Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and Chiari malformation Type I in patients with hereditary disorders of connective tissue

• Published in: Journal of neurosurgery. Spine Vol. 7; no. 6; pp. 601 - 609
• Main Authors: MILHORAT, Thomas H, BOLOGNESE, Paolo A, NISHIKAWA, Misao, MCDONNELL, Nazli B, FRANCOMANO, Clair A
• Format: Journal Article
• Language: English
• Published: Charlottesville, VA American Association of Neurological Surgeons 01-12-2007
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Arnold-Chiari Malformation - complications; Arnold-Chiari Malformation - diagnostic imaging; Arnold-Chiari Malformation - therapy; Atlanto-Axial Joint - diagnostic imaging; Atlanto-Occipital Joint - diagnostic imaging; Biological and medical sciences; Child; Child, Preschool; Cohort Studies; Connective Tissue Diseases - complications; Connective Tissue Diseases - genetics; Connective Tissue Diseases - therapy; Ehlers-Danlos Syndrome - complications; Ehlers-Danlos Syndrome - genetics; Female; Genes, Dominant; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Joint Instability - diagnostic imaging; Joint Instability - etiology; Male; Medical sciences; Middle Aged; Neurosurgery; Orthopedic surgery; Prospective Studies; Skull - diagnostic imaging; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Syndrome; Tomography, X-Ray Computed; Traction; Human; Skin disease; Nervous system diseases; Ehlers-Danlos syndrome; Elastic tissue disease; Diseases of the osteoarticular system; craniocervical instability; joint hypermobility; Joint; Congenital disease; Genetic disease; Cerebral disorder; Connective tissue; Arnold-Chiari malformation; Malformation; cranial settling; Systemic disease; Central nervous system disease; connective tissue disorders; Instability; Chiari malformation
• ISSN: 1547-5654; 1547-5646
• DOI: 10.3171/SPI-07/12/601

Chiari malformation Type I (CM-I) is generally regarded as a disorder of the paraxial mesoderm. The authors report an association between CM-I and hereditary disorders of connective tissue (HDCT) that can present with lower brainstem symptoms attributable to occipitoatlantoaxial hypermobility and cranial settling.
The prevalence of HDCT was determined in a prospectively accrued cohort of 2813 patients with CM-I. All patients underwent a detailed medical and neuroradiological workup that included an assessment of articular mobility. Osseous structures composing the craniocervical junction were investigated morphometrically using reconstructed 3D computed tomography and plain x-ray images in 114 patients with HDCT/CM-I, and the results were compared with those obtained in patients with CM-I (55 cases) and healthy control individuals (55 cases).
The diagnostic criteria for Ehlers-Danlos syndrome and related HDCT were met in 357 (12.7%) of the 2813 cases. Hereditability was generally compatible with a pattern of autosomal dominant transmission with variable expressivity. The diagnostic features of HDCT/CM-I were distinguished from those of CM-I by clinical stigmata of connective tissue disease, a greater female preponderance (8:1 compared with 3:1, p < 0.001), and a greater incidence of lower brainstem symptoms (0.41 compared with 0.11, p < 0.001), retroodontoid pannus formation (0.71 compared with 0.11, p < 0.001), and hypoplasia of the oropharynx (0.44 compared with 0.02, p < 0.001). Measurements of the basion-dens interval, basion-atlas interval, atlas-dens interval, dens-atlas interval, clivus-atlas angle, clivus-axis angle, and atlas-axis angle were the same in the supine and upright positions in healthy control individuals and patients with CM-I. In patients with HDCT/CM-I, there was a reduction of the basion-dens interval (3.6 mm, p < 0.001), an enlargement of the basion-atlas interval (3.0 mm, p < 0.001), and a reduction of the clivus-axis angle (10.8 degrees, p < 0.001), clivus-atlas angle (5.8 degrees, p < 0.001), and atlas-axis angle (5.3 degrees, p < 0.001) on assumption of the upright position. These changes were reducible by cervical traction or returning to the supine position.
The identification of HDCT in 357 patients with CM-I establishes an association between two presumably unrelated mesodermal disorders. Morphometric evidence in this cohort-cranial settling, posterior gliding of the occipital condyles, and reduction of the clivus-axis angle, clivus-atlas angle, and atlas-axis angle in the upright position-suggests that hypermobility of the occipitoatlantal and atlantoaxial joints contributes to retroodontoid pannus formation and symptoms referable to basilar impression.