GAD 65 Antibody-associated Epilepsy
Conditions
Brief summary
The purpose of this study is to determine whether diazepam reduces the frequency of seizures in GAD65 antibody associated epilepsy.
Detailed description
GAD65 is an intracellular enzyme that plays a key role in the conversion of glutamate to gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. Benzodiazepines augment the sensitivity of the GABA-A receptor to GABA, prolonging its inhibitory effect, perhaps enhancing the potential for neural inhibition in conditions in which GABA is depleted. GAD65 antibodies have been identified in a subset of patients with drug resistant focal epilepsy and limbic encephalitis. While it has not been definitively determined that these antibodies cause GAD65 inhibition and GABA depletion directly, diazepam, a common benzodiazepine, has been established as a mainstay of therapy for stiffperson's syndrome, a condition that is commonly associated with GAD65 antibody positivity. Given these observations, diazepam has been used by the investigators in a small number of patients with intractable epilepsy in the setting of GAD65 antibody positivity, with some encouraging anecdotal results with one patient being rendered seizure free for three years. The purpose of this study is to generate prospective data on use of diazepam in patients with epilepsy related to high-titer GAD65 antibody positivity.
Interventions
DRUGDiazepam
5 mg twice daily oral for 1 week and then increase to 10 mg twice daily oral
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* High-titer serum GAD65 positivity \> 20 nmol/L High-titer serum GAD65 IgG seropositivity titer \>20 nmol/L and/or CSF GAD65 seropositivity titer \> 0.02 nmol/L. * Drug-resistant focal epilepsy, having failed 2 previous anti-seizure medications. * Stable treatment for the 1 month prior to enrollment. * Patients must be able to give informed consent or have an appropriate representative available to do.
Exclusion criteria
* Alternative etiology for epilepsy. * Already on another benzodiazepine. * On a regularly scheduled opiate. * Co-existing antibodies associated with seizures. * Pregnancy or breast feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in seizure frequency | Baseline, 3 months | Median percentage change in the mean monthly frequency of seizures as measured by patient recorded seizure frequency |
Countries
United States
Outcome results
None listed