- Doctors Community Hospital, Georgetown University Hospital, United States
- Computational Biodynamics LLC., Yale University, United States
- Dartmouth-Hitchcock Medical Center, Georgetown University Hospital, United States
- Bethesda MRI & CT, Georgetown University Hospital, United States
- University of Alabama Medical Center, Georgetown University Hospital, United States
- Kettering University, United States
- Thomas Jefferson University Hospital, United States
- Cleveland Clinic Foundation, United States
Fraser C. Henderson
Cleveland Clinic Foundation, United States
DOI:10.4103/2152-7806.66461© 2010 Henderson FC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Henderson FC, Wilson WA, Mott S, Mark A, Schmidt K, Berry JK, Vaccaro A, Benzel E. Deformative stress associated with an abnormal clivo-axial angle: A finite element analysis. Surg Neurol Int 16-Jul-2010;1:30
How to cite this URL: Henderson FC, Wilson WA, Mott S, Mark A, Schmidt K, Berry JK, Vaccaro A, Benzel E. Deformative stress associated with an abnormal clivo-axial angle: A finite element analysis. Surg Neurol Int 16-Jul-2010;1:30. Available from: http://sni.wpengine.com/surgicalint_articles/deformative-stress-associated-with-an-abnormal-clivo-axial-angle-a-finite-element-analysis/
Background:Chiari malformation, functional cranial settling and subtle forms of basilar invagination result in biomechanical neuraxial stress, manifested by bulbar symptoms, myelopathy and headache or neck pain. Finite element analysis is a means of predicting stress due to load, deformity and strain. The authors postulate linkage between finite element analysis (FEA)-predicted biomechanical neuraxial stress and metrics of neurological function.
Methods:A prospective, Internal Review Board (IRB)-approved study examined a cohort of 5 children with Chiari I malformation or basilar invagination. Standardized outcome metrics were used. Patients underwent suboccipital decompression where indicated, open reduction of the abnormal clivo-axial angle or basilar invagination to correct ventral brainstem deformity, and stabilization/ fusion. FEA predictions of neuraxial preoperative and postoperative stress were correlated with clinical metrics.
Results:Mean follow-up was 32 months (range, 7-64). There were no operative complications. Paired t tests/ Wilcoxon signed-rank tests comparing preoperative and postoperative status were statistically significant for pain, bulbar symptoms, quality of life, function but not sensorimotor status. Clinical improvement paralleled reduction in predicted biomechanical neuraxial stress within the corticospinal tract, dorsal columns and nucleus solitarius.
Conclusion:The results are concurrent with others, that normalization of the clivo-axial angle, fusion-stabilization is associated with clinical improvement. FEA computations are consistent with the notion that reduction of deformative stress results in clinical improvement. This pilot study supports further investigation in the relationship between biomechanical stress and central nervous system (CNS) function.
Keywords: Chiari malformation, clivo-axial angle, craniocervical junction, deformative stress, finite element analysis, stretch myelopathy
Ventral brainstem compression (VBSC) from basilar invagination is a well-known cause of encephalomyelopathy in the setting of Chiari malformation[
In a novel approach, the authors applied a finite element analysis (FEA) research tool to compute estimates of preoperative and postoperative mechanical stress within the brainstem and spinal cord in 5 children with medullary kinking due to kyphotic clivo-axial angulation in the context of Chiari malformation or basilar invagination. These stresses were compared with clinical metrics.
Finite element analysis is a mathematical method that reduces a continuous structure into discrete finite brick elements. This method allows the approximation of partial differential equations with a linear system of ordinary differential equations, which can then be solved by numerical methods with the appropriate boundary conditions. In this particular case, the equations concern mechanical strain, out-of-plane loading and material properties such as Young’s modulus of elasticity or Poisson’s ratio.
A model of the brainstem and spinal cord that incorporates patient-specific anatomical data such as deformity over the odontoid process, lengthening of brainstem and spinal cord with flexion, and numerous other features such as compression of the spinal cord by a herniated disc or spur has been developed to parametrically generate specific finite element models for each patient. The computations derived from these models undergoing flexion and extension generate estimates of the stresses existing within the brainstem and spinal cord in the neutral, flexion and extension conditions. The estimated stresses reflect the dynamic change in stress exerted on the neural tissue. The importance of biomechanical stress has recently been demonstrated in the neurobiological, clinical, experimental and biomechanical literature.
The FEA estimations of deformative strain, generated postoperatively, were used to test the hypothesis that reduction of abnormal stresses improved neurological deficits. The 5 patients studied herein underwent open reduction (normalization of the clivo-axial angle) and posterior translation to normalize the craniospinal relationship. This reduction was followed by occipitocervical fusion and stabilization.[
From 2003 to 2007, 5 children with encephalomyelopathy due to medullary kinking, basilar invagination or Chiari malformation were evaluated by a pediatric neurologist and referred for neurosurgical evaluation. The study was IRB approved for neurological assessment, evaluation of quality of life (SF-36), American Spinal Injury Association (ASIA) impairment scale, pain (Visual Analog Scale [VAS], Oswestry Neck Disability Index), function (Karnofsky Index) and assessment of bulbar symptoms (the Brainstem Disability Index — 20 questions relating to bulbar symptoms,
Rationale for surgery
The following surgical criteria were used in the deliberation as to whether subjects were candidates for surgery: first, signs of cervical myelopathy (sensorimotor findings, hyper-reflexia); second, bulbar symptoms (lower cranial nerve dysfunction, respiratory disorder, changes in vision or tracking, auditory vestibular symptoms, dysautonomia) listed in
Each of the 5 patients studied were placed in a neck brace for at least 2 weeks prior to surgery to determine whether immobilization improved their clinical presentation; all showed significant improvement of clinical symptoms while in the brace. The response to the neck brace represented a subjective indicator that immobilization in a neutral or slightly extended position lessened the headache and/ or neck pain.
Each patient was positioned prone in a Mayfield head-holder with extension at the cervicothoracic junction and gentle flexion at the craniocervical junction to facilitate both subperiosteal exposure of the subocciput and upper two or three vertebrae and placement of the suboccipital plate. Sensory and motor evoked potentials were monitored throughout. A suboccipital craniectomy was performed to the extent necessary to decompress the Chiari malformations, but with care to leave available bone surface area for the subsequent fusion. A suboccipital plate (Altius™, Biomet, Parsippany, NJ) was contoured to the occiput and fastened to the skull with screw lengths appropriate to the bone thickness as determined by preoperative CT scan. At the midline (the “keel”), the skull thickness was approximately 10 mm. Laterally, the mantle is thinner, usually accommodating a 6-mm screw.
The surgeon considered but did not perform occipito-ganglial neurectomies[
Open intraoperative reduction of the craniocervical junction deformity was performed under fluoroscopy, evoked potential monitoring and direct visual inspection, and in the manner described by Kim, Rekate and Sonntag[
Finite element analysis
An FEA program (PRIMEGen) was adapted for the purpose of modeling the brainstem and cervical and upper thoracic spinal cord under dynamic loading and strain. The resulting Spinal Cord Stress Injury Analysis (SCOSIA©) technology computes probable magnitude and location of stress within the brainstem and upper spinal cord. The Von Mises stress is the aggregate of both in-line strain, or stretching; and the stress due to “out-of-plane loading,” such as from odontoid compression.
Computer-driven stress analysis–based finite element formulations provide a unique perspective on the biomechanical behavior of the human cervical spine under normal, degenerative and iatrogenically surgically altered conditions. Due to the reproducibility and repeatability of finite element models, detailed parametric analysis with regards to the geometrical conditions and material property changes can be performed, and biomechanical responses can be evaluated using FEA. FEA is routinely used to study spine mechanics.[
Due to the displacement-based formulation of structural finite elements, nodal displacements are primary output variables and nodal stresses are computed variables using nodal displacements. In other words, stresses are predicted based upon the deformation or stretching of specific nodes, with specific Cartesian coordinates within the system.
The SCOSIA system utilizes a simplified model of the brainstem and spinal cord, assuming isotropy for gray matter tracts and for the white matter tracts, constant material properties regardless of stress, boundary conditions at the pons and mid thorax, and Young’s modulus of elasticity for bovine gray and white matter provided by Ichihara et al.[
The Grabb-Oakes measurement was used to determine degree of focal compression due to VBSC.[
VBSC = Δ – 9, in mm
The acquired images were transferred to the dedicated processing workstation via DICOM; for each anatomical level, anatomical coordinates were manually specified to assemble the model of the spine. Following generation of the model, boundary conditions were imposed by fixing the model at the T6 level, displacing it into the flexed position that the patient’s spinal cord assumed as determined by flexion x-rays, and adding out-of-plane loading to the medulla equivalent to the VBSC number described above. The analysis yielded the overall Von Mises stress for each voxel within the model: σ = 3J2, where J2 is the second deviatoric stress invariant. A more detailed description of how the finite element method computes Von Mises stresses may be found in the work of Huebner et al.[
Standard parameters for diagnosing basilar invagination have been defined for MRI.[
Bulbar symptoms index
Bulbar symptoms previously described[
Analyses were performed preoperatively and at the last follow-up postoperatively. Due to small sample size, both parametric (paired t tests) and nonparametric (Wilcoxon signed-rank tests) statistical tests were used for SF-36 physical component summary (PCS) scores and mental component summary (MCS) scores, VAS pain scores, summed ASIA scores, Karnofsky Index, Bulbar Symptoms Index, and SCOSIA-derived stress values. Pearson’s correlation coefficient (rp) was used to determine the extent to which SCOSIA-derived stress values were correlated preoperatively and postoperatively with VAS, brainstem disability indices, Karnofsky values and SF-36 scores. Statistical significance was set at P = .05.
Two males and 3 females, ages 8-17 years, were followed for 24 to 64 months (mean follow-up, 36 months). The presenting diagnoses, radiological findings, overall clinical outcome and complications are listed in
Preoperative and postoperative B-pC2 measurements were read independently by a neuroradiologist (A.M.) and are presented in
All patients presented with the following symptoms: headache or neck pain, weakness in the upper or lower extremities, sensory changes (hypoesthesias or paresthesias in the upper and lower extremities), clumsiness with frequent falls, uncertain gait, fatigue, gastroesophageal disturbance (reflux or irritable bowel syndrome), respiratory disturbance (including respiratory arrest [pt. #1]), and other respiratory disorders which manifested as sleep apnea, snoring or history of frequent awakening. Most reported vestibular, auditory or visual disturbance and bowel and/ or bladder dysfunction. Trophic changes, including abnormal response of circulation to cold weather or profuse sweating, occurred in only 1 patient [
Preoperative neurological findings included weakness (especially hand weakness), poor muscle tone and poor posture, sensory changes, hyper-reflexia and dysdiadochokinesia. One patient was observed to have scoliosis. Sensory changes (hypoesthesia to pinprick) were never painful or unpleasant, and were frequently ignored or not recognized by the patient. The gag reflex was decreased or absent in all subjects, though usually not associated with dysphagia [
Postoperatively, strength, sensation and posture improved in 1 month. Patient # 2 improved from mild weakness to normal strength. The scoliosis resolved to normal within the first month in patient # 4. Four of the 5 patients are performing at academic and athletic levels above their preoperative state. Substantial behavioral improvement was reported by the parents of the 4 subjects with neurobehavioral disorders, but measurement of behavior was beyond the scope of this study.
Metrics were obtained from the subjects and their parents by a research technician (I.M.). Visual analog pain was reduced from a preoperative mean of 64 (on a “0 to 100” scale) to a postoperative mean of 12 (t= 6.15, P= .0002 for parametric; V= 15, P= .029 for nonparametric). SF-36 physical component summary (PCS) scores improved following surgery (mean, 40-57). These improvements were statistically significant (t= –2.59, P= .030 for parametric; P= .031 for nonparametric) and postoperatively were above the normal mean (sample mean = 56.5 versus normal mean = 50 ± 10 SD). Mental component summary (MCS) scores also improved (mean, 38-57), with significance (t= –2.48, P= .033 for parametric; P= .031 for nonparametric). Summed ASIA scores increased from a mean of 268.2 to a mean of 309.2, though this increase failed to achieve significance on both parametric and nonparametric tests (t= –1.83, P= .071 for parametric; P= .050 for nonparametric). The bulbar symptom index showed significantly fewer bulbar symptoms following surgery (preop. mean= 57%, postop. mean= 30%; t = 6.78, P= .001 for parametric; V= 15, P= .029 for nonparametric). Karnofsky scores significantly improved (mean, 69 preop. to 100 postop., t= –3.97, P= .008 for parametric; P= .028 for nonparametric).
SCOSIA-derived stress values paralleled the patients’ clinical conditions [Figures
With every clinical metric, higher preoperative stress values correlated with greater disability (r= 0.36 to 0.72), lower Karnofsky values (r= –0.43 to –0.98) and lower physical component summary scores (r= –0.34 to –0.60). Correlations between stress values and mental component summary scores were more variable (r= 0.21 to –0.69). The low sample size (n= 5) for these cross-patient comparisons implied that most of these correlations approached, but did not achieve, statistical significance. A very strong correlation between computed stress in the corticospinal tract and Karnofsky score (which achieved significance at r= –0.98, P= .003) was observed.
The analysis of within-patient changes in SCOSIA estimates of neuraxial stress and patient condition metrics yielded similar results. Patients exhibiting larger decreases in SCOSIA-derived stress values experienced proportionate decreases in disability (r= 0.36 to 0.52), increases in Karnofsky values (r= –0.08 to –0.99) and increases in PCS (r= –0.22 to –0.35) and MCS scores (r= –0.10 to r= –0.37). The relationship between changes in corticospinal stress and changes in Karnofsky values was strong (r= –0.99, P= .001).
The axial view through C2 shows high stress (45-60 N/cm2) in the posterior and lateral columns, correlating with the widespread sensory changes, hyper-reflexia and Babinski sign. Even higher stress (70 N/cm2) is seen in the anterior gray matter, possibly underlying the tongue thrusting on presentation of the patient
There were no neurological deficits resulting from surgery, and no wound problems. Subject # 4 (with a history of craniosynostosis, and cat-eye syndrome) had undergone a limited suboccipital craniectomy for Chiari malformation. Six months later, headaches recurred and were suspected to represent occipital neuralgia. The patient’s family refused diagnostic block of the occipital nerve. The surgeon (F.C.H.) sent the child for evaluation of craniosynostosis; and, later, monitoring of ICP, which was normal (<10 cm H20). Eighteen months after surgery, the parents sought enlargement of the suboccipital craniectomy; at 3 years, the headaches appear to have resolved.
No subject required blood transfusion. The average duration of surgery was 3.5 hours. All subjects were discharged within 3 days after surgery. Subjects were placed in hard cervical collars (Miami J™ collars). CT scans at 3 months showed bone fusion in every case [
Deformative stress in the brainstem and upper cervical spinal cord
Mechanical compression at the cervicomedullary junction occurs in Chiari 1 malformation,[
The patients in this series were referred for disabling neurological symptoms, which included headaches, bulbar findings and myelopathy. All subjects shared abnormality of the clivo-axial angle. The authors consider the CAA to be a surrogate measure of deformative stress in the brainstem and upper spinal cord. Neuraxial strain is accentuated with flexion of the craniocervical junction [Figures
The overall deformative stress generated at the craniocervical junction may reach levels where nerve function becomes attenuated; indeed, the axon is rendered nonconductive and develops pathological changes at a strain ε = 0.2.[
An abnormal CAA is described in the literature to manifest variously as a consequence of basilar invagination — in the setting of congenital maldevelopment of the chondrocranium, from acquired causes of bone softening in Paget’s disease, spondyloepiphyseal dysplasia, acro-osteolysis, Hurler’s syndrome, osteomalacia, Ricket’s disease, achondromalacia, renal osteodystrophy, hyperparathyroidism and in degenerative disease such as rheumatoid arthritis.[
Building upon earlier work concerning the importance of deformative stress in the brainstem and spinal cord,[
Clinical improvement after “relief of brainstem angulation” has been attributed to improvement in blood supply and CSF dynamics.[
The concept that the spinal cord elongates with flexion of the neck and that medullospinal kyphosis results in deleterious axial strain is well established.[
The importance of deformative stress in myelopathy and encephalopathy is supported in clinical reports,[
Maximum stress values from the corticospinal tracts, dorsal columns, nuclei solitarius and dorsal motor nucleus were chosen to compare with clinical findings. The computed stress within each tract decreased after surgery. Moreover, stress values and measures of patient condition were always in the predicted direction — higher stress values were associated with higher pain levels and reduced SF-36 (quality of life) scores. The concordance of computed neuraxial stresses and clinical metrics support the concept that biomechanical stresses generated by stretch and “out-of-plane” loading are important determinants of neurological dysfunction.
The authors recognize that FEA modeling in the neuraxis is nascent and simplistic. The stresses are virtual computations and do not integrate measurements of stress over time and over the full length of the tract. The analysis assigns different moduli of elasticity to white and gray matter but assumes stereotypic response and uniform properties under various degrees of strain and compression. The authors have used moduli of elasticity that were described for bovine spinal cord. However, compression of the bovine cervical spinal cord produced the same histopathological changes as compression of the human cervical spinal cord,[
While other recently described systems[
While these shortcomings clearly need to be addressed, the authors concur with others that FEA-generated stress calculations are helpful in understanding the underlying pathophysiology of a variety of spinal and brainstem conditions.[
Clinical metrics and outcomes
Improvements reached statistical significance for all clinical metrics: the VAS, ASIA scale, Karnofsky Index, SF-36: physical component, SF36: mental component and the Bulbar Symptoms Index. The data presented here was collected by a research assistant. The SF-36 is a widely approved instrument for measurement of physical functioning, bodily pain, general health, vitality, social functioning and mental health. It has been shown to be valid when tested against outcome instruments.[
The statistically significant improvement of all clinical metrics viz., VAS, SF-36, Karnofsky Index, ASIA and Bulbar Symptom Index, is in agreement with the findings from the work of others — that reduction of the medullary kinking or VBSC through normalization of the craniospinal relationship, and fusion and stabilization improve neurological performance and relieve pain in subjects with traditional and “nontraditional” forms of basilar invagination.[
The authors emphasize the breadth of associated comorbidities in this small cohort — respiratory disorders and gastroesophageal reflux disease, personality disorders, leg tremors, tongue protrusion (“trombone tongue”) and scoliosis [
The authors performed open reduction with manual distraction and extension of the cranium, as described by Kim et al.[
Postoperatively, a C2 pedicle screw was observed to be adjacent to the vertebral artery in 1 patient (patient # 2), in whom the subsequent MRA was normal. The headaches in patient # 4 were thought to be due to occipital neuralgia. Hence the authors recommend placement of C1 screws in a manner that avoids encumbrance of the exiting C2 roots.
Kim et al. reported a 36% complication rate, but with the exception of 1 patient in whom hyperostosis necessitated a posterior decompression, these were minor complications.[
A concern in children is the limitation of neck rotation after craniospinal fusion. Fifty percent of neck rotation occurs between C1 and C2, and approximately 21° of flexion is observed between the occiput and cervical spine.[
The authors emphasize the risk associated with injury to the vertebral artery.[
Conventional radiographic assessment of basilar invagination does not reveal the more subtle forms of ventral brainstem compression and deformation. Open reduction of craniospinal deformity (normalization of clivo-axial angle), stabilization and surgical fusion are effective in improving pain and neurological function in subjects with cervicomedullary disorders resulting from deformative stress. The growing body of neurobiological literature supports the concept that deformative stress is important in both direct and epigenetic mechanisms of neurological dysfunction.
We have used FEA to compute neuraxial deformative stress in the context of cervicomedullary disorders due to Chiari malformation and basilar invagination. Surgical correction of the deformity resulted in improvement of computed Von Mises stress in selected anatomical structures, which was concordant with relief of pain and neurological deficits. FEA may offer new insight into the effect of pressure and strain on the neuraxis at the cervicomedullary junction. Further investigations are warranted to validate the concept that deformative stress is an important determinant of neurological function.
The authors wish to acknowledge the intellectual contributions of Dr. Robert Keating, Chairman, Department of Neurosurgery, National Children’s Hospital; and Lars Gibson, PhD, Cleveland Clinic. The authors are grateful to Inge Molzahn for the dedicated gathering of data for this manuscript. Original insights from Dr. Jennian Ford Geddes Montagu and Professor A. Breig were fundamental to the development of this work. We thank Kathrin Riller, Executive Assistant, Dept. of Neurosurgery, for her contribution to this work.
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