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

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Object

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.

Methods

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).

Results

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°, p < 0.001), clivus–atlas angle (5.8°, p < 0.001), and atlas–axis angle (5.3°, p < 0.001) on assumption of the upright position. These changes were reducible by cervical traction or returning to the supine position.

Conclusions

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.

Abbreviations used in this paper:CCJ = craniocervical junction; CM-I = Chiari malformation Type I; CT = computed tomography; EDS = Ehlers–Danlos syndrome; HDCT = hereditary disorders of connective tissue; KPS = Karnofsky Performance Scale; MASS = mitral valve, aorta, skeleton, and skin; MR = magnetic resonance; POTS = postural orthostatic tachycardia syndrome; SD = standard deviation; TGFβ = transforming growth factor–β.

Article Information

Address correspondence to: Thomas H. Milhorat, M.D., Department of Neurosurgery, The Chiari Institute, Harvey Cushing Institutes of Neuroscience, North Shore–LIJ Health System, 300 Community Drive, Manhasset, New York 11030. email: Milhorat@nshs.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Midsagittal reconstructed 2D CT scans obtained in control individuals with normal anatomy, showing lines (left) and measurement intervals (right) for assessing osseous structures at the CCJ: Line A, plane of posterior surface of anterior arch of atlas; Line B, that between lowest point of anterior arch of atlas and lowest point of posterior arch of atlas. Arrowheads identify the basion–atlas interval; upper arrow with dotted lines defines the basion–dens interval; lower arrow with dotted lines indicates the interval between the dens and Line B (the atlas–dens interval); and the star identifies atlas–dens interval. ADI = interval between posterior surface of anterior arch of atlas and dens; BAI = interval between basion and Line A; BDI = interval between basion and top of dens; DAI = interval between top of dens and Line B.

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    Lines and angles for assessing osseous structures at the CCJ on midsagittal reconstructed 2D CT scans in control individuals with normal anatomy: Line C, superior plane of the clivus; Line D, plane of posterior surface of dens; and Line E, that between the top of anterior arch of atlas and lowest point of posterior arch of atlas. AXA = angle between atlas (Line E) and axis (Line D); CAA = angle between clivus (Line C) and atlas (Line E); CXA = angle between clivus (Line C) and axis (Line D).

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    Evidence of functional cranial settling in a 25-year-old woman with HDCT/CM-I. Left: The results of midsagittal reconstructed 2D CT scanning in the supine position indicated a baseline basion–dens interval of 5.1 mm. Center and Right: The results of plain radiography indicated a decrease of the basion–dens interval (2.2 mm) in the sitting position and an increase of the basion–dens interval (5.7 mm) during traction with a 20-lb weight.

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    Evidence of posterior gliding of the occipital condyle in a 33-year-old woman with HDCT/CM-I. Results of midsagittal reconstructed 2D CT scanning with the patient in the supine position, showing baseline basion–atlas interval of 3.1 mm (upper left) and normal articulation of occipital condyle (OC) (lower left). Results of plain radiography (center and right) show an increase of the basion–atlas interval (7.2 mm) in the sitting position and a decrease of the basion–atlas interval (2.8 mm) during traction with a 20-lb weight. The occipitoatlantal joint (outlined by dotted line) glides posteriorly in the sitting position (curved arrow) and is reduced by traction (thick arrow). Line A, plane of the posterior surface of the anterior arch of the atlas.

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    Evidence of anterior flexion of occipital condyles in a 41-year-old woman with HDCT/CM-I. Results of midsagittal reconstructed 2D CT scanning in supine position (left) indicate baseline clivus–axis angle of 148°. Results of plain radiography (center and right) indicate a decrease of the clivus–axis angle (138°) in the sitting position and an increase of the clivus–axis angle (150°) during traction with a 20-lb weight. Line C, superior plane of clivus; Line D, plane of posterior surface of dens. Angle between clivus (Line C) and axis (Line D).

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    Results of vertical MR imaging in a 27-year-old woman with HDCT/CM-I. Midsagittal image in supine position (left) showing normal basion–dens interval (7.7 mm), normal basion–atlas interval (3.5 mm), normal clivus–axis angle (141°), large retroodontoid pannus, and low-lying cerebellar tonsils. On assumption of the upright position (right), there is evidence of cranial settling (2.6 mm decrease of basion–dens interval), posterior gliding of occipital condyles (4.3 mm increase of basion–atlas interval), anterior flexion of the occipitoatlantal joint (8° decrease of clivus–axis angle), increased basilar impression, and cerebellar ptosis with downward displacement of cerebellar tonsils to C-1 (white arrow). Note the greatly increased impaction of the foramen magnum anteriorly and posteriorly. Line C, superior plane of the clivus; Line D, plane of the posterior surface of the dens. Asterisk indicates the retroodontoid pannus.

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