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Carl E. Stafstrom. Don’t Get BUM’d Out: Bumetanide May yet Prove Beneficial for Neonatal Seizures. Epilepsy Currents 2021, 1 .
AMA StyleCarl E. Stafstrom. Don’t Get BUM’d Out: Bumetanide May yet Prove Beneficial for Neonatal Seizures. Epilepsy Currents. 2021; ():1.
Chicago/Turabian StyleCarl E. Stafstrom. 2021. "Don’t Get BUM’d Out: Bumetanide May yet Prove Beneficial for Neonatal Seizures." Epilepsy Currents , no. : 1.
Neocortical Slow Oscillations Implicated in the Generation of Epileptic Spasms Lee CH, Le JT, Ballester-Rosado CJ, et al. Ann Neurol [published online ahead of print, Oct ober17, 2020]. 2020;89(2);10.1002/ana.25935. doi:10.1002/ana.25935 Epileptic spasms are a hallmark of severe seizure disorders. The neurophysiological mechanisms and the neuronal circuit(s) that generate these seizures are unresolved and are the focus of studies reported here. In the tetrodotoxin model, we used 16-channel microarrays and microwires to record electrophysiological activity in neocortex and thalamus during spasms. Chemogenetic activation was used to examine the role of neocortical pyramidal cells in generating spasms. Comparisons were made to recordings from infantile spasm patients. Current source density and simultaneous multiunit activity analyses indicate that the ictal events of spasms are initiated in infragranular cortical layers. A dramatic pause of neuronal activity was recorded immediately prior to the onset of spasms. This preictal pause is shown to share many features with the down states of slow-wave sleep. In addition, the ensuing interictal up states of slow-wave rhythms are more intense in epileptic than control animals and occasionally appear sufficient to initiate spasms. Chemogenetic activation of neocortical pyramidal cells supported these observations, as it increased slow oscillations and spasm numbers and clustering. Recordings also revealed a ramp-up in the number of neocortical slow oscillations preceding spasms, which was also observed in infantile spasm patients. Our findings provide evidence that epileptic spasms can arise from the neocortex and reveal a previously unappreciated interplay between brain state physiology and spasm generation. The identification of neocortical up states as a mechanism capable of initiating epileptic spasms will likely provide new targets for interventional therapies.
Carl E. Stafstrom. Using the TTX Model to Better Understand the Pathophysiology of a DREADDed Epilepsy—Infantile (Epileptic) Spasms. Epilepsy Currents 2021, 21, 129 -131.
AMA StyleCarl E. Stafstrom. Using the TTX Model to Better Understand the Pathophysiology of a DREADDed Epilepsy—Infantile (Epileptic) Spasms. Epilepsy Currents. 2021; 21 (2):129-131.
Chicago/Turabian StyleCarl E. Stafstrom. 2021. "Using the TTX Model to Better Understand the Pathophysiology of a DREADDed Epilepsy—Infantile (Epileptic) Spasms." Epilepsy Currents 21, no. 2: 129-131.
The diagnosis of childhood absence epilepsy (CAE) is typically based on history and description of spells, supported by an office-based positive hyperventilation test and confirmed by routine electroencephalography (EEG). In the current coronavirus disease 2019 (COVID-19) pandemic, many pediatric neurologists have switched to telemedicine visits for nonemergent outpatient evaluations. We present a series of children diagnosed as having CAE on the basis of a positive hyperventilation test performed during remote televisits. Several of these children were begun on treatment for CAE prior to obtaining an EEG, with significant seizure reduction. Our series documents the feasibility of CAE diagnosis and management by telemedicine.
Carl E. Stafstrom; Lisa R. Sun; Eric H. Kossoff; Ania K. Dabrowski; Samata Singhi; Sarah A. Kelley. Diagnosing and managing childhood absence epilepsy by telemedicine. Epilepsy & Behavior 2020, 115, 107404 .
AMA StyleCarl E. Stafstrom, Lisa R. Sun, Eric H. Kossoff, Ania K. Dabrowski, Samata Singhi, Sarah A. Kelley. Diagnosing and managing childhood absence epilepsy by telemedicine. Epilepsy & Behavior. 2020; 115 ():107404.
Chicago/Turabian StyleCarl E. Stafstrom; Lisa R. Sun; Eric H. Kossoff; Ania K. Dabrowski; Samata Singhi; Sarah A. Kelley. 2020. "Diagnosing and managing childhood absence epilepsy by telemedicine." Epilepsy & Behavior 115, no. : 107404.
Treatment of pediatric status epilepticus (SE) remains challenging as up to 50 % of patients are refractory to conventional anti-seizure medications. The glycolytic intermediate, fructose-1,6-bisphosphate (FBP), has been reported to exert significant anticonvulsant effects in both adult animals and in in vitro models of seizures. This study aims to examine FBP efficacy in controlling seizures in a rat model of juvenile SE. Sprague Dawley rats (P11-P17) were injected with pilocarpine (300 mg/kg, i.p.) to induce SE, which was monitored by video-electroencephalography (v-EEG). Thirty minutes into SE, FBP was administrated (500 or 1000 mg/kg, i.p.). v-EEG recording was continued for ∼60 additional minutes to assess the anticonvulsant effect of FBP, compared with vehicle (saline) treatment. SE consistently occurred in rat pups 10−15 min after pilocarpine injection and persisted over the 90-min recording period. Neither saline nor a lower dose of FBP (500 mg/kg) treatment stopped behavioral and electrographic seizures. At higher doses (1000 mg/kg), FBP terminated SE in ∼15 min in 60 % (6 of 10) of the rat pups. The endogenous glycolytic metabolite, FBP, promptly suppresses ongoing seizure activity and represents a potential alternative metabolic therapy to improve the treatment of SE in the juvenile age range.
Remi Janicot; Carl E. Stafstrom; Li-Rong Shao. The efficacy of fructose-1,6-bisphosphate in suppressing status epilepticus in developing rats. Epilepsy Research 2020, 168, 106500 .
AMA StyleRemi Janicot, Carl E. Stafstrom, Li-Rong Shao. The efficacy of fructose-1,6-bisphosphate in suppressing status epilepticus in developing rats. Epilepsy Research. 2020; 168 ():106500.
Chicago/Turabian StyleRemi Janicot; Carl E. Stafstrom; Li-Rong Shao. 2020. "The efficacy of fructose-1,6-bisphosphate in suppressing status epilepticus in developing rats." Epilepsy Research 168, no. : 106500.
Carl E. Stafstrom. Mechanism-Based Treatment for Neonatal Seizures: Still on the Horizon. Epilepsy Currents 2020, 20, 53S -55S.
AMA StyleCarl E. Stafstrom. Mechanism-Based Treatment for Neonatal Seizures: Still on the Horizon. Epilepsy Currents. 2020; 20 (6_suppl):53S-55S.
Chicago/Turabian StyleCarl E. Stafstrom. 2020. "Mechanism-Based Treatment for Neonatal Seizures: Still on the Horizon." Epilepsy Currents 20, no. 6_suppl: 53S-55S.
Potassium Channel Dysfunction in Human Neuronal Models of Angelman Syndrome Sun AX, Yuan Q, Fukuda M, Yu W, Yan H, Lim GGY, Nai MH, D’Agostino GA, Tran H-D, Itahana Y, Wang D, Lokman H, Itahana K, Lim SWL, Tang J, Chang YY, Zhang M, Cook SA, Rackham OJL, Lim CT, Tan EK, Ng HH, Lim KL, Jiang Y-H, Je HS. Science. 2019;366(6472):1486-1492. doi: 10.1126/science.aav5386 Disruptions in the ubiquitin protein ligase E3A (UBE3A) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium and voltage-dependent big potassium (BK) channels. We provide evidence that augmented BK channel activity manifests as increased intrinsic excitability in individual neurons and subsequent network synchronization. Big potassium antagonists normalized neuronal excitability in both human and mouse neurons and ameliorated seizure susceptibility in an AS mouse model. Our findings suggest that BK channelopathy underlies epilepsy in AS and support the use of human cells to model human developmental diseases.
Carl E. Stafstrom. How Many Angels Can Dance on the Head of a Patch Pipette? Understanding Neuronal Hyperexcitability in Angelman Syndrome. Epilepsy Currents 2020, 20, 309 -311.
AMA StyleCarl E. Stafstrom. How Many Angels Can Dance on the Head of a Patch Pipette? Understanding Neuronal Hyperexcitability in Angelman Syndrome. Epilepsy Currents. 2020; 20 (5):309-311.
Chicago/Turabian StyleCarl E. Stafstrom. 2020. "How Many Angels Can Dance on the Head of a Patch Pipette? Understanding Neuronal Hyperexcitability in Angelman Syndrome." Epilepsy Currents 20, no. 5: 309-311.
The ongoing worldwide pandemic of the novel human coronavirus SARS-CoV-2 and the ensuing disease, COVID-19, has presented enormous and unprecedented challenges for all medical specialists. However, to date, children, especially neonates, have been relatively spared from the devastating consequences of this infection. Neurologic involvement is being increasingly recognized among adults with COVID-19, who can develop sensory deficits in smell and taste, delirium, encephalopathy, headaches, strokes, and peripheral nervous system disorders. Among neonates and children, COVID-19-associated neurological manifestations have been relatively rare, yet reports involving neurologic dysfunction in this age range are increasing. As discussed in this review, pediatric neurologists and other pediatric specialists should be alert to potential neurological involvement by this virus, which might have neuroinvasive capability and carry long-term neuropsychiatric and medical consequences.
Carl E. Stafstrom; Lauren L. Jantzie. COVID-19: Neurological Considerations in Neonates and Children. Children 2020, 7, 133 .
AMA StyleCarl E. Stafstrom, Lauren L. Jantzie. COVID-19: Neurological Considerations in Neonates and Children. Children. 2020; 7 (9):133.
Chicago/Turabian StyleCarl E. Stafstrom; Lauren L. Jantzie. 2020. "COVID-19: Neurological Considerations in Neonates and Children." Children 7, no. 9: 133.
Objective Neonatal status epilepticus (SE) is a life‐threatening medical emergency. Unfortunately, up to 50% of neonates with SE are resistant to current antiseizure drugs, highlighting the need for better treatments. This study aims to explore a novel metabolic approach as a potential alternative treatment to control neonatal SE, using the glycolytic inhibitor 2‐deoxyglucose (2‐DG). Methods SE was induced by pilocarpine (300 mg/kg, intraperitoneally [ip]) in neonatal Sprague Dawley rats (postnatal day 10 [P10]‐P17) and was monitored by video‐electroencephalography (V‐EEG). After 30 minutes of SE, 2‐DG or one of two conventional antiseizure drugs with different mechanisms of action, phenobarbital or levetiracetam, was administrated ip, and V‐EEG recording was continued for ~60 additional minutes. The time to seizure cessation after drug injection, EEG scores, and power spectra before and after drug or saline treatment were used to assess drug effects. Results Once SE became sustained, administration of 2‐DG (50, 100, or 500 mg/kg, ip) consistently stopped behavioral and electrographic seizures within 10‐15 minutes; lower doses took longer (25‐30 minutes) to stop SE, demonstrating a dose‐dependent effect. Administration of phenobarbital (30 mg/kg, ip) or levetiracetam (100 mg/kg, ip) also stopped SE within 10‐15 minutes in neonatal rats. Significance Our results suggest that the glycolysis inhibitor 2‐DG acts quickly to reduce neuronal hyperexcitability and effectively suppress ongoing seizure activity, which may provide translational value in the treatment of neonatal SE.
Remi Janicot; Carl E. Stafstrom; Li‐Rong Shao. 2‐Deoxyglucose terminates pilocarpine‐induced status epilepticus in neonatal rats. Epilepsia 2020, 61, 1 .
AMA StyleRemi Janicot, Carl E. Stafstrom, Li‐Rong Shao. 2‐Deoxyglucose terminates pilocarpine‐induced status epilepticus in neonatal rats. Epilepsia. 2020; 61 (7):1.
Chicago/Turabian StyleRemi Janicot; Carl E. Stafstrom; Li‐Rong Shao. 2020. "2‐Deoxyglucose terminates pilocarpine‐induced status epilepticus in neonatal rats." Epilepsia 61, no. 7: 1.
The book is entitled “Pediatrics: A Case-Based Review” Michaela Kreckmann, MD, Thieme Publishers, 2019. ISBN 978–3132053618. This case-based review manual provides a series of 85 cases of common and uncommon pediatric disorders, presented in an interactive fashion to mimic the situation in actual practice, be it the emergency department or outpatient clinic. The cases cover the entire breadth of pediatrics, forming a useful learning tool for learners exploring the field of pediatrics or preparing for board examinations. The cases are realistic and incorporate challenges unique to pediatrics such as health policy considerations affecting children, counseling families about management options and prognosis, and inclusion of disorders spanning the pediatric age range from neonates to adolescents. The book's format fosters critical thinking by emphasizing patterns of symptoms, encouraging the reader to work through the history and examination before formulating a differential diagnosis and treatment plan. The author frames each case by providing a brief history, then guides the reader through a set of directed questions that comprise both immediate next steps and long-term options. Each case is supplemented by a “Comments” section that highlights relevant information including etiology, pathogenesis, treatment, and prognosis. Of the 85 cases, only two are directly related to epilepsy, with another 10 or so dealing with other neurologic conditions (e.g., concussion, gait abnormalities, nervous system tumors, behavioral problems). One case describes a toddler with new-onset seizure in the context of fever, with the diagnosis of simple febrile seizure. While the ensuing discussion adequately outlines some of the basic issues of febrile seizure diagnosis and management, unfortunately, several misconceptions and even erroneous statements are made. First of all, hospital admission is suggested, even for a brief simple febrile seizure. Current practice, at least in the United States, is not to admit routine cases where there is no concern for meningitis or other acute neurologic process. The author also recommends laboratory work up for all cases, including a complete blood count, which is defensible, but also sedimentation rate, blood gas analysis, and blood cultures! While these extra tests may be appropriate in some situations, most do not necessitate that extreme. The author does not clarify which children should receive an extensive work up (including electroencephalogram) and which should not. Finally, the criteria for simple febrile seizures rightly include a duration of less than 15 minutes and generalized onset, but the equally valid criterion of a single seizure within that fever is not mentioned. The author recommends treating subsequent fevers aggressively with antipyretics, not cautioning that this protocol is not based on evidence. Finally, she erroneously states that 3 to 4% of children with febrile seizures go on to develop epilepsy, not distinguishing subgroups at lesser or greater risk. It would have been optimal to also provide information as to when a febrile seizure does not have a benign prognosis but rather portends a subsequent epilepsy syndrome such as Dravet syndrome. The second case relevant to epilepsy involved a teenage girl who lost consciousness and collapsed during a school trip. A witness described a cry, followed by facial cyanosis, fall, and tonic-clonic movements of all extremities. The author provides a reasonable differential diagnosis, concluding that the girl suffered a “grand mal” convulsion (an outdated term but certainly still used by the lay public; the author's discussion also mentions “petit mal” seizures). The recommended work up included hospital admission (appropriate) and extensive laboratory evaluation including prolactin level (inappropriate!). Otherwise, the author provides a sensible approach to the work up and management, but then, inexplicably, states that a blood and urine toxicologic examination in such a case is “not generally recommended” (in fact, that is among the most important tests in a case like this!). If it is concluded that a child requires prophylactic seizure prevention, the author suggests treatment options include carbamazepine, valproate, or phenobarbital, but there is no mention of the dozens of antiseizure medicines developed in the past two decades that are most widely prescribed in this era. While trying to not be too critical of the author's understanding of current epilepsy nomenclature, evaluation, and treatment (she is a general pediatrician), these writings nevertheless exemplify the tremendous amount of misinformation promulgated by resources being marketed to the primary health care provider. Fortunately, in many areas of the world, specialty care is available to most accurately provide diagnosis, management, and counseling of children with seizures and epilepsy.
Barbara A. Dietrick; Carl E. Stafstrom. Pediatrics: A Case-Based Review. Journal of Pediatric Epilepsy 2020, 9, 055 -056.
AMA StyleBarbara A. Dietrick, Carl E. Stafstrom. Pediatrics: A Case-Based Review. Journal of Pediatric Epilepsy. 2020; 9 (2):055-056.
Chicago/Turabian StyleBarbara A. Dietrick; Carl E. Stafstrom. 2020. "Pediatrics: A Case-Based Review." Journal of Pediatric Epilepsy 9, no. 2: 055-056.
Segregation of Seizures and Spreading Depolarization Across Cortical Layers Zakharov A, Chernova K, Burkhanova G, Holmes GL, Khazipov R. Epilepsia. 2019;60(12):2386-2397. doi:10.1111/epi.16390. Cortical spreading depolarization (SD) and seizures are often co-occurring electrophysiological phenomena. However, the cross-layer dynamics of SD during seizures and the effect of SD on epileptic activity across cortical layers remain largely unknown. We explored the spatial–temporal dynamics of SD and epileptic activity across layers of the rat barrel cortex using direct current silicone probe recordings during flurothyl-induced seizures. Spreading depolarization occurred in half of the flurothyl-evoked seizures. Spreading depolarization always started from the superficial layers and spread downward either through all cortical layers or stopping at the L4/L5 border. In cases without SD, seizures were characterized by synchronized population firing across all cortical layers throughout the entire seizure. However, when SD occurred, epileptic activity was transiently silenced in layers involved with SD but persisted in deeper layers. During partial SD, epileptiform activity persisted in deep layers throughout the entire seizure, with positive signals at the cortical surface reflecting passive sources of population spikes generated in deeper cortical layers. During full SD, the initial phase of SD propagation through the superficial layers was similar to partial SD, with suppression of activity at the superficial layers and segregation of seizures to deep layers. Further propagation of SD to deep layers resulted in a wave of transient suppression of epileptic activity through the entire cortical column. Thus, vertical propagation of SD through the cortical column creates dynamic network states during which epileptiform activity is restricted to layers without SD. Our results point to the importance of vertical SD spread in the SD-related depression of epileptiform activity across cortical layers.
Carl E. Stafstrom. Stopped At the Border: Cortical Spreading Depolarization Blocks Seizure Propagation. Epilepsy Currents 2020, 20, 171 -172.
AMA StyleCarl E. Stafstrom. Stopped At the Border: Cortical Spreading Depolarization Blocks Seizure Propagation. Epilepsy Currents. 2020; 20 (3):171-172.
Chicago/Turabian StyleCarl E. Stafstrom. 2020. "Stopped At the Border: Cortical Spreading Depolarization Blocks Seizure Propagation." Epilepsy Currents 20, no. 3: 171-172.
Arzimanoglou A, O'Hare A, Johnston MV, Ouvrier R, eds. Aicardi's Diseases of the Nervous System in Childhood. 4th ed. London: Mac Keith Press, 2018 (1496 pp). Price: £199.95 (UK). ISBN 9781909962804 Weighing in at nearly 8 pounds and 3.5 inches tall, the most recent (4th) edition of Aicardi's Diseases of the Nervous System in Childhood (edited by A Arzimanoglou, A O'Hare, MV Johnston, R Ouvrier), is a heavyweight indeed! It is a 1,496-page book which comprises a huge and systematic compendium covering the entire spectrum of pediatric neurological disorders. The first two editions, written predominantly by Prof. Jean Aicardi, represented a tour de force, the accumulated wisdom a lifetime of professional engagement with children who have neurological diseases. When the 3rd edition appeared in 2009, something was lost and gained. We lost the unique perspective and keen observations of a single-acknowledged genius but gained insights by extending those of Prof. Aicardi's with those of other experts. As this book review is intended for a pediatric epilepsy audience, my comments will focus on that section of the volume. However, first I want to highlight some nonepilepsy chapters that I found exceptionally clear and well written. Specifically, the chapters on fetal and neonatal neurology and brain development were written beautifully, with clear illustrations and diagrams that clarify the complicated molecular and cellular processes by which conjunction of sperm and egg ultimately results in the complexity and beauty of the developed brain. And of course, this developmental information is pivotal to our understanding of seizures and epilepsy in the young patient. The epilepsy section is comprehensive, to say the least, comprising 139 pages, with no fewer than 1,200 references. All the major topics of pediatric epilepsy are covered, including mechanisms, etiology (including a good coverage of the burgeoning list of genetic mutations that give rise to epilepsy), pathology, semiology (the presentation of epilepsy syndromes by age of onset is very helpful), and treatment. Yet, this section also has some disappointing deficiencies. My main concern is the dearth of updated references. Most of the references throughout the chapter appear to be simply copied forward from older editions of the textbook (the majority are from the 80s and 90s). Classification is discussed extensively, but the authors could have focused more on the currently revised classification scheme and less on the schemes from the 80s and 90s. While acknowledging the foundational aspects of earlier classification schemes and older references, current readers expect discussion of the most up-to-date classification schemes and controversies surrounding them. The coverage of mechanisms is far too cursory and does not include a discussion of the critical developmental mechanisms in the developing brain that predispose a child to seizures and epilepsy; again, the references are largely from the 90s and much knowledge about mechanisms has been gained since then. Curiously, while carbamazepine is included in the tables and text, oxcarbazepine, arguably among the most often prescribed antiseizure medications, is not (whereas newer and less commonly prescribed agents such as perampanel are included). The authors of the epilepsy section are to be congratulated for their comprehensive coverage of all aspects of seizures and epilepsy in children, including an especially useful discussion of seizure mimics. Indeed, this section could be book unto itself! However, the references and citations should have been comprehensively updated and revised, in keeping with modern viewpoints. In summary, I do recommend this book as a comprehensive treatise on child neurology and disorders of the developing nervous system. Overall, the 4th edition stays true to Aicardi's vision, with an emphasis on clinical findings in a format and readable style accessible to the clinician. It is a fitting tribute to the vision and genius of Jean Aicardi, and with tighter editing, should continue to be an important resource for the child neurologist and epileptologist.
Carl E. Stafstrom. Aicardi's Diseases of the Nervous System in Childhood. Journal of Pediatric Epilepsy 2020, 1 .
AMA StyleCarl E. Stafstrom. Aicardi's Diseases of the Nervous System in Childhood. Journal of Pediatric Epilepsy. 2020; ():1.
Chicago/Turabian StyleCarl E. Stafstrom. 2020. "Aicardi's Diseases of the Nervous System in Childhood." Journal of Pediatric Epilepsy , no. : 1.
Infantile spasms (IS) is an epileptic encephalopathy with unique clinical and electrographic features, which affects children in the middle of the first year of life. The pathophysiology of IS remains incompletely understood, despite the heterogeneity of IS etiologies, more than 200 of which are known. In particular, the neurobiological basis of why multiple etiologies converge to a relatively similar clinical presentation has defied explanation. Treatment options for this form of epilepsy, which has been described as “catastrophic” because of the poor cognitive, developmental, and epileptic prognosis, are limited and not fully effective. Until the pathophysiology of IS is better clarified, novel treatments will not be forthcoming, and preclinical (animal) models are essential for advancing this knowledge. Here, we review preclinical IS models, update information regarding already existing models, describe some novel models, and discuss exciting new data that promises to advance understanding of the cellular mechanisms underlying the specific EEG changes seen in IS—interictal hypsarrhythmia and ictal electrodecrement.
Remi Janicot; Li-Rong Shao; Carl Stafstrom. Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms. Children 2020, 7, 5 .
AMA StyleRemi Janicot, Li-Rong Shao, Carl Stafstrom. Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms. Children. 2020; 7 (1):5.
Chicago/Turabian StyleRemi Janicot; Li-Rong Shao; Carl Stafstrom. 2020. "Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms." Children 7, no. 1: 5.
Epilepsy, a complex neurological disorder of recurrent seizures, is associated with significant impacts on the developing brain. Patients commonly face multiple comorbidities, including debilitating effects on cognition, behavior, and psychiatric outcomes. These conditions can be a source of great distress for patients that may even be greater than the burden of epilepsy itself. Here we investigate the relationship between seizures and the development of these comorbidities, specifically cognition, memory, learning, behavior, and psychiatric disorders. We first delineate the current research methodology in clinical and basic science that is employed to study the impact of epilepsy and seizures. We then explore neurobiological mechanisms underlying the development of seizures and cognitive and behavioral outcomes. Potential avenues of intervention to best support individuals and optimize their neurodevelopmental progress are also highlighted.
Katerina Lin; Carl E. Stafstrom. Cognition, Behavior, and Psychosocial Effects of Seizures in the Developing Brain. Current Topics in Behavioral Neurosciences 2020, 1 -13.
AMA StyleKaterina Lin, Carl E. Stafstrom. Cognition, Behavior, and Psychosocial Effects of Seizures in the Developing Brain. Current Topics in Behavioral Neurosciences. 2020; ():1-13.
Chicago/Turabian StyleKaterina Lin; Carl E. Stafstrom. 2020. "Cognition, Behavior, and Psychosocial Effects of Seizures in the Developing Brain." Current Topics in Behavioral Neurosciences , no. : 1-13.
Artwork is a valuable and underutilized technique for exploring the self-esteem and psychological challenges facing children and adolescents with epilepsy and other chronic diseases. Having children with epilepsy draw a picture of their seizure correlates reliably with seizure type, provides insight into the child's developmental level, and allows expression of inner feelings such as helplessness, vulnerability, and self-concept. Art therapy focus groups are beneficial in helping children with epilepsy express their feelings nonverbally and get to know peers facing similar challenges. On the occasion of Epilepsy and Behavior's 20th anniversary, this article reviews the usefulness of art for exploring the self-concept of patients with epilepsy and acknowledges the journal's support of this informative, inexpensive, and empowering adjunctive technique. "Special Issue: Epilepsy & Behavior's 20th Anniversary"
Carl E. Stafstrom. Using artwork to understand and address the psychosocial challenges facing children and adolescents with epilepsy. Epilepsy & Behavior 2019, 101, 106572 .
AMA StyleCarl E. Stafstrom. Using artwork to understand and address the psychosocial challenges facing children and adolescents with epilepsy. Epilepsy & Behavior. 2019; 101 ():106572.
Chicago/Turabian StyleCarl E. Stafstrom. 2019. "Using artwork to understand and address the psychosocial challenges facing children and adolescents with epilepsy." Epilepsy & Behavior 101, no. : 106572.
SYNGAP1 is a gene that encodes the cytosolic protein SYNGAP1 (SYNaptic GTPase Activating Protein), an essential component of the postsynaptic density at excitatory glutamatergic neurons. SYNGAP1 plays critical roles in synaptic development, structure, function, and plasticity. Mutations in SYNGAP1 result in a neurodevelopmental disorder termed Mental retardation-type 5 (MRD5, OMIM #612621) with a phenotype consisting of intellectual disability, motor impairments, and epilepsy, attesting to the importance of this protein for normal brain development. Here we review the clinical and pathophysiological aspects of SYNGAP1 mutations with a focus on their effect on synaptogenesis, neural circuit function, and cellular plasticity. We conclude by comparing the molecular pathogenesis of SYNGAP1 mutations with those of another neurodevelopmental disorder that affects dendritic function and cellular plasticity, fragile X syndrome. Insights into the molecular similarities and differences underlying these disorders could lead to rationale therapy development.
Mudit Agarwal; Michael V. Johnston; Carl E. Stafstrom. SYNGAP1 mutations: Clinical, genetic, and pathophysiological features. International Journal of Developmental Neuroscience 2019, 78, 65 -76.
AMA StyleMudit Agarwal, Michael V. Johnston, Carl E. Stafstrom. SYNGAP1 mutations: Clinical, genetic, and pathophysiological features. International Journal of Developmental Neuroscience. 2019; 78 (1):65-76.
Chicago/Turabian StyleMudit Agarwal; Michael V. Johnston; Carl E. Stafstrom. 2019. "SYNGAP1 mutations: Clinical, genetic, and pathophysiological features." International Journal of Developmental Neuroscience 78, no. 1: 65-76.
Mechanisms underlying seizures and epilepsy have traditionally been considered to involve abnormalities of ion channels or synaptic function. Those considerations gave rise to the excitation/inhibition (E/I) imbalance theory, whereby increased excitation, decreased inhibition, or both favor a hyperexcitable state and an increased propensity for seizure generation and epileptogenesis. Several recent findings warrant reconsideration and expansion of the E/I hypothesis: novel genetic mutations have been identified that do not overtly affect E/I balance; neurotransmitters may exert paradoxical effects, especially during development; anti-seizure medications do not necessarily work by decreasing excitation or increasing inhibition; and metabolic factors participate in the regulation of neuronal and network excitability. These novel conceptual and experimental advances mandate expansion of the E/I paradigm, with the expectation that new and exciting therapies will emerge from this broadened understanding of how seizures and epilepsy arise and progress.
Li-Rong Shao; Christa W. Habela; Carl E. Stafstrom. Pediatric Epilepsy Mechanisms: Expanding the Paradigm of Excitation/Inhibition Imbalance. Children 2019, 6, 23 .
AMA StyleLi-Rong Shao, Christa W. Habela, Carl E. Stafstrom. Pediatric Epilepsy Mechanisms: Expanding the Paradigm of Excitation/Inhibition Imbalance. Children. 2019; 6 (2):23.
Chicago/Turabian StyleLi-Rong Shao; Christa W. Habela; Carl E. Stafstrom. 2019. "Pediatric Epilepsy Mechanisms: Expanding the Paradigm of Excitation/Inhibition Imbalance." Children 6, no. 2: 23.
Focal-onset seizures are among the most common forms of seizures in children and adolescents and can be caused by a wide diversity of acquired or genetic etiologies. Despite the increasing array of antiseizure drugs available, treatment of focal-onset seizures in this population remains problematic, with as many as one-third of children having seizures refractory to medications. This review discusses contemporary concepts in focal seizure classification and pathophysiology and describes the antiseizure medications most commonly chosen for this age group. As antiseizure drug efficacy is comparable in children and adults, here we focus on pharmacokinetic aspects, drug–drug interactions, and side effect profiles. Finally, we provide some suggestions for choosing the optimal medication for the appropriate patient.
Clare E. Stevens; Carl E. Stafstrom. Pharmacotherapy for Focal Seizures in Children and Adolescents. Drugs 2018, 78, 1321 -1337.
AMA StyleClare E. Stevens, Carl E. Stafstrom. Pharmacotherapy for Focal Seizures in Children and Adolescents. Drugs. 2018; 78 (13):1321-1337.
Chicago/Turabian StyleClare E. Stevens; Carl E. Stafstrom. 2018. "Pharmacotherapy for Focal Seizures in Children and Adolescents." Drugs 78, no. 13: 1321-1337.
Conventional antiseizure medications reduce neuronal excitability through effects on ion channels or synaptic function. In recent years, it has become clear that metabolic factors also play a crucial role in the modulation of neuronal excitability. Indeed, metabolic regulation of neuronal excitability is pivotal in seizure pathogenesis and control. The clinical effectiveness of a variety of metabolism‐based diets, especially for children with medication‐refractory epilepsy, underscores the applicability of metabolic approaches to the control of seizures and epilepsy. Such diets include the ketogenic diet, the modified Atkins diet, and the low‐glycemic index treatment (among others). A promising avenue to alter cellular metabolism, and hence excitability, is by partial inhibition of glycolysis, which has been shown to reduce seizure susceptibility in a variety of animal models as well as in cellular systems in vitro. One such glycolytic inhibitor, 2‐deoxy‐d‐glucose (2DG), increases seizure threshold in vivo and reduces interictal and ictal epileptiform discharges in hippocampal slices. Here, we review the role of glucose metabolism and glycolysis on neuronal excitability, with specific reference to 2DG, and discuss the potential use of 2DG and similar agents in the clinical arena for seizure management.
Li‐Rong Shao; Jong M. Rho; Carl E. Stafstrom. Glycolytic inhibition: A novel approach toward controlling neuronal excitability and seizures. Epilepsia Open 2018, 3, 191 -197.
AMA StyleLi‐Rong Shao, Jong M. Rho, Carl E. Stafstrom. Glycolytic inhibition: A novel approach toward controlling neuronal excitability and seizures. Epilepsia Open. 2018; 3 (S2):191-197.
Chicago/Turabian StyleLi‐Rong Shao; Jong M. Rho; Carl E. Stafstrom. 2018. "Glycolytic inhibition: A novel approach toward controlling neuronal excitability and seizures." Epilepsia Open 3, no. S2: 191-197.
Natalie L. Ullman; Constance L. Smith-Hicks; Sonal Desai; Carl E. Stafstrom. De Novo HECW2 Mutation Associated With Epilepsy, Developmental Decline, and Intellectual Disability: Case Report and Review of Literature. Pediatric Neurology 2018, 85, 76 -78.
AMA StyleNatalie L. Ullman, Constance L. Smith-Hicks, Sonal Desai, Carl E. Stafstrom. De Novo HECW2 Mutation Associated With Epilepsy, Developmental Decline, and Intellectual Disability: Case Report and Review of Literature. Pediatric Neurology. 2018; 85 ():76-78.
Chicago/Turabian StyleNatalie L. Ullman; Constance L. Smith-Hicks; Sonal Desai; Carl E. Stafstrom. 2018. "De Novo HECW2 Mutation Associated With Epilepsy, Developmental Decline, and Intellectual Disability: Case Report and Review of Literature." Pediatric Neurology 85, no. : 76-78.
Seizures in neonates represent a neurologic emergency requiring prompt recognition, determination of etiology, and treatment. Yet, the definition and identification of neonatal seizures remain challenging and controversial, in part due to the unique physiology of brain development at this life stage. These issues are compounded when considering seizures in premature infants, in whom the complexities of brain development may engender different clinical and electrographic seizure features at different points in neuronal maturation. In extremely premature infants (< 28 weeks gestational age), seizure pathophysiology has not been explored in detail. This review discusses the physiological and structural development of the brain in this developmental window, focusing on factors that may lead to seizures and their consequences at this early time point. We hypothesize that the clinical and electrographic phenomenology of seizures in extremely preterm infants reflects the specific pathophysiology of brain development in that age window.
Melisa Carrasco; Carl E. Stafstrom. How Early Can a Seizure Happen? Pathophysiological Considerations of Extremely Premature Infant Brain Development. Developmental Neuroscience 2018, 40, 417 -436.
AMA StyleMelisa Carrasco, Carl E. Stafstrom. How Early Can a Seizure Happen? Pathophysiological Considerations of Extremely Premature Infant Brain Development. Developmental Neuroscience. 2018; 40 (5-6):417-436.
Chicago/Turabian StyleMelisa Carrasco; Carl E. Stafstrom. 2018. "How Early Can a Seizure Happen? Pathophysiological Considerations of Extremely Premature Infant Brain Development." Developmental Neuroscience 40, no. 5-6: 417-436.