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Defining the Effect of Cervical Manipulation on Vertebral Artery Integrity: Establishment of an Animal Model
ORIGINAL ARTICLES DEFINING THE EFFECT OF CERVICAL MANIPULATION ON VERTEBRAL ARTERY INTEGRITY: ESTABLISHMENT OF AN ANIMAL MODEL Gregory N. Kawchuk, DC, PhD,a Shari Wynd, DC,b and Todd Anderson, MDc
ABSTRACT Background: Cervical spine manipulation is most often performed to affect relief of musculoskeletal complaints of the head and neck. Performed typically without complication, this modality is thought to be a potential cause of cerebrovascular injury, although a cause-effect relation has yet to be established. To explore this relation, an experimental platform is needed that is accessible and biologically responsive. Objective: To establish an animal model capable of accommodating (1) direct study of its vertebral arteries and (2) creation of controlled interventions simulating arterial injury. Study Design: Descriptive. Methods: Under fluoroscopic guidance, an ultrasonic catheter was inserted into the left vertebral artery of 3 anesthetized dogs. The ultrasonic probe was then drawn proximally through the artery at a specific rate, and cross-sectional images of the vessel were collected. These images were then reconstructed to provide a variety of 2- and 3-dimensional representations of the vessel. This procedure was repeated after the overinflation and/or displacement of an angiographic balloon within the vertebral artery itself. Results: The resulting ultrasonic images were able to delineate the structural layers that constitute the vertebral artery. Analysis of 2- and 3-dimensional reconstructions before and after angiographic intervention revealed the creation of discrete vascular injuries (aneurysm or dissection). Conclusions: For the first time, an animal model has been established that permits direct interrogation of the internal structures of the vertebral artery. This model can also be manipulated to create bpreexistingQ vascular injuries that are thought to be possible prerequisites for cerebrovascular injury associated with manipulation. As a result, an experimental platform has been established that is capable of providing investigators of all backgrounds with the ability to quantify biologic and mechanical outcomes of cervical manipulation. (J Manipulative Physiol Ther 2004;27:539-546) Key Indexing Terms: Manipulation; Chiropractic; Vertebral Artery; Animals; Model
a
Faculty of Rehabilitation Medicine, University of Alberta, Alberta, Canada. b Graduate Student, University of Calgary, Alberta, Canada. c Faculty of Medicine, University of Calgary, Alberta, Canada. Sources of support: Financial support for materials used in this work was provided in part by the Canadian Chiropractic Protective Association. The authors receive salary support through the Canadian Institutes of Health Research and the Canadian Chiropractic Association (Dr Kawchuk), the Alberta Provincial CIHR Training Program in Bone and Joint Health (Dr Wynd), and by the Alberta Heritage Foundation for Medical Research (Dr Anderson). Submit requests for reprints to: Greg Kawchuk, DC, PhD, Faculty of Rehabilitation Medicine, University of Alberta, 2-28 Corbett Hall, Edmonton, Alberta, Canada T6G 2G4 (e-mail: [email protected]). Paper submitted May 19, 2003. 0161-4754/$30.00 Copyright D 2004 by National University of Health Sciences. doi:10.1016/j.jmpt.2004.10.005
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ervical spine manipulation (cSMT) is a treatment technique most often performed by chiropractors for relief of musculoskeletal complaints of the head and neck. Although performed typically without complication, cSMT has been identified as a potential cause of cerebrovascular accidents (eg, stroke) via mechanical injury to the vertebral artery.1-5 Given that an estimated 119 million cervical manipulations are performed every year in the United States (extrapolated from 13 million per year in Canada)6 and that public use of this therapy is increasing,7,8 the possibility that cSMT is a cause of cerebrovascular injury is of public importance. Although most practitioners of manipulation take a professional oath that includes the phrase bdo no harm,Q such a statement presupposes that the practitioner understands how harm is created and when it occurs. Without 539
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Fig 1. Fluoroscopic image of the canine cervical spine. Injected contrast medium demonstrates the insertion of an internal mammary catheter into the vertebral artery.
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Fig 3. IVUS image of the vertebral artery in cross-section. The ultrasonic catheter itself is visualized within the lumen of the artery.
bid risk factors such as hyperhomocysteinemia.19 Therefore, to investigate this topic adequately, an experimental platform is needed that is accessible, adaptable, and biologically responsive—an animal model. With that in mind, the objective of this study was to establish an animal model capable of accommodating (1) direct study of its vertebral arteries and (2) creation of controlled injuries simulating arterial injury.
METHODS
Fig 2. An anteroposterior fluoroscopic view demonstrating the placement of a guide wire in the vertebral artery to the level of the first cervical vertebra. such knowledge, adherence to this ideal is impossible regardless of how noble the intention. Therefore, to bdo no harm,Q the clinical community must endeavor to bdo know harmQ—that is, acquire understanding of the mechanisms by which iatrogenic injury may occur. For cervical manipulation, this ability does not exist presently and is the impetus for this project. Although numerous case reports describe a temporal link between cervical manipulation and arterial injury,2-4,9-11 a cause-effect relation has yet to be established for several reasons. First, population studies which define risk are vulnerable to misdiagnosis/underreporting12 and, by design, are unable to determine causation.13 Alternatively, traditional cadaveric studies are incapable of recognizing biologic responses to injury such as thrombosis,14,15 vasospasm,16-18 or the modulating effects of suspected premor-
For the purposes of this study, we have adapted a standard imaging technique used in coronary artery assessment, known as intravascular ultrasound (IVUS),20,21 for use in visualizing the internal structures of the vertebral artery. Specifically, 3 large canines were sedated intravenously with 5% pentothal at 1 mL/kg, then intubated. Anesthesia was created with a combination of 0.6 L nitrous oxide, 0.4 L oxygen, and 1.0% to 1.5% halothane. In each of these animals, the left brachial or left axillary artery was exposed, and a 2.67-mm sheath was inserted to maintain the vessel lumen. An internal mammary catheter was then inserted under fluoroscopic guidance into the origin of the left vertebral artery (Fig 1). A 0.356-mm percutaneous coronary intervention guide wire was advanced down the vertebral artery under fluoroscopic guidance. A 2.9-Fr (0.97 mm) IVUS catheter (Boston Scientific, USA) was advanced over the guide wire. The wire track can be seen at the level of the first cervical vertebra in Fig 2. Once the IVUS transducer was placed in the desired arterial position by fluoroscopic guidance, cross-sectional images of the artery were collected (Fig 3). To characterize entire regions of the artery as opposed to single cross-sections, the IVUS probe was positioned distally in the vessel then withdrawn proximally by an
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Fig 4. Schematic representing overinflation of an angiographic balloon in the vertebral artery to create aneurysm.
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Fig 6. Cross-section of the vertebral artery before angiographic intervention. The catheter has been removed digitally from the vessel lumen.
translated back and forth within the vessel by manual control (n = 1, Fig 5). After this procedure, the structural integrity of the vessel was then reassessed with IVUS by using the procedure described above. Each animal was then killed with a 240-mg concentration of sodium pentothal (Euthanyl, 2 mL/4.5 kg). Qualitative comparisons were then made between 2- and 3-dimensional images obtained before and after angiographic intervention. All of the above procedures were approved in advance by the Animal Care Committee of the University of Calgary.
RESULTS
Fig 5. Schematic representing inflation and translation of an angiographic balloon in the vertebral artery to create dissection.
electromechanical stepping motor at a specific rate of 0.5 mm/s. Images were collected on a video card at 15 frames per second (640 480 pixels, National Instruments, USA). In this study, the collection of these images was not synchronized to systolic or diastolic events. This procedure produced a series of cross-sectional images along the path of the artery. The resulting image bstackQ was then processed with standard imaging software (Scion Image) to create 2and 3-dimensional reconstructions of the vessel (eg, coronal sections, 3-dimensional transparencies). After imaging of the vessel in this manner, the IVUS transducer was removed, and an angiographic balloon was placed into the lumen of the vertebral artery under fluoroscopic guidance. Once in place at the desired location, the balloon was either overinflated (n = 2, Fig 4) or inflated and
Two-dimensional cross-section images displayed the lumen of the vertebral artery clearly (Figs 3 and 6). As the ultrasonic probe is rotated mechanically within the vessel to obtain these images, the transducer itself can be seen within the lumen. From these images, various structural elements of the vessel can be visualized. Depending on the level where the cross-sectional image was captured, other structures outside the main vessel could be visualized including accessory vessels and the transverse foramen. Three-dimensional reconstructions showed the overall size and shape of the vessel as well as some anatomic features which span several cross-sectional slices (Fig 7). The wavy contour of the lumen observed in Fig 7 is because of the lack of synchrony between image collection times and pressure waves in the vessel—images were collected at various points in the cardiac cycle, and thus the dimension of the lumen varied. Both 2- and 3-dimensional images show the presence of vascular injury after angiographic perturbation. In Figs 8 and 9, a qualitative dilatation of the vessel with an associated increase in its lumen diameter can be seen after
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Fig 7. Three-dimensional reconstruction of the vertebral artery.
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Fig 9. Coronal section of the reconstructed vertebral artery demonstrating an increase in vessel lumen after balloon overinflation.
Fig 8. Cross-section of the vertebral artery after balloon overinflation.
Fig 10. Cross-section of the vertebral artery after balloon inflation and translation.
angiographic balloon overinflation (ie, aneurysm). In Figs 10 and 11, the tunica intima has been separated from the vessel wall consistent with a progressing dissection22 located where the angiographic balloon was inflated and then translated manually within the vessel.
DISCUSSION The ability of a canine model to support direct interrogation of its vertebral arteries was investigated in this study. Intravascular ultrasound was used to generate 2-dimensional images of vessel structure from within the vessel itself. These images displayed the layers which constitute the vessel wall, whereas various reconstructions of this image data revealed the longitudinal nature of the artery and its associated structures. Image reconstruction techniques were used successfully to show the presence of vascular injury after either overinflation of an angiographic
balloon (aneurysm) or manual translation of an inflated balloon within the vessel (dissection). IVUS is a well-entrenched clinical technique used to visualize coronary artery pathologies and to help identify locations for the delivery of therapeutic agents (eg, stents, pharmaceuticals).23,24 The application of this technology is limited only by the diameter of the ultrasound transducer (~1 mm) and the ability to place and operate the catheter from a remote access point. For these reasons, we supposed that IVUS would be an excellent technique to study the fine structures of the vertebral arteries in vivo. At present, IVUS is not approved for human use in vertebral arteries. Most typically, human vertebral arteries arise from the subclavian artery in 90% of the population.25 After exiting the subclavian artery, each vessel enters osseous foramina located on the transverse processes of the cervical vertebrae beginning typically at the sixth cervical vertebra. Vertebral
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Fig 11. Coronal section of the reconstructed vertebral artery demonstrating the presence of an intimal flap lesion (dissection) after balloon inflation and translation. arteries are unique in that they pass within rigid channels and are linked by connective tissue attachments to these channels at each of the vertebral segments they transcend. As a result, vertebral arteries are thought to undergo constant positional alterations from neck movement.25,26 After entering the transverse foramina of the sixth cervical vertebra, the course of the artery is superior and linear until the third cervical vertebrae. After exiting the third transverse foramina, the vertebral artery courses more laterally, then sharply cephalad, creating a loop as it passes through the atlanto-occipital membrane and into the subarachnoid space.25 The guidance wire of our catheter system can be seen at this level in Fig 2. After the vertebral artery passes through each foramen, it unites with its counterpart to form the basilar artery which, in normal circumstances, provides approximately 10% of the blood to the brain.27 The supply of blood from the vertebral artery to the brain may become interrupted through direct injury from a variety of mechanisms such as motor vehicle accidents.28 Because spinal manipulation is a therapeutic agent which is defined as the manual application of an external force over a short period resulting in movements of the vertebrae, some feel that this therapeutic modality is a potential form of trauma that may cause injury to the vertebral artery.29-33 While evidence exists to support the use of cervical manipulation for providing relief of musculoskeletal complaints of the head and neck,34-37 a number of cases have been reported which make a temporal link to the application of cervical manipulation and injury to the vertebral artery.2-4,9-11 Such an injury may in turn cause symptoms of downstream ischemia including nausea, nystagmus, ataxia, tinnitus, and anesthesia.38,39 These symptoms range from being transient in nature to those that are permanently disabling or, in rare circumstances, fatal. Unfortunately, these case studies are typically inadequate in their description of the performed manipulation and/or the evaluation of iatrogenic injury. Of approximately 115 cases of vertebral artery injury after manipulation reported in the English literature, only 2 cases exist in which investigators
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interviewed the practitioner to obtain an accurate description of the procedure used.40 Therefore, only 2 reports exist which contain accurate information regarding the manipulative procedure.40 Although these case studies make plausible the idea that a link between manipulation and cerebrovascular injury exists, the lack of information within these case reports is of little use toward establishing a causeeffect relation. To further assess a potential relation between vertebral injury and cervical manipulation, other investigative approaches have been used. These include cadaveric, imaging, and population investigations. The limitations of these approaches are discussed below. As a whole, cadaveric studies which perfuse the vertebral artery artificially have shown a diminished flow in the contralateral vertebral artery with ipsilateral neck rotation.41-44 Although some studies have shown the opposite of this generalization,45,46 a popular notion has surfaced which contends that the rotational component of cSMT reduces blood flow to the brain which leads to cerebrovascular injury. This is an unlikely mechanism given the extremely short time the neck is rotated during cSMT 47,48 and the presence of other vessels to compensate for decreased cerebral flow.49 A more plausible injury mechanism is that neck rotation during cSMT injures the vertebral artery which then creates a sustained interruption of blood flow to the posterior brain. To investigate this possibility, investigators have used cadaveric preparations to determine the strain on unperfused vertebral arteries during neck rotation. The resulting strain during cSMT was then expressed as a percentage of the strain required for the isolated vessel to fail when stretched along its long axis.50 Although results from this study suggest that it is bvery unlikelyQ that the vertebral artery is damaged during neck manipulation, there has been no recorded case that would suggest that this mode of failure (long-axis distraction) is physiologically relevant. More importantly, this approach, like all cadaveric approaches, cannot determine if biologic injuries occur in the vessel before the onset of overt damage (ie, microtearing, thrombus formation, vasospasm). Events such as these would require a biologically viable system, which is not the case in cadaveric preparations. Like cadaveric studies, various imaging techniques have been used to address how cervical manipulation may disrupt vertebral artery flow. These include Doppler ultrasound50,51 and magnetic resonance angiography.52,53 Unfortunately, each of these studies possesses limitations that inhibit study of the vertebral artery in vivo. Doppler ultrasound is capable of visualizing only gross alterations in vessel size or flow in small portions of the artery because of the size and shape of the transducer and the inability for ultrasonic waves to pass through the osseous transverse foramen.54 Magnetic resonance angiography is limited in that its resolution can only describe significant alterations in vessel contour.52,53 Although these limitations provide support for investigators
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who have concluded that these imaging techniques55-57 and clinical tests of forced rotation58 are of little value in predicting persons at risk for cSMT-induced injury, they do not provide the resolution or coverage necessary to determine if small-magnitude injuries or biologic responses to those injuries occur after manipulation. Whereas cadaveric and imaging studies attempt to observe direct injury to the vertebral artery after cSMT, other investigators have used a population-based approach to estimate the risk of cSMT-induced injury in relation to cerebrovascular accidents. These population studies have generated risk estimates that range in value from 1 in 1.3 million to 1 in 400 000.13,40 Unfortunately, this approach has severe limitations—a reflection of the wide range of published risk values. Specifically, population studies of risk tend to be disadvantaged by insufficient sample sizes because of the general infrequency of the condition. In addition, they may be corrupted because of underreporting and/or misdiagnosis of the condition.12 More importantly, population studies are limited in that they describe only the temporal probability between cSMT and cerebrovascular symptoms— these studies cannot define causation. As noted by the authors of one population-based study which created a risk estimate, bStatements about attributable rates imply a causal association and assume that observed relative risk values are unaffected by bias. This study design does not permit us to estimate the number of cases that are truly the result of trauma sustained during manipulation.Q13 Creation of an animal-model toward the study of manipulation/vascular relations would solve many problems of the experimental approaches listed above and was the impetus for this project. Through use of IVUS, we have shown that the internal structures of the canine artery can be observed in vivo. This possibility provides an opportunity to apply mechanical forces to the model and determine the models’ biologic and mechanical responses. Assuming that more than 1 animal can be tested, this technique can solve the sample size limitations of case studies. The high-resolution and indwelling nature of IVUS means that under physiologic conditions, the model can be probed for small structural aberrations and biologic responses to injury to manipulation—an impossibility in cadaveric studies. The ability to know the condition of the system before the application of a manipulative force provides the possibility that this model can delineate cause and effect relations between vascular injury and manipulation. Furthermore, the ability to create arterial injuries (aneurysm, dissection) in the model additionally provides an opportunity to determine how force application to the model may extend or aggravate preexisting vascular injuries. It is the aggravation of these preexisting injuries or premorbid conditions by manipulation which is presently thought by many to be a significant mechanism by which cervical manipulation causes cerebrovascular injury. Specifically, given the large number of uneventful cSMT
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applications every year and the large number of vertebral artery strokes which do not involve cSMT, it has been suggested that persons who experience cSMT-induced stroke may have a preexisting vascular injury,6,59 genetic susceptibility,60-62 or altered biochemistry.19,63-66 These conditions may in turn create symptoms (ie, headache, neck pain) that cause care-seeking behavior. Should that care provider deliver a manipulation, it may be conceivable that the cSMT application (1) would aggravate or extend the preexisting injury or (2) is independent of the lesion’s progress, making treatment coincidental, but temporally linked to the onset of cerebrovascular symptoms. In either case, current investigative techniques based on cadaveric, imaging, or population-based studies are ill-suited to investigate this possibility. Although advantageous in many respects, the animal model described here has limitations. Techniques used to synchronize the collection of IVUS images with the cardiac cycle and to register the IVUS images with the local anatomy must be used. In addition, we do not understand presently how congruent a canine model is to specific aspects of human vertebral artery physiology and the responses of the system to applied manipulation. This includes potential differences in the vascular stiffness of the model when compared with human beings who exhibit hypertension and atherosclerosis. Although no animal model is a perfect facsimile for human investigation, animal models provide a unique opportunity to increase our knowledge beyond the status quo when human investigation is not possible.
CONCLUSION The 2 goals of this project were met. The canine model developed in this project is capable of direct study of its vertebral arteries (via IVUS) and can accommodate creation of controlled interventions resulting in arterial injury (dissection, aneurysm). The long-term impact of this project will be the availability of an experimental platform capable of providing investigators of all backgrounds with the means to quantify the biologic outcomes of cervical manipulation. Information from these studies is needed desperately to evaluate current treatment efficacies, therapeutic dosage, and safety. As a result, regulatory agencies will possess the data needed to make meaningful recommendations regarding cSMT safety in the face of increasing public use. Without adequate tools for investigation, the cause-effect relation between cSMT and vascular injury will remain speculative.
ACKNOWLEDGMENT The authors thank the valuable technical assistance of Ms Wendy Leschuk, Ms Heather Finch, Ms Lorraine Johannson, Ms Dawn Martin, Dr James Davies, and Dr Merle Olson.
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REFERENCES 1. Wood MJ, Lang EK, Woolhandler GJ, Faludi HK. Traumatic vertebral artery thrombosis. J La State Med Soc 1971;123:413-4. 2. Schellhas KP, Latchaw RE, Wendling LR, Gold LH. Vertebrobasilar injuries following cervical manipulation. JAMA 1980;244:1450-3. 3. Hufnagel A, Hammers A, Schonle PW, Bohm KD, Leonhardt G. Stroke following chiropractic manipulation of the cervical spine. J Neurol 1999;246:683-8. 4. Nadgir RN, Loevner LA, Ahmed T, Moonis G, Chalela J, Slawek K, Imbesi S. Simultaneous bilateral internal carotid and vertebral artery dissection following chiropractic manipulation: case report and review of the literature. Neuroradiology 2003; 45:311-4. 5. Mann T, Refshauge KM. Causes of complications from cervical spine manipulation. Aust J Physiother 2001;47:255-66. 6. Haldeman S, Carey P, Townsend M, Papadopoulos C. Arterial dissections following cervical manipulation: the chiropractic experience. Can Med Assoc J 2001;165:905-6. 7. Kessler RC, Davis RB, Foster DF, Van Rompay MI, Walters EE, Wilkey SA, Kaptchuk TJ, Eisenberg DM. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med 2001;135:262-8. 8. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280:1569-75. 9. Davidson KC, Weiford EC, Dixon GD. Traumatic vertebral artery pseudoaneurysm following chiropractic manipulation. Radiology 1975;115:651-2. 10. Parkin PJ, Wallis WE, Wilson JL. Vertebral artery occlusion following manipulation of the neck. N Z Med J 1978;88:441-3. 11. Zak SM, Carmody RF. Cerebellar infarction from chiropractic neck manipulation: case report and review of the literature. Ariz Med 1984;41:333-7. 12. Kapral MK, Bondy SJ. Cervical manipulation and risk of stroke. Can Med Assoc J 2001;165:907-8. 13. Rothwell DM, Bondy SJ, Williams JI. Chiropractic manipulation and stroke: a population-based case-control study. Stroke 2001;32:1054-60. 14. Pan G, Wright KC. Clot embolic stroke in the vertebrobasilar system of rabbits: a transfemoral angiographic technique. Cardiovasc Intervent Radiol 1987;10:285-90. 15. Nakahara T, Oki S, Muttaqin Z, Kuwabara S, Uozumi T. A new model of brainstem ischemia by embolization technique in cats. Neurosurg Rev 1991;14:221-9. 16. Megyesi JF, Vollrath B, Cook DA, Findlay JM. In vivo animal models of cerebral vasospasm: a review. Neurosurgery 2000;46:448-60. 17. Marshall LF, Bruce DA, Bruno L, Langfitt TW. Vertebrobasilar spasm: a significant cause of neurological deficit in head injury. J Neurosurg 1978;48:560-4. 18. Soustiel JF, Bruk B, Shik B, Hadani M, Feinsod M. Transcranial Doppler in vertebrobasilar vasospasm after subarachnoid hemorrhage. Neurosurgery 1998;43:282-91. 19. Pezzini A, Del Zotto E, Padovani A. Hyperhomocysteinemia: a potential risk factor for cervical artery dissection following chiropractic manipulation of the cervical spine. J Neurol 2002;249:1401-3. 20. Nissen SE. Application of intravascular ultrasound to characterize coronary artery disease and assess the progression or regression of atherosclerosis. Am J Cardiol 2002;89:24B-31B. 21. Nissen S. Coronary angiography and intravascular ultrasound. Am J Cardiol 2001;87:15A-20A.
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22. Dmowski AT, Carey MJ. Aortic dissection. Am J Emerg Med 1999;17:372-5. 23. Honda Y, Grube E, de la Fuente LM, Yock PG, Stertzer SH, Fitzgerald PJ. Novel drug-delivery stent: intravascular ultrasound observations from the first human experience with the QP2-eluting polymer stent system. Circulation 2001;104: 380-3. 24. Regar E, Serruys PW. Ten years after introduction of intravascular ultrasound in the catheterization laboratory: tool or toy? Z Kardiol 2002;91(Suppl 3):89-97. 25. Thiel H. Gross morphology and pathoanatomy of the vertebral arteries. J Manipulative Physiol Ther 1991;14:133-41. 26. Chopard R, Hubner De Miranda Neto M, Lucas G, Chopard M. The vertebral artery: its relationship with adjoining tissues in its course intra and inter transverse processes in man. Rev Paul Med 1992;110:245-50. 27. Ekestrom S, Retamal E. Hemodynamic condition of the subclavian steal syndrome. Scand J Thorac Cardiovasc Surg 1967;1:161-4. 28. Ahmad HA, Gerraty RP, Davis SM, Cameron PA. Cervicocerebral artery dissections. J Accid Emerg Med 1999;16:422-4. 29. Mehalic T, Farhat SM. Vertebral artery injury from chiropractic manipulation of the neck. Surg Neurol 1974;2:125-9. 30. Sherman DG, Hart RG, Easton JD. Abrupt change in head position and cerebral infarction. Stroke 1981;12:2-6. 31. Sherman MR, Smialek JE, Zane WE. Pathogenesis of vertebral artery occlusion following cervical spine manipulation. Arch Pathol Lab Med 1987;111:851-3. 32. Nakamura CT, Lau JM, Polk NO, Popper JS. Vertebral artery dissection caused by chiropractic manipulation. J Vasc Surg 1991;14:122-4. 33. Siegel D, Neiders T. Vertebral artery dissection and pontine infarct after chiropractic manipulation. Am J Emerg Med 2001;19:171-2. 34. Dagenais S, Haldeman S. Chiropractic. Prim Care 2002;29: 419-37. 35. Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining ‘‘whiplash’’ and its management. Spine 1995;20:1S-73S. 36. Gurumoorthy D, Twomey L. The Quebec Task Force on Whiplash-Associated Disorders. Spine 1996;21:897-8. 37. Astin JA, Ernst E. The effectiveness of spinal manipulation for the treatment of headache disorders: a systematic review of randomized clinical trials. Cephalalgia 2002;22:617-23. 38. Terret AGJ. Current concepts in vertebrobasilar complications following spinal manipulation. Des Moines (IA)7 NCMIC; 2001. p. 42. 39. Lee KP, Carlini WG, McCormick GF, Albers GW. Neurologic complications following chiropractic manipulation: a survey of California neurologists. Neurology 1995;45:1213-5. 40. Haldeman S, Kohlbeck F, McGregor M. Risk factors and precipitating neck movements causing vertebrobasilar artery dissection after cervical trauma and spinal manipulation. Spine 1999;24:785-94. 41. Murai T, Inui H, Miyahara H, Matsunaga T, Takano H. Hemodynamics of a simulation of the vertebrobasilar system using silicone tube. Acta Otolaryngol Suppl 1998; 533:30-5. 42. Chong BW, Kerber CW, Buxton RB, Frank LR, Hesselink JR. Blood flow dynamics in the vertebrobasilar system: correlation of a transparent elastic model and MR angiography. AJNR Am J Neuroradiol 1994;15:733-45. 43. Li YK, Zhang YK, Lu CM, Zhong SZ. Changes and implications of blood flow velocity of the vertebral artery during
545
546
Kawchuk et al Vertebral Artery Integrity
44. 45.
46. 47.
48. 49. 50. 51.
52. 53.
54.
55.
rotation and extension of the head. J Manipulative Physiol Ther 1999;22:91-5. Sheth TN, Winslow JL, Mikulis DJ. Rotational changes in the morphology of the vertebral artery at a common site of artery dissection. Can Assoc Radiol J 2001;52:236-41. Fox MW, Piepgras DG, Bartleson JD. Anterolateral decompression of the atlantoaxial vertebral artery for symptomatic positional occlusion of the vertebral artery. Case report. J Neurosurg 1995;83:737-40. Sakai F, Ishii K, Igarashi H, Suzuki S, Kitai N, Kanda T, Tazaki Y. Regional cerebral blood flow during an attack of vertebrobasilar insufficiency. Stroke 1988;19:1426-30. Vicenzino B, Neal R, Collins D, Wright A. The displacement, velocity and frequency profile of the frontal plane motion produced by the cervical lateral glide treatment technique. Clin Biomech (Bristol, Avon) 1999;14:515-21. Kawchuk GN, Herzog W. Biomechanical characterization (fingerprinting) of five novel methods of cervical spine manipulation. J Manipulative Physiol Ther 1993;16:573-7. Faris A, Poser C, Wilmore D, Agnew C. Radiologic visualization of neck vessels in healthy men. Neurology 1963;13: 386-96. Symons BP, Leonard T, Herzog W. Internal forces sustained by the vertebral artery during spinal manipulative therapy. J Manipulative Physiol Ther 2002;25:504-10. Simon H, Niederkorn K, Horner S, Duft M, Schrockenfuchs M. Effect of head rotation on the vertebrobasilar system. A transcranial Doppler ultrasound contribution to the physiology. HNO 1994;42:614-8. Licht PB, Christensen HW, Hoilund-Carlsen PF. Vertebral artery volume flow in human beings. J Manipulative Physiol Ther 1999;22:363-7. Vaccaro A, Klein G, Flanders AE, Albert T, Balderston R, Cotler J. Long-term evaluation of vertebral artery injuries following cervical spine trauma using magnetic resonance angiography. Spine 1998;23:789-94. Haynes MJ, Cala LA, Melsom A, Mastaglia FL, Milne N, McGeachie JK. Vertebral arteries and cervical rotation: modeling and magnetic resonance angiography studies. J Manipulative Physiol Ther 2002;25:370-83. Alayon A, McKinney WM. Normal vertebral artery hemodynamics and pathology, vascular ultrasound of the neck. In:
Journal of Manipulative and Physiological Therapeutics November/December 2004
56.
57.
58. 59.
60. 61.
62.
63. 64. 65. 66.
Alayon A , McKinney W , editors. Vascular ultrasound of the neck: an interpretive atlas. Philadelphia7 Lippincott Williams and Wilkins; 2001 p. 107-19. Rivett DA, Sharples KJ, Milburn PD. Effect of premanipulative tests on vertebral artery and internal carotid artery blood flow: a pilot study. J Manipulative Physiol Ther 1999; 22:368-75. Licht PB, Christensen HW, Hojgaard P, Marving J. Vertebral artery flow and spinal manipulation: a randomized, controlled and observer-blinded study. J Manipulative Physiol Ther 1998;21:141-4. Licht PB, Christensen HW, Hoilund-Carlsen PF. Is there a role for premanipulative testing before cervical manipulation? J Manipulative Physiol Ther 2000;23:175-9. Cote P, Kreitz BG, Cassidy JD, Thiel H. The validity of the extension-rotation test as a clinical screening procedure before neck manipulation: a secondary analysis. J Manipulative Physiol Ther 1996;19:159-64. Rothwell D, Bondy S, Williams I. Chiropractic manipulation and stroke: a population-based case-control study. Stroke 2001;32:1054-60. Haldeman S, Kohlbeck FJ, McGregor M. Unpredictability of cerebrovascular ischemia associated with cervical spine manipulation therapy: a review of sixty-four cases after cervical spine manipulation. Spine 2002;27:49-55. Mayer SA, Rubin BS, Starman BJ, Byers PH. Spontaneous multivessel cervical artery dissection in a patient with a substitution of alanine for glycine (G13A) in the alpha 1 (I) chain of type I collagen. Neurology 1996;47: 552-6. Mettinger KL, Ericson K. Fibromuscular dysplasia and the brain: I. Observations on angiographic, clinical and genetic characteristics. Stroke 1982;13:46-52. Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of heritable connective tissue disorders. A review. Stroke 1994;25:889-903. Lu CY, Hou JW, Wang PJ, Chiu HH, Wang TR. Homocystinuria presenting as fatal common carotid artery occlusion. Pediatr Neurol 1996;15:159-62. van den Berg JS, Limburg M, Kappelle LJ, Pals G, Arwert F, Westerveld A. The role of type III collagen in spontaneous cervical arterial dissections. Ann Neurol 1998;43:494-8.
ABSTRACT Background: Cervical spine manipulation is most often performed to affect relief of musculoskeletal complaints of the head and neck. Performed typically without complication, this modality is thought to be a potential cause of cerebrovascular injury, although a cause-effect relation has yet to be established. To explore this relation, an experimental platform is needed that is accessible and biologically responsive. Objective: To establish an animal model capable of accommodating (1) direct study of its vertebral arteries and (2) creation of controlled interventions simulating arterial injury. Study Design: Descriptive. Methods: Under fluoroscopic guidance, an ultrasonic catheter was inserted into the left vertebral artery of 3 anesthetized dogs. The ultrasonic probe was then drawn proximally through the artery at a specific rate, and cross-sectional images of the vessel were collected. These images were then reconstructed to provide a variety of 2- and 3-dimensional representations of the vessel. This procedure was repeated after the overinflation and/or displacement of an angiographic balloon within the vertebral artery itself. Results: The resulting ultrasonic images were able to delineate the structural layers that constitute the vertebral artery. Analysis of 2- and 3-dimensional reconstructions before and after angiographic intervention revealed the creation of discrete vascular injuries (aneurysm or dissection). Conclusions: For the first time, an animal model has been established that permits direct interrogation of the internal structures of the vertebral artery. This model can also be manipulated to create bpreexistingQ vascular injuries that are thought to be possible prerequisites for cerebrovascular injury associated with manipulation. As a result, an experimental platform has been established that is capable of providing investigators of all backgrounds with the ability to quantify biologic and mechanical outcomes of cervical manipulation. (J Manipulative Physiol Ther 2004;27:539-546) Key Indexing Terms: Manipulation; Chiropractic; Vertebral Artery; Animals; Model
a
Faculty of Rehabilitation Medicine, University of Alberta, Alberta, Canada. b Graduate Student, University of Calgary, Alberta, Canada. c Faculty of Medicine, University of Calgary, Alberta, Canada. Sources of support: Financial support for materials used in this work was provided in part by the Canadian Chiropractic Protective Association. The authors receive salary support through the Canadian Institutes of Health Research and the Canadian Chiropractic Association (Dr Kawchuk), the Alberta Provincial CIHR Training Program in Bone and Joint Health (Dr Wynd), and by the Alberta Heritage Foundation for Medical Research (Dr Anderson). Submit requests for reprints to: Greg Kawchuk, DC, PhD, Faculty of Rehabilitation Medicine, University of Alberta, 2-28 Corbett Hall, Edmonton, Alberta, Canada T6G 2G4 (e-mail: [email protected]). Paper submitted May 19, 2003. 0161-4754/$30.00 Copyright D 2004 by National University of Health Sciences. doi:10.1016/j.jmpt.2004.10.005
C
ervical spine manipulation (cSMT) is a treatment technique most often performed by chiropractors for relief of musculoskeletal complaints of the head and neck. Although performed typically without complication, cSMT has been identified as a potential cause of cerebrovascular accidents (eg, stroke) via mechanical injury to the vertebral artery.1-5 Given that an estimated 119 million cervical manipulations are performed every year in the United States (extrapolated from 13 million per year in Canada)6 and that public use of this therapy is increasing,7,8 the possibility that cSMT is a cause of cerebrovascular injury is of public importance. Although most practitioners of manipulation take a professional oath that includes the phrase bdo no harm,Q such a statement presupposes that the practitioner understands how harm is created and when it occurs. Without 539
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Fig 1. Fluoroscopic image of the canine cervical spine. Injected contrast medium demonstrates the insertion of an internal mammary catheter into the vertebral artery.
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Fig 3. IVUS image of the vertebral artery in cross-section. The ultrasonic catheter itself is visualized within the lumen of the artery.
bid risk factors such as hyperhomocysteinemia.19 Therefore, to investigate this topic adequately, an experimental platform is needed that is accessible, adaptable, and biologically responsive—an animal model. With that in mind, the objective of this study was to establish an animal model capable of accommodating (1) direct study of its vertebral arteries and (2) creation of controlled injuries simulating arterial injury.
METHODS
Fig 2. An anteroposterior fluoroscopic view demonstrating the placement of a guide wire in the vertebral artery to the level of the first cervical vertebra. such knowledge, adherence to this ideal is impossible regardless of how noble the intention. Therefore, to bdo no harm,Q the clinical community must endeavor to bdo know harmQ—that is, acquire understanding of the mechanisms by which iatrogenic injury may occur. For cervical manipulation, this ability does not exist presently and is the impetus for this project. Although numerous case reports describe a temporal link between cervical manipulation and arterial injury,2-4,9-11 a cause-effect relation has yet to be established for several reasons. First, population studies which define risk are vulnerable to misdiagnosis/underreporting12 and, by design, are unable to determine causation.13 Alternatively, traditional cadaveric studies are incapable of recognizing biologic responses to injury such as thrombosis,14,15 vasospasm,16-18 or the modulating effects of suspected premor-
For the purposes of this study, we have adapted a standard imaging technique used in coronary artery assessment, known as intravascular ultrasound (IVUS),20,21 for use in visualizing the internal structures of the vertebral artery. Specifically, 3 large canines were sedated intravenously with 5% pentothal at 1 mL/kg, then intubated. Anesthesia was created with a combination of 0.6 L nitrous oxide, 0.4 L oxygen, and 1.0% to 1.5% halothane. In each of these animals, the left brachial or left axillary artery was exposed, and a 2.67-mm sheath was inserted to maintain the vessel lumen. An internal mammary catheter was then inserted under fluoroscopic guidance into the origin of the left vertebral artery (Fig 1). A 0.356-mm percutaneous coronary intervention guide wire was advanced down the vertebral artery under fluoroscopic guidance. A 2.9-Fr (0.97 mm) IVUS catheter (Boston Scientific, USA) was advanced over the guide wire. The wire track can be seen at the level of the first cervical vertebra in Fig 2. Once the IVUS transducer was placed in the desired arterial position by fluoroscopic guidance, cross-sectional images of the artery were collected (Fig 3). To characterize entire regions of the artery as opposed to single cross-sections, the IVUS probe was positioned distally in the vessel then withdrawn proximally by an
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Fig 4. Schematic representing overinflation of an angiographic balloon in the vertebral artery to create aneurysm.
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Fig 6. Cross-section of the vertebral artery before angiographic intervention. The catheter has been removed digitally from the vessel lumen.
translated back and forth within the vessel by manual control (n = 1, Fig 5). After this procedure, the structural integrity of the vessel was then reassessed with IVUS by using the procedure described above. Each animal was then killed with a 240-mg concentration of sodium pentothal (Euthanyl, 2 mL/4.5 kg). Qualitative comparisons were then made between 2- and 3-dimensional images obtained before and after angiographic intervention. All of the above procedures were approved in advance by the Animal Care Committee of the University of Calgary.
RESULTS
Fig 5. Schematic representing inflation and translation of an angiographic balloon in the vertebral artery to create dissection.
electromechanical stepping motor at a specific rate of 0.5 mm/s. Images were collected on a video card at 15 frames per second (640 480 pixels, National Instruments, USA). In this study, the collection of these images was not synchronized to systolic or diastolic events. This procedure produced a series of cross-sectional images along the path of the artery. The resulting image bstackQ was then processed with standard imaging software (Scion Image) to create 2and 3-dimensional reconstructions of the vessel (eg, coronal sections, 3-dimensional transparencies). After imaging of the vessel in this manner, the IVUS transducer was removed, and an angiographic balloon was placed into the lumen of the vertebral artery under fluoroscopic guidance. Once in place at the desired location, the balloon was either overinflated (n = 2, Fig 4) or inflated and
Two-dimensional cross-section images displayed the lumen of the vertebral artery clearly (Figs 3 and 6). As the ultrasonic probe is rotated mechanically within the vessel to obtain these images, the transducer itself can be seen within the lumen. From these images, various structural elements of the vessel can be visualized. Depending on the level where the cross-sectional image was captured, other structures outside the main vessel could be visualized including accessory vessels and the transverse foramen. Three-dimensional reconstructions showed the overall size and shape of the vessel as well as some anatomic features which span several cross-sectional slices (Fig 7). The wavy contour of the lumen observed in Fig 7 is because of the lack of synchrony between image collection times and pressure waves in the vessel—images were collected at various points in the cardiac cycle, and thus the dimension of the lumen varied. Both 2- and 3-dimensional images show the presence of vascular injury after angiographic perturbation. In Figs 8 and 9, a qualitative dilatation of the vessel with an associated increase in its lumen diameter can be seen after
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Fig 7. Three-dimensional reconstruction of the vertebral artery.
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Fig 9. Coronal section of the reconstructed vertebral artery demonstrating an increase in vessel lumen after balloon overinflation.
Fig 8. Cross-section of the vertebral artery after balloon overinflation.
Fig 10. Cross-section of the vertebral artery after balloon inflation and translation.
angiographic balloon overinflation (ie, aneurysm). In Figs 10 and 11, the tunica intima has been separated from the vessel wall consistent with a progressing dissection22 located where the angiographic balloon was inflated and then translated manually within the vessel.
DISCUSSION The ability of a canine model to support direct interrogation of its vertebral arteries was investigated in this study. Intravascular ultrasound was used to generate 2-dimensional images of vessel structure from within the vessel itself. These images displayed the layers which constitute the vessel wall, whereas various reconstructions of this image data revealed the longitudinal nature of the artery and its associated structures. Image reconstruction techniques were used successfully to show the presence of vascular injury after either overinflation of an angiographic
balloon (aneurysm) or manual translation of an inflated balloon within the vessel (dissection). IVUS is a well-entrenched clinical technique used to visualize coronary artery pathologies and to help identify locations for the delivery of therapeutic agents (eg, stents, pharmaceuticals).23,24 The application of this technology is limited only by the diameter of the ultrasound transducer (~1 mm) and the ability to place and operate the catheter from a remote access point. For these reasons, we supposed that IVUS would be an excellent technique to study the fine structures of the vertebral arteries in vivo. At present, IVUS is not approved for human use in vertebral arteries. Most typically, human vertebral arteries arise from the subclavian artery in 90% of the population.25 After exiting the subclavian artery, each vessel enters osseous foramina located on the transverse processes of the cervical vertebrae beginning typically at the sixth cervical vertebra. Vertebral
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Fig 11. Coronal section of the reconstructed vertebral artery demonstrating the presence of an intimal flap lesion (dissection) after balloon inflation and translation. arteries are unique in that they pass within rigid channels and are linked by connective tissue attachments to these channels at each of the vertebral segments they transcend. As a result, vertebral arteries are thought to undergo constant positional alterations from neck movement.25,26 After entering the transverse foramina of the sixth cervical vertebra, the course of the artery is superior and linear until the third cervical vertebrae. After exiting the third transverse foramina, the vertebral artery courses more laterally, then sharply cephalad, creating a loop as it passes through the atlanto-occipital membrane and into the subarachnoid space.25 The guidance wire of our catheter system can be seen at this level in Fig 2. After the vertebral artery passes through each foramen, it unites with its counterpart to form the basilar artery which, in normal circumstances, provides approximately 10% of the blood to the brain.27 The supply of blood from the vertebral artery to the brain may become interrupted through direct injury from a variety of mechanisms such as motor vehicle accidents.28 Because spinal manipulation is a therapeutic agent which is defined as the manual application of an external force over a short period resulting in movements of the vertebrae, some feel that this therapeutic modality is a potential form of trauma that may cause injury to the vertebral artery.29-33 While evidence exists to support the use of cervical manipulation for providing relief of musculoskeletal complaints of the head and neck,34-37 a number of cases have been reported which make a temporal link to the application of cervical manipulation and injury to the vertebral artery.2-4,9-11 Such an injury may in turn cause symptoms of downstream ischemia including nausea, nystagmus, ataxia, tinnitus, and anesthesia.38,39 These symptoms range from being transient in nature to those that are permanently disabling or, in rare circumstances, fatal. Unfortunately, these case studies are typically inadequate in their description of the performed manipulation and/or the evaluation of iatrogenic injury. Of approximately 115 cases of vertebral artery injury after manipulation reported in the English literature, only 2 cases exist in which investigators
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interviewed the practitioner to obtain an accurate description of the procedure used.40 Therefore, only 2 reports exist which contain accurate information regarding the manipulative procedure.40 Although these case studies make plausible the idea that a link between manipulation and cerebrovascular injury exists, the lack of information within these case reports is of little use toward establishing a causeeffect relation. To further assess a potential relation between vertebral injury and cervical manipulation, other investigative approaches have been used. These include cadaveric, imaging, and population investigations. The limitations of these approaches are discussed below. As a whole, cadaveric studies which perfuse the vertebral artery artificially have shown a diminished flow in the contralateral vertebral artery with ipsilateral neck rotation.41-44 Although some studies have shown the opposite of this generalization,45,46 a popular notion has surfaced which contends that the rotational component of cSMT reduces blood flow to the brain which leads to cerebrovascular injury. This is an unlikely mechanism given the extremely short time the neck is rotated during cSMT 47,48 and the presence of other vessels to compensate for decreased cerebral flow.49 A more plausible injury mechanism is that neck rotation during cSMT injures the vertebral artery which then creates a sustained interruption of blood flow to the posterior brain. To investigate this possibility, investigators have used cadaveric preparations to determine the strain on unperfused vertebral arteries during neck rotation. The resulting strain during cSMT was then expressed as a percentage of the strain required for the isolated vessel to fail when stretched along its long axis.50 Although results from this study suggest that it is bvery unlikelyQ that the vertebral artery is damaged during neck manipulation, there has been no recorded case that would suggest that this mode of failure (long-axis distraction) is physiologically relevant. More importantly, this approach, like all cadaveric approaches, cannot determine if biologic injuries occur in the vessel before the onset of overt damage (ie, microtearing, thrombus formation, vasospasm). Events such as these would require a biologically viable system, which is not the case in cadaveric preparations. Like cadaveric studies, various imaging techniques have been used to address how cervical manipulation may disrupt vertebral artery flow. These include Doppler ultrasound50,51 and magnetic resonance angiography.52,53 Unfortunately, each of these studies possesses limitations that inhibit study of the vertebral artery in vivo. Doppler ultrasound is capable of visualizing only gross alterations in vessel size or flow in small portions of the artery because of the size and shape of the transducer and the inability for ultrasonic waves to pass through the osseous transverse foramen.54 Magnetic resonance angiography is limited in that its resolution can only describe significant alterations in vessel contour.52,53 Although these limitations provide support for investigators
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who have concluded that these imaging techniques55-57 and clinical tests of forced rotation58 are of little value in predicting persons at risk for cSMT-induced injury, they do not provide the resolution or coverage necessary to determine if small-magnitude injuries or biologic responses to those injuries occur after manipulation. Whereas cadaveric and imaging studies attempt to observe direct injury to the vertebral artery after cSMT, other investigators have used a population-based approach to estimate the risk of cSMT-induced injury in relation to cerebrovascular accidents. These population studies have generated risk estimates that range in value from 1 in 1.3 million to 1 in 400 000.13,40 Unfortunately, this approach has severe limitations—a reflection of the wide range of published risk values. Specifically, population studies of risk tend to be disadvantaged by insufficient sample sizes because of the general infrequency of the condition. In addition, they may be corrupted because of underreporting and/or misdiagnosis of the condition.12 More importantly, population studies are limited in that they describe only the temporal probability between cSMT and cerebrovascular symptoms— these studies cannot define causation. As noted by the authors of one population-based study which created a risk estimate, bStatements about attributable rates imply a causal association and assume that observed relative risk values are unaffected by bias. This study design does not permit us to estimate the number of cases that are truly the result of trauma sustained during manipulation.Q13 Creation of an animal-model toward the study of manipulation/vascular relations would solve many problems of the experimental approaches listed above and was the impetus for this project. Through use of IVUS, we have shown that the internal structures of the canine artery can be observed in vivo. This possibility provides an opportunity to apply mechanical forces to the model and determine the models’ biologic and mechanical responses. Assuming that more than 1 animal can be tested, this technique can solve the sample size limitations of case studies. The high-resolution and indwelling nature of IVUS means that under physiologic conditions, the model can be probed for small structural aberrations and biologic responses to injury to manipulation—an impossibility in cadaveric studies. The ability to know the condition of the system before the application of a manipulative force provides the possibility that this model can delineate cause and effect relations between vascular injury and manipulation. Furthermore, the ability to create arterial injuries (aneurysm, dissection) in the model additionally provides an opportunity to determine how force application to the model may extend or aggravate preexisting vascular injuries. It is the aggravation of these preexisting injuries or premorbid conditions by manipulation which is presently thought by many to be a significant mechanism by which cervical manipulation causes cerebrovascular injury. Specifically, given the large number of uneventful cSMT
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applications every year and the large number of vertebral artery strokes which do not involve cSMT, it has been suggested that persons who experience cSMT-induced stroke may have a preexisting vascular injury,6,59 genetic susceptibility,60-62 or altered biochemistry.19,63-66 These conditions may in turn create symptoms (ie, headache, neck pain) that cause care-seeking behavior. Should that care provider deliver a manipulation, it may be conceivable that the cSMT application (1) would aggravate or extend the preexisting injury or (2) is independent of the lesion’s progress, making treatment coincidental, but temporally linked to the onset of cerebrovascular symptoms. In either case, current investigative techniques based on cadaveric, imaging, or population-based studies are ill-suited to investigate this possibility. Although advantageous in many respects, the animal model described here has limitations. Techniques used to synchronize the collection of IVUS images with the cardiac cycle and to register the IVUS images with the local anatomy must be used. In addition, we do not understand presently how congruent a canine model is to specific aspects of human vertebral artery physiology and the responses of the system to applied manipulation. This includes potential differences in the vascular stiffness of the model when compared with human beings who exhibit hypertension and atherosclerosis. Although no animal model is a perfect facsimile for human investigation, animal models provide a unique opportunity to increase our knowledge beyond the status quo when human investigation is not possible.
CONCLUSION The 2 goals of this project were met. The canine model developed in this project is capable of direct study of its vertebral arteries (via IVUS) and can accommodate creation of controlled interventions resulting in arterial injury (dissection, aneurysm). The long-term impact of this project will be the availability of an experimental platform capable of providing investigators of all backgrounds with the means to quantify the biologic outcomes of cervical manipulation. Information from these studies is needed desperately to evaluate current treatment efficacies, therapeutic dosage, and safety. As a result, regulatory agencies will possess the data needed to make meaningful recommendations regarding cSMT safety in the face of increasing public use. Without adequate tools for investigation, the cause-effect relation between cSMT and vascular injury will remain speculative.
ACKNOWLEDGMENT The authors thank the valuable technical assistance of Ms Wendy Leschuk, Ms Heather Finch, Ms Lorraine Johannson, Ms Dawn Martin, Dr James Davies, and Dr Merle Olson.
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REFERENCES 1. Wood MJ, Lang EK, Woolhandler GJ, Faludi HK. Traumatic vertebral artery thrombosis. J La State Med Soc 1971;123:413-4. 2. Schellhas KP, Latchaw RE, Wendling LR, Gold LH. Vertebrobasilar injuries following cervical manipulation. JAMA 1980;244:1450-3. 3. Hufnagel A, Hammers A, Schonle PW, Bohm KD, Leonhardt G. Stroke following chiropractic manipulation of the cervical spine. J Neurol 1999;246:683-8. 4. Nadgir RN, Loevner LA, Ahmed T, Moonis G, Chalela J, Slawek K, Imbesi S. Simultaneous bilateral internal carotid and vertebral artery dissection following chiropractic manipulation: case report and review of the literature. Neuroradiology 2003; 45:311-4. 5. Mann T, Refshauge KM. Causes of complications from cervical spine manipulation. Aust J Physiother 2001;47:255-66. 6. Haldeman S, Carey P, Townsend M, Papadopoulos C. Arterial dissections following cervical manipulation: the chiropractic experience. Can Med Assoc J 2001;165:905-6. 7. Kessler RC, Davis RB, Foster DF, Van Rompay MI, Walters EE, Wilkey SA, Kaptchuk TJ, Eisenberg DM. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med 2001;135:262-8. 8. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA 1998;280:1569-75. 9. Davidson KC, Weiford EC, Dixon GD. Traumatic vertebral artery pseudoaneurysm following chiropractic manipulation. Radiology 1975;115:651-2. 10. Parkin PJ, Wallis WE, Wilson JL. Vertebral artery occlusion following manipulation of the neck. N Z Med J 1978;88:441-3. 11. Zak SM, Carmody RF. Cerebellar infarction from chiropractic neck manipulation: case report and review of the literature. Ariz Med 1984;41:333-7. 12. Kapral MK, Bondy SJ. Cervical manipulation and risk of stroke. Can Med Assoc J 2001;165:907-8. 13. Rothwell DM, Bondy SJ, Williams JI. Chiropractic manipulation and stroke: a population-based case-control study. Stroke 2001;32:1054-60. 14. Pan G, Wright KC. Clot embolic stroke in the vertebrobasilar system of rabbits: a transfemoral angiographic technique. Cardiovasc Intervent Radiol 1987;10:285-90. 15. Nakahara T, Oki S, Muttaqin Z, Kuwabara S, Uozumi T. A new model of brainstem ischemia by embolization technique in cats. Neurosurg Rev 1991;14:221-9. 16. Megyesi JF, Vollrath B, Cook DA, Findlay JM. In vivo animal models of cerebral vasospasm: a review. Neurosurgery 2000;46:448-60. 17. Marshall LF, Bruce DA, Bruno L, Langfitt TW. Vertebrobasilar spasm: a significant cause of neurological deficit in head injury. J Neurosurg 1978;48:560-4. 18. Soustiel JF, Bruk B, Shik B, Hadani M, Feinsod M. Transcranial Doppler in vertebrobasilar vasospasm after subarachnoid hemorrhage. Neurosurgery 1998;43:282-91. 19. Pezzini A, Del Zotto E, Padovani A. Hyperhomocysteinemia: a potential risk factor for cervical artery dissection following chiropractic manipulation of the cervical spine. J Neurol 2002;249:1401-3. 20. Nissen SE. Application of intravascular ultrasound to characterize coronary artery disease and assess the progression or regression of atherosclerosis. Am J Cardiol 2002;89:24B-31B. 21. Nissen S. Coronary angiography and intravascular ultrasound. Am J Cardiol 2001;87:15A-20A.
Kawchuk et al Vertebral Artery Integrity
22. Dmowski AT, Carey MJ. Aortic dissection. Am J Emerg Med 1999;17:372-5. 23. Honda Y, Grube E, de la Fuente LM, Yock PG, Stertzer SH, Fitzgerald PJ. Novel drug-delivery stent: intravascular ultrasound observations from the first human experience with the QP2-eluting polymer stent system. Circulation 2001;104: 380-3. 24. Regar E, Serruys PW. Ten years after introduction of intravascular ultrasound in the catheterization laboratory: tool or toy? Z Kardiol 2002;91(Suppl 3):89-97. 25. Thiel H. Gross morphology and pathoanatomy of the vertebral arteries. J Manipulative Physiol Ther 1991;14:133-41. 26. Chopard R, Hubner De Miranda Neto M, Lucas G, Chopard M. The vertebral artery: its relationship with adjoining tissues in its course intra and inter transverse processes in man. Rev Paul Med 1992;110:245-50. 27. Ekestrom S, Retamal E. Hemodynamic condition of the subclavian steal syndrome. Scand J Thorac Cardiovasc Surg 1967;1:161-4. 28. Ahmad HA, Gerraty RP, Davis SM, Cameron PA. Cervicocerebral artery dissections. J Accid Emerg Med 1999;16:422-4. 29. Mehalic T, Farhat SM. Vertebral artery injury from chiropractic manipulation of the neck. Surg Neurol 1974;2:125-9. 30. Sherman DG, Hart RG, Easton JD. Abrupt change in head position and cerebral infarction. Stroke 1981;12:2-6. 31. Sherman MR, Smialek JE, Zane WE. Pathogenesis of vertebral artery occlusion following cervical spine manipulation. Arch Pathol Lab Med 1987;111:851-3. 32. Nakamura CT, Lau JM, Polk NO, Popper JS. Vertebral artery dissection caused by chiropractic manipulation. J Vasc Surg 1991;14:122-4. 33. Siegel D, Neiders T. Vertebral artery dissection and pontine infarct after chiropractic manipulation. Am J Emerg Med 2001;19:171-2. 34. Dagenais S, Haldeman S. Chiropractic. Prim Care 2002;29: 419-37. 35. Spitzer WO, Skovron ML, Salmi LR, Cassidy JD, Duranceau J, Suissa S, Zeiss E. Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining ‘‘whiplash’’ and its management. Spine 1995;20:1S-73S. 36. Gurumoorthy D, Twomey L. The Quebec Task Force on Whiplash-Associated Disorders. Spine 1996;21:897-8. 37. Astin JA, Ernst E. The effectiveness of spinal manipulation for the treatment of headache disorders: a systematic review of randomized clinical trials. Cephalalgia 2002;22:617-23. 38. Terret AGJ. Current concepts in vertebrobasilar complications following spinal manipulation. Des Moines (IA)7 NCMIC; 2001. p. 42. 39. Lee KP, Carlini WG, McCormick GF, Albers GW. Neurologic complications following chiropractic manipulation: a survey of California neurologists. Neurology 1995;45:1213-5. 40. Haldeman S, Kohlbeck F, McGregor M. Risk factors and precipitating neck movements causing vertebrobasilar artery dissection after cervical trauma and spinal manipulation. Spine 1999;24:785-94. 41. Murai T, Inui H, Miyahara H, Matsunaga T, Takano H. Hemodynamics of a simulation of the vertebrobasilar system using silicone tube. Acta Otolaryngol Suppl 1998; 533:30-5. 42. Chong BW, Kerber CW, Buxton RB, Frank LR, Hesselink JR. Blood flow dynamics in the vertebrobasilar system: correlation of a transparent elastic model and MR angiography. AJNR Am J Neuroradiol 1994;15:733-45. 43. Li YK, Zhang YK, Lu CM, Zhong SZ. Changes and implications of blood flow velocity of the vertebral artery during
545
546
Kawchuk et al Vertebral Artery Integrity
44. 45.
46. 47.
48. 49. 50. 51.
52. 53.
54.
55.
rotation and extension of the head. J Manipulative Physiol Ther 1999;22:91-5. Sheth TN, Winslow JL, Mikulis DJ. Rotational changes in the morphology of the vertebral artery at a common site of artery dissection. Can Assoc Radiol J 2001;52:236-41. Fox MW, Piepgras DG, Bartleson JD. Anterolateral decompression of the atlantoaxial vertebral artery for symptomatic positional occlusion of the vertebral artery. Case report. J Neurosurg 1995;83:737-40. Sakai F, Ishii K, Igarashi H, Suzuki S, Kitai N, Kanda T, Tazaki Y. Regional cerebral blood flow during an attack of vertebrobasilar insufficiency. Stroke 1988;19:1426-30. Vicenzino B, Neal R, Collins D, Wright A. The displacement, velocity and frequency profile of the frontal plane motion produced by the cervical lateral glide treatment technique. Clin Biomech (Bristol, Avon) 1999;14:515-21. Kawchuk GN, Herzog W. Biomechanical characterization (fingerprinting) of five novel methods of cervical spine manipulation. J Manipulative Physiol Ther 1993;16:573-7. Faris A, Poser C, Wilmore D, Agnew C. Radiologic visualization of neck vessels in healthy men. Neurology 1963;13: 386-96. Symons BP, Leonard T, Herzog W. Internal forces sustained by the vertebral artery during spinal manipulative therapy. J Manipulative Physiol Ther 2002;25:504-10. Simon H, Niederkorn K, Horner S, Duft M, Schrockenfuchs M. Effect of head rotation on the vertebrobasilar system. A transcranial Doppler ultrasound contribution to the physiology. HNO 1994;42:614-8. Licht PB, Christensen HW, Hoilund-Carlsen PF. Vertebral artery volume flow in human beings. J Manipulative Physiol Ther 1999;22:363-7. Vaccaro A, Klein G, Flanders AE, Albert T, Balderston R, Cotler J. Long-term evaluation of vertebral artery injuries following cervical spine trauma using magnetic resonance angiography. Spine 1998;23:789-94. Haynes MJ, Cala LA, Melsom A, Mastaglia FL, Milne N, McGeachie JK. Vertebral arteries and cervical rotation: modeling and magnetic resonance angiography studies. J Manipulative Physiol Ther 2002;25:370-83. Alayon A, McKinney WM. Normal vertebral artery hemodynamics and pathology, vascular ultrasound of the neck. In:
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56.
57.
58. 59.
60. 61.
62.
63. 64. 65. 66.
Alayon A , McKinney W , editors. Vascular ultrasound of the neck: an interpretive atlas. Philadelphia7 Lippincott Williams and Wilkins; 2001 p. 107-19. Rivett DA, Sharples KJ, Milburn PD. Effect of premanipulative tests on vertebral artery and internal carotid artery blood flow: a pilot study. J Manipulative Physiol Ther 1999; 22:368-75. Licht PB, Christensen HW, Hojgaard P, Marving J. Vertebral artery flow and spinal manipulation: a randomized, controlled and observer-blinded study. J Manipulative Physiol Ther 1998;21:141-4. Licht PB, Christensen HW, Hoilund-Carlsen PF. Is there a role for premanipulative testing before cervical manipulation? J Manipulative Physiol Ther 2000;23:175-9. Cote P, Kreitz BG, Cassidy JD, Thiel H. The validity of the extension-rotation test as a clinical screening procedure before neck manipulation: a secondary analysis. J Manipulative Physiol Ther 1996;19:159-64. Rothwell D, Bondy S, Williams I. Chiropractic manipulation and stroke: a population-based case-control study. Stroke 2001;32:1054-60. Haldeman S, Kohlbeck FJ, McGregor M. Unpredictability of cerebrovascular ischemia associated with cervical spine manipulation therapy: a review of sixty-four cases after cervical spine manipulation. Spine 2002;27:49-55. Mayer SA, Rubin BS, Starman BJ, Byers PH. Spontaneous multivessel cervical artery dissection in a patient with a substitution of alanine for glycine (G13A) in the alpha 1 (I) chain of type I collagen. Neurology 1996;47: 552-6. Mettinger KL, Ericson K. Fibromuscular dysplasia and the brain: I. Observations on angiographic, clinical and genetic characteristics. Stroke 1982;13:46-52. Schievink WI, Michels VV, Piepgras DG. Neurovascular manifestations of heritable connective tissue disorders. A review. Stroke 1994;25:889-903. Lu CY, Hou JW, Wang PJ, Chiu HH, Wang TR. Homocystinuria presenting as fatal common carotid artery occlusion. Pediatr Neurol 1996;15:159-62. van den Berg JS, Limburg M, Kappelle LJ, Pals G, Arwert F, Westerveld A. The role of type III collagen in spontaneous cervical arterial dissections. Ann Neurol 1998;43:494-8.