Epilepsy is one of the most common and disabling neurologic conditions, yet we have an incomplete understanding of the detailed pathophysiology and, thus, treatment rationale for much of epilepsy. ...This article reviews the clinical aspects of seizures and epilepsy with the goal of providing neuroscientists an introduction to aspects that might be amenable to scientific investigation. Seizures and epilepsy are defined, diagnostic methods are reviewed, various clinical syndromes are discussed, and aspects of differential diagnosis, treatment, and prognosis are considered to enable neuroscientists to formulate basic and translational research questions.
Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in children are becoming increasingly apparent as the coronavirus disease (COVID‐19) pandemic continues. ...While children manifest relatively milder features of the disease, accumulating evidence warrants concern that COVID‐19 exacts both acute‐ and long‐term effects on the developing central and peripheral nervous systems. This review focuses on the relatively underinvestigated topic of the effects of SARS‐CoV‐2 on the brain in infancy and childhood, concluding that clinicians should be attentive to both the acute effects and long‐term consequences of COVID‐19 from a neurological perspective.
It is well established that epilepsy is associated with numerous neurobehavioral comorbidities, with a bidirectional relationship; people with epilepsy have an increased incidence of depression, ...anxiety, learning and memory difficulties, and numerous other psychosocial challenges, and the occurrence of epilepsy is higher in individuals with those comorbidities. Although the cause‐and‐effect relationship is uncertain, a fuller understanding of the mechanisms of comorbidities within the epilepsies could lead to improved therapeutics. Here, we review recent data on epilepsy and its neurobehavioral comorbidities, discussing mainly rodent models, which have been studied most extensively, and emphasize that clinically relevant information can be gained from preclinical models. Furthermore, we explore the numerous potential factors that may confound the interpretation of emerging data from animal models, such as the specific seizure induction method (e.g., chemical, electrical, traumatic, genetic), the role of species and strain, environmental factors (e.g., laboratory environment, handling, epigenetics), and the behavioral assays that are chosen to evaluate the various aspects of neural behavior and cognition. Overall, the interplay between epilepsy and its neurobehavioral comorbidities is undoubtedly multifactorial, involving brain structural changes, network‐level differences, molecular signaling abnormalities, and other factors. Animal models are well poised to help dissect the shared pathophysiological mechanisms, neurological sequelae, and biomarkers of epilepsy and its comorbidities.
Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain ...cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat - or at least ameliorate symptoms of - these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more "natural" treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.
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"
•Artwork is a valuable, under-utilized way to explore self-esteem and psychological challenges of children with epilepsy.•Children's seizure drawings correlate reliably with seizure type and reveal evidence of low self-esteem and vulnerability.•Focus groups provide mutual support and the opportunity to express inner feelings and share coping strategies.
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.
Epilepsy-Linked Kinase CDKL5 Phosphorylates Voltage-Gated Calcium Channel Cav2.3, Altering Inactivation Kinetics and Neuronal Excitability
Sampedro-Castañeda M, Baltussen LL, Lopes AT, Qiu Y, Sirvio ...L, Mihaylov SR, Claxton S, Richardson JC, Lignani G, Ultanir SK. Nat Commun. 2023;14(1):7830. doi:10.1038/s41467-023-43475-w
Developmental and epileptic encephalopathies (DEEs) are a group of rare childhood disorders characterized by severe epilepsy and cognitive deficits. Numerous DEE genes have been discovered thanks to advances in genomic diagnosis, yet putative molecular links between these disorders are unknown. CDKL5 deficiency disorder (CDD, DEE2), one of the most common genetic epilepsies, is caused by loss-of-function mutations in the brain enriched kinase CDKL5. To elucidate CDKL5 function, we looked for CDKL5 substrates using a SILAC-based phosphoproteomic screen. We identified the voltage-gated Ca2+ channel Cav2.3 (encoded by CACNA1E) as a physiological target of CDKL5 in mice and humans. Recombinant channel electrophysiology and interdisciplinary characterization of Cav2.3 phosphomutant mice revealed that loss of Cav2.3 phosphorylation leads to channel gain-of-function via slower inactivation and enhanced cholinergic stimulation, resulting in increased neuronal excitability. Our results thus show that CDD is partly a channelopathy. The properties of unphosphorylated Cav2.3 closely resemble those described for CACNA1E gain-of-function mutations causing DEE69, a disorder sharing clinical features with CDD. We show that these two single-gene diseases are mechanistically related and could be ameliorated with Cav2.3 inhibitors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Heterozygous GABAA Receptor β3 Subunit N110D Knock-In Mice Have Epileptic Spasms Qu S, Jackson LG, Zhou C, Shen D, Shen W, Nwosu G, Howe R, Catron MA, Flamm C, Biven M, Kang J-Q, Macdonald RL. ...Epilepsia. 2023;64(4):1061-1073. doi:10.1111/epi.17470
Objective:
Infantile spasms is an epileptic encephalopathy of childhood, and its pathophysiology is largely unknown. We generated a heterozygous knock-in mouse with the human infantile spasms-associated de novo mutation GABRB3 (c.A328G, p.N110D) to investigate its molecular mechanisms and to establish the Gabrb3+/N110D knock-in mouse as a model of infantile spasms syndrome.
Methods:
We used electroencephalography (EEG) and video monitoring to characterize seizure types, and a suite of behavioral tests to identify neurological and behavioral impairment in Gabrb3+/N110D knock-in mice. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded from layer V/VI pyramidal neurons in somatosensory cortex, and extracellular multi-unit recordings from the ventral basal nucleus of the thalamus in a horizontal thalamocortical slice were used to assess spontaneous thalamocortical oscillations.
Results:
The infantile spasms-associated human de novo mutation GABRB3 (c.A328G, p.N110D) caused epileptic spasms early in development and multiple seizure types in adult Gabrb3+/N110D knock-in mice. Signs of neurological impairment, anxiety, hyperactivity, social impairment, and deficits in spatial learning and memory were also observed. Gabrb3+/N110D mice had reduced cortical mIPSCs and increased duration of spontaneous oscillatory firing in the somatosensory thalamocortical circuit.
Significance:
The Gabrb3+/N110D knock-in mouse has epileptic spasms, seizures, and other neurological impairments that are consistent with infantile spasms syndrome in patients. Multiple seizure types and abnormal behaviors indicative of neurological impairment both early and late in development suggest that Gabrb3+/N110D mice can be used to study the pathophysiology of infantile spasms. Reduced cortical inhibition and increased duration of thalamocortical oscillatory firing suggest perturbations in thalamocortical circuits.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Pediatric-onset Huntington disease (PoHD) presents differently from adult-onset disease. Children typically exhibit regression in school performance, psychiatric features such as inattention, and ...oral motor dysfunction. Unlike adult-onset HD, in which seizures occur at approximately the rate of the general public, at least half of children with HD develop epilepsy, and seizures can be a presenting feature of PoHD. Here we present the case of a 10-year-old boy with a history of language delay, motor regression, oral motor dysfunction, and tremor who presented with a first lifetime seizure. Given a family history of Huntington disease in his father, PoHD was considered, and a pathogenic allele with 88 repeats was confirmed in the child. As symptoms progressed, history alone could not differentiate abnormal movements from seizures. Continuous video electroencephalography helped to demonstrate epileptic myoclonic jerks and guide treatment.
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