Abstract
Objective: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.
Methods: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.
Results: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2).
Conclusions: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.
Clinicaltrialsgov identifier: NCT00572195.
Classification of evidence: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.
Geller EB, Skarpaas TL, Gross RE, Goodman RR, Barkley GL, Bazil CW, Berg MJ, Bergey GK, Cash SS, Cole AJ, Duckrow RB, Edwards JC, Eisenschenk S, Fessler J, Fountain NB, Goldman AM, Gwinn RP, Heck C, Herekar A, Hirsch LJ, Jobst BC, King-Stephens D, Labar DR, Leiphart JW, Marsh WR, Meador KJ, Mizrahi EM, Murro AM, Nair DR, Noe KH, Park YD, Rutecki PA, Salanova V, Sheth RD, Shields DC, Skidmore C, Smith MC, Spencer DC, Srinivasan S, Tatum W, Van Ness PC, Vossler DG, Wharen RE Jr, Worrell GA, Yoshor D, Zimmerman RS, Cicora K, Sun FT, Morrell MJ. Brain-responsive neurostimulation in patients with medically intractable mesial temporal lobe epilepsy. Epilepsia. 2017 Jun;58(6):994-1004. doi: 10.1111/epi.13740. Epub 2017 Apr 11. PMID: 28398014.
Abstract
Objective: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin.
Methods: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events.
Results: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices).
Significance: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.
Jobst BC, Kapur R, Barkley GL, Bazil CW, Berg MJ, Bergey GK, Boggs JG, Cash SS, Cole AJ, Duchowny MS, Duckrow RB, Edwards JC, Eisenschenk S, Fessler AJ, Fountain NB, Geller EB, Goldman AM, Goodman RR, Gross RE, Gwinn RP, Heck C, Herekar AA, Hirsch LJ, King-Stephens D, Labar DR, Marsh WR, Meador KJ, Miller I, Mizrahi EM, Murro AM, Nair DR, Noe KH, Olejniczak PW, Park YD, Rutecki P, Salanova V, Sheth RD, Skidmore C, Smith MC, Spencer DC, Srinivasan S, Tatum W, Van Ness P, Vossler DG, Wharen RE Jr, Worrell GA, Yoshor D, Zimmerman RS, Skarpaas TL, Morrell MJ. Brain-responsive neurostimulation in patients with medically intractable seizures arising from eloquent and other neocortical areas. Epilepsia. 2017 Jun;58(6):1005-1014. doi: 10.1111/epi.13739. Epub 2017 Apr 7. PMID: 28387951.
Abstract
Objective: Evaluate the seizure-reduction response and safety of brain-responsive stimulation in adults with medically intractable partial-onset seizures of neocortical origin.
Methods: Patients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset.
Results: There were 126 patients with seizures of neocortical onset. The average follow-up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty-six percent of patients experienced at least one seizure-free period of 6 months or longer and 14% experienced at least one seizure-free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices.
Significance: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.
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