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Familial Occurrence of Spontaneous Spinal CSF Leaks: Underlying Connective Tissue Disorder (CME)
Article first published online: 20 DEC 2007
Headache: The Journal of Head and Face Pain
Volume 48, Issue 1, pages 146–149, January 2008
How to Cite
Mokri, B. (2008), Familial Occurrence of Spontaneous Spinal CSF Leaks: Underlying Connective Tissue Disorder (CME). Headache: The Journal of Head and Face Pain, 48: 146–149. doi: 10.1111/j.1526-4610.2007.00979.x
Conflict of Interest: None
- Issue published online: 20 DEC 2007
- Article first published online: 20 DEC 2007
- Accepted for publication August 15, 2007.
- spontaneous CSF leaks;
- acquired chiari;
- connective tissue disorder
Two sisters developed spontaneous cerebrospinal fluid (CSF) leaks from meningeal diverticula. Both had recurrences from non diverticular sites. Both patients, a sister, and their mother had joint hypermobility and there was a strong family history of thoracic and abdominal aorta aneurysms. To my knowledge, this is the first report of familial occurrence of CSF leaks. It also points to the role of a pre-existing dural weakness, likely related to a disorder of connective tissue matrix.
Pre-existing dural weakness likely related to an underlying disorder of connective tissue has been considered as a potential underlying etiology in some of the patients with spontaneous spinal cerebrospinal fluid (CSF) leaks.1 In this communication, 2 sisters are reported, both with clinical stigmata and family history suggestive of disorder of connective tissue matrix. Both sisters developed spontaneous CSF leaks.
Familial occurrence of spontaneous CSF leaks has not been previously reported. This is an additional and stronger evidence in favor of the hypothesis that a pre-existing dural weakness is an etiologic factor in at least some of the patients with this disorder.
In August 2005, at age 12 years, this right-handed female junior high school student developed non-throbbing, holocephalic headaches with fluctuating intensity associated with mild photophobia. In December 2005, the headaches exhibited orthostatic features. Neurologic examination was normal. She had hyperflexible joints. Head magnetic resonance imaging (MRI) showed diffuse pachymeningeal enhancement and descent of the cerebellar tonsils below the foramen magnum. Subsequent computerized tomography (CT) myelography revealed extra-arachnoid fluid from T1 through T10, 2 meningeal diverticulae (at T11-12 and at T7-8 interspace levels). The T7-8 diverticulum was noted to be the site of CSF leakage (Fig., right upper image). A lumbar epidural blood patch did not help. At surgery, a large CSF-weeping meningeal diverticulum was identified in the axilla of the left T7 nerve root sleeve herniating through a dural defect. This was packed with gelfoam, which was then soaked with fibrin glue. The patient was essentially headache free for approximately 2 weeks. Then the orthostatic headaches gradually recurred accentuated by Valsalva-type maneuvers and accompanied by posterior neck, interscapular, and low back pain. CT myelography approximately 3 months following the surgery showed extra-arachnoid fluid from T4 to L1-2, most marked at T6-7. Approximately 4 months following the first surgery, she underwent a second operation. The T6 dural root sleeve was noted to be attenuated, weeping CSF. The area was reinforced with muscle and fibrin sealant.
Patient was seen approximately 3 months later with less drastic orthostatic headaches. Dynamic CT myelography showed contained extra-arachnoid fluid but no evidence of CSF leakage. Head MRI showed resolution of pachymeningeal enhancement and ascend of the cerebellar tonsils to a normal appearing position. On follow-up, headaches have markedly improved.
In October 1999, at age 10 years, this older sister of patient I had developed severe orthostatic headaches and photophobia. Neurologic examination was normal. She had joint hypermobility and hyperextensible skin. Head MRI showed diffuse pachymeningeal enhancement and low lying cerebellar tonsils. On CT myelography, there was a 1-cm diverticulum at T12-L1 and extra-arachnoid fluid extending from the low thoracic to T5 level (Fig., right lower image). CSF opening pressure was unmeasurable. Echocardiogram showed dilated aortic root. Genetic consultation led to dermal biopsy. Collagen fibrils had normal regular banding pattern. No abnormalities were seen to point to Ehlers-Danlos Syndrome. Treatment with caffeine was ineffective. An upper lumbar epidural blood patch brought complete relief for 2 days. A subsequent lower thoracic epidural blood patch was ineffective. She subsequently underwent a T12 hemilaminectomy with identification of a diverticulum arising from the axilla of left T12 nerve root sleeve. This meningeal diverticulum was ligated and the related dural defect was repaired. A piece of muscle was sutured over the closure and secured with fibrin glue. She became asymptomatic and quickly resumed her usual activities. Two weeks later, she fell from a flight of stairs, and within 2 days, her orthostatic headaches reoccurred. A subsequent CT myelography revealed leak at C7-T1, but no leak at the site of prior repair. She was treated with bed rest and caffeine and later with 2 more epidural blood patches. She then developed a rebound intracranial hypertension with nonorthostatic headaches, nausea, and sometimes emesis. Head MRI abnormalities had resolved, CT-myelography showed no leak. CSF opening pressure was noted to be 200 mm H2O. She was treated with acetazolamide, and the headaches resolved within several days. This treatment was continued for only 3-4 months. She has resumed her usual activities, and is attending college and holding a job.
This was extraordinary. On paternal side, at least 4 individuals had thoracic aorta aneurysms (3 uncles, 1 aunt). The patient's father had elected not to be tested. Additionally, 2 paternal cousins were quite tall, slender, and had scoliosis.
On maternal side, there were at least 4 individuals with abdominal aorta aneurysms (great grandfather, grandfather, great aunt, and great uncle).
Furthermore, the patients' mother as well as her third daughter (younger than the second patient and older than the first patient), similar to the 2 patients, also had joint hypermobility (Fig., left upper and lower panels).
The impact of MRI on identification of patients with spontaneous spinal CSF leaks has been enormous, leading to identification of far greater number of patients than before and broad expansion of the clinical and imaging spectrum of this disorder. Despite these advancements, the etiology of spontaneous spinal CSF leaks in many cases remains unclear. Essentially, 2 sets of factors are hypothesized: trivial traumas and a pre-existing weakness of the dural sac.
Many patients with spontaneous CSF leaks report history of a trivial trauma in the preceding few days to few weeks. These may include coughing, lifting, pushing, sneezing, pulling, sports activities, trivial falls, and the like.1 Evidence for dural abnormality is mounting.2,3 Dural sac ectasia, meningeal diverticula, and CSF leaks have been noted in patients with Marfan's syndrome,4-9 a heritable disorder of elastin and fibrillin. Stigmata of disorders of connective tissue matrix have been noted in a significant minority of the patients with spontaneous spinal CSF leaks.2 In one study, minor skeletal features of Marfan's syndrome were seen in 4 of 20 patients with spontaneous spinal CSF leaks.3 All of these patients displayed abnormalities of fibrillin I on analysis of dermal fibroblast cultures, while in only one of the 4, these abnormalities were typical for Marfan's. A study on surgical anatomy of the spontaneous spinal CSF leaks has documented dural defects with complex configurations including those at root sleeves or nerve root axilla and with attenuated dural margins often not amenable to suturing10 leading to intraoperative surgical challenges.
Familial occurrence of spontaneous CSF leaks with documented complex surgical anatomy of the leak and the strongly positive family history suggestive of presence of a heritable disorder of connective tissue matrix is a confirmatory evidence that a pre-existing dural defect based on a disorder of connective tissue matrix is a definite etiologic factor in some of the patients with spontaneous spinal CSF leaks. There is a realistic likelihood that trivial trauma in conjunction with pre-existing dural weakness might be the etiologic core in many if not most of the patients with spontaneous spinal CSF leaks.
- 4Spontaneous intracranial hypotension from a CSF leak in a patient with Marfan's syndrome. J Neurol Neurosurg Pyschiatry. 1995;59:519-519., , .