapeutically modulated to treat epilepsy.

It's time to change our documentation philosophy: writing better neurology notes without the burnout.

Succinct clinical documentation is vital to effective twenty-first-century healthcare. Recent changes in outpatient and inpatient evaluation and management (E/M) guidelines have allowed neurology practices to make changes that reduce the documentation burden and enhance clinical note usability. Despite favorable changes in E/M guidelines, some neurology practices have not moved quickly to change their documentation philosophy. We argue in favor of changes in the design, structure, and implementation of clinical notes that make them shorter yet still information-rich. A move from physician-centric to team documentation can reduce work for physicians. Changing the documentation philosophy from "bigger is better" to "short but sweet" can reduce the documentation burden, streamline the writing and reading of clinical notes, and enhance their utility for medical decision-making, patient education, medical education, and clinical research. We believe that these changes can favorably affect physician well-being without adversely affecting reimbursement.

Automated sleep detection reveals differences in sleep patterns in an animal model of neocortical epilepsy.

Sleep in epilepsy is best studied in longitudinal preclinical animal models, where state changes can have significant effects on epileptic activities. Voluminous data makes it very difficult to mark sleep stages manually. This demands an automated way to detect sleep and wake states. We developed an approach to characterize sleep-wake states in continuous video-electroencephalography (EEG) recordings in animals. We compared brute force approach based on frequency band-power based thresholding with machine learning algorithms to detect sleep in 600 hours of EEG data from 4 epileptic and 2 control animals. We found that conventional delta and theta band-powers were prominent in sleep; however, this was not sufficient to detect sleep algorithmically. We therefore extracted a set of novel frequency bands to robustly differentiate individual sleep states by using brute-force algorithm and machine learning models, among which k-nearest neighbors (KNN) was the best predictor of sleep with 94% accuracy. We subsequently characterized sleep patterns in animals with chronically induced epileptic spiking in the neocortex from tetanus toxin injections using brute-force algorithm. We found that epileptic spiking animals (without seizures) sleep more frequently, with significantly longer sleep segments and overall daily sleep time, as compared to control animals. This automated algorithm could help expedite sleep studies and help us understand the relationship between sleep and patients with epilepsy.

Multi-modal data integration platform combining clinical and preclinical models of post subarachnoid hemorrhage epilepsy.

Subarachnoid hemorrhage (SAH) is a devastating neurological injury that can lead to many downstream complications including epilepsy. Predicting who will get epilepsy in order to find ways to prevent it as well as stratify patients for future interventions is a major challenge given the large number of variables not only related to the injury itself, but also to what happens after the injury. Extensive multimodal data are generated during the process of SAH patient care. In parallel, preclinical models are under development that attempt to imitate the variables observed in patients. Computational tools that consider all variables from both human data and animal models are lacking and demand an integrated, time-dependent platform where researchers can aggregate, store, visualize, analyze, and share the extensive integrated multimodal information. We developed a multi-tier web-based application that is secure, extensible, and adaptable to all available data modalities using flask micro-web framework, python, and PostgreSQL database. The system supports data visualization, data sharing and downloading for offline processing. The system is currently hosted inside the institutional private network and holds [Formula: see text] of data from 164 patients and 71 rodents. Clinical Relevance-Our platform supports clinical and preclinical data management. It allows users to comprehensively visualize patient data and perform visual analytics. These utilities can improve research and clinical practice for subarachnoid hemorrhage and other brain injuries.

Recruitment in a research study via chatbot versus telephone outreach: a randomized trial at a minority-serving institution.

Chatbots are software applications to simulate a conversation with a person. The effectiveness of chatbots in facilitating the recruitment of study participants in research, specifically among racial and ethnic minorities, is unknown. The objective of this study is to compare a chatbot versus telephone-based recruitment in enrolling research participants from a predominantly minority patient population at an urban institution. We randomly allocated adults to receive either chatbot or telephone-based outreach regarding a study about vaccine hesitancy. The primary outcome was the proportion of participants who provided consent to participate in the study. In 935 participants, the proportion who answered contact attempts was significantly lower in the chatbot versus telephone group (absolute difference -21.8%; 95% confidence interval [CI] -27.0%, -16.5%; P < 0.001). The consent rate was also significantly lower in the chatbot group (absolute difference -3.4%; 95% CI -5.7%, -1.1%; P = 0.004). However, among participants who answered a contact attempt, the difference in consent rates was not significant. In conclusion, the consent rate was lower with chatbot compared to telephone-based outreach. The difference in consent rates was due to a lower proportion of participants in the chatbot group who answered a contact attempt.

Highly consistent temporal lobe interictal spike networks revealed from foramen ovale electrodes.

OBJECTIVE: A major challenge that limits understanding and treatment of epileptic events from mesial temporal structures comes from our inability to detect and map interictal networks reproducibly using scalp electrodes. Here, we developed a novel approach to map interictal spike networks and demonstrate their relationships to seizure onset and lesions in patients with foramen ovale electrode implantations. METHODS: We applied the direct Directed Transfer Function to reveal interictal spike propagation from bilateral foramen ovale electrodes on 10 consecutive patients and co-registered spatially with both seizure onset zones and temporal lobe lesions. RESULTS: Highly reproducible, yet unique interictal spike networks were seen for each patient (correlation: 0.93 ±â€¯0.13). Interictal spikes spread in both anterior and posterior directions within each temporal lobe, often reverberating between sites. Spikes propagated to the opposite temporal lobe predominantly through posterior pathways. Patients with structural lesions (N = 4), including tumors and sclerosis, developed reproducible spike networks adjacent to their lesions that were highly lateralized compared to patients without lesions. Only 5% of mesial temporal lobe spikes were time-locked with scalp electrode spikes. Our preliminary observation on two lesional patients suggested that along with lesion location, Interictal spike networks also partially co-registered with seizure onset zones suggesting interrelationship between seizure onset and a subset of spike networks. CONCLUSIONS: This is the first demonstration of patient-specific, reproducible interictal spike networks in mesial temporal structures that are closely linked to both temporal lobe lesions and seizure onset zones. SIGNIFICANCE: Interictal spike connectivity is a novel approach to map epileptic networks that could help advance invasive and non-invasive epilepsy treatments.

Consensus Statement for the Management and Treatment of Sturge-Weber Syndrome: Neurology, Neuroimaging, and Ophthalmology Recommendations.

BACKGROUND: Sturge-Weber syndrome (SWS) is a sporadic, neurocutaneous syndrome involving the skin, brain, and eyes. Because of the variability of the clinical manifestations and the lack of prospective studies, consensus recommendations for management and treatment of SWS have not been published. OBJECTIVE: This article consolidates the current literature with expert opinion to make recommendations to guide the neuroimaging evaluation and the management of the neurological and ophthalmologic features of SWS. METHODS: Thirteen national peer-recognized experts in neurology, radiology, and ophthalmology with experience treating patients with SWS were assembled. Key topics and questions were formulated for each group and included (1) risk stratification, (2) indications for referral, and (3) optimum treatment strategies. An extensive PubMed search was performed of English language articles published in 2008 to 2018, as well as recent studies identified by the expert panel. The panel made clinical practice recommendations. CONCLUSIONS: Children with a high-risk facial port-wine birthmark (PWB) should be referred to a pediatric neurologist and a pediatric ophthalmologist for baseline evaluation and periodic follow-up. In newborns and infants with a high-risk PWB and no history of seizures or neurological symptoms, routine screening for brain involvement is not recommended, but brain imaging can be performed in select cases. Routine follow-up neuroimaging is not recommended in children with SWS and stable neurocognitive symptoms. The treatment of ophthalmologic complications, such as glaucoma, differs based on the age and clinical presentation of the patient. These recommendations will help facilitate coordinated care for patients with SWS and may improve patient outcomes.

Selective time-dependent changes in activity and cell-specific gene expression in human postmortem brain.

As a means to understand human neuropsychiatric disorders from human brain samples, we compared the transcription patterns and histological features of postmortem brain to fresh human neocortex isolated immediately following surgical removal. Compared to a number of neuropsychiatric disease-associated postmortem transcriptomes, the fresh human brain transcriptome had an entirely unique transcriptional pattern. To understand this difference, we measured genome-wide transcription as a function of time after fresh tissue removal to mimic the postmortem interval. Within a few hours, a selective reduction in the number of neuronal activity-dependent transcripts occurred with relative preservation of housekeeping genes commonly used as a reference for RNA normalization. Gene clustering indicated a rapid reduction in neuronal gene expression with a reciprocal time-dependent increase in astroglial and microglial gene expression that continued to increase for at least 24 h after tissue resection. Predicted transcriptional changes were confirmed histologically on the same tissue demonstrating that while neurons were degenerating, glial cells underwent an outgrowth of their processes. The rapid loss of neuronal genes and reciprocal expression of glial genes highlights highly dynamic transcriptional and cellular changes that occur during the postmortem interval. Understanding these time-dependent changes in gene expression in post mortem brain samples is critical for the interpretation of research studies on human brain disorders.

Modulation of locomotor behaviors by location-specific epileptic spiking and seizures.

INTRODUCTION: Epilepsy is a debilitating neurological condition characterized by spontaneous seizures as well as significant comorbid behavioral abnormalities. In addition to seizures, epileptic patients exhibit interictal spikes far more frequently than seizures, often, but not always observed in the same brain areas. The exact relationship between spiking and seizures as well as their respective effects on behavior are not well understood. In fact, spiking without overt seizures is seen in various psychiatric conditions including attention-deficit hyperactivity disorder. METHODS: In order to study the effects of spiking and seizures on behavior in an epileptic animal model, we used long-term video-electroencephalography recordings at six cortical recording sites together with behavioral activity monitoring. Animals received unilateral injections of tetanus toxin into either the somatosensory or motor cortex. RESULTS: Somatosensory cortex-injected animals developed progressive spiking ipsilateral to the injection site, while those receiving the injection into the motor cortex developed mostly contralateral spiking and spontaneous seizures. Animals with spiking but no seizures displayed a hyperactive phenotype, while animals with both spiking and seizures displayed a hypoactive phenotype. Not all spikes were equivalent as spike location strongly correlated with distinct locomotor behaviors including ambulatory distance, vertical movements, and rotatory movement. CONCLUSIONS: Together, our results demonstrate relationships between brain region-specific spiking, seizures, and behaviors in rodents that could translate into a better understanding for patients with epileptic behavioral comorbidities and other neuropsychiatric disorders.

Enhancing epilepsy self-management and quality of life for adults with epilepsy with varying social and educational backgrounds using PAUSE to Learn Your Epilepsy.

PURPOSE: People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. METHODS: Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8-12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. RESULTS: The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. CONCLUSION: This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.

Disease propagation in amyotrophic lateral sclerosis (ALS): an interplay between genetics and environment.

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease affecting the neuromuscular system. While there have been a number of important genetic discoveries, there are no therapeutics capable of stopping its insidious progression. Lessons from clinical histories reveal that ALS can start focally at a single limb, but then segmentally spread up and down the spinal cord as well as in the motor cortex and cortex of frontal and temporal lobes until respiratory muscles fail. With or without a clear genetic etiology, often there is no explanation as to why it starts in one region of the body versus another. Similarly, once the disease starts the mechanisms by which the neurodegenerative process spreads are not known. Here, we summarize recent work in animal models that support the hypothesis that critical environmental contributions, such as a nerve injury, can initiate the disease process. We also propose that pathological axoglial signaling by the glial growth factor neuregulin-1 leads to the slow propagation of neuroinflammation resulting in neurodegeneration up and down the spinal cord and that locally applied drugs that block neuregulin-1 signaling could slow or halt the spread of disease.

Unique Characteristics of Epilepsy Development in Neurocysticercosis.

The parasitic helminth infection neurocysticercosis (NCC) is the most common cause of adult-acquired epilepsy in the world. Despite the serious consequences of epilepsy due to this infection, an in-depth review of the distinct characteristics of epilepsy due to neurocysticercosis has never been conducted. In this review, we evaluate the relationship between NCC and epilepsy and the unique characteristics of epilepsy caused by NCC. We also discuss recent advances in our understanding of NCC-related epilepsy, including the importance of anti-inflammatory therapies, the association between NCC and temporal lobe epilepsy, and the recent discovery of biomarkers of severe epilepsy development in individuals with NCC and seizures.