Letter: Considering Cerebrospinal Fluid Leaks in Ehlers-Danlos Patients: Raising Awareness Amongst Neurosurgeons

Abstract

To the Editor: A review of the literature indicates that across the last 7 yr, there is a lack of studies regarding the correlation between cerebrospinal fluid (CSF) leaks and dural laxity in Ehlers-Danlos Syndrome (EDS) patients, possibly because EDS patients are considered high risk surgical candidates. A neurosurgeon may be hesitant to investigate an EDS patient for a leak due to increased risk of impaired wound healing from attenuated and fragile dura. Other factors potentially contributing to the neurosurgeon’s hesitancy include the overlap seen between CSF leak symptoms and other problems common in patients with EDS such as headaches, myelopathy, and cranio-cervical and spinal segmental instability. Perhaps worst of all, patients with Ehlers Danlos often suffer from chronic pain. The innate ligamentous laxity that riddles all forms of EDS confers substantial risk of chronic multifocal joint, tendon, and spinal pain.1 These other complaints may obscure the clarity of orthostatic headache in a brief clinical interview of EDS patients. There are 2 studies which address the aforementioned concerns. The most recent is by Reinstein et al2 wherein the authors analyzed data obtained from a prospective study that enrolled a group of 50 patients referred for CSF leak consultation. The patients were examined for the presence of connective tissue abnormalities based on echocardiography, eye exam, histopathological skin examination, and dural biopsies, which were then confirmed with genetic testing. A total of 9 patients were identified to have heritable connective tissue disorders, 4 of which were EDS hypermobility type and 2 EDS classic type. The study concluded that patients with spontaneous CSF leaks had higher chances of having an underlying connective tissue abnormality. A prior prospective study conducted by Schievink et al3 examined a group of 18 patients with connective tissue disorders who exhibited spontaneous CSF leaks as well. More specifically, 11% of patients had EDS Type 2, which had not been previously documented to present with spontaneous CSF leaks. The study also reported that the success rate of surgical CSF leak repair remains unchanged regardless of the presence of underlying hereditary connective tissue disorders.3 Nevertheless, further research is warranted to better stratify the associated surgical risks based on the correlation between the type and severity of EDS to the possibility of developing spontaneous CSF leaks. The tenacity needed by a neurosurgeon pursuing a CSF leak in this high risk group should be informed by four evolving understandings that disrupt the classic teachings about CSF leaks: 1) Opening pressure is most often normal in patients with CSF leaks and fails to distinguish between patients with and without CSF leaks visible on spinal imaging4; 2) Pachymeningeal enhancement on brain magnetic resonance imaging (MRI) may be present in only a minority of patients with CSF leaks5; 3) Subtle brainstem measurements such as suprasellar distance, mamillopontine distance, and prepontine distance may be as important as the more classic and obvious pachymeningeal enhancement to predict finding a spinal CSF leak6; and 4) New imaging techniques demonstrate that spinal CSF leak into epidural and paravertebral veins (so-called CSF-venous fistulas) are much more common than previously appreciated and will be missed by conventional MRI, magnetic resonance myelogram, and computed tomography myelogram—with falsely reassuring spine imaging results. These may only become apparent with lateral decubitus digital subtraction myelogram, a technique not yet widely practiced or available.7 Together, these evolving understandings, published after the original reports on EDS, suggest neurosurgeons should: 1) Have a higher index of suspicion for CSF leaks in the EDS population; 2) View with humility our current ability to exclude spinal CSF leaks with opening pressure and imaging; 3) Have a low threshold to expend effort to identify and treat this fixable cause of chronic disability; and 4) Heed the guidance encompassed by the International Classification of Headache Disorders (ICHD-3) which states, “In patients with typical orthostatic headache and no apparent cause, and after exclusion of postural orthostatic tachycardia syndrome, it is reasonable in clinical practice to provide autologous lumbar epidural blood patch”.8 As gatekeepers in the evaluation and treatment of suspected CSF leaks, a neurosurgeon’s clinical decision to vigorously pursue CSF leak in an EDS patient with an orthostatic headache will likely determine the entire clinical course for that patient.