Academic Editor: Rafael Franco
Background: The frequent association of basilar invagination (BI) makes the understanding of the pathogenesis of Chiari malformation type I (CMI) difficult. The influence of group B type of BI (the BI without obvious atlantoaxial instability) on the skeletal morphology has not been thoroughly studied. The objective of this study is to evaluate the skeletal alterations in the posterior cranial fossa (PCF) of adult CMI cases with and without group B BI. Methods: Fifty-four adult CMI without BI cases (CMI-only group) and 30 adult CMI with group B BI cases (CMI-BI group) were retrospectively studied. Fifty-six adult patients with unruptured intracranial aneurysms were included as the controls. Several linear and angular variables, and the bony volume of the PCF were analyzed based on thin-slice computed tomography data. Results: Morphological analysis revealed a significant difference in several variables from controls compared to CMI-only, and CMI-BI patients. The clivus and occipital bone, shortened and elevated in CMI-only patients, were further flattened in BI-associated CMI patients. Furthermore, although out of the scope for the diagnostic threshold of BI, the CMI-only cases also had a tendency to form BI. The association of BI modified several variables, without further reducing the bony PCF volume. Conclusions: These findings indicate that the variables associated with group B BI tend to be a continuum of the same pathological abnormalities that originate from the same pathological alterations in CMI patients.
Chiari malformation and basilar invagination (BI) are common malformations of the craniocervical junction (CVJ) in adults . BI is defined as the invagination of the high cervical spine into the cranial base [1, 2, 3, 4]. Chiari malformation type I (CMI) is characterized by the caudal herniation of the cerebellar tonsils through the foramen magnum into the spinal canal [2, 4, 5, 6].
BI may also result in CMI in some patients [7, 8]. Each of these two clinical entities can be present individually, but they frequently occur synchronously [1, 4, 9, 10]. The term “CMI” was used in previous studies, without excluding BI-associated cases, which limits our knowledge regarding the pathogenesis of the underlying CMI . Goel divided BI into two groups, based on the presence (group A) or absence (group B) of the instability of the atlantoaxial region, as demonstrated by an abnormal increase in the atlanto-dental interval  (Fig. 1). Due to the differences in the pathogenesis, manifestation and treatment , the group A BI-associated CMI cases were excluded from this study.
The reconstructed mid-sagittal CT and MRI T2-WI image of three types of craniocervical junction malformation. (a,b) CMI with Group A BI. (c,d) CMI with Group B BI. (e,f) CMI without BI. Red line, the Chamberlain line; Red arrow, the tip of dens; Green line, the McRae line; Green arrow, the tip of herniated cerebellar tonsil.
It is generally believed that CMI patients tend to have reduced volume in the posterior cranial fossa (PCF) [2, 6, 13]. Our previous study confirmed decreased bony PCF volume in simple CMI cases without BI or atlantoaxial dislocation . Despite numerous studies, the origin and pathophysiology of CMI, especially the subset combined with BI, remains controversial [15, 16, 17, 18, 19]. A thorough comparative analysis of the skeletal structures of the PCF in simple CMI and BI-associated CMI cases has not been reported . The objective of this study was to evaluate the differences of the CVJ skeleton in CMI with and without BI, based on data derived from thin-slice computer tomography (CT).
We retrospectively studied 120 adult CMI cases who had received foramen magnum decompression (FMD) in the Neurosurgical Department of the First Affiliated Hospital of Chongqing Medical University from January 2015 to April 2020. CMI cases with or without group B type of BI were designated as the CMI-BI group or CMI-only group, respectively. Cases combined with atlantoaxial instability were diagnosed as atlantoaxial dislocation (AAD), and excluded from this study. Gender and age matched patients with un-ruptured intracranial aneurysms were included as the controls. The control cases underwent regular CT angiography, to eliminate the inclusion of patients with BI or AAD. An informed consent of all participants was obtained. All procedures performed in studies involving human participants were approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University.
The diagnostic criteria for CMI was defined as the presence of cerebellar tonsils which protruded through the foramen magnum by more than 5 mm in the sagittal MRI T2 image (Fig. 1). BI was diagnosed if the tip of the dens was more than 5 mm above Chamberlain’s line in the reconstructed mid-sagittal CT image (Fig. 1). AAD was diagnosed if the atlanto-dental interval was more than 3 mm on CT, or in the presence of instability which was confirmed on dynamic X-rays of the CVJ. The inclusion criteria were as following: (1) a diagnosis of CMI; (2) patients older than 18 years. The exclusion criteria were: (1) cases associated with AAD (group A BI), or other bone malformations in the CVJ; (2) cases with acquired cerebellar tonsil herniation; (3) cases with other spinal cord malformations, such as the tethered cord syndrome; (4) cases associated with spine surgery or trauma.
CT scans (0.6 mm each slice) were obtained for each CMI patient, with the neck in a neutral position, on a 128-slice multi-detector CT scanner (Siemens, Germany). The images in DICOM format were reconstructed in three orthogonal planes using RadiAnt DICOM Viewer, version 5.5.0. (Medixant, Poland) software. The images of the control group obtained from the CT angiography were also analyzed using the same methods. Eight linear and 9 angular parameters (Table 1) were measured on the mid-sagittal image, according to our previous method  (Fig. 2), using RadiAnt or iPhotoDraw V2.6 software (Simen Wu, Canada). The first author evaluated all of the exams to minimize variations in measurements.
Diagrams showing the linear and angular measurements on a mid-sagittal image. (a,b) Chamberlain’s line (HO), McRae line (BO), clivus length or CL (DB), Supraoccipital length or SOL (IO), anterio-posterior length of PCF or AP-PCF (DI), Klaus height index or KHI (PA), axial length or AL (AC). b, magnification of the dashed rectangle in a. The green line, Violation of the Chamberlain’s line (VC); the blue line, Violation of the McRae line (VM). A, the tip of the dens; B, basion; C, midpoint of the inferior endplate of C2 vertebrae; D, top of the dorsum dorsum; H, posterior margin of the hard palate; I, internal occipital protuberance; P, the point on the line of TI shortest to the tip dens axis; O, opisthion; T, tuberculum sellae. (c,d) BA, basal angle; CA, clivus angle; CAA, clivus axial angle; CChA, clivus Chamberlain’s line angle; OA, occipital angle; OCA, occipital cannal angle; OChA, occipital Chamberlain’s line angle; TA, tentorial angle; TDA, tentorial dorsum sellae angle. d, local magnification of c.
|AL||axial length||distance from the midpoint of the inferior margin of axis to the tip of dens|
|AP-PCF||anteroposterior diameter of posterior cranial fossa||distance from the center of the internal occipital protuberance to the dorsum sellae|
|CL||clivus length||distance between the top of the dorsum sellae and the basion|
|KHI||Klaus height index||the vertical line from the dens tip to the line between internal occipital protuberance and the tuberculum sellae|
|ML||McRae line||distance from the opisthion to basion|
|SOL||supraoccipital length||distance from the center of the internal occipital protuberance to the opisthion|
|VC||violation of the Chamberlain’s line||distance from the tip of dens above the line extending from the palate to the opisthion|
|VM||violation of the McRae line||distance from the tip of dens above the line extending from basion to the opisthion|
|BA||basal angle||angle measured from the base of the anterior cranial fossa and a line drawn between the top of the dorsum sellae and the basion|
|CA||clivus angle||angle formed by the MaRae line and the line along the inferior half of the clivus|
|CAA||clivus axial angle||angle formed by a line along the posterior margin of the dens and the line along the inferior half of the clivus|
|CChA||clivus Chamberlain’s line angle||angle measured by a line drawn along the inferior half of the clivus and the Chamberlain’s line|
|OA||occipital angle||angle formed by the line of SOL and the McRae line|
|OCA||occipital canal angle||angle formed by the SOL and the line along the posterior wall of the C1-2 canal|
|OChA||occipital Chamberlain’s line angle||angle formed by the SOL and the Chamberlain’s line|
|TA||tentorial angle||angle formed by the tentorium and the line of SOL|
|TDA||tentorial dorsum sellae angle||angle formed by the tentorium and the line from the dorsum sellae to the internal occipital protuberance|
|The values of VC and VM were recorded as negative when the dens tip was below the corresponding line.|
The volume of the bony PCF was calculated using Mimics Research, version 22.214.171.1245 (Materialise NV, Leuven, Belgium), according to a previous method . Briefly, a mask was constructed to define the bony boundary in the axial, sagittal and coronary planes, and the tool of region growing was used to reconstruct a 3-D model. Thus, the volume of the bony PCF was calculated automatically (Fig. 3).
Illustration of the measurement of the bony PCF using Mimics Research software. A mask was constructed to define the bony boundary in axial (a), sagittal (b) and coronary image (c), and a 3D model (d,e) was reconstructed using the tool of region growing in Mimics.
IBM SPSS 19.0 software (IBM Corp., Armonk, NY, USA) was used for statistical
analysis. The descriptive statistics are presented as the means, standard
deviations, ranges, and 95% confidence intervals (CIs). The adherence
chi-squared test was used to analyze the difference in gender. The value of VM,
CL, AP-PCF, KHI, BA, CChA, CAA, OCA, TA and TDA were compared using parametric
ANONA. The age, VC, AL, ML, SOL, CA, OA and OChA were compared using
Kruska-Wallis tests and subsequent peer evaluation. Measures of multiple linear
correlation were obtained between several variables, using Spearman to evaluate
the possible associative inferences. Statistically significance was indicated by
Of the 120 CMI cases, 36 were excluded due to missing or incomplete images. Finally, 54, 30 and 56 cases were included in CMI-only, CMI-BI and control group, respectively.
There were 41 females and 11 males in CMI-only group, with a mean age of 46.63
All CMI patients presented with neurological symptoms, including neuropathic pain, limb numbness, sensory disturbance, muscle weakness and ataxia. Seventy-six patients (90.48%; 49 cases in CMI-only group, and 27 cases in CMI-BI group) had syringomyelia.
Results of linear measurements are summarized in Table 2.
|(95% CI L to U)||(95% CI L to U)||(95% CI L to U)|
|(–1.54 to 0.22)||(0.34 to 1.99)||(6.88 to 10.20)|
|(3.85 to 4.10)||(3.28 to 3.49)||(2.62 to 2.94)|
|(4.39 to 4.60)||(4.06 to 4.24)||(3.84 to 4.08)|
|(4.16 to 4.40)||(3.70 to 3.96)||(3.76 to 4.17)|
|(3.27 to 3.43)||(3.09 to 3.21)||(3.06 to 3.24)|
|(–5.39 to –4.54)||(–4.94 to –4.24)||(–3.35 to –2.27)|
|(3.41 to 3.54)||(3.32 to 3.45)||(3.33 to 3.77)|
|(8.15 to 8.41)||(8.12 to 8.41)||(8.29 to 8.65)|
|(118.68 to 122.37)||(126.16 to 130.63)||(140.82 to 148.25)|
|(106.51 to 109.96)||(111.11 to 114.89)||(114.23 to 120.29)|
|(66.45 to 68.53)||(61.92 to 64.73)||(54.93 to 59.99)|
|(156.48 to 161.25)||(149.00 to 152.75)||(135.76 to 143.42)|
|(133.52 to 136.89)||(137.91 to 142.67)||(136.02 to 143.46)|
|(126.35 to 130.00)||(126.88 to 131.17)||(114.27 to 123.56)|
|(133.88 to 139.69)||(136.20 to 142.48)||(137.93 to 150.08)|
|(95.49 to 99.79)||(91.58 to 96.51)||(89.79 to 95.95)|
|(39.73 to 43.24)||(38.86 to 43.03)||(37.02 to 41.08)|
|PCF volume (mL)||159.58
|(154.69 to 164.47)||(132.42 to 143.77)||(136.43 to 148.44)|
|Compared with Control: |
(a) VC and KHI. The VC increased, and KHI diminished progressively from the
control to CMI-only, and CMI-BI group, with significant differences (p
(b) VM. VM of CMI-BI patients were significantly larger than the control (p = 0.000) and CMI-only group (p = 0.000), however, no significant differences were observed between the control and CMI-only group (p = 0.546).
(c) CL, SOL and AL. CL, SOL and AL in CMI-BI (p = 0.000, p = 0.011, and p = 0.007) and CMI-only group (p = 0.000, p = 0.000, and p = 0.000) were significantly smaller than those in the control, however no significant differences were observed between the two CMI groups (p = 0.063, p = 0.269, and p = 0.926).
(d) ML and AP-PCF. No significant differences were observed between either of
these 3 groups (p
Results of angular measurements are summarized in Table 2.
(a) BA, CChA, CA and CAA. BA and CA increased progressively from the control to CMI-only (p = 0.001, p = 0.000), and CMI-BI group (p = 0.027, p = 0.000). While, CChA and CAA diminished progressively from the control group to CMI-only (p = 0.000, p = 0.000), and CMI-BI group (p = 0.000, p = 0.000).
(b) OChA. The value of OChA in CMI-BI (p = 0.015) and CMI-only group (p = 0.001) was significantly larger than the control, but there was no significant difference between the two CMI groups (p = 0.897).
(c) OA. OA in CMI-BI group was significantly smaller than the CMI-only group (p = 0.000) and the control (p = 0.000). There was no significant difference between CMI-only and the control group (p = 0.324).
(d) OCA and TA. OCA and TA in CMI-BI group were significantly larger than the control (p = 0.036, p = 0.039). No significant differences were observed in the CMI-only group when compared with CMI-BI (p = 0.289, p = 1.000) and the control group (p = 0.867, p = 0.081).
(e) TDA. No significant differences were observed between either of these 3
The volumes of bony PCF in CMI-BI (p = 0.000) and the CMI-only group (p = 0.000) were significantly decreased than the control, but there was no significant difference between the two CMI groups (p = 0.943) (Table 2).
Correlations were calculated among the major variables. Mild and moderate correlations were obtained. The findings are summarized in Table 3.
|VC||R = –0.545||R = –0.022||R = –0.749||R = 0.829||R = –0.522||R = –0.527||R = 0.316||R = –0.184|
|p = 0.000||p = 0.796||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.030|
|CL||R = 1.000||R = 0.183||R = 0.679||R = –0.599||R = 0.317||R = 0.399||R = –0.409||R = 0.417|
|p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000|
|SOL||R = 0.183||R = 1.000||R = 0.331||R = –0.079||R = 0.155||R = 0.112||R = –0.203||R = 0.540|
|p = 0.000||p = 0.000||p = 0.000||p = 0.353||p = 0.070||p = 0.051||p = 0.018||p = 0.000|
|KHI||R = 0.679||R = 0.331||R = 1.000||R = –0.776||R = 0.556||R = 0.558||R = –0.472||R = 0.431|
|p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000|
|CA||R = –0.599||R = –0.079||R = –0.776||R = 1.000||R = –0.599||R = –0.746||R = 0.452||R = –0.254|
|p = 0.000||p = 0.353||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.002|
|CAA||R = 0.317||R = 0.155||R = 0.556||R = –0.599||R = 1.000||R = 0.617||R = –0.508||R = 0.219|
|p = 0.000||p = 0.070||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.010|
|CChA||R = 0.399||R = 0.112||R = 0.558||R = –0.746||R = 0.617||R = 1.000||R = 0.190||R = 0.266|
|p = 0.000||p = 0.051||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.001||p = 0.000|
|BA||R = –0.409||R = –0.409||R = –0.472||R = 0.452||R = –0.508||R = 0.190||R = 1.000||R = –0.275|
|p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.000||p = 0.001||p = 0.000||p = 0.001|
|PCF volume||R = 0.417||R = 0.540||R = 0.431||R = –0.254||R = 0.219||R = 0.266||R = –0.275||R = 1.000|
|p = 0.000||p = 0.000||p = 0.000||p = 0.002||p = 0.010||p = 0.000||p = 0.001||p = 0.000|
Our research studied the skeletal alterations in the PCF of CMI cases associated with and without BI, and confirmed that the association of BI aggravates the invagination of the clivus and occipital bones of the CMI, without further reducing the volume of the bony PCF. Furthermore, although not diagnosed as BI, according to the threshold of 5 mm, the CMI-only cases also had a tendency to form BI.
CMI is defined as the herniation of the cerebellar tonsil by more than 5 mm below the foramen magnum [2, 4, 5, 6]. However, this simplistic definition masks the complex nature of this heterogeneous abnormality . The etiology and pathogenesis of CMI still remain poorly defined since its initial description [2, 21]. The theory of a developmentally reduced PCF is not applicable in all CMI cases. Therefore, the conclusions from different studies have varied considerably [2, 5, 11, 19, 22, 23, 24, 25, 26, 27, 28]. Most studies have supported a smaller PCF in adult CMI [5, 11, 23, 24, 25, 26], while others reported no difference [19, 27, 28]. Furthermore, nearly all studies failed to exclude BI-associated cases [5, 11, 19, 23, 24, 25, 26, 27, 28]. Recently, we reported that simple CMI, associated without BI and AAD, presents with a reduced bony PCF volume .
BI is defined as the violation of Chamberlain’s line by the odontoid process of the axis. The limit of 5.0 mm is most frequently used for the diagnosis . BI can be divided into two groups, according to the presence (group A) or absence (group B) of obvious atlantoaxial instability . Since the etiology, pathogenesis, and treatment are largely different, our study examined only group B BI-associated cases, which usually present without foramen magnum invasion . As BI is diagnosed based on the skeletal abnormality, theoretically the PCF volume of the BI-associated CMI cases may also be affected.
Although they are frequently found simultaneously, CMI and BI can present independently [1, 4, 9, 10]. The pathogenesis of CMI with BI remains controversial [15, 16, 17, 18]. This study found that all CMI cases, with or without BI, present with decreased bony PCF volume. Surprisingly, the association of BI did modify some linear and angular parameters of the PCF, but not the bony PCF volume of CMI.
All the decreased linear dimensions (AL, CL and SOL) are measurements in the rostral-caudal direction. It may be concluded that the hypoplasia of the clivus and occipital bone may be the cause of these morphological changes, although the three parameters were not further reduced in the BI-associated cases. Since the ML and AP-PCF remained unchanged, the value of CL and SOL may have affected the PCF volume, which was demonstrated by the moderate correlations in Table 3. This analysis revealed a difference in several variables in the 3 groups, including VC, KHI, BA, CA, CChA and CAA. The VC and KHI reflect the degree of the dens prolapsing towards the posterior cranial base, which indicates that CMI-only cases also have a tendency to form BI, even though these alterations are not significant enough for these CMI cases to be diagnosed as BI. The CA and CAA reflect the degree of ventral compression to the brainstem. These changes may result from the shortening and flattening of the clivus. The inclination of the tentorium and the shape of the occipital bone may modify the values of TA and TDA. As the TDA remains stable, the flattening of the occipital bone may exist in the BI-associated cases.
The FMD was reported as the cornerstone of the treatment strategy for CMI [2, 15, 29]. A greater increase in the postoperative PCF volume has been associated with a greater likelihood of clinical improvements in CMI patients [30, 31, 32]. Larger increases in the caudal portion of the PCF volume are also associated with a greater likelihood of improvement in syrinx and cervicomedullary kinking . BI is a significant predictor of poor outcomes in CMI after FMD . Since CMI-BI patients present without further reduction in the bony PCF volume, the size of FMD may not be the only factor that determines the prognosis. Effective decompression of the brain stem is determined not only by the size of the FMD, but also the resection of the posterior arch of the atlas, the performance of a duraplasty, and tonsil resection. A relatively larger size of FMD to further increase the caudal portion of the PCF volume, might be a potential treatment for these patients . However, the optimal patient-specific PCF volume increase is difficult to determine, and might be better predicted on the basis of the individual preoperative neuroimaging. Our study suggests that FMD size could be tailored to the individual PCF volume in CMI patients. However, in some CMI cases with severe BI (present with larger CA and smaller CCA), the FMD is not enough to relieve the ventral compression to the brainstem. Odontoidectomy may be a better choice for these special cases .
This study confirmed that the pathophysiology of both CMI and group B BI involves hypoplasia of the skull at the CVJ region, especially the clivus and the occipital bone. Our findings suggest that the hypoplasia of the clivus and occipital bones underlie the pathologies of CMI, and that CMI cases without BI also have a tendency to form BI. The association of BI may aggravate the flattening, rather than the reduction, of the clivus and occipital bone. Together, it indicates that BI may be a continuum of the same pathological phenomenon that originates from the same pathological alterations seen in CMI patients.
The authors are not aware of any other study that attempted to elucidate the role of group B type of BI in the morphology of CMI. There are several limitations with this study. 89% of the cases in our series were associated with syringomyelia, higher than the 20–72% in previous reports . Since syringomyelia is usually secondary to tonsillar herniation, and syringomyelia formation is irrelevant to the PCF volume , these differences should not affect our conclusions. Secondly, CT images may be more difficult to show the tentorium in all slices, compared to MRI , so the bony PCF in this study does not include the upper part of the total PCF under the tentorium. An evaluation based on MRI may provide more information on the total PCF volume. Due to the discrepancy in races, districts and gender, further studies are needed to better understand the morphological changes of CMI in patients with various backgrounds and ethnicities.
Our study indicates that CMI exhibits hypoplasia in both the occipital bone and the clivus, and the tendency to form BI. The association of BI further aggravates the hypoplasia of these bones, by invagination of the posterior cranial fossa base, without further reduction of the length of the clivus, the occipital bone, and the bony PCF volume. This suggests that Group B BI may be a continuum of the same pathological phenomenon that originates from the same pathological alterations in CMI. These results provide new insights into skeletal change in CMI, which may help to further understand the pathogenesis of CMI.
AAD, atlantoaxial dislocation; AL, axial length; AP-PCF, anteroposterior diameter of the posterior cranial fossa; BA, basal angle; BI, basilar invagination; CA, clivus angle; CAA, clivus axial angle; CL, clivus length; CMI, Chiari malformation type I; CVJ, craniocervical junction; Dis-Cham, distance between the dens tip and the Chamberlain line; Dis-McRae, distance between dens tip and the McRae line; FMD, foramen magnum decompression; KHI, Klaus height index; ML, McRae line; OA, occipital angle; OCA, occipital canal angle; PCF, posterior cranial fossa; SOL, supraoccipital length; TA, tentorial angle; TDA, tentorial dorsum sellae angle; VC, violation of the Chamberlain’s line. VM, violation of the McRae line.
YZX and YY conceived and designed the experiments; SXW and YZX collected and analyzed the data; HJX and WT reviewed and validated the data; YZX wrote the paper.
An informed consent of all participants were obtained. All procedures performed in studies involving human participants were approved by the institutional research committee of the First Affiliated Hospital of Chongqing Medical University (No. 2020-315).
We thank Wenyuan Tang of the First Affiliated Hospital of Chongqing Medical University for excellent criticism of the article.
This study was supported by grants from the science and health joint project of Chongqing City (No. 2020FYYX233) and the subject cultivation project of the First Affiliated Hospital of Chongqing Medical University.
The authors declare no conflict of interest.