title: Testing causal mechanisms of nonsyndromic craniosynostosis using path analysis of cranial contents in rabbits with uncorrected craniosynostosis.
abstract: OBJECTIVE
  Various causal mechanisms of familial nonsyndromic craniosynostosis have been presented. One hypothesis suggests that overproduction of bone at the suture is the primary origin of craniosynostosis, which affects brain and cranial growth secondarily through altered intracranial pressure (Primary Suture Fusion Model). Other hypotheses suggest that decreased cranial base growth or abnormal brain growth are the primary cause of craniosynostosis (Cranial Base, Brain Parenchyma Models, respectively). This study was designed to investigate which model best describes neurocranial changes associated with craniosynostosis in a rabbit model through multivariate path analysis.
  
  
  METHODS
  Serial magnetic resonance imaging scans and intracranial pressure measurements were obtained at 10, 25, and 42 days of age from 18 rabbits: six controls, six with delayed-onset synostosis, and six with early-onset synostosis. Five variables were collected from each rabbit: calvarial thickness at the affected suture, cranial base length, brain volume, cerebrospinal fluid volume, and intracranial pressure. This data set was used to test causal pathway relationships generated by the proposed models. Goodness of fit was measured by experimental group for each model.
  
  
  RESULTS
  Primary Suture Fusion Model best explained the variables in both delayed-onset and early-onset synostotic rabbits (Goodness of fit = 93%, 97%, respectively). Cranial Base Model (Goodness of fit = 94%) best explained the data in control rabbits.
  
  
  CONCLUSIONS
  Results suggest that the primary site of craniosynostosis in craniosynostotic rabbits is most likely the synostosed suture. Other cranial vault anomalies are most likely secondary compensatory changes. Results of the present study may provide insight regarding the causal pathway of craniosynostosis.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. fellowsmaylew@upmc.edu
authors.forename: Wendy
authors.initials: W
authors.lastname: Fellows-Mayle
authors.forename: T Kevin
authors.initials: TK
authors.lastname: Hitchens
authors.forename: Elena
authors.initials: E
authors.lastname: Simplaceanu
authors.forename: Joyce
authors.initials: J
authors.lastname: Horner
authors.forename: Timothy
authors.initials: T
authors.lastname: Barbano
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Losee
authors.forename: H Wolfgang
authors.initials: HW
authors.lastname: Losken
authors.forename: Michael I
authors.initials: MI
authors.lastname: Siegel
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mooney
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development; D002555:Cerebrospinal Fluid / Q000502:physiology; D003393:Cranial Sutures / Q000254:growth & development / Q000503:physiopathology*; D003398:Craniosynostoses / Q000209:etiology*; D007427:Intracranial Pressure / Q000502:physiology; D008279:Magnetic Resonance Imaging; D023421:Models, Animal; D011817:Rabbits; D012886:Skull / Q000033:anatomy & histology; D019291:Skull Base / Q000033:anatomy & histology; D013997:Time Factors