Neurological manifestations of Ehlers-Danlos syndrome(s): A review

Abstract

The term "Ehlers-Danlos syndrome" (EDS) groups together an increasing number of heritable connective tissue disorders mainly featuring joint hypermobility and related complications, dermal dysplasia with abnormal skin texture and repair, and variable range of the hollow organ and vascular dysfunctions. Although the nervous system is not considered a primary target of the underlying molecular defect, recently, increasing attention has been posed on neurological manifestations of EDSs, such as musculoskeletal pain, fatigue, headache, muscle weakness and paresthesias. Here, a comprehensive overview of neurological findings of these conditions is presented primarily intended for the clinical neurologist. Features are organized under various subheadings, including pain, fatigue, headache, stroke and cerebrovascular disease, brain and spine structural anomalies, epilepsy, muscular findings, neuropathy and developmental features. The emerging picture defines a wide spectrum of neurological manifestations that are unexpectedly common and potentially disabling. Their evaluation and correct interpretation by the clinical neurologist is crucial for avoiding superfluous investigations, wrong therapies, and inappropriate referral. A set of basic tools for patient's recognition is offered for raising awareness among neurologists on this underdiagnosed group of hereditary disorders.

Keywords: Brain; Developmental Delay; Ehlers-Danlos Syndrome; Fatigue; Headache; Neuromuscular.

Figure 1

Examples of cutaneous and articular manifestations of Ehlers-Danlos syndrome (EDS). Papyraceous scars at knees in a adult man (A) and woman (B) with classic EDS. Various degrees of skin hyperextensibility (C, D). Extensive easy bruising due to capillary fragility in a adult (E) and child (F). Joint hypermobility at fingers (G). Genu recurvatum (H)

Figure 2

Periventricular heterotopias in a 37-year-old woman with features of classic Ehlers-Danlos syndrome

Figure 3

Summary of the Beighton and Bulbena scores for assessing joint hypermobility. The picture of the Beighton score is freely available at: http://www.hypermobility.org/beighton.php