Abstracts

Rationale: The hypothalamic hamartoma (HH) is a rare tumor characteristically associated with gelastic seizures. Over time, many patients with HH will develop additional seizure types, including partial onset and generalized tonic-clonic seizures. Seizure foci may develop in other parts of the brain, a process used as a model of secondary epileptogenesis. It is not known if this process is associated with structural brain changes outside of the HH. The aim of our study was to examine differences in gray matter and white matter integrity between HH patients with only gelastic seizures and age matched patients with multiple seizure types using voxel-based morphometry. Methods: MRI images obtained from presurgical assessment were analyzed. Patients <5 years of age, with prior surgical or radiation treatment, identified genetic mutations causing HH or brain abnormalities not related to the HH were excluded. Eight patients with only gelastic seizures were identified, with a mean age of 120 months (range 63-203 months). They were age matched 1:2 with 16 patients with multiple seizure types, with a mean age of 121 months (range 58-209 months). Participants had imaging on either a 1.5 Tesla (T) or a 3 T GE scanner at Barrow Neurological Institute for preoperative planning. The images were collected using SPGR, T1-weighted, 3D acquisition. Image processing and statistical analyses were performed using SPM5. After ensuring adequate quality, images were registered to a pediatric brain template (CCHMC2_fp) with a voxel size of 1mm3, segmented to gray matter (GM), white matter (WM) and cerebral spinal fluid images, and smoothed to 12-mm3. Total intercranial volume (TIV) and age were used as covariates. Group comparisons were performed at p = 0.01. Results: The multiple seizure group showed significantly greater WM density in the left temporal (SPM(T) = 4.25; 10746 voxels) and right temporal-occipital (SPM(T) = 3.77; 10325 voxels) lobes and bilateral cerebellum (right: SPM(T) = 3.99, 7,999; voxels, left: SPM(T) = 3.83; 7860 voxels) compared to the gelastic seizure only group. There were no regions in which the gelastic seizure only group showed significantly more WM density than the multiple seizure group. No significant differences were found in gray matter density between the groups. Conclusions: Patients with HH and multiple seizure types demonstrate greater WM density in multiple brain regions compared with age matched HH patients with only gelastic seizures. Our hypothesis prior to this study was that the development of multiple seizure types would be damaging to the developing brain, causing decreased GM and WM density as a "downstream phenomena". Our results were surprising, showing that greater WM density is associated with the development of seizures outside of the HH, a potential “upstream phenomena” which may be related to better white matter maturation in this group. These findings provide evidence that better white matter integrity is associated with the development of multiple seizure types in HH, a model of secondary epileptogenesis.