Study considers VNS as treatment for new-onset refractory status epilepticus


In a recent Perspective, investigators proposed examining vagus nerve stimulation (VNS) during the early and late stages of the manifestation of new-onset refractory status epilepticus (NORSE).

They also hypothesized a potential additional benefit from transplantation in the acute phase, although this should be pursued in the context of clinical trials.

“A study planned within our UK-wide NORSE-UK network will show whether VNS may be of benefit in aborting persistent status epilepticus, modulating seizure induction and reducing long-term chronic seizure burden. It will answer the question of how,” the authors write. frontiers of neurology.

NORSE and its subcategory febrile infection-associated epilepsy syndrome (FIRES) are rare conditions. They are also associated with long-term morbidity, but treatment is not supported by controlled studies. Furthermore, resistance to pharmacotherapy is a major obstacle in patient management.

Up to two-thirds of NORSE survivors have functional impairment, and others subsequently experience chronic epilepsy.

“Whether network desynchronization by VNS can improve seizure control remains an open question,” the researchers explained.

This paper evaluated the evidence behind the use of VNS in adult and pediatric patients. One human study showed that seizures stimulated using VNS had reduced ictal spread and reduced effects on cardiovascular function.

Recent developments have also used VNS as an anti-inflammatory therapy. Thus, “the application of VNS in patients with NORSE may provide an immediate and controllable method of modulating seizure induction and further brain damage due to constant seizures and inflammation,” the authors wrote.

Searches of the ClinicalTrials.gov and PubMed databases revealed varying levels of detail in reported cases. Descriptions of VNS stimulation protocols were also uneven.

Fifteen cases of NORSE were identified. Of these, 10 were adult patients, 5 were pediatric patients, 9 were male, and 6 were female. Eight cases met the fire criteria, including five pediatric cases. The patient had tried multiple antiepileptic drugs and anesthetics, including propofol, ketamine, and midazolam.

Five patients underwent VNS transplantation during the acute phase of NORSE or within the first 30 days of onset. Transplanted in chronic phase of 7 patients with treatment-resistant epilepsy. Furthermore, the authors wrote that the most commonly used initial stimulation frequency was 20–30 Hz.

“VNS resulted in significant clinical changes in 10 cases, with a mean of 16.3 days post-transplant (range, 3–42 days) at time of recording,” the researchers noted.

Observed results include:

  • Cessation of the ultra-refractory condition was due to 2 acutely and 2 chronically transplanted VNS
  • Two patients documented subsequent relapse of seizure improvement, one patient had no response, and three patients documented sustained seizure relief. Two cases went from 30% to 40%, and the third was able to wean off the anesthetic.intensive care unit
  • Twelve long-term outcomes were available and recorded from 1 month to 26 years after transplantation. Two of his acutely transplanted patients died of multiple organ failure or comorbidities.
  • Three patients were documented as seizure-free survivors and seven had chronic epilepsy

The only adverse event recorded was bradycardia.

The researchers concluded that the low level of cases reported in the literature and the inconsistent amount of available information mean that the overall level of evidence supporting the use of VNS in NORSE is low. said there is.

However, the researchers were able to largely conclude that VNS was a well-tolerated intervention with no significant short-term or long-term adverse effects.

“Although it is impossible to determine the effect of stimulation thresholds on seizure arrest, most patients switch on their VNS at conventional (not high-frequency) cycling rates immediately after implantation or within the first few weeks, The output current increased for a short period of time (days to weeks),” they wrote.

reference

Ritter LM and Selway R. Perspectives: vagus nerve stimulation in the treatment of new-onset refractory status epilepticus. front new roll. Published online on April 20, 2023. doi:10.3389/fneur.2023.1172898



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