Abstracts

RATIONALE: Refractory status epilepticus ( RSE), defined as SE that fails to respond to second-line therapy,and its treatments are associated with high morbidity and mortality. Thus, new therapies are needed that are safe with no drug interactions. Vagus nerve stimulation (VNS) is a safe, minimally invasive therapy with no drug interactions. We investigated high output current VNS with rapid cycling as adjunct therapy in refractory status epilepticus. Participants should be able to undertand the role VNS may have in management of RSE.
METHODS: Patients who had persistent RSE which had not responded to intravenous benzodiazepines, phenytoin, phenobarbital and valproic acid and did not have a deteriorating/progressive neurologic/systemic etiology of the RSE were considered for compassionate use of VNS from 2000- current. RSE was confirmed by continuous EEG recording with impaired consciousness. Age, SE etiology, duration of SE prior to VNS,concomitant treatments and MRI results were reviewed and fully considered in the implantation decision. Time to RSE termination was confirmed by EEG and clinical outcome with 1 year followup was assessed by phone followup. Surgical complications, stimulation parameters including output current, signal frequency, on/off time and pulse width were registered.
RESULTS: Three patients (of 10 potential RSE cases) met criteria for compassionate use of VNS for RSE (2 males- age 20, 82; 1 female- age 64). All had EEG confirmed persistent RSE and all were in a clinically subtle status with loss of consciousness. Each had a history of medication refractory multifocal partial epilepsy and the etiology of SE in each patient was antiepileptic drug (AED) withdrawal. All patients failed to respond to lorazepam, supratherapeutic levels of phenytoin (serum range 25-27), valproic acid ( serum range 90-110) and phenobarbital ( serum range 50-65). Two patients failed trials of general anesthesia with periods of generalized EEG suppression. MRI of the brain showed no evidence of stroke or CNS tumor. Duration of SE prior to any treatment was 12-36 hours whereas duration of SE prior to VNS treatment was 1week to 5 weeks. All patients had VNS implanted under general anesthesia with no surgical complications. All patients had continuous EEG monitoring pre and postoperatively. VNS was quickly ramped up to maximum output current of 3 mamp at a signal frequency of 30 hz, pulse width 500, on time 60 seconds, off time 1 minute. No pulmonary or cardiac problems were encountered. All patients remained on their concomitant phenobarbital and/or phenytoin, valproic acid. Time to RSE termination with EEG confirmation after VNS implantation was 3-5 days. All patients were subsequently discharged from the hospital. At 1 year followup, 2 patients remain with the VNS at lower stimulation parameters, one patient ( age 82 years) died 1 year later after full recovery from RSE from complications from a generalized tonic clonic seizure.
CONCLUSIONS: Adjunct high output current VNS with rapid cycling is potentially useful in RSE cases that lack poor prognotic etiologies. VNS and other stimulation techniques should be investigated in RSE due to AED withdrawal and other RES etiologies with less dire prognosis. Further studies assessing RSE and its treatment are needed.
(Disclosure: Grant - Dr. Sirven had a research grant with Cyberonics in 1999., Honoraria - Dr. Sirven has recived honoraria for speaking.)