CMS Prevalence and Neurological Manifestations
Craniocervical instability (CCI) and cervical medullary syndrome (CMS) are complex, underrecognized disorders involving pathological motion or compression at the craniovertebral junction. CCI typically arises from structural defects or ligamentous laxity, often associated with hereditary connective tissue disorders (HCTDs) such as Ehlers-Danlos syndrome (EDS), and may result in a range of symptoms including headache, visual disturbances, dysautonomia, and sensorimotor deficits.
CMI describes the clinical consequences of compression or mechanical deformation of the lower brainstem and upper cervical spinal cord, leading to functional neurological impairment. Despite their significant morbidity, both conditions lack a defined epidemiological prevalence in the general population. The majority of literature is limited to case series, imaging studies, and surgical cohorts. For instance, Henderson et al. (2019) reported on a case series of 22 patients with HCTDs and Chiari malformation who underwent posterior fossa and craniocervical fusion, demonstrating radiographic improvements and symptom relief, yet without providing population-level prevalence data. Similarly, Russek and Crowell (2022) described physical therapy outcomes in a small cohort of hypermobile patients with upper cervical instability, emphasizing the need for greater diagnostic awareness and multidisciplinary care. Nicholson et al. (2023) used upright dynamic MRI to establish normative reference values for craniocervical motion in asymptomatic individuals, while Rezakhah et al. (2023) reported cervical spine instability in 14% of rheumatoid arthritis patients, though their sample was limited to only 50 individuals. In the absence of robust prevalence estimates, broader contextual data, such as those from the Global Burden of Disease Study (Safiri et al., 2020), reflect the widespread impact of cervical spine morbidity but do not differentiate between etiologies. Similarly, cervical spondylotic myelopathy (CSM)—a degenerative condition with defined epidemiological parameters (Nouri et al., 2015)—does not encompass the dynamic instability and brainstem compression central to CCI and CMI.
Mounting clinical evidence indicates that CCI and CMS are associated with a range of autonomic neurological dysfunctions. Compression of the cervicomedullary junction can disrupt respiratory and cardiovascular regulation as well as cranial nerve function. Henderson et al. (2019) reported that patients with connective tissue disorders and CMS frequently presented with symptoms such as syncope, orthostatic intolerance, palpitations, fatigue, and cognitive impairment—symptoms that improved significantly following occipitocervical stabilization. This is consistent with findings from Hauser et al. (2025), who introduced the concept of “cervicovagopathic dysautonomia” to describe how cervical ligamentous laxity may compromise vagus nerve and sympathetic function, resulting in measurable heart rate variability (HRV) changes and multi-system dysautonomia. Gag reflex impairment, resulting from compression of cranial nerves IX and X, has been similarly observed in CMS patients, with restoration of function following surgical decompression (Gautschi et al., 2007; Medical Journals, 2019). Additionally, central sleep apnea has been reported in both pediatric and adult patients with CMS and CCI, often with a positional component, further implicating medullary deformation as a contributing factor (DelRosso et al., 2012; Powell et al., 2021; Zamora-Niño et al., 2018). Despite these findings, most studies are small and observational, and lack standardized autonomic testing protocols. Large-scale, prospective studies are needed to define the scope and mechanisms of autonomic dysfunction in CMS and CCI, particularly in genetically susceptible populations.
References
DelRosso, L. M., Hoque, R., & Chesson, A. L. (2012). Medullary compression causing central sleep apnea. Neurology, 79(13), 1350. https://doi.org/10.1212/WNL.0b013e3182752cc9
Gautschi, O. P., Cadosch, D., & Zellweger, R. (2007). Transection of the cervical spinal cord and medulla oblongata: A fatal complication. Spinal Cord, 45, 291–294.
https://doi.org/10.1038/sj.sc.3101975
Hauser, R. A., et al. (2025). The ligamentous cervical instability etiology of cervicovagopathic dysautonomia. Frontiers in Neurology, 16, 1572863.
https://www.frontiersin.org/articles/10.3389/fneur.2025.1572863/full
Henderson, F. C., Francomano, C. A., Koby, M., Tuchman, K., Adcock, J., Patel, A., & Sheikh, T. (2019). Cervical medullary syndrome secondary to craniocervical instability in hereditary disorders of connective tissue: A case series. Neurosurgical Review, 42(2), 517–530. https://doi.org/10.1007/s10143-018-01070-4
Medical Journals. (2019). Cranial nerve IX–X dysfunction following cervical injury. Journal of Rehabilitation Medicine.
https://www.medicaljournals.se/jrm/content/html/10.2340/20030711-1000022
Nicholson, K. J., Quencer, R. M., Arlet, V., & Jain, S. K. (2023). Quantitative upright dynamic imaging of the craniovertebral junction: Establishing normative data. La Radiologia Medica, 128(5), 543–552. https://doi.org/10.1007/s11547-023-01588-8
Nouri, A., Tetreault, L., Singh, A., Karadimas, S. K., & Fehlings, M. G. (2015). Degenerative cervical myelopathy: Epidemiology, genetics, and pathogenesis. Spine, 40(12), E675–E693. https://doi.org/10.1097/BRS.0000000000000912
Powell, S. K., et al. (2021). Positional central sleep apnea in a child with cervical instability. ATS Journals Case Report.
https://www.researchgate.net/publication/349515774_Positional_Central_Sleep_Apnea_in_a_C hild_with_Cervical_Instability
Rezakhah, A., et al. (2023). Prevalence of cervical spine instability in rheumatoid arthritis patients. Egyptian Journal of Neurosurgery, 38, 13. https://doi.org/10.1186/s41984-023-00241-w
Russek, L. N., & Crowell, M. (2022). Presentation and physical therapy management of upper cervical instability in symptomatic generalized joint hypermobility: A retrospective case series. Frontiers in Medicine, 9, 1072764. https://doi.org/10.3389/fmed.2022.1072764
Safiri, S., Kolahi, A.-A., Cross, M., Hill, C., Smith, E., Bettampadi, D., et al. (2020). Global, regional, and national burden of neck pain in 204 countries and territories, 1990–2019: A
systematic analysis for the Global Burden of Disease Study 2019. The Lancet Rheumatology, 2(10), e605–e614. https://doi.org/10.1016/S2665-9913(20)30207-9
Zamora-Niño, A. M., et al. (2018). Positional central sleep apnea associated with medullary compression. Case Reports in Pulmonology, 2018, 1–5.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361311
This preliminary literature review was prepared by Aritro Ray, Research and Advocacy Intern at the InclusiVibe Foundation. For questions or further information, please contact: Aritro.Ray@InclusiVibe.org.