Authors :
Presenting Author: Emily Spelbrink, MD, PHD – Stanford University
Carrie Best, MPH – Brown University; sydney Cooper, MS – UT Southwestern; jennifer Elacio, BS – Brown University; Arushi Gehani, BS – Stanford; Sweta Patnaik, MS – Stanford; tanya Brown, PHD – Tess Research Foundation; Kimberley Goodspeed, MD – UT Southwestern; Judy Liu, MD, PhD – Brown University; Kim Nye, BA – Tess Research Foundation; Rayann Solidum, MS – Stanford; brenda Porter, MD, PhD – Stanford
Rationale:
TESS Research Foundation funded a natural history and biomarker discovery study to prospectively characterize clinical aspects of SLC13A5 citrate transporter disorder (DEE 25) including epilepsy. The goal is to understand what currently available medications are helpful for treating seizures, the long-term epilepsy prognosis and identify outcome measures useful for future clinical trials.
Methods:
Subjects were identified by the TESS Foundation, confirmatory genetic testing was required and the study was open to subjects of all ages and clinical status. Here we report interim data from two natural history studies with periodic visits scheduled over a two year period for remote subjects (outside the US) and in person (within the US). Data was collected from all caregivers at the baseline 3, 6, 9, 12, 16, 20 and the 24 month visits. Caregiver Clinical Global Impression (CGI), caregiver reported seizure diary for the three months prior to the visit, and anti-seizure medication history; all data was entered into Stanford Redcap. Here we report interim data analysis for this ongoing study.
Results:
We report data on 27 patients,
age range at time of enrollment was 4 months to 30 years, average 10.4 years, with 15 males and 12 females. Over 122 visits the CGI was unchanged at 45% , slightly improved at 30 % and at 11% of the visits both slightly improved or slightly worse. Caregivers reported no change over the prior three months in seizure frequency at 85 visits, and seizure duration at 99 visits. Eight patients were seizure free at all visits, six patients were seizure free prior to some but not all visits and 11 patients were not seizure free prior to any of their visits (Figure 1a).
Average seizure burden over the three month window varied widely with some patients having multiple seizure per day see (Figure 1b). Seventeen different anti-seizure medications were reported to be used for seizure control (Table 1), of anti-seizure medications used by four or more subjects: valproic acid, phenobarbital, acetazolamide, topiramate and lacosamide were most often associated with seizure freedom.
Conclusions:
There is a wide spectrum of seizure burden across the SLC13A5 related epilepsy spectrum with seizure control on anti-seizure medications possible in only about a third. Most subjects, even with polypharmacy did not obtain persistent seizure freedom and a few had an immense seizure burden. Several currently available anti-seizure medications, valproic acid, phenobarbital, acetazolamide, topiramate and lacosamide, appear more likely to be associated with seizure freedom. Epilepsy is a lifelong risk for most patients with SLC13A5 citrate transporter disorder. Seizure burden and anti-seizure medication usage should be incorporated into future clinical trial design.
Funding: Tess Research Foundation