Vagus nerve stimulation in children with mitochondrial electron transport chain deficiencies

Arthur, Todd M.; Saneto, Russell P.; Menezes, Márcio Sotero de; Devinsky, Orrin; LaJoie, Josiane; Murphy, Patricia; Cook, William B.; Ojemann, Jeffrey G.

doi:10.1016/j.mito.2007.04.003

Cited by 22 publications

(27 citation statements)

References 14 publications

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“…58 Seizures stopped after vagus nerve stimulation (VNS) in a 16year-old girl with MERRF, and there were no further episodes of status epilepticus during 1.5 years of follow-up. 60 Palliative functional hemispherectomy was reported to allow a child with Alpers syndrome and refractory status epilepticus to be extubated and discharged home. 60 Palliative functional hemispherectomy was reported to allow a child with Alpers syndrome and refractory status epilepticus to be extubated and discharged home.…”

Section: Managementmentioning

confidence: 99%

Mitochondrial diseases and status epilepticus

Rahman

2018

Epilepsia

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This narrative review focuses on the pathophysiology, diagnosis, and management of status epilepticus in the context of primary mitochondrial disease. Epilepsy is common in mitochondrial disease, reported in >20% of adult cases and 40%-60% of pediatric cohorts. Status epilepticus is less frequently reported and appears to be associated with particular subgroups of mitochondrial disorders, namely defects of the mitochondrial DNA and its maintenance, and disorders of mitochondrial translation and dynamics. Mechanisms underlying mitochondrial status epilepticus are incompletely understood, and may include bioenergetic failure, oxidative stress, immune dysfunction, and impaired mitochondrial dynamics. Treatments tried in mitochondrial status epilepticus include antiepileptic drugs, anesthetic agents, magnesium, high-dose steroids, immune globulins, vagus nerve stimulation, and surgical procedures, all with variable success. The outcome of mitochondrial status epilepticus is extremely poor, and effective therapeutic options have not been reported. Improved understanding of the mechanisms underpinning mitochondrial status epilepticus is needed in order to develop more effective treatments.

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Section: Managementmentioning

confidence: 99%

Mitochondrial diseases and status epilepticus

Rahman

2018

Epilepsia

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“…Duration of VNS and seizure frequency was followed over a period of 3.4 to 10.75 years. None of the children had reduced seizure activity with VNS placement [40, Class IV]. There is also anecdotal evidence among the coauthors of this article that VNS devices have been unsuccessful in decreasing epilepsy in mitochondrial disease patients.…”

Section: Treatmentmentioning

confidence: 99%

A modern approach to the treatment of mitochondrial disease

Parikh

Saneto²,

Falk³

et al. 2009

Curr Treat Options Neurol

295

274

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Opinion statement The treatment of mitochondrial disease varies considerably. Most experts use a combination of vitamins, optimize patients' nutrition and general health, and prevent worsening of symptoms during times of illness and physiologic stress. We agree with this approach, and we agree that therapies using vitamins and cofactors have value, though there is debate about the choice of these agents and the doses prescribed. Despite the paucity of high-quality scientific evidence, these therapies are relatively harmless, may alleviate select clinical symptoms, and theoretically may offer a means of staving off disease progression. Like many other mitochondrial medicine physicians, we have observed significant (and at times life-altering) clinical responses to such pharmacologic interventions. However, it is not yet proven that these therapies truly alter the course of the disease, and some experts may choose not to use these medications at all. At present, the evidence of their effectiveness does not rise to the level required for universal use. Based on our clinical experience and judgment, however, we agree that a therapeutic trial of coenzyme Q10, along with other antioxidants, should be attempted. Although individual specialists differ as to the exact drug cocktail, a common approach involves combinations of antioxidants that may have a synergistic effect. Because almost all relevant therapies are classified as medical foods or over-the-counter supplements, most physicians also attempt to balance the apparent clinical benefit of mitochondrial cocktails with the cost burden that these supplements pose for the family.

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“…As this protocol is uncontrolled, VNS effectiveness may have been overestimated. Indeed, several other studies observed no seizure frequency reduction in some of their study population 7,8,11,12,22,24 or in the entire study population 26,27 …”

Section: Discussionmentioning

confidence: 96%

“…The effectiveness of VNS might be more variable in children than in adults. Numerous prospective and retrospective studies at various centres worldwide describing more than 650 children, aged 0 to 19 years, have reported a reduction in seizure frequency of more than 50% in 0 to 90% 3–28 . However, these studies were uncontrolled, and there was a large variation in study groups, for example regarding age, epilepsy syndromes, and follow‐up duration, which varied from 3 months to 10 years.…”

mentioning

confidence: 99%

Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial

Klinkenberg

Aalbers

Vles

et al. 2012

Develop Med Child Neuro

112

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AED Antiepileptic drug VNS Vagus nerve stimulationAIM The aim of this study was to evaluate the effects of vagus nerve stimulation (VNS) in children with intractable epilepsy on seizure frequency and severity and in terms of tolerability and safety.METHOD In this study, the first randomized active controlled trial of its kind in children, 41 children (23 males; 18 females; mean age at implantation 11y 2mo, SD 4y 2mo, range 3y 10mo-17y 8mo) were included. Thirty-five participants had localization-related epilepsy (25 symptomatic; 10 cryptogenic), while six participants had generalized epilepsy (four symptomatic; two idiopathic). During a baseline period of 12 weeks, seizure frequency and severity were recorded using seizure diaries and the adapted Chalfont Seizure Severity Scale (NHS3), after which the participants entered a blinded active controlled phase of 20 weeks. During this phase, half of the participants received high-output VNS (maximally 1.75mA) and the other half received low-output stimulation (0.25mA). Finally, all participants received high-output stimulation for 19 weeks. For both phases, seizure frequency and severity were assessed as during the baseline period. Overall satisfaction and adverse events were assessed by semi-structured interviews.RESULTS At the end of the randomized controlled blinded phase, seizure frequency reduction of 50% or more occurred in 16% of the high-output stimulation group and in 21% of the low-output stimulation group (p=1.00). There was no significant difference in the decrease in seizure severity between participants in the stimulation groups. Overall, VNS reduced seizure frequency by 50% or more in 26% of participants at the end of the add-on phase The overall seizure severity also improved (p<0.001).INTERPRETATION VNS is a safe and well-tolerated adjunctive treatment of epilepsy in children.Our results suggest that the effect of VNS on seizure frequency in children is limited. However, the possible reduction in seizure severity and improvement in well-being makes this treatment worth considering in individual children with intractable epilepsy.Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for individuals with medically refractory epilepsy who are not eligible for epilepsy surgery or in whom surgery has failed, and in whom non-epileptic events are excluded. VNS consists of chronic intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator (neurocybernetic prosthesis [NCP]; Cyberonics Inc, Webster, TX, USA).Randomized active controlled trials, which have predominantly included adults, have demonstrated the safety and efficacy of VNS: 1,2 seizure frequency decreased by more than 50% in 23 to 31% of individuals in the treatment groups compared with 13 to 15% in the placebo group. These trials led to the U.S. Food and Drug Administration approval in 1997 of the use of VNS as adjunctive therapy in individuals older than 12 years with partial epilepsy refractory to treatment with...

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Vagus nerve stimulation in children with mitochondrial electron transport chain deficiencies

Cited by 22 publications

References 14 publications

Mitochondrial diseases and status epilepticus

Mitochondrial diseases and status epilepticus

A modern approach to the treatment of mitochondrial disease

Vagus nerve stimulation in children with intractable epilepsy: a randomized controlled trial

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