Chiari malformation and basilar invagination (BI) are common malformations of the craniocervical junction (CVJ) in adults [1]. 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 [11]. 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 [12] (Fig. 1). Due to the differences in the pathogenesis, manifestation and treatment [10], the group A BI-associated CMI cases were excluded from this study.

Fig. 1.

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 [14]. 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 [10]. 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).

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 $\pm$ 10.72 years (range 18–64 years); 16 females and 14 males in CMI-BI group, with a mean age of 46.07 $\pm$ 12.04 years (range 18–69 years); 35 females and 21 males in the control group, with a mean age of 48.04 $\pm$ 10.96 years (range 21–75 years). There were no differences between 3 groups in age (p = 0.578) and gender (chi-square test: p = 0.091).

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.

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 [20]. 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 [14].

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 [4]. BI can be divided into two groups, according to the presence (group A) or absence (group B) of obvious atlantoaxial instability [12]. 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 [12]. 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 [30]. BI is a significant predictor of poor outcomes in CMI after FMD [33]. 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 [34]. 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 [17].

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 [5]. Since syringomyelia is usually secondary to tonsillar herniation, and syringomyelia formation is irrelevant to the PCF volume [35], these differences should not affect our conclusions. Secondly, CT images may be more difficult to show the tentorium in all slices, compared to MRI [14], 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.