Improved seizure burden and cognitive performance in a child treated with responsive neurostimulation (RNS) following febrile infection related epilepsy syndrome (FIRES)

Abstract

Responsive neurostimulation (RNS) is an emerging therapy for patients with refractory focal epilepsy who are not candidates for surgical resection, with limited published experience in the pediatric population. We report a case of refractory multifocal epilepsy following febrile infection related epilepsy syndrome (FIRES) in which surgical resection was not feasible due to multifocal independent seizures and risk of cognitive deficit, and RNS was pursued. Relevant RNS data and neuropsychological testing results were reviewed. By eight months after implantation, decreased frequency and severity of clinical seizures were noted, and RNS data revealed decreased “long episodes,” reduced spread of electrographic seizures, and fewer detections. Neuropsychological assessment, though potentially confounded by stimulant medication, revealed significant improvement in multiple cognitive domains, particularly working memory and processing speed, at six months. These findings illustrate success in detecting and aborting seizures, and additionally suggest a neuromodulatory effect of RNS stimulation. Our case demonstrates feasibility, efficacy and safety of RNS in a pediatric patient with FIRES, with evidence to also suggest cognitive improvement.

International consensus recommendations for management of new onset refractory status epilepticus including febrile infection‐related epilepsy syndrome: Statements and supporting evidence

“…However, based on the possible anti‐inflammatory effect of VNS 111 and the long‐term use in several other forms of therapy‐refractory epilepsies, including RSE, 112–114 neuromodulation with VNS can also play a role in NORSE/FIRES and should be considered. Likewise, recent case reports of positive effects using brain‐responsive neurostimulation in FIRES 115 and in autoimmune encephalitis 116 as well as a recent review on neuromodulation in SRSE 117 indicate a need for further studies in these areas. Current evidence does not support the usefulness of deep brain stimulation (DBS) for postacute epilepsy (M = 8, MA = 8, MP = 7.5, LA = 70.8%, LD = 6.3%).The use of DBS in NORSE has been highlighted in a case report where centromedian thalamic nuclei DBS (in combination with anakinra) reduced the burden of generalized seizures but had no effect on focal seizures in a patient with medically intractable epilepsy following FIRES 118 . With such limited experience and scarce published data, the panel did not believe that it was feasible to provide a recommendation until further evidence is available.…”

“…However, based on the possible anti‐inflammatory effect of VNS 111 and the long‐term use in several other forms of therapy‐refractory epilepsies, including RSE, 112 , 113 , 114 neuromodulation with VNS can also play a role in NORSE/FIRES and should be considered. Likewise, recent case reports of positive effects using brain‐responsive neurostimulation in FIRES 115 and in autoimmune encephalitis 116 as well as a recent review on neuromodulation in SRSE 117 indicate a need for further studies in these areas. Current evidence does not support the usefulness of deep brain stimulation (DBS) for postacute epilepsy (M = 8, MA = 8, MP = 7.5, LA = 70.8%, LD = 6.3%).…”

Utility of hybrid PET/MRI in stereoelectroencephalography guided radiofrequency thermocoagulation in MRI negative epilepsy patients

“…Although a promising outcome was obtained with seizure frequency reduction of >50% in most of the included patients, the sample in these studies was exceedingly small, thus limiting the generalizability of the efficacy of neuromodulation for patients with multifocal epilepsy (Elder et al, 2019;Theroux et al, 2020;Herrera et al, 2021). The implantation of DBS or VNS devices could bring about risks of complications including infection and rejection.…”

“…Recently neurostimulation therapies, including deep brain stimulation (DBS), responsive neurostimulation (RNS), and vagal nerve stimulation (VNS) have been used in the treatment of multifocal epilepsy ( Giordano et al, 2017 ; Sisterson et al, 2019 ; Rincon et al, 2021 ). Although a promising outcome was obtained with seizure frequency reduction of >50% in most of the included patients, the sample in these studies was exceedingly small, thus limiting the generalizability of the efficacy of neuromodulation for patients with multifocal epilepsy ( Elder et al, 2019 ; Theroux et al, 2020 ; Herrera et al, 2021 ). The implantation of DBS or VNS devices could bring about risks of complications including infection and rejection.…”

“…Among the 19 patients with concordant findings between the two modalities, seizure freedom was achieved in eight (42%). PET/MRI is better in expanding the range of possible SOZs rather than confirming a specific EZ to be resected based on that the hypometabolism area usually extend to a larger area beyond the structural lesion (Theodore et al, 1986;Ryvlin et al, 1992). SEEG findings could be used when presurgical examination were not congruent and hybrid PET/MRI alone cannot serve as a definite prognostic factor in epileptic patients.…”