Authors :
Presenting Author: Rujuta Sathe, BS – University of California, Los Angeles
Aria Terango, BS – University of California, Los Angeles; David Tabibzadeh, BS – University of California, Los Angeles; Norah Gidanian, BS – University of California, Los Angeles; Hiroki Nariai, MD PhD – University of California, Los Angeles; Rajsekar Rajaraman, MD – University of California, Los Angeles; Shaun Hussain, MD – University of California, Los Angeles
Rationale:
Infantile epileptic spasms syndrome (IESS) is an often catastrophic form of childhood epilepsy. Vigabatrin (VGB) is a moderately efficacious first-line therapy for IESS, although its use has been limited by reports of retinotoxicity. Albeit lesser known, a more significant concern in treating IESS is the risk of VGB-associated brain abnormalities on MRI (VABAM). VABAM are reversible and usually asymptomatic, T2 hyperintense signal changes in the thalami, basal ganglia, brainstem tegmentum, and cerebellar nuclei. In symptomatic cases (sVABAM), patients may present with severe encephalopathy, movement disorders, bradycardia, or a combination thereof. Prior studies have linked asymptomatic VABAM (aVABAM) to high dosage, and several case reports suggest that sVABAM may be associated with concomitant hormonal therapy (corticosteroids or ACTH). Using a large cohort of children with IESS, we set out to do the following: (1) test the hypothesized association between sVABAM and concomitant hormonal therapy, and (2) verify the association of aVABAM with peak VGB dosage.
Methods:
Patients with IESS were identified using a clinical database at UCLA. First, brain MRI reports for all subjects were serially reviewed without knowledge of VGB exposure to ascertain VABAM. In cases where VABAM was encountered, patient records were systematically reviewed to ascertain VABAM. Subjects’ progress notes were reviewed separately and in a sequential manner to determine dates and dosages of VGB and hormonal therapy.
Results:
We identified 410 brain MRI studies among 198 patients with IESS. VGB treatment was documented in 114 children, of whom 56 had at least one MRI during VGB treatment. Among 42 patients who underwent MRI for reasons other than VABAM evaluation, 6 (14%) exhibited aVABAM. Among 14 patients who underwent MRI to specifically evaluate for sVABAM, 11 (79%) exhibited typical MRI features. All 11 subjects with sVABAM were treated simultaneously with VGB and hormonal therapy, compared with 46/103 (45%) of subjects without sVABAM ( P = 0.001 ). Similarly, among the 56 subjects with MRI during VGB treatment, 15/17 (88%) subjects with VABAM (symptomatic or asymptomatic) received simultaneous hormonal therapy, compared with 17/39 (44%) of subjects without VABAM ( P = 0.003). Presence of VABAM (aVABAM or sVABAM) was associated with neither VGB treatment duration nor peak dosage.
Conclusions:
We have demonstrated that VABAM is associated with simultaneous treatment with VGB and hormonal therapy. We did not replicate a prior observation that aVABAM is associated with peak dosage. Risk of VABAM should be considered when utilizing combination therapy for the treatment of IESS.
Funding:
This study was accomplished with support from the John C. Hench Foundation, the Elsie and Isaac Fogelman Endowment, the Mohammed F. Alibrahim Endowment, the Hughes Family Foundation, and the UCLA Children’s Discovery and Innovation Institute.