Abnormalities of the craniovertebral junction (CVJ) and spine in Ehlers-Danlos Syndrome: a systematic review on diagnosis


There is continued debate regarding the extent that defects of the brain and spine such as Chiari Malformation and craniocervical instability are involved in the neurological manifestations of Ehlers-Danlos Syndrome (EDS), and this has led to controversy surrounding surgical management. In 2015, the EDS Expert Panel met to clarify indications for neurosurgical intervention, however, recommendations did not include definitive criteria to qualify surgical candidacy. Good clinical decision-making depends on improving our understanding of these defects, and requires the development and validation of outcome measures for neurological symptoms and functional pathology of the craniovertebral junction.


This review aims to summarize the diagnostic features of defects discussed by the EDS Expert Panel, with special interest in Chiari Malformation, cranial and cervical instability (CCI), basilar impression, and platybasia.


Protocol development relied on PRISM-P and is registered by PROSPERO. All studies looking at the clinical and/or radiological features of the defects are eligible for inclusion. To capture a sufficiently large number of studies, the population will not be limited to EDS. Articles will be screened by two independent reviewers using Covidence ©, and any disagreement will be resolved by a third party. Data collection will focus on clinical measures and radiological findings. Outcomes of surgical procedures will also be considered.


This review will synthesize data by combining findings from studies of sufficient quality using quantitative descriptions. If studies are highly heterogeneous, data will be described in narrative form and presented in tables or by tabulation.

Interim report

The initial search returned 2954 studies. After screening, approximately 1200 were eligible for full review. A sample of 250 articles were selected to pilot data collection. Given the limited consistency and comparability between studies, a general review of study design is required to identify what data is feasible to collect and how.