Siddharth Srivastava1, Anna K Prohl1, Benoit Scherrer1, Kush Kapur1, Darcy A Krueger1, Simon K Warfield1, Mustafa Sahin2. 1. From the Departments of Neurology (S.S., K.K., M.S.) and Radiology (A.K.P., B.S., S.K.W.), Boston Children's Hospital, Harvard Medical School, Boston, MA; and Department of Pediatrics (D.A.K.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH. 2. From the Departments of Neurology (S.S., K.K., M.S.) and Radiology (A.K.P., B.S., S.K.W.), Boston Children's Hospital, Harvard Medical School, Boston, MA; and Department of Pediatrics (D.A.K.), Division of Neurology, Cincinnati Children's Hospital Medical Center, OH. mustafa.sahin@childrens.harvard.edu.
Abstract
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.
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.
Authors: Michelle L Krishnan; Olivier Commowick; Shafali S Jeste; Neil Weisenfeld; Arne Hans; Matthew C Gregas; Mustafa Sahin; Simon K Warfield Journal: Pediatr Neurol Date: 2010-02 Impact factor: 3.372
Authors: Kit Sing Au; Aimee T Williams; E Steve Roach; Lori Batchelor; Steven P Sparagana; Mauricio R Delgado; James W Wheless; James E Baumgartner; Benjamin B Roa; Carolyn M Wilson; Teresa K Smith-Knuppel; Min-Yuen C Cheung; Vicky H Whittemore; Terri M King; Hope Northrup Journal: Genet Med Date: 2007-02 Impact factor: 8.822
Authors: Catherine J Chu-Shore; Philippe Major; Susana Camposano; David Muzykewicz; Elizabeth A Thiele Journal: Epilepsia Date: 2009-12-22 Impact factor: 5.864
Authors: Marian E Williams; Deborah A Pearson; Jamie K Capal; Anna W Byars; Donna S Murray; Robin Kissinger; Sarah E O'Kelley; Ellen Hanson; Nicole M Bing; Bridget Kent; Joyce Y Wu; Hope Northrup; E Martina Bebin; Mustafa Sahin; Darcy Krueger Journal: Am Psychol Date: 2019-04
Authors: Banu Ahtam; Mathieu Dehaes; Danielle D Sliva; Jurriaan M Peters; Darcy A Krueger; Elizabeth Martina Bebin; Hope Northrup; Joyce Y Wu; Simon K Warfield; Mustafa Sahin; Patricia Ellen Grant Journal: J Neuroimaging Date: 2019-07-14 Impact factor: 2.486
Authors: F Machado-Rivas; O Afacan; S Khan; B Marami; C K Rollins; C Ortinau; C Velasco-Annis; S K Warfield; A Gholipour; C Jaimes Journal: AJNR Am J Neuroradiol Date: 2021-01 Impact factor: 3.825
Authors: Jana E Jones; Miya R Asato; Mesha-Gay Brown; Julia L Doss; Elizabeth A Felton; Jennifer A Kearney; Delia Talos; Penny A Dacks; Vicky Whittemore; Annapurna Poduri Journal: Epilepsy Curr Date: 2020-01-23 Impact factor: 7.500