title: White matter disruption is associated with persistent seizures in tuberous sclerosis complex.
abstract: White matter is diffusely altered in tuberous sclerosis complex (TSC), and these alterations appear to be more evident in subjects with a more severe neurologic phenotype. However, little is known on the correlation between white matter alterations and epilepsy in TSC. The aims of this study were to evaluate the effects of early onset and refractory seizures on white matter by using diffusion tensor imaging (DTI).
  
  
  
  We enrolled 20 children with TSC and epilepsy onset in the first 3years of life and grouped them according to seizure persistence or freedom. All patients underwent brain MRI with DTI. Specific ROIs have were placed to generate tracks to calculate fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Statistical analysis was performed by ANOVA.
  
  
  
  Children with persistent seizures presented an overall reduced FA, with statistically significant differences on the cingulum (right p=0.003, left p=0.016), the left cerebral peduncle (p=0.020), the superior cerebellar peduncles (right p=0.008, left p=0.002), the posterior limbs of internal capsule (right p=0.037, left p=0.015), the external capsule (right p=0.018, left p=0.031), the inferior frontooccipital fasciculus (right p=0.010, left p=0.026), and the temporal trunk (right p=0.017, left p=0.001).
  
  
  
  Our study demonstrated that children with persistent seizures present more significant alterations of brain connectivity in areas crucial for global cognitive maturation, executive functions, and verbal abilities, implying a higher risk of cognitive impairment, attention-deficit hyperactivity disorder, and autism.
authors.affiliation: Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Viale Oxford 81, 00133 Rome, Italy; Neuroscience Department, Neurology Unit, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy. Electronic address: rominamoavero@hotmail.com.
authors.forename: Romina
authors.initials: R
authors.lastname: Moavero
authors.affiliation: Enterprise Risk Management, Medical Physics Department, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Napolitano
authors.affiliation: Neuroscience Department, Neurology Unit, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cusmai
authors.affiliation: Neuroscience Department, Neurology Unit, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Vigevano
authors.affiliation: Neuroradiology Unit, Imaging Department, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Figà-Talamanca
authors.affiliation: Anesthesiology Unit, DEA-ARCO "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calbi
authors.affiliation: Systems Medicine Department, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Viale Oxford 81, 00133 Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Curatolo
authors.affiliation: Neuroradiology Unit, Imaging Department, "Bambino Gesù" Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bernardi
mesh_terms: D017668:Age of Onset; D016880:Anisotropy; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology; D000067877:Autism Spectrum Disorder / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology; D056324:Diffusion Tensor Imaging; D004351:Drug Resistance; D056344:Executive Function; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000209:etiology; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging; D011446:Prospective Studies; D012640:Seizures / Q000000981:diagnostic imaging* / Q000209:etiology* / Q000523:psychology; D014402:Tuberous Sclerosis / Q000150:complications* / Q000000981:diagnostic imaging* / Q000523:psychology; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: Autism; Cognitive impairment; Diffusion tensor imaging; Epilepsy; Tuberous sclerosis complex; White matter