Fatimah M Albazron1, Joel Bruss1, Robin M Jones1, Torunn I Yock1, Margaret B Pulsifer1, Alexander L Cohen1, Peg C Nopoulos1, Annah N Abrams1, Mariko Sato1, Aaron D Boes2. 1. From the Neuroimaging and Noninvasive Brain Stimulation Laboratory (F.M.A., J.B., A.D.B.), Departments of Pediatrics, Neurology, and Psychiatry, University of Iowa Hospitals and Clinics, Iowa City; Department of Pediatric Neurology (R.M.J.), Department of Radiation Oncology (T.I.Y.), Department of Psychiatry (M.B.P.), and Department of Child and Adolescent Psychiatry and Pediatric Hematology Oncology (A.N.A.), Massachusetts General Hospital; Department of Neurology (A.L.C.), Boston Children's Hospital, MA; Department of Psychiatry (P.C.N.), University of Iowa Hospitals and Clinics, Iowa City; and Department of Pediatric Hematology Oncology (M.S.), Stead Family Children's Hospital, Iowa City, IA. 2. From the Neuroimaging and Noninvasive Brain Stimulation Laboratory (F.M.A., J.B., A.D.B.), Departments of Pediatrics, Neurology, and Psychiatry, University of Iowa Hospitals and Clinics, Iowa City; Department of Pediatric Neurology (R.M.J.), Department of Radiation Oncology (T.I.Y.), Department of Psychiatry (M.B.P.), and Department of Child and Adolescent Psychiatry and Pediatric Hematology Oncology (A.N.A.), Massachusetts General Hospital; Department of Neurology (A.L.C.), Boston Children's Hospital, MA; Department of Psychiatry (P.C.N.), University of Iowa Hospitals and Clinics, Iowa City; and Department of Pediatric Hematology Oncology (M.S.), Stead Family Children's Hospital, Iowa City, IA. aaron-boes@uiowa.edu.
Abstract
OBJECTIVE: To evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS). METHODS: The postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individuals with CCAS were matched to 2 participants without CCAS by sex, age, and lesion volume. Lesion analyses included both a hypothesis-driven evaluation of the cerebellar outflow pathway (deep nuclei and superior cerebellar peduncles) and data-driven multivariate lesion symptom mapping. Lesion-associated networks were evaluated by comparing connectivity patterns between the lesion location of cases with and those without CCAS with resting-state functional connectivity MRI data from large normative adult and pediatric cohorts. RESULTS: CCAS was present in 48 of 195 participants (24.6%) and was strongly associated with cerebellar outflow tract lesions (p < 0.0001). Lesion symptom mapping also highlighted the cerebellar outflow pathway, with peak findings in the fastigial nuclei extending into the inferior vermis. Lesion network mapping revealed that the cerebellar region most associated with CCAS was functionally connected to the thalamic mediodorsal nucleus, among other sites, and that higher connectivity between lesion location and the mediodorsal nucleus predicts CCAS occurrence (p < 0.01). A secondary analysis of 27 participants with mutism revealed similar localization of lesions and lesion-associated networks. CONCLUSION: Lesions of the cerebellar outflow pathway and inferior vermis are associated with major cognitive and affective disturbances after pediatric cerebellar tumor resection, and disrupted communication between the cerebellum and the thalamic mediodorsal nucleus may be important.
OBJECTIVE: To evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS). METHODS: The postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individuals with CCAS were matched to 2 participants without CCAS by sex, age, and lesion volume. Lesion analyses included both a hypothesis-driven evaluation of the cerebellar outflow pathway (deep nuclei and superior cerebellar peduncles) and data-driven multivariate lesion symptom mapping. Lesion-associated networks were evaluated by comparing connectivity patterns between the lesion location of cases with and those without CCAS with resting-state functional connectivity MRI data from large normative adult and pediatric cohorts. RESULTS: CCAS was present in 48 of 195 participants (24.6%) and was strongly associated with cerebellar outflow tract lesions (p < 0.0001). Lesion symptom mapping also highlighted the cerebellar outflow pathway, with peak findings in the fastigial nuclei extending into the inferior vermis. Lesion network mapping revealed that the cerebellar region most associated with CCAS was functionally connected to the thalamic mediodorsal nucleus, among other sites, and that higher connectivity between lesion location and the mediodorsal nucleus predicts CCAS occurrence (p < 0.01). A secondary analysis of 27 participants with mutism revealed similar localization of lesions and lesion-associated networks. CONCLUSION: Lesions of the cerebellar outflow pathway and inferior vermis are associated with major cognitive and affective disturbances after pediatric cerebellar tumor resection, and disrupted communication between the cerebellum and the thalamic mediodorsal nucleus may be important.
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