The epilepsy–autism spectrum disorder phenotype in the era of molecular genetics and precision therapy

Specchio, Nicola; Micco, Valentina Di; Trivisano, Marina; Ferretti, Alessandro; Curatolo, Paolo

doi:10.1111/epi.17115

Cited by 24 publications

(23 citation statements)

References 101 publications

(164 reference statements)

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“…Several studies reveal a strong relationship between epilepsy in individuals with autism and autism in those with epilepsy ( Viscidi et al, 2013 ; Reilly et al, 2015 ; Sundelin et al, 2016 ), with the prevalence of epilepsy in ASD doubling in adolescence (26%) compared to childhood (12%) ( Hara, 2007 ; Woolfenden et al, 2012 ; Sharma et al, 2021 ). Likely explanations supporting the conjugation of the two conditions include an imbalance in neuronal excitation/inhibition ( Bourgeron, 2009 ; Nelson and Valakh, 2015 ; Specchio et al, 2022 ). In the Cntnap2 –/– mouse model of autism with focal epilepsy, global tau knockdown prevents epileptic activity in addition to other autistic-like behaviors ( Tai et al, 2020 ), indicating an epileptogenic role of tau in ASD.…”

Section: Role Of Tau In Epileptic Activitymentioning

confidence: 99%

Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms

Hwang

Vaknalli

Addo-Osafo

et al. 2022

Front. Aging Neurosci.

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Tau is a microtubule-associated protein known to bind and promote assembly of microtubules in neurons under physiological conditions. However, under pathological conditions, aggregation of hyperphosphorylated tau causes neuronal toxicity, neurodegeneration, and resulting tauopathies like Alzheimer’s disease (AD). Clinically, patients with tauopathies present with either dementia, movement disorders, or a combination of both. The deposition of hyperphosphorylated tau in the brain is also associated with epilepsy and network hyperexcitability in a variety of neurological diseases. Furthermore, pharmacological and genetic targeting of tau-based mechanisms can have anti-seizure effects. Suppressing tau phosphorylation decreases seizure activity in acquired epilepsy models while reducing or ablating tau attenuates network hyperexcitability in both Alzheimer’s and epilepsy models. However, it remains unclear whether tauopathy and epilepsy comorbidities are mediated by convergent mechanisms occurring upstream of epileptogenesis and tau aggregation, by feedforward mechanisms between the two, or simply by coincident processes. In this review, we investigate the relationship between tauopathies and seizure disorders, including temporal lobe epilepsy (TLE), post-traumatic epilepsy (PTE), autism spectrum disorder (ASD), Dravet syndrome, Nodding syndrome, Niemann-Pick type C disease (NPC), Lafora disease, focal cortical dysplasia, and tuberous sclerosis complex. We also explore potential mechanisms implicating the role of tau kinases and phosphatases as well as the mammalian target of rapamycin (mTOR) in the promotion of co-pathology. Understanding the role of these co-pathologies could lead to new insights and therapies targeting both epileptogenic mechanisms and cognitive decline.

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Section: Role Of Tau In Epileptic Activitymentioning

confidence: 99%

Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms

Hwang

Vaknalli

Addo-Osafo

et al. 2022

Front. Aging Neurosci.

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“…Было высказано предположение об общих как биологических, так и молекулярных механизмах РАС и эпилепсии, например при комплексе туберозного склероза. Гипотетические объяснения, подтверждающие взаимосвязь двух состояний, включают аномалии роста синапсов, дисбаланс возбуждения/торможения нейронов и аномальную синаптическую пластичность [29]. В текущее десятилетие возрос интерес к пониманию генетических причин, приводящих к РАС, нарушениям интеллектуального развития и эпилепсии.…”

Section: полноэкзомное секвенированиеunclassified

“…В значительной степени это обусловлено внедрением современных геномных технологий, которые помогают идентифицировать причину заболевания и на основании полученных данных проводить персонифицированное лечение таких пациентов. При исследовании генетической основы было выделено множество генов, связанных с аномалиями ионных каналов, синаптической функции и структуры, а также регуляторами транскрипции пути mTOR [29].…”

Section: полноэкзомное секвенированиеunclassified

Opportunities and achievements of using massive parallel sequencing in the diagnosis of neurodevelopmental diseases

Кожанова

2023

Èpilepsiâ paroksizmalʹnye sostoâ.

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The contribution of genetic factors to development of neurological diseases has long been recognized, and the majority of the advances coupled to using molecular genetic technologies resulted in identifying genes associated with the pathology of developing nervous system. The review is aimed at demonstrating opportunities and achievements of using massive parallel sequencing technology in the diagnosis of a disease with damage to nervous system. Currently, next-generation sequencing (NGS) technology in the genetic diagnosis of epilepsy relies on targeted gene panels, whole exome sequencing or whole genome sequencing. Integrating genetic and genomic analysis into clinical practice to establish clear molecular diagnoses for previously undiagnosed patients will avoid further unnecessary diagnosis and therefore lead to greater healthcare cost savings over time. The use of biomarkers will contribute to the prediction of disease outcome and therapy decision-making.

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“…Categorization of the behavioral severity of seizures is critical for determining disease stage – for example, chronic epilepsy is defined by the occurrence of two or more behavioral seizures. In addition to studies of epilepsy, video-neurophysiology recordings are becoming widely used in rodent studies of other pathologies that are sometimes comorbid with epileptiform activity including depression (Sadeghi et al, 2021), Alzheimer’s Disease (Harris et al, 2010; reviewed in Vossel et al, 2017), and autism (Lewis et al, 2018; Eisenberg et al, 2021; reviewed in Specchio et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Low-cost platform for multi-animal chronic local field potential video monitoring with graphical user interface (GUI) for seizure detection and behavioral scoring

Tarcsay

Boublil

Ewell

2022

Preprint

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Experiments employing chronic monitoring of neurophysiological signals and video are commonly used in studies of epilepsy to characterize behavioral correlates of seizures. Our objective was to design a low-cost platform that enables chronic monitoring of several animals simultaneously, synchronizes bilateral local field potential and video streams in real-time, and parses recorded data into manageable file sizes. We present a hardware solution leveraging Intan and Open Ephys acquisition systems and a software solution implemented in Bonsai. The platform was tested in 48-hour continuous recordings simultaneously from multiple mice (male and female) with chronic epilepsy. To enable seizure detection and scoring, we developed a graphical user interface (GUI) that reads the data produced by our workflow and allows a user with no coding expertise to analyze events. Our Bonsai workflow was designed to maximize flexibility for a wide variety of experimental applications, and our use of the Open Ephys acquisition board would allow for scaling recordings up to 128 channels per animal.SIGNIFICANCE STATEMENTWe present a low-cost hardware and software solution intended for multi-animal chronic seizure monitoring, that prioritizes experimental freedom, and requires no coding expertise of the user. We provide details for using an Intan adapter board to enable user freedom regarding the type of electrodes used. Video and local field potential data streams are synchronized and parsed in Bonsai – an open-source visual programming language that has pre-written libraries that allow our workflow to be adapted to other data types or to integrate with open-source toolboxes. Finally, for those intending to use our platform for seizure monitoring, we provide an accessible GUI to aid in seizure detection and behavioral scoring.

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The epilepsy–autism spectrum disorder phenotype in the era of molecular genetics and precision therapy

Cited by 24 publications

References 101 publications

Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms

Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms

Opportunities and achievements of using massive parallel sequencing in the diagnosis of neurodevelopmental diseases

Low-cost platform for multi-animal chronic local field potential video monitoring with graphical user interface (GUI) for seizure detection and behavioral scoring

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