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

OBJECTIVE: In this cohort analysis, we studied 1-year-old infants with tuberous sclerosis complex (TSC), correlating volumes of cerebellar structures with neurodevelopmental measures.

METHODS: 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 TSC1 or TSC2 . 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.

RESULTS: There were 70 participants (mean age 1.03 [0.11] years): n = 11 had a TSC1 mutation; n = 59 had a TSC2 mutation. For patients with TSC2 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], p < 0.001). For patients with TSC1 mutation, the relationship between cerebellar volume and MSEL composite score was not statistically significant (β = -10.88 [95% confidence interval -22.16, 0.41], p = 0.06). For patients with TSC2 mutation, there were positive slopes when regressing expressive language and visual reception skills with volumes of nearly all cerebellar structures ( p ≤ 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 ( p ≤ 0.014).

CONCLUSIONS: Cerebellar volume loss-perhaps reflecting Purkinje cell degeneration-may predict neurodevelopmental severity in patients with TSC2 mutations.