Lack of effects of vagus nerve stimulation on drug-resistant epilepsy in eight pediatric patients with autism spectrum disorders: A prospective 2-year follow-up study
ABSTRACT Vagus nerve stimulation (VNS) therapy has been reported to reduce seizure frequency in some children with drug-resistant epilepsy who are not suitable candidates for epilepsy surgery. It has been suggested that there may be positive cognitive and/or behavioral effects independent of seizure control. We describe the effects of VNS with respect to seizure frequency, cognition, and autistic symptoms and behavior in eight children and adolescents with medically intractable epilepsy and autism. In comparison to baseline, seizure frequency had not decreased in anyone in our series at the 2-year follow-up. In three cases, minor improvements in general functioning were noted, but there were no positive cognitive effects. This open prospective pilot study highlights the need for more prospective studies to prevent false expectations of improvement in this severely disabled group.
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ABSTRACT: Background The mechanism of action of vagus nerve stimulation (VNS) in intractable epilepsy is not entirely clarified. It is believed that VNS causes alterations in cytokines, which can lead to rebalancing the release of neurotoxic and neuroprotective tryptophan metabolites. We aimed to evaluate VNS effects on tryptophan metabolites and on epileptic seizures and investigated whether the antiepileptic effectiveness correlated with changes in tryptophan metabolism. Methods Forty-one children with intractable epilepsy were included in a randomized, active-controlled, double-blind study. After a baseline period of 12 weeks, all children underwent implantation of a vagus nerve stimulator and entered a blinded active-controlled phase of 20 weeks. Half of the children received high-output (therapeutic) stimulation (n = 21), while the other half received low-output (active control) stimulation (n = 20). Subsequently, all children received high-output stimulation for another 19 weeks (add-on phase). Tryptophan metabolites were assessed in plasma and cerebrospinal fluid (CSF) by use of liquid chromatography–tandem mass spectrometry (LC–MS/MS) and compared between high- and low-output groups and between the end of both study phases and baseline. Seizure frequency was recorded using seizure diaries. Mood was assessed using Profile of Mood States (POMS) questionnaires. Results Regarding tryptophan metabolites, anthranilic acid (AA) levels were significantly higher at the end of the add-on phase compared with baseline (p = 0.002) and correlated significantly with improvement of mood (τ = − 0.39, p = 0.037) and seizure frequency reduction (τ = − 0.33, p < 0.01). No significant changes were found between high- and low-output groups regarding seizure frequency. Conclusion Vagus nerve stimulation induces a consistent increase in AA, a neuroprotective and anticonvulsant tryptophan metabolite. Moreover, increased AA levels are associated with improvement in mood and reduction of seizure frequency.Epilepsy & Behavior 08/2014; 37:133–138. DOI:10.1016/j.yebeh.2014.06.001 · 2.06 Impact Factor
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ABSTRACT: Electrophysiological findings implicate site-specific impairment of the nucleus tractus solitarius (NTS) in autism. This invites hypothetical consideration of a large role for this small brainstem structure as the basis for seemingly disjointed behavioral and somatic features of autism. The NTS is the brain's point of entry for visceral afference, its relay for vagal reflexes, and its integration center for autonomic control of circulatory, immunological, gastrointestinal, and laryngeal function. The NTS facilitates normal cerebrovascular perfusion, and is the seminal point for an ascending noradrenergic system that modulates many complex behaviors. Microvascular configuration predisposes the NTS to focal hypoxia. A subregion-the "pNTS"-permits exposure to all blood-borne neurotoxins, including those that do not readily transit the blood-brain barrier. Impairment of acetylcholinesterase (mercury and cadmium cations, nitrates/nitrites, organophosphates, monosodium glutamate), competition for hemoglobin (carbon monoxide, nitrates/nitrites), and higher blood viscosity (net systemic oxidative stress) are suggested to potentiate microcirculatory insufficiency of the NTS, and thus autism.International Journal of Environmental Research and Public Health 12/2013; 10(12):6955-7000. DOI:10.3390/ijerph10126955 · 1.99 Impact Factor