INTRODUCTION
The pathogenesis and treatment of Chiari malformations (CMs) with type II basilar invagination (CM+II-BI) remain highly debated [1-3]. Our preliminary study [4] highlighted that patients with CM+II-BI often present with atlanto-occipital instability (AOI), suggesting the need for foramen magnum decompression combined with occipitocervical fusion (FMD+OCF). We categorized the morphology of the atlanto-occipital joint (AOJ) into types I (classic bulb-and-socket joint), II (shallow bulb-and-socket joint), and III (tilted plane joint) [5]. Furthermore, we observed a close correlation between AOJ types and CM with or without II-BI. Specifically, all AOJs in healthy individuals were type I, 87.8% of AOJs in patients with pure CM were type II, and 94.4% of CM+II-BI cases were type III. Interestingly, 6.8% of pure CM cases were classified as type III-AOJ, and 3.7% of CM+II-BI cases were categorized as type II-AOJ. Furthermore, we discovered that all type III-AOJs (100%) exhibited instability, with 1.4% of type II-AOJs also showing instability based on dynamic computed tomography (CT) measurements. Consequently, we questioned whether AOJ morphological types should be the primary consideration when determining OCF.
To address this question, we retrospectively recruited clinical patients with CM and CM+II-BI who underwent surgery at our single center. Through a clinical prognostic assessment, we validated that FMD+OCF should be the primary treatment strategy for type III-AOJ joint instability. Therefore, we aimed to assess the feasibility of tailoring surgical strategies for CM and II-BI patients based on AOJ morphology.
MATERIALS AND METHODS
1. Patient Enrollment
We reviewed and screened 1958 medical records of patients admitted to our department from January 2011 to September 2023 who underwent cervical CT examinations. Among these, 812 patients were diagnosed with CM, and 360 eligible patients were enrolled for further analysis (Supplementary Fig. 1 and Supplementary Table 1). The inclusion criteria were as follows: (1) confirmed diagnosis of CM (tonsillar hernia extending 5 mm beyond the foramen magnum); (2) absence of significant atlantoaxial dislocation (AAD); (3) absence of a tethered cord, hydrocephalus, or other diseases that may cause tonsillar hernia; (4) absence of craniovertebral junction (CVJ) maldevelopment resulting from osteochondrodysplasia, Ehlers-Danlos syndrome, or similar syndromes; (5) absence of osteoporosis, spinal degeneration, rheumatism, or other factors contributing to CVJ deformity; (6) treatment with either FMD alone or in conjunction with OCF, without involving dural incision or tonsillectomy; (7) primary surgery was performed, with no history of internal fixation or another cervical fusion surgery; and (8) availability of functional scores and follow-up data. A patient flowchart is presented in Supplementary Fig. 1.
2. Study Population and Surgical Strategy
After screening, 298 eligible patients with CM were initially included. Among them, 19 patients declined surgery, 10 were lost to follow-up, 4 missed their follow-up appointments, 1 experienced adverse reaction to anesthesia, and 48 underwent surgical procedures that did not meet study criteria (including dural resection or tonsillectomy) (Supplementary Fig. 1 and Supplementary Table 1). Consequently, 216 CM patients, with or without II-BI, who underwent either FMD alone or combined with OCF were retrospectively enrolled. Surgical procedures for FMD and OCF are detailed in our previously publication [4].
Among the 81 patients diagnosed with CM+II-BI, 77 with type III-AOJ underwent FMD+OCF. The remaining 4 patients with II-AOJ, who underwent either FMD alone (2 cases, after the AOJ morphology identification in January 2021) or FMD+OCF (2 cases, before January 2021), were excluded due to their limited number. Among the 135 patients diagnosed with CM, 120 underwent FMD alone, while 15 underwent OCF combined with FMD (after January 2021). Ultimately, all 212 enrolled patients were categorized into 4 groups (Figs. 1, 2 and Table 1): (1) pure CM with type II-AOJ who underwent FMD (CM-II-FMD); (2) pure CM with type III-AOJ who underwent FMD+OCF (CM-III-OCF); (3) CM-III-FMD; and (4) CM+II-BI with type III-AOJ who underwent FMD+OCF (BI-III-OCF).
The same neurosurgeon conducted all surgeries. The distribution of patients in the BI-III-OCF, CM-III-OCF, CM-II-FMD, and CM-III-FMD groups was 77, 15, 91, and 29, respectively. Baseline variables were comparable across all treatment groups (Table 2).
3. Data Acquisition and Evaluation
To assess surgical outcomes, we compared patients’ preoperative and final follow-up data, including demographics (sex and age), baseline work status and American Society of Anesthesiologists physical status class [6], clinical manifestations (symptoms [7], complications, and long-term recovery), imaging findings (syringomyelia length and width, tonsillar herniation length, and cistern magnum volume) [4], and surgical characteristics (operative time and intraoperative blood loss). The data also included neurological assessments using the visual analogue scale (VAS), Neck Disability Index (NDI; range, 0–100, with higher scores indicating greater disability) [8,9], Japanese Orthopaedic Association (JOA) scale (range, 0–17, with higher scores indicating less myelopathy) [10], and the Chicago Chiari Outcome Scale (CCOS) [11].
All patients underwent routine preoperative neurological assessments and were required to return for magnetic resonance imaging (MRI) review at 6 and 12 months postoperatively, followed by annual examinations. The final score was based on the most recent follow-up evaluation.
4. Bias and Ethics
The surgeons involved did not participate in clinical data collection or neurological evaluations to avoid observation bias. This retrospective study was approved by the Institutional Review Board of Nanfang Hospital, Southern Medical University (NFEC-202006-K3) and all individuals participating in this research have provided informed consent.
5. Statistical Analysis
Statistical analysis was conducted using IBM SPSS Statistics ver. 26.0 (IBM Co.). Craniometric data are presented as the mean±standard deviation. Age was compared using the Wilcoxon rank-sum test, and sex was compared using the chi-square test. Following normal distribution analysis, a paired t-test (2-tailed) was used to compare the parameters within groups and between preoperative and final follow-up outcomes. Additionally, we conducted intraclass correlation coefficient analyses for the 2 measurers and the same measurer at different time points (interobserver and intraobserver reliabilities). Statistical significance was set at p<0.05.
For sample size estimate, PASS software (ver. 15.0, NCSS, LLC, UT, USA) was used. A sample size of 45 for group CM-II-FMD achieved more than 90% power to detect a mean paired differences of 0.90, with an estimated standard deviation of 1.53 based on the pilot test, accounting for a 20% dropout rate. The power for the change was calculated based on a 2-sided paired t-test and a 1-sided Wilcoxon signed-rank test with a significance level of 5%. The sample sizes for group BI-III-OCF, group CM-III-FMD, group CM-III-OCF were 38, 14, and 7, respectively.
RESULTS
1. Intraobserver and Interobserver Reliabilities
The intraclass correlation coefficient of the 2 measures at all data points ranged from 0.91 to 0.96 (p<0.01). Conversely, the intraclass correlation coefficient of the same measurer at 2-time points ranged from 0.92 to 0.98 (p<0.01). These results indicate high consistency in the data.
2. Surgery-Related Parameters
As shown in Supplementary Fig. 2, patients who underwent the same surgical strategy exhibited similar data on surgery-related parameters (p>0.05). However, irrespective of whether patients had CM or CM+II-BI, those undergoing OCF experienced longer operating times, greater surgical bleeding, and extended hospital stays compared to those undergoing FMD (p<0.05). Among patients with type III-AOJ CM, those who underwent OCF exhibited similar characteristics to those who underwent pure FMD.
3. Surgical Outcomes
1) Clinical manifestations
During the last follow-up, patients in the BI-III-OCF, CM-III-OCF, and CM-II-FMD groups showed significant improvements in pain, sensory disturbance, motor weakness, gait ataxia, and bladder and bowel dysfunction (p<0.05) (Fig. 3). However, patients in the CM-III-FMD group showed no improvement in these symptoms. The VAS scores for pain (Fig. 4) revealed significant reductions in occipitocervical pain, neuropathic pain, and headache among the BI-III-OCF, CM-III-OCF, and CM-II-FMD groups (p<0.05). Conversely, these types of pain were not alleviated in the CM-III-FMD group. Among CM patients with type III-AOJ, those undergoing OCF showed significant improvement in clinical symptoms compared to pure FMD cases (Fig. 5).
2) Neurologic assessment
The statistical results of the JOA-17 and NDI (Fig. 6A) revealed that the degree of neurological deficits in the BI-III-OCF, CM-III-OCF, and CM-II-FMD groups was significantly reduced at the latest follow-up. In contrast, this phenomenon was not observed in the CM-III-FMD group. The degree of improvement in neurological impairment was significantly higher in the CM-III-OCF group than in the CM-III-FMD group (Fig. 6B and Table 1). Furthermore, 77.9%, 94.5%, and 93.3% of patients in the BI-III-OCF, CM-III-OCF, and CM-II-FMD groups, respectively, had CCOS scores>12 points, indicating good surgical outcomes. Conversely, only 2 patients (6.9%) in the III-FMD group scored>12 points (Fig. 7).
3) Imaging findings
At the most recent follow-up, patients in the BI-III-OCF, CM-III-OCF, and CM-II-FMD groups exhibited significant improvements in the number of syringomyelic segments, syringomyelia width, tonsillar herniation distance, and cistern magnum volume (p<0.05). However, the CM-III-FMD group did not demonstrate similar improvements in the MRI results (Fig. 8A). Furthermore, the improvement in imaging parameters in the CM-III-OCF group significantly surpassed that of the CM-III-FMD group (Fig. 8B).
4) Complications
In the BI-III-OCF group, 4 patients (5.2%) experienced postoperative complications, including 2 (2.6%) classified as major complications. No patients in the CM-III-OCF group (0%) experienced postoperative complications. Three patients in the CM-II-FMD group (3.3%) and 1 patient in the CM-III-FMD group (3.4%) had postoperative complications, all of which were minor (Supplementary Table 2). From another perspective, complications occurred in 4 patients undergoing FMD+OCF (4.3%) and 4 undergoing FMD alone (3.3%).
DISCUSSION
The treatment of craniocervical junction malformations has progressed over the past 6 decades [1], with experts like Menezes from the United States [12], Klekamp from Germany [13], and Goel from India [14] contributing valuable insights. However, no universally accepted treatment strategy or consistently satisfactory outcomes exist for CM and II-BI patients. Understanding the disease’s pathogenesis is crucial for developing surgical treatment strategies. Currently, discussions primarily revolve around the rationale for decompression versus fixation. Decompression advocates argue for posterior cranial fossa (PCF) overcrowding [1,11], while fixation proponents suggest AAD as the primary issue [15,16]. Our previous research, however, revealed pathogenic differences between CM and II-BI, particularly in the morphology and stability of the AOJ [5]. We hypothesized that treatment strategies should be tailored to AOJ morphological types. Therefore, this study was designed to validate this approach through clinical follow-up and prognostic evaluation.
A previous study categorized the adult AOJ into 3 morphological types (Fig. 2) [5]. Type I-AOJ represents a typical bulb-and-socket structure characterized by a concave-shaped articular surface of the lateral mass of the atlas, forming a bulb-and-socket joint with a nearly spherical, protruding occipital condyle. Type II-AOJ exhibits a shallow bulb-and-socket joint where the bulb-and-socket shape is still discernible. Type III-AOJ is character-ized by a tilted plane joint with severe deformities, resulting in the complete disappearance of the bulb-and-socket morphology. As reported by Klimo et al. [17] dynamic CT imaging in flexion and extension positions indicates potential AOI if the distance between the anterior margin of the occipital condyle and the atlas lateral mass is more than 1.0 mm. Based on this criterion, AOI is identified when there is a C0–1 distance change value exceeding 1.0 mm. Types I-AOJ and II-AOJ, associated with minimal AOI, are predominantly found in healthy individuals and patients with pure CM, respectively. In contrast, type III-AOJ represents an unstable joint morphology primarily distributed in patients with CM+II-BI. Moreover, we observed that some pure CM patients exhibited type III-AOJ, while a small subset of II-BI patients had type II-AOJ. This realization suggests that previous surgical treatment strategies based solely on disease type may not have been optimal. Considering the correlation between joint morphology and stability, we propose that OCF should be considered for patients with unstable type III-AOJ. Conversely, traditional FMD may be more appropriate for patients without type III-AOJ, aligning better with their pathological mechanism.
Morphologically, type III-AOJ features vanishing posterior protuberances on the atlas’s lateral masses, increased atlas tilt, and occipital condyle sliding (Fig. 1A). This leads to degeneration and eventual AOI. While joint fixation is necessary for type III-AOJ, we propose OCF as the primary treatment rather than the atlantoaxial fixation which was suggested by Goel [15] In our previous study [4], we described the presence of atlantoaxial instability in patients with II-BI, characterized by left-right asymmetrical motion and rotational instability. Aatlantoaxial instability in type II-BI differs from that in type I-BI, with atlantoaxial-related ligaments in patients with II-BI remain normal. This was confirmed by the unchanged atlantodental distance and odontoid positioning relative to the McRae line (Fig. 1A). Xia et al. [18] demonstrated that odontoid process and lateral joint deformities might be the primary causes of AAD in BI. However, our morphological study found no corresponding changes in patients with II-BI [5]. Given that the atlantoaxial joint is the most active joint in the human body, we propose that AOJ instability in II-BI is likely secondary to AOI, causing upper cervical spine imbalance characterized by unstable left-right movement, including a deviation of the odontoid process. Hence, asymmetric movement resulting from abnormal bone development in the AOJ may initiate upper cervical spine instability in II-BI. The favorable prognosis of patients in the BI-III-OCF and CM-III-OCF groups in this study supports this theory, suggesting OCF as the preferred treatment for patients with type III-AOJ.
Our previous study revealed decreased clivoaxial angles (CXAs) and increased ventral compression in patients with II-BI or type III-AOJ [4]. The CXA is increasingly recognized as an important indicator for assessing the risk of ventral brainstem compression [19,20]. A decreased CXA can elevate axial stress on the brainstem, resulting in ventral compression and clinical deterioration. Correcting postoperative CXA improves clinical outcomes [21]. Hence, expanding the CXA and reversing ventral compression during surgery is crucial. To address this, we use intervertebral distractors to release atlas axis joints, implant angled facet spacers to pull down the odontoid process, and perform OCF with cantilever techniques. Subsequently, OCF was conducted using cantilever techniques. This approach not only allows for the pulldown of the odontoid process, but also facilitates the realization of bilateral anterior open-mouth atlantoaxial facets to easily expand the CXA.
Out of the 121 patients with type III-AOJ in this cohort, 77 were diagnosed with CM+II-BI, all of whom received treatment with FMD+OCF. Another 44 patients were diagnosed with pure CM, with 29 and 15 patients undergoing simple FMD and FMD+OCF, respectively. Clinical follow-up results (Figs. 3–6, and 8) indicate that regardless of whether the patients had pure CM or CM+II-BI, employing FMD+OCF yielded favorable outcomes when III-AOJ was present. Conversely, simple FMD did not yield benefits; instead, the condition of these patients deteriorated. These findings support our previous systematic morphological studies [5], suggesting AOJ instability is a key pathogenic factor in type III-AOJ, alongside PCF stenosis. The poor outcomes with simple FMD challenge the view that CM and II-BI are unrelated to mechanical instability [2,22,23].
Ultimately, even if OCF is chosen, FMD remains indispensable and cannot serve as a substitute treatment for patients with III-AOJ. While our research indicates that CVJ instability is the primary pathogenic factor, the shortening of the clivus and supraocciput results in a narrow PCF, which serves as a compelling reason for secondary tonsillar herniation and represents another mechanism for III-AOJ occurrence [5]. Clinical follow-up results (Figs. 5, 6, and 8) further underscore the importance of considering PCF decompression and AOJ stability reconstruction when devising treatment strategies in treating III-AOJ. Employing either method alone proved ineffective, underscoring the necessity of combining both techniques [1,3,13,19].
Except for patients with III-AOJ, 91 patients with II-AOJ were diagnosed with pure CM in this cohort, all of whom underwent simple FMD. The clinical follow-up results (Figs. 3, 4, 6, and 8) show that if CM patients do not exhibit III-AOJ morphology, simple FMD yields favorable outcomes. This suggests that overcrowding of the PCF due to skull base deformities, particularly clivus deformities, remains the most probable mechanism for II-AOJ, consistent with previous reports [24-26]. Unfortunately, patients in the CM-II-OCF group were excluded from this study due to their small cohort size, limiting the clinical evidence for the efficacy of OCF in treating patients with II-AOJ. However, employing simple FMD has benefited patients. At the same time, OCF inherently carries drawbacks such as limited neck mobility, high implantation cost, and additional bleeding (Supplementary Fig. 2) [27]. Therefore, we are confident that simple FMD represents the optimal treatment strategy for patients with II-AOJ.
In addition to the inherent limitations of selection bias and confounding factors in retrospective observational studies, this study is limited by significant sample size and follow-up time disparities among the 4 groups and insufficient sample sizes in certain groups. Additionally, since we did not discover the 3 morphological types of AOJ and their correlation with joint stability until January 2021, this directly resulted in a shorter follow-up period for the CM-III-OCF group compared to others. Nevertheless, the average follow-up time of 2.5 years might still be sufficient to demonstrate the surgical outcomes. Therefore, we are conducting a prospective clinical study to better elucidate the rationale behind formulating surgical strategies for CM or II-BI based on AOJ morphological types. Of course, this retrospective study can also provide some evidence for this approach.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Full text via PMC
Download Citation
Supplement
Print
