2.4 Statistical analysis
All statistical analyses were performed using SPSS 23 (SPSS Inc., Chicago, IL) and Excel 2010 (Microsoft, Redmond, WA). The demographic characteristics, comorbidities, and preoperative symptoms of the improved and unimproved groups were compared, followed by a comparison of the morphological data for the 2 groups. Bivariate data were compared using Pearson chi-square test. In terms of continuous variables, the distributions of the improved and unimproved groups were tested separately using the Shapiro–Wilk method to determine normality; this was followed by Levene's equality of variances test to gauge the similarity of the data distributions. An independent-samples t test was performed if the data of the 2 groups were normally distributed and their variances were equal. Otherwise, the data were analyzed using the Mann–Whitney U test. The statistical results for continuous variables were recorded as means ± SD, median (IQR), or median (range) according to the data distribution. All tests were 2-tailed, and a P value <. 05 was considered to indicate statistical significance.
Of the 39 patients who underwent PFD, 24 (61.5%) showed improvement and 15 (38.5%) showed no improvement after surgery. Table 3 lists the demographic characteristics, preoperative comorbidities, and preoperative symptoms of the 2 groups.
The 18 females and 6 males in the improved group had a mean age of 49.7 ± 9.9 years. The mean age of the 11 females and 4 males in the unimproved group was 45.9 ± 9.4 years. There was no statistically significant difference in the sex (P = .91) or age (P = .24) distributions of the 2 groups. The median durations of preoperative symptoms were 30 months and 12 months (P = .65) and the median follow-up durations were 26 and 24 months (P = .65) in the improved group and unimproved group, respectively. Of the 24 patients in the improved group, 21 had syringomyelia, 4 had scoliosis, and 3 had hydrocephalus. Of the 15 patients in the unimproved group, 14 had syringomyelia, 2 had scoliosis, and none had hydrocephalus. There were no differences between the groups regarding preoperative comorbidities, indicating that the latter were unlikely to have influenced the outcomes after PFD. According to the pain location, preoperative pain occurred as headache, neck pain, shoulder pain, back pain, upper limb pain, and lower limb pain. There were no significant differences in the preoperative pain symptoms of the 2 groups. Of the patients with preoperative non-pain symptoms, patients in the unimproved were more likely than improved patients to exhibit numbness (odds ratio [OR] = 10, P = .02) or muscle weakness (OR = 4.86, P = .02) in the upper limbs. Upper limb numbness was reported by 14 (58%) of the 24 patients in the improved group and 14 (93%) of the 15 patients in the unimproved group. Upper limb weakness was reported by 7 (29%) patients in the improved group and 10 (67%) in the unimproved group. The differences between the groups in lower limb numbness, lower limb weakness, muscular atrophy, dizziness, and gait instability were not significant. Table 4 summarizes the statistical results of the 13 liner parameters, 8 angular parameters, 4 areal parameters, and 4 relative ratios evaluated in this study. Contrary to our expectations, there were no significant differences in the PCF morphology of the improved and unimproved groups.
The pathogenesis of CMI is unclear, but it has been attributed to an anterior cephalic mesodermal defect that occurs during embryonic development and contributes to occipital bone hypoplasia, resulting in a reduction of PCF volume. Brain structures, such as the cerebellum, continue to develop normally, but the narrow PCF cannot accommodate them, leading to the herniation of the cerebellar tonsil into the spinal canal and the obstruction of CSF flow. These pathological changes damage the cerebellum, brainstem, spinal cord, lower cranial nerves, and upper cervical nerves, leading to clinical symptoms of pain, sensory or motor dysfunction, muscle atrophy, and, eventually, ataxia. After nearly 70 years of technical development, PFD is now widely used in the treatment of CMI. By partly removing the bony structures of the occiput and posterior atlas, PFD reconstructs the subdural environment and increases the volume of the PCF and cervical spinal canal, which relieves the compression of nerve structures in the narrow PCF and improves CSF flow in the craniocervical junction. The postoperative improvement rates reported in the literature vary widely, ranging from 46% to 89%,[3,6,23–28] most likely reflecting differences in inclusion criteria, surgical effect assessment, operation type, and follow-up time. The postoperative improvement rate in our series was 61.5%. Although the symptoms of a majority of patients improved or disappeared, there were still some patients whose symptoms were unchanged or had even worsened. This lack of a positive outcome after PFD was likely the result of poor patient selection. If not all patients with CMI will benefit from PFD, a method to preoperatively predict the surgical outcome is needed.
In 2015, Greenberg et al developed the Chiari Severity Index, based on the clinical manifestations and imaging features of CMI, to predict the efficacy of PFD. The presence of myelopathic symptoms, such as numbness, weakness, hyperreflexia, or unsteady gait, predicted a worse outcome. In their study of the relationship between preoperative symptoms and surgical effect, Hekman et al applied the CCOS scale to 167 patients with CMI and demonstrated that sensory deficits correlated with poor outcomes after PFD. This result is consistent with our own findings. In our patients, the myelopathic symptoms were further subdivided into upper limb numbness, upper limb weakness, lower limb numbness, lower limb weakness, and muscle atrophy. Upper limb numbness and upper limb weakness were identified as unfavorable factors affecting the efficacy of PFD. The improvement rates of patients with postoperative upper limb numbness and upper limb weakness were 50% and 41%, respectively. Limb numbness and weakness are common symptoms of syringomyelia, but the relationship between preoperative syringomyelia and surgical outcome is controversial. Greenberg's study determined a lower improvement rate in patients with a syrinx >6 mm (55% vs 74% in those with a syrinx <6 mm). The authors suggested that a larger syrinx represents more serious spinal cord injury and, therefore, the more likely persistence of related symptoms. However, Hekman et al reported a postoperative improvement rate that was 3.94 times higher in patients with than without syringomyelia. In a retrospective study, Kalb evaluated 104 patients with CMI who underwent PFD. Patients with syringomyelia had a slightly lower rate of improvement in headache and sensorimotor dysfunction (62% vs 73%), but the authors found no relationship between symptom deterioration and syringomyelia. In our patients, neither the presence of syringomyelia nor preoperative syrinx size influenced the surgical outcome after PFD, perhaps because CMI often causes the formation of non-communicating syringes. The dilated central canal exhibits a propensity to dissect into the spinal cord parenchyma and even to extend through the pial surface to communicate with the subarachnoid space. The CSF in the damaged central canal flows out along the pressure gradient, causing the collapse of the cavity wall. As seen on the MR images, the syrinx shrinks or even disappears completely.[30,31] The rates of syrinx reduction range from 44% to 100%. Batztorf et al retrospectively analyzed the medical records of 177 adult patients with Chiari malformation and concluded that postoperative symptomatic improvement related to syringomyelia was associated with a reduction in syrinx cavity size. However, other researchers found no correlation between postoperative clinical condition and syrinx size. This discrepancy might be due to the fact that the symptoms of syringomyelia are related primarily to the degree of injury to the spinal cord parenchyma. By contrast, because of spontaneous drainage between the syrinx cavity and the subarachnoid space, the syrinx size is not proportional to the degree of spinal cord injury. In patients with irreversible structural damage to the spinal cord due to preoperative syringomyelia, the resulting neurological dysfunction will persist even if the syrinx shrinks after surgery.
Despite our analysis of a relatively large number of morphological parameters of PCF, including lines, angles, areas, and relative ratios, we were unable to distinguish any radiological factors predictive of surgical outcome. In 2016, Alperin et al conducted a prospective study using preoperative MR images to predict the short-term outcomes of CMI patients. Several morphometric parameters were similar to those evaluated in the current study, including tonsillar herniation, clivus length, supraocciput length, and clivoaxial angle, but these authors were also unable to identify predictive morphological factors and considered physiological measures to be stronger predictors than morphological measures. Utilizing cine phase-contrast MR imaging (a dynamic MR technique) prior to surgery, Alperin et al found that preoperative maximal cord displacement in the upper cervical region and intracranial volume change (ICVC) during a cardiac cycle were predictors of decompression outcome in patients with CMI. During the systolic phase, intracranial pressure (ICP) increases rapidly because arterial blood flows increasingly into the skull while the amount of intracranial CSF entering the spinal canal is insufficient. The cerebellum, medulla oblongata, and upper cervical cord move downward to accommodate the increased ICP. The greater maximal displacement of the upper cervical cord indirectly reflects the greater fluctuation of ICP in a cardiac cycle as well as the larger degree of CSF-flow obstruction at the foramen magnum. Regarding the ICVC, a smaller change implies that the cranial cavity is too small to accommodate the normal fluctuation in intracranial blood volume and CSF volume along with the beating heart. Patients with greater maximal upper cervical cord displacement and a lower ICVC during the cardiac cycle are more likely to respond favorably to PFD that appropriately increases PCF volume, enlarges the buffer space against an ICP fluctuation, and resolves the impairment of CSF flow.[6,8,33] Another study used cine phase-contrast MR imaging to directly analyze the relationship between preoperative CSF flow dynamics and the efficacy of PFD. The authors concluded that patients with obstructed hindbrain CSF flow respond better to decompression than do patients with a normal CSF flow. The degree of hindbrain CSF flow obstruction was associated with preoperative symptoms and may thus be relevant in predicting the surgical response. The study's authors also speculated that symptoms in patients with normal hindbrain CSF flow are multifactorial in origin.
Although the standard for the diagnosis of CMI is a cerebellar tonsil that descends >5 mm below the foramen magnum, the degree of tonsillar descent was shown to be a poor sole predictor of the development of symptoms,[2,34] as many asymptomatic patients have a low cerebellar tonsil position, and symptomatic patients may have a normally positioned tonsil. Several studies have also demonstrated that the degree of tonsillar descent does not influence the improvement in symptoms after PFD, which was also observed in our study.[2,34]
In the absence of a 3-dimensional reconstruction protocol during preoperative MRI, we could not calculate the exact volume of the PCF. Furthermore, the calculation is complicated and often requires professional software, which limits its clinical application. The volumes of different structures in the skull cavity, including the intracranial volume, PCF volume, supratentorial volume, herniated volume, 4th ventricle volume, and hindbrain volume, have been measured,[4,5,8] but the volumetric measurements failed to predict the response of CMI patients to PFD. As the brain tissue on either side of the median sagittal plane approximates a mirror-symmetric distribution, relevant areas in the median sagittal plane of the PCF are commonly used as morphological parameters.[17–19] We measured the PCF area, PCF osseous area, tonsillar descent area, and piston area in our study, but none of these morphological indicators was predictive of improvement after PFD. This was probably because the main pathogenesis of CMI is the mismatch between the dysplastic PCF and the normally developed hindbrain, the degree of which depends on the skeletal anatomy of the individual patient. Moreover, sex, ethnic background, or body mass index may interfere with measurements of the PCF and intracranial volume. A study with a small sample concluded that the response to PFD correlated positively with the magnitude of the increase in PCF volume after surgery. Symptoms related to CMI were completely relieved, without complications, when the PCF volume increased by 15%. A pediatric study of CMI found that an increase in the postoperative PCF volume, especially the volume of the cisterna magna, was associated with a greater likelihood of headache resolution. It also confirmed the important role of CSF flow disturbances in the pathology of CMI. Our study likewise failed to identify radiological predictive factors based on preoperative conventional MRI. Unlike cine phase-contrast MR imaging, conventional MR imaging, cannot display either CSF flow dynamics or indirect indicators thereof, such as maximal displacement of the upper cervical cord.
The present study had several limitations. First, because it was a retrospective analysis, there was no unified study protocol established before the study. Second, some patients were excluded due to lack of preoperative MR imaging data, which very likely caused selection bias. Although we strived to obtain preoperative clinical information from the hospital medical records and follow-up records, the lack of a unified CMI-related symptom questionnaire at admission may have resulted in the omission from the patient history of minor symptoms that did not cause obvious discomfort. Additionally, only cranial-cervical MR imaging examinations were preoperatively performed in most patients in our cohort, which prevented measurements of the size and length of the syrinx in the thoracolumbar region. Moreover, none of the patients with CMI underwent preoperative computed tomography, which would have displayed the bony structure more accurately than MR imaging. To ensure the homogeneity of the included patients, strict inclusion and exclusion criteria were formulated. However, after the elimination of patients who did not meet our criteria and those who were lost to follow up, the sample size was relatively small, which limited the study's statistical power. Future prospective large-sample studies will overcome most of the above limitations.
Patients with CMI who present with preoperative upper limb numbness or upper limb weakness are less likely to improve after PFD. PCF morphology is not predictive of the outcome of therapeutic surgical decompression. Instead, pathophysiological factors, such as irreversible structural damage of the spinal cord parenchyma and impairment of the CSF flow in the craniocervical junction, seem to be of greater predictive value.
Conceptualization: Zheng Liu, Meihua Li.
Data curation: Zheng Liu, Zheng Hao.
Formal analysis: Zheng Liu, Si Hu, Yeyu Zhao.
Funding acquisition: Meihua Li.
Investigation: Meihua Li.
Methodology: Zheng Liu, Yeyu Zhao.
Project administration: Meihua Li.
Resources: Meihua Li.
Software: Zheng Liu, Si Hu.
Supervision: Meihua Li.
Writing – original draft: Zheng Liu.
Writing – review & editing: Zheng Hao, Si Hu, Yeyu Zhao, Meihua Li.
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Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
Chiari malformation type I; morphology; posterior cranial fossa; posterior fossa decompression; surgical outcome