Abstracts

Rationale: The cyclin-dependent kinase-like 5 gene (CDKL5) is involved in brain development and maturation. Children with CDKL5 have neurodevelopmental impairment and early-onset medically refractory epilepsy. Brain structural and functional characteristics have not been well documented in the literature. The aim of this study is to describe the findings of quantitative post process analysis of brain MRI and FDG-PET in two young female patients with a CDKL5 mutation compared to age matched control children. Methods: We studied two patients with confirmed CDKL5 mutation (see Table 1) and 10 age-matched controls with an age range of 3-4 years. Using FreeSurfer, the 3D T1-weighted MRI was processed to obtain gray matter volume of each cerebral region. Volumetric data for each lobar region were reported as percentages of reduction compared to average of controls. FDG PET finding was reported in Patient 1. Quantitative PET was performed on Siemens Biograph PET CT using Syngo.via software (Siemens), with comparison to a scanner-specific normal database.  Results: There was generalized atrophy in gray matter volume across all brain regions in both CDKL5 patients (see Table 1). Occipital and parietal lobes were the regions more affected on both patients. Patient 1 had more severe atrophy of the corpus callosum and cingulate gyrus than Patient 2 but reasons for this difference needs further analysis. FDG PET in Patient 1 showed asymmetric (right more than left) diffuse cortical hypometabolism involving the temporal, parietal, and frontal lobes and symmetric hippocampal hypermetabolism bilaterally. Quantitative PET analysis confirmed diffuse hypometabolism bilaterally with maximum hypometabolism in the right fronto-parietal region. Conclusions: Generalized gray matter atrophy was present in both patients with CDKL5 mutation but the atrophy severity, at age 3 years, exhibited a posterior to anterior pattern similar to the one followed by brain maturation. Qualitative and quantitative PET analysis confirmed the findings in one patient. Further study of CDKL5 patients in different age groups will help better understand the anatomo-pathological changes in this disease. Funding: None.