Vagus Nerve Stimulation in Intractable Epilepsy Associated With <i>SCN1A</i> Gene Abnormalities

Fulton, Stephen; Poppel, Kate Van; McGregor, Amy; Mudigoudar, Basanagoud; Wheless, James W.

doi:10.1177/0883073816687221

Cited by 25 publications

(24 citation statements)

References 15 publications

(26 reference statements)

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“…In Lennox-Gastaut syndrome there were promising results 36 , with a 58% reduction in seizure frequency six months after implantation in a multicenter retrospective study of 50 patients 37 . SCN1A gene mutations might improve as well, as reported by Fulton et al 38 , who described a 75% rate of responders in 12 patients.…”

supporting

confidence: 52%

The role of vagus nerve stimulation in refractory epilepsy

Oliveira

Francisco

Demartini

et al. 2017

Arq. Neuro-Psiquiatr.

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Vagus nerve stimulation is an adjunctive therapy used to treat patients with refractory epilepsy who are not candidates for resective surgery or had poor results after surgical procedures. Its mechanism of action is not yet fully comprehended but it possibly involves modulation of the locus coeruleus, thalamus and limbic circuit through noradrenergic and serotonergic projections. There is sufficient evidence to support its use in patients with focal epilepsy and other seizure types. However, it should be recognized that improvement is not immediate and increases over time. The majority of adverse events is stimulation-related, temporary and decreases after adjustment of settings. Future perspectives to improve efficacy and reduce side effects, such as different approaches to increase battery life, transcutaneous stimulation and identification of prognostic factors, should be further investigated.Keywords: vagus nerve stimulation; epilepsy. RESUMOA estimulação vagal é uma terapia paliativa utilizada no tratamento de pacientes com epilepsia refratária que não são candidatos à cirurgia ressectiva ou naqueles com evolução insatisfatória após o procedimento cirúrgico. Seu mecanismo de ação ainda não foi completamente elucidado mas possivelmente envolve a modulação do locus coeruleus, tálamo e circuito límbico através de projeções noradrenérgicas e serotoninérgicas. Atualmente há evidência suficiente para corroborar o uso desta terapia em pacientes com epilepsia focal e outros tipos de crise, com resultados que, apesar de não imediatos, melhoram progressivamente no longo prazo. Os eventos adversos são, em sua maioria, relacionados à estimulação e auto-limitados. Perspectivas futuras para aumentar a eficácia e reduzir os efeitos colaterais como a utilização de baterias com maior durabilidade, estimulação transcutânea e identificação de fatores prognósticos devem ser investigadas. Palavras-chave: estimulação do nervo vago; epilepsia.Epilepsy is one of the most common chronic neurologic diseases and affects at least 50 million people worldwide 1 . Although much has been understood about its causes, epilepsy is still extremely stigmatizing and many patients are victims of prejudice and social exclusion. The quality of life of those affected by the disease is remarkably compromised due to seizures, antiepileptic drugs (AED), cognitive impairment and physical limitations.Those who do not achieve adequate seizure control, even with multiple AED trials, are considered refractory. Currently, medically resistant epilepsy is regarded as a worldwide health issue as it is endured by approximately one third of epileptic patients. The financial burden is substantial and, among all health costs of uncontrolled patients, nearly 50% are related to epilepsy care costs 2 . For these individuals, whose treatment is generally complex, epilepsy surgery may be indicated and can provide up to 80% seizure control, depending on distinct aspects such as time of follow-up and epileptic focus localization. Figure 1 illustrates the therapy ...

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supporting

confidence: 52%

The role of vagus nerve stimulation in refractory epilepsy

Oliveira

Francisco

Demartini

et al. 2017

Arq. Neuro-Psiquiatr.

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“…Several studies showed the effectiveness of VNS in DS patients. 10,[29][30][31][32] However, how early in the disease process, VNS should be used is unclear. Dibué-Adjei et al performed a meta-analysis of 68 patients from 13 studies and found 52.9% of patients had more than 50% seizure reduction.…”

Section: Vagus Nerve Stimulation and Epilepsy Surgeriesmentioning

confidence: 99%

Changing Landscape of Dravet Syndrome Management: An Overview

Samanta

2020

Neuropediatrics

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Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is a severe developmental and epileptic encephalopathy caused by loss-of-function mutations in one copy of SCN1A (haploinsufficiency), located on chromosome 2q24, with decreased function of Nav1.1 sodium channels in GABAergic inhibitory interneurons. Pharmacoresistant seizures in DS start in the infancy in the form of hemiclonic febrile status epilepticus. Later, other intractable seizure types develop including myoclonic seizures. Early normal development in infancy evolves into moderate to severe intellectual impairment, motor impairment, behavioral abnormalities, and later a characteristic crouching gait. Clobazam, valproate, levetiracetam, topiramate, zonisamide, ketogenic diet, and vagus nerve stimulation had been shown to be effective, but even with polytherapy, only 10% of patients get adequate seizure control. The author provides a narrative review of the current treatment paradigm as well as recent advances in the management of DS based on a comprehensive literature review (MEDLINE using PubMed and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. In recent years, the treatment paradigm of DS is changing with the approval of pharmaceutical-grade cannabidiol oil and stiripentol. Another novel antiepileptic drug (AED), fenfluramine, had also shown excellent efficacy in phase 3 studies of DS. However, these AEDs primarily control seizures without addressing the underlying pathogenesis and other important common comorbidities such as cognitive impairment, autistic behavior, neuropsychiatric abnormalities, and motor impairment including crouching gait. Several agents targeted for DS are in the developmental stage: TAK935, lorcaserin, clemizole, huperzine analog, ataluren, selective sodium channel modulators and activators, antisense oligonucleotide therapy, and adenoviral vector therapy. As DS is associated with a high risk of sudden unexpected death in epilepsy, seizure detection devices can be used in this population for testing and clinical validation of these devices.

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“…Fulton et al placed the vagus nerve stimulation for 12 patients with Dravet syndrome and assessed the seizure control after 6 months. Nine of them showed >50% reduction in generalized tonic-clonic seizures, and four of them showed the cognitive function improvement [87]. Neuroscientist screened the potential therapeutic agents and tested their effectiveness in vivo in the experimental setting.…”

Section: Treatment To Dravet Syndrome and Therapeutic Responsementioning

confidence: 99%

Genetic Defects of Voltage-Gated Sodium Channel α Subunit 1 in Dravet Syndrome and the Patients’ Response to Antiepileptic Drugs

Li¹

2018

Ion Channels in Health and Sickness

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In the past decade, hundreds of mutations have been found in the SCN1A (sodium voltage-gated channel α subunit 1) gene in the epileptic patients. The functioning of the SCN1A gene products is intensively studied in the neuroscience field. The loss-of-function mutations of the SCN1A gene are the causative factor of Dravet syndrome, an intractable epilepsy syndrome. With the loss-of-function Na v 1.1 (the protein encoded by SCN1A gene), the selective dysfunction of the inhibitory parvalbumin (PV) interneurons impairs the balance of excitatory and inhibitory synaptic inputs to the downstream neurons, and causes the hyperexcitability of the neuronal network. The underlying mechanism is that the axon initial segments (AISs) of inhibitory parvalbumin interneurons predominantly express Na v 1.1, particularly in the proximal end of the AISs. The deficiency of Na v 1.1 weakens the excitability of the inhibitory parvalbumin neurons and leads to the hyperexcitability of the neuronal network. The sodium channel blockers, one category of the antiepileptic drugs (AEDs) that specifically block the activity of VGSCs, may potentially worsen the defect of Na v 1.1 of the PV interneurons in the patients with the SCN1A gene loss-of-function mutations, aggravate the clinical manifestation, and increase the seizure frequency of those patients.

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Vagus Nerve Stimulation in Intractable Epilepsy Associated With SCN1A Gene Abnormalities

Cited by 25 publications

References 15 publications

The role of vagus nerve stimulation in refractory epilepsy

The role of vagus nerve stimulation in refractory epilepsy

Changing Landscape of Dravet Syndrome Management: An Overview

Genetic Defects of Voltage-Gated Sodium Channel α Subunit 1 in Dravet Syndrome and the Patients’ Response to Antiepileptic Drugs

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