Spontaneous Intracranial Hypotension Associated with Marfan Syndrome: A Case Report

Introduction Spontaneous intracranial hypotension (SIH) is an uncommon and frequently misdiagnosed condition characterized by a lower-than-normal volume of cerebrospinal fluid (CSF) caused by leakage of CSF through the dural membrane. The primary manifestation of SIH is an orthostatic headache, which is frequently accompanied by nausea and vomiting. Patients with connective tissue disorders are at increased risk for spontaneous CSF leaks due to the structural weakness of their dural membranes. Case Report An 18-year-old woman with no reported past medical history presented to the emergency department with 10 days of a bifrontal headache that was orthostatic in nature with associated nausea and vomiting. She was noted to have several marfanoid features on physical examination. Spontaneous intracranial hypotension was ultimately diagnosed and treated successfully with an epidural blood patch. Subsequent genetic testing revealed a diagnosis of Marfan syndrome. Conclusion Spontaneous intracranial hypotension is an uncommon cause of headache. Individuals with connective tissue disorders such as Marfan syndrome are at increased risk for SIH. Knowledge of the relationship between these two conditions allows for a more rapid diagnosis of SIH.


INTRODUCTION
First described in 1938, spontaneous intracranial hypotension (SIH) is a condition characterized by a lowerthan-normal volume of cerebrospinal fluid (CSF) caused by leakage of CSF through the dural membrane. 1,2Patients with connective tissue disorders are at increased risk for spontaneous CSF leaks due to the structural weakness of their dural membranes. 3The primary manifestation of SIH is an orthostatic headache that may be accompanied by nausea, tinnitus, and photophobia. 4We report the case of a young woman with previously undiagnosed Marfan syndrome who presented with SIH.

CASE REPORT
An 18-year-old woman presented to the emergency department (ED) complaining of a bifrontal headache present for 10 days.The headache was of insidious onset and was significantly worse in the upright position, better when supine.She reported nausea with the headache and one episode of vomiting two days earlier.On physical examination, she had several marfanoid features including a tall, slender build with disproportionately long arms, legs, and fingers.

CASE REPORTS
Computed tomography of her brain showed no significant abnormalities and magnetic resonance imaging (MRI) of the brain with venogram was ordered because of concern for possible dural venous sinus thrombosis.The MRI showed dural thickening and increased dural enhancement suggestive of intracranial hypotension.The patient was admitted to the hospital, and MRI of the cervical, thoracic, and lumbar spine performed the next day showed no extradural fluid collections to suggest a CSF leak.She had modest improvement of her headache after an epidural blood patch and was discharged on hospital day three.
The patient returned to the ED five days later complaining of a return of the headache.A second MRI of the spine was performed that showed a meningeal diverticulum arising from the left first and second thoracic level with an adjacent pleural effusion concerning for a possible ruptured nerve root sleeve diverticulum (Image).She received a second epidural blood patch with complete, longstanding relief of the headache.Subsequent outpatient genetic testing revealed a pathogenic variant of the FBN1 gene consistent with a diagnosis of Marfan syndrome.

DISCUSSION
Spontaneous intracranial hypotension is distinguished from other causes of CSF leaks of known cause such as spinal surgery, craniospinal trauma, and, most commonly, lumbar puncture or spinal anesthesia.Spontaneous intracranial hypotension is an uncommon cause of headache in the ED, with an estimated annual incidence of 5/100,000 individuals-half the incidence of subarachnoid hemorrhage. 5Women are diagnosed with SIH more frequently than men, with a female-male ratio of approximately 2:1. 6 Spontaneous intracranial hypotension is often initially misdiagnosed, with 94% of patients receiving an incorrect initial diagnosis in one study. 7The headache caused by SIH is believed to be the result of downward displacement of the brain due to loss of CSF buoyancy, resulting in traction on pain-sensitive fibers in the dura mater. 3,6The orthostatic headache caused by SIH is typically described as diffuse, occipital, or frontal. 4Other associated symptoms are often present (Table 1).The location of the CSF leak with SIH is often not determined since spinal CSF leaks generally do not cause local symptoms. 6Extradural spinal CSF collections are found in approximately half of all patients with SIH. 2 The majority of identified spinal CSF leaks occur at the thoracic or cervicothoracic spine level. 8Spinal CSF leaks occur via three main mechanisms: meningeal diverticula; ventral dural tears; and CSF-venous fistulas, with diverticula being most common. 9Patients with genetic connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome Type II, and autosomal dominant polycystic kidney disease are at higher risk for spontaneous CSF leaks due to the structural weakness of their dural membranes. 3,10One prospective study found that up to two-thirds of patients with spontaneous spinal CSF leaks had some evidence of a connective tissue disorder. 10iagnostic criteria for SIH have been proposed (Table 2). 2,11Brain MRI with contrast is the most sensitive imaging study for diagnosing SIH. 4,9Smooth, generalized dural enhancement is the feature most commonly seen, present in 73% of patients with SIH. 2,4Many cases of SIH resolve spontaneously with no specific treatment required. 12nitial conservative treatments of bed rest, oral hydration, and caffeine are effective in approximately 25% of patients. 4pidural blood patching is the most commonly performed intervention for spinal CSF leaks, with estimates of efficacy ranging from 36-90%. 9

CONCLUSION
Spontaneous intracranial hypotension is an uncommon cause of headache and is frequently misdiagnosed.Individuals with Marfan syndrome and other connective tissue disorders are at increased risk for SIH due to the structural weakness of their dural membranes predisposing to spontaneous CSF leaks.Knowledge of the relationship between these associated conditions allows for more rapid diagnosis of SIH.

Table 1 .
4Symptoms associated with the headache of spontaneous intracranial hypotension.
How might this improve emergency medicine practice?Knowledge of the predilection of patients with connective tissue disorders for SIH may assist clinicians in the diagnosis of similar cases.Image.Magnetic resonance imaging (coronal view) showing a meningeal diverticulum at the first and second thoracic level (arrow).