Abstracts

RATIONALE: Medically refractory generalized epilepsy can be a devastating condition, with few treatment options. Adjunctive vagus nerve stimulation (VNS) therapy is indicated in the US for patients with refractory partial epilepsy based on double-blind randomized multi-center trials (Cyberonics E03/E05). Some multi-center data (Cyberonics E04; Labar et al., Neurology 1999;52: 1510-2) suggest that patients with generalized syndromes also benefit. The current study directly compares the response of patients with refractory partial and generalized epilepsy syndromes at one experienced center. At the end of this activity, participants should be able to compare response rates in these syndromes and apply this knowledge in considering VNS therapy.
METHODS: Partial and generalized syndromes were classified by UCSD epileptologists based on clinical history, exam, family history, EEG, neuroimaging and ictal video-EEG recordings. Patients offered VNS were not candidates for resective surgery. Outcome data was retrospectively analyzed for 81 sequential patients age 7-63 implanted with VNS since FDA approval in 1997. Seizure calendars for 3 months prior to implant provided a mean baseline seizure frequency (MBSF). Percent seizure reduction (%SR) from MBSF was calculated for the 1-4, 5-8 and 9-12 month periods post-implant. Responders were defined those with %SR[gte]50%. Median %SR comparisons were made for the groups using independent unmatched student T-tests. Multiple regression analyses were performed to compare demographic and etiologic variables to the dependent variable of %SR at 9-12 months.
RESULTS: 9 patients were excluded (6 noncompliant, 2 infections, 1 new non-epileptic seizures). Adverse events were similar to published series. 72 patients were classified with partial (n=43) and generalized (n=29) syndromes. Groups had balanced gender ratios with similar duration of epilepsy (25y) and medication burdens. They differed in percent with mental retardation (Part/Gen=35%/79.5%), average seizure onset age (Part/Gen=12/5, p=.003) and MBSF (Part/Gen=28/85 per mo., p=.003). Multiple regression analyses revealed higher MBSF (p= 0.003) and earlier age at onset of seizures (p=0.027) as significantly correlated with a good %SR at 9 to 12 months.
Comparative seizure reductions:
At 1-4 months: Median %SR (Part/Gen=29.9%/43.3%, p=.1566); %Responders (Part/Gen=34.9%/44.8%);
At 5-8 months: Median %SR (Part/Gen=61.5%/45.2%, p=.7171); %Responders (Part/Gen=53.5%/51.7%);
At 9-12 months: Median %SR (Part/Gen=59.1%/57.5%, p=.8176); %Responders (Part/Gen=53.5%/55.2%).
CONCLUSIONS: Patients with partial and generalized epilepsy syndromes respond comparably to adjunctive VNS, with over 50% of each group achieving at least a 50% seizure reduction during the first year. There was a trend for the partial group to respond later, but no statistically significant differences were seen at any time point. The generalized group did well despite a higher MBSF and more cognitive impairment. These results support the use of VNS in generalized epilepsy and suggest the need for more trials in this group.
[Supported by: NIH Summer Research Training Grant to CQ.]; (Disclosure: Honoraria - Cyberonics (EST))