Authors :
Presenting Author: Alexandra Geffrey, MD – Massachusetts General Hospital, Harvard Medical School
Lily Grossmann, MD – Massachusetts General Hospital, Harvard Medical School
Razina Aziz-Bose, MD – Massachusetts General Hospital, Harvard Medical School
Mia Bothwell, MD, PhD – Massachusetts General Hospital, Harvard Medical School
Majed Alomar, MBBS – Massachusetts General Hospital, Harvard Medical School
Yekaterina Salnikova, MD – Massachusetts General Hospital, Harvard Medical School
David Burdette, MD – Corewell Health
Kristopher Kahle, MD, PhD – Massachusetts General Hospital
Mark Richardson, MD, PhD – Massachusetts General Hospital
Catherine Chu, MD, MSC – Massachusetts General Hospital, Harvard Medical School, Kennedy Krieger Institute, Johns Hopkins University
Rationale:
Responsive neurostimulation (RNS) is a promising treatment option to reduce seizures in patients with drug-refractory epilepsy (DRE). Parameters that optimally disrupt seizures are poorly understood. We report a novel, dysharmonic, low-frequency thalamic RNS stimulation paradigm, which was well-tolerated and corresponded to rapid reduction in seizures in two children in whom high-frequency stimulation was ineffective. Methods:
We conducted retrospective review of two pediatric patients with these novel parameters.Results:
Case 1: 11-year-old boy with TSC and DRE characterized by 20s focal impaired awareness seizures occurring 8 times/day presented to the pediatric intensive care unit (PICU) with up to 150 longer, ~2 min bifrontal seizures/day. 2 years before admission, he underwent partial ablation and partial resection of a dominant left frontal tuber followed by left frontal cortico-cortical RNS implantation, contributing to reduced seizure clusters. In the PICU, he was treated with escalating therapies, achieving complete suppression, with return of near-continuous seizures when suppression was lightened. After discussion in the multidisciplinary pediatric epilepsy surgery conference, on hospital day (HD) 7, a second RNS system was placed, and SEEG leads placed to target the anterior nucleus of the thalamus and an ipsilateral frontal tuber bilaterally. HD 7-26, pentobarbital was weaned off; several high-frequency RNS stimulation parameters, frequent medication boluses, and ketogenic diet were trialed. Despite these treatments, he had up to ~70 seizures/day. His course was also notable for episodes of ventricular tachycardia and sepsis. On HD 26, low frequency (2 Hz) thalamic stimulation was programmed. Seizures were concurrently noted to be shorter, more fragmented, and fewer; med taper was initiated that day enabling extubation on HD 38. On HD 46, a paradigm of alternating 5 and 2 Hz stimulation was programmed to reduce rhythmic delta observed on EEG, coinciding with resolution of loss of consciousness (LOC) during clinical seizures. He was discharged on HD 50 after >24 h without seizures. 3 months (mos) later, several medications were tapered and ketogenic diet discontinued with sustained improvement in clinical seizures (~0-3 brief, ~ 3 second seizures/day without LOC).
Case 2: 14-year old boy with generalized DRE of unknown etiology characterized by frequent, daily absence seizures, ~10 generalized tonic clonic seizures/month, and 1-2 drop seizures/month underwent RNS implantation targeting bilateral centromedian nuclei 32 mos prior. Over the first 30 mos, charge density, duration, and frequency (142.9-333 Hz) stimulation parameters were increased without improvement. At 30 mos post-operatively, a dysharmonic paradigm of alternating 5 and 2 Hz stimulation was programmed without change in other parameters. Concurrently, absence seizures resolved. There was reduction in generalized tonic clonic and drop seizures; improvement has been sustained for 2 mos without negative effects.
Conclusions:
Dysharmonic low-frequency thalamic responsive stimulation may have acute and sustained impact to disrupt seizures with LOC in select patients.Funding:
NIH NINDS R01NS119483