Neurological and spinal manifestations of the Ehlers–Danlos syndromes

Abstract

The Ehlers–Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression. This report also discusses increased prevalence of migraine, idiopathic intracranial hypertension, Tarlov cysts, tethered cord syndrome, and dystonia, where associations with EDS have been anecdotally reported, but where epidemiological evidence is not yet available. Chiari Malformation Type I (CMI) has been reported to be a comorbid condition to EDS, and may be complicated by craniocervical instability or basilar invagination. Motor delay, headache, and quadriparesis have been attributed to ligamentous laxity and instability at the atlanto‐occipital and atlantoaxial joints, which may complicate all forms of EDS. Discopathy and early degenerative spondylotic disease manifest by spinal segmental instability and kyphosis, rendering EDS patients prone to mechanical pain, and myelopathy. Musculoskeletal pain starts early, is chronic and debilitating, and the neuromuscular disease of EDS manifests symptomatically with weakness, myalgia, easy fatigability, limited walking, reduction of vibration sense, and mild impairment of mobility and daily activities. Consensus criteria and clinical practice guidelines, based upon stronger epidemiological and pathophysiological evidence, are needed to refine diagnosis and treatment of the various neurological and spinal manifestations of EDS. © 2017 Wiley Periodicals, Inc.

Diagnosis of Atlantoaxial Instability Requires Clinical Suspicion to Drive the Radiological Investigation

“…Examination often demonstrates tenderness over C1-C2, altered mechanics of neck rotation, hyperreflexia, dysdiadochokinesia, hypoesthesia to pinprick. Weakness is not a constant feature of AAI [4,[23][24][25][26][27].…”

“…Radiological features may show atlanto-dental interval (ADI) >2.5 mm in an adult, or 5 mm in a child, on lateral flexion x-rays (Figure 1) or rotation of C1 upon C2 >41° [4,28] (Figure 2). Excessive rotation occurs opposite to the side of an incompetent alar ligament.…”

“…Excessive rotation occurs opposite to the side of an incompetent alar ligament. Alar ligament incompetence is the most frequent cause of AAI in the population of patients with hypermobility connective tissue disorders [4]. Thus diagnosis of AAI in EDS, or related connective tissue disorders, is best made with supine computerized tomography (CT), from occiput to C2, with full neck rotation (90° if possible) to left and to right.…”

“…Failure of any of the components of the atlantoaxial ligament complex requires dorsal surgical fusion [35]. This is most often accomplished with posterior screw constructs, transarticular screw fixation [24], or C1-C2 lateral mass/pedicle screws and interposed graft [4,25,26] (Figure 5). Aberrant vertebral artery anatomy may preclude the desired screw placement in 18% to 23% of patients [36,37], and the surgery may be complicated in EDS by small bone architecture.…”

“…Three patients were thought to have chronic instability, most likely to have resulted from ligamentous laxity, possibly EDS [4,5].…”