DEGENERATIVE DISEASE State of the Art in Degenerative Cervical Myelopathy: An Update on Current Clinical Evidence ∗ Jefferson R. Wilson, MD, PhD Degenerative cervical myelopathy (DCM) is a common cause of spinal cord dysfunction ‡ Lindsay A. Tetreault, PhD that confronts clinicians on a daily basis. Research performed over the past few decades has Downloaded from https://academic.oup.com/neurosurgery/article-abstract/80/3S/S33/3045012 by guest on 29 July 2019 Jun Kim, MD§ provided improved insight into the diagnosis, evaluation, and treatment of this disorder. Mohammed F. Shamji, MD, We aim to provide clinicians with an update regarding the state of the art in DCM, focusing on more recent research pertaining to pathophysiology, natural history, treatment, consid- PhD‡ eration of the minimally symptomatic patient, surgical outcome prediction, and outcome ¶ James S. Harrop, MD measurement. Current concepts of pathophysiology focus on the combination of static Thomas Mroz, MD|| and dynamic elements leading to breakdown of the blood–spinal cord barrier at the Samuel Cho, MD§ site of compression resulting in local inflammation, cellular dysfunction, and apoptosis. Michael G. Fehlings, MD, PhD∗ With respect to treatment, although there is a dearth of high-quality studies comparing surgical to nonoperative treatment, several large prospective studies have recently ∗Department of Surgery, Division of associated surgical management with clinically and statistically significant improvement Neurosurgery, St. Michael’s Hospital, in functional, disability, and quality of life outcome at long-term follow-up. When selecting University of Toronto, Toronto, Canada; ‡Department of Surgery, Division of the specific surgical intervention for a patient with DCM, anterior (discectomy, corpectomy, Neurosurgery, Toronto Western Hospital, hybrid discectomy/corpectomy), posterior (laminectomy and fusion, laminoplasty), and University of Toronto, Toronto, Canada; combined approaches may be considered as options depending on the specifics of the §Department of Orthopedic Surgery, Icahn School of Medicine, New York, patient in question; evidence supporting each of these approaches is reviewed in detail. New York; ¶Division of Neurosurgery Recently developed clinical prediction models allow for accurate forecasting of postoper- and Orthopedics, Thomas Jefferson ative outcomes, permitting enhanced communication and management of patient expec- University Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; tations in the preoperative setting. Finally, an overview of outcome measures recom- ||Division of Neurosurgery, Cleveland mended for use in the assessment of DCM patients is provided. Clinic, Cleveland, Ohio KEY WORDS: Degenerative cervical myelopathy, Cervical spondylotic myelopathy, Surgery, Pathophysiology, Correspondence: Natural history, Outcome prediction, Outcome measures, Review Michael G. Fehlings, MD, PhD, FRCSC, Toronto Western Hospital, Neurosurgery 80:S33–S45, 2017 DOI:10.1093/neuros/nyw083 www.neurosurgery-online.com West Wing 4th floor, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada. E-mail: [email protected] egenerative cervical myelopathy (DCM) by gait imbalance, loss of hand dexterity, represents a collection of pathological and sphincter dysfunction.1 Although epidemi- Received, August 15, 2016. D entities, which individually, or in combi- ological studies are sparse in the literature, DCM Accepted, September 22, 2016. nation, cause compression of the cervical spinal is one of the most common causes of spinal cord cord, resulting in a clinical syndrome typified dysfunction internationally, with an estimated Copyright C 2016 by the annual incidence of 41 per million in North Congress of Neurological Surgeons America; from a surgical perspective, DCM ABBREVIATIONS: ACDF, anterior cervical ranks amongst the most common of indications discectomy and fusion; BSCB, blood–spinal for surgery on the cervical spine.2-4 cord barrier; CI, confidence interval; CSM, In this review, we provide an overview of cervical spondylotic myelopathy; DCM, Degen- the state of the art in DCM, with a focus erative cervical myelopathy; DTI, diffusion tensor imaging; FA, fractional anisotropy; JOA, Japanese on updating the modern day spine surgeon Orthopaedic Association; mJOA, modified JOA; on the current evidence surrounding patho- MCID, minimally clinical important difference; MRI, physiology, natural history, imaging, outcome magnetic resonance imaging; NDI, Neck Disability measures, and outcome prediction tools. Further, Index; OPLL, ossification of the posterior longi- with respect to treatment, we provide an tudinal ligament; RCT, randomized control trial; overview of the evidence for surgical vs nonop- RR, relative risk; SI, signal intensity; WI, weighted erative management, a summary of the liter- images ature surrounding the most commonly employed NEUROSURGERY VOLUME 80 | NUMBER 3 | MARCH 2017 Supplement | S33 WILSON ET AL Downloaded from https://academic.oup.com/neurosurgery/article-abstract/80/3S/S33/3045012 by guest on 29 July 2019 FIGURE. Artist depiction of anatomic and pathological changes that may occur in the setting of DCM. Reused with permission from Nouri A, Tetreault L, Singh A, Karadimas SK, Fehlings MG. Degenerative cervical myelopathy: epidemiology, genetics, and pathogenesis. Spine. 2015;40:E675-E693. S34 | VOLUME 80 | NUMBER 3 | MARCH 2017 Supplement www.neurosurgery-online.com STATE OF THE ART IN DEGENERATIVE CERVICAL MYELOPATHY ological and, in the setting of degenerative subluxation, patho- TABLE 1. Overview of the Factors involved in the Pathophysiology of logical motion of the cervical spine.8 DCM5,8 When considering injury to the spinal cord itself, there is histopathological evidence to suggest that in addition to physical Static factors compression, there is a reduction in blood supply leading to 1) Spondylosis 8 2) Disk degeneration considerable ischemia within the cord. Pathological features 3) Ossification of the posterior longitudinal ligament of DCM include gray and white matter degeneration, anterior 4) Ossification of the ligamentum flavum horn cell loss, cystic cavitation, and Wallerian degeneration of 5) Congenital stenosis the posterior columns adjacent to the site of compression. In Dynamic Factors rat models, Karadimas et al9 demonstrated decreased capillary Downloaded from https://academic.oup.com/neurosurgery/article-abstract/80/3S/S33/3045012 by guest on 29 July 2019 1) Degenerative spondylolisthesis density in the compressed spinal cord compared to controls, 2) Physiological narrowing of canal diameter with neck extension 3) Strain and stretch forces placed on spinal cord with physiological thereby indicating blood–spinal cord barrier (BSCB) disruption neck movements in the setting of progressive stenosis from DCM. This correlated Biomolecular factors with a progression from a narrow-based normal gait to a broad- 1) Ischemic injury due to chronic compression of spinal cord based gait with chronic compression in rat models. In the setting vasculature and break down of blood–spinal cord barrier of such vascular insufficiency, local ischemia can lead to neuronal 2) Increased local inflammatory response ionic imbalance and cellular dysfunction resulting in excitotoxic 3) Increased local expression of CX3CR1 glutamate release and an expanded zone of neural tissue injury.9,10 4) Glutamate-mediated excitotoxicity 5) Oligodendrocyte and neuronal apoptosis In addition to the above, with breakdown of the normal BSCB, a secondary cascade of neuroinflammation consisting of microglia activation and macrophage recruitment occurs at the site of mechanical compression within the spinal cord. In the noncompressed nonmyelopathic spinal cord, the BSCB is surgical approaches and a description of novel and less accepted isolated from the peripheral immune system; however, chronic surgical techniques. compression renders the cord susceptible to cell infiltration that may be involved in neural degeneration. Recent liter- Terminology ature has delved into the inflammatory pathways implicated in DCM is used to describe myelopathy resulting from degener- DCM. Specifically, with respect to gene expression, increased ative pathology in the cervical spine including spondylosis, degen- local expression of CX3CR1 has been associated with increased erative disk disease, ossification of the posterior longitudinal microglia and macrophage accumulation at compression sites.11 ligament (OPLL), and ossification of the ligamentum flavum Current research is focused on further defining the role of the (Figure).3 While each of these pathological entities may immune response, as well as the specific inflammatory pathways, be discussed individually (ie, the term cervical spondylotic underlying the pathobiology of DCM. myelopathy [CSM] may be used when considering spondy- In addition to the above, with respect to OPLL, substantial lotic disease alone), when considering these entities together, the progress has been made in understanding the genetics and patho- term DCM is increasingly preferred and employed throughout biology underlying this disorder. The reader is referred to one of the literature. Throughout this manuscript, unless discussing several recent reviews on this topic.12 evidence pertinent to specific pathology (CSM or OPLL alone), the term DCM will be used. NATURAL HISTORY PATHOPHYSIOLOGY Traditionally, the natural history of patients presenting with The pathogenesis of DCM is composed of static and dynamic myelopathy