Cerebellar volume as an imaging marker of development in infants with tuberous sclerosis complex.

Abstract

In this cohort analysis, we studied 1-year-old infants with tuberous sclerosis complex (TSC), correlating volumes of cerebellar structures with neurodevelopmental measures. We analyzed data from a prospective biomarker study in infants with TSC (ClinicalTrials.gov NCT01780441). We included participants aged 12 months with an identified mutation of <i>TSC1</i> or <i>TSC2</i>. Using MRI segmentation performed with the PSTAPLE algorithm, we measured relative volumes (structure volume divided by intracranial contents volume) of the following structures: right/left cerebellar white matter, right/left cerebellar exterior, vermal lobules I-V, vermal lobules VI-VII, and vermal lobules VIII-X. We correlated relative volumes to Mullen Scales of Early Learning (MSEL) scores. There were 70 participants (mean age 1.03 [0.11] years): n = 11 had a <i>TSC1</i> mutation; n = 59 had a <i>TSC2</i> mutation. For patients with <i>TSC2</i> mutation, for every percentage increase in total cerebellar volume, there was an approximate 10-point increase in MSEL composite score (β = 10.47 [95% confidence interval 5.67, 15.27], <i>p</i> < 0.001). For patients with <i>TSC1</i> mutation, the relationship between cerebellar volume and MSEL composite score was not statistically significant (β = -10.88 [95% confidence interval -22.16, 0.41], <i>p</i> = 0.06). For patients with <i>TSC2</i> mutation, there were positive slopes when regressing expressive language and visual reception skills with volumes of nearly all cerebellar structures (<i>p</i> ≤ 0.29); there were also positive slopes when regressing receptive language skills, gross motor skills, and fine motor skills with volumes of cerebellar right/left exterior (<i>p</i> ≤ 0.014). Cerebellar volume loss-perhaps reflecting Purkinje cell degeneration-may predict neurodevelopmental severity in patients with <i>TSC2</i> mutations.