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. 2021 Feb 22;14(2):e239880. doi: 10.1136/bcr-2020-239880

Neurofibromatosis type 1 with subarachnoid haemorrhage from the left vertebral arteriovenous fistula: case presentation and literature review

Toshinori Nishizawa 1,2,✉, Takahiro Tsuchiya 3, Yoshihiro Terasawa 2,4, Yasuhiro Osugi 2,5
PMCID: PMC7903112  PMID: 33619142

Abstract

We present the case of a 47-year-old woman with neurofibromatosis type 1 (NF1) with subarachnoid haemorrhage (SAH) from the left vertebral arteriovenous fistula, along with a review of previous cases. Our patient had a family history of NF1 and presented to the emergency department with a sudden-onset severe headache and neck pain. CT scan showed SAH. CT angiography revealed a left vertebral arteriovenous fistula and an epidural haematoma. She underwent direct surgery and was discharged without neurologic deficits. To our knowledge, this is the first case of SAH caused by perimedullary drainage of a vertebral arteriovenous fistula associated with NF1. In a literature search, we identified 40 cases of vertebral arteriovenous fistula associated with NF1. The majority of vertebral arteriovenous fistulas occurred on the left side and in women. Patients with vertebral arteriovenous fistula typically experience neck pain, radiculopathy, radiculomyelopathy and bruits.

Keywords: dermatology, general practice / family medicine, coma and raised intracranial pressure, headache (including migraines)

Background

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant genetic disorder with generalised neuroectodermal and mesodermal dysplasia that affects the skin, nervous system, skeleton and vascular system.1 Vascular abnormalities associated with NF1 occur in 0.4%–6.4% of patients and most commonly involve the aorta and renal arteries.2–4 Vertebral arteriovenous fistula related to NF1 is relatively rare; however, its incidence is reportedly increasing. Here, we report a patient with NF1 who presented with subarachnoid haemorrhage (SAH) caused by bleeding from the left vertebral arteriovenous fistula, and review 40 previous cases of vertebral arteriovenous fistula with NF1. To our knowledge, this is the first case of SAH caused by perimedullary drainage of a vertebral arteriovenous fistula associated with NF1.

Case presentation

A 47-year-old woman with a family history of NF1 presented to the emergency department with a sudden-onset severe headache and neck pain. NF1 was diagnosed at the age of 20 years on the basis of pathological examination. She had a medical history of left vertebral arteriovenous fistula and was treated with endovascular treatment (coil embolisation) 8 years prior at another hospital. She was alert and oriented to person, place and time. Physical examination revealed multiple neurofibromas and café-au-lait spots across the trunk (figure 1). She had cervical bruit on the left side and neck stiffness. Other neurological examinations were unremarkable. CT scan showed SAH predominantly in the ambient cistern and the prepontine cistern (figure 2). She was diagnosed with SAH and was transferred to another tertiary emergency hospital with a neurosurgical unit.

Figure 1.

Figure 1

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Subcutaneous neurofibroma and diffuse café-au-lait spot on the trunk.

Figure 2.

Figure 2

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Subarachnoid haemorrhage in the ambient cistern and the prepontine cistern.

Investigations

CT angiography did not indicate any apparent intracranial aneurysm or any intracranial vascular malformation, but revealed a recurrent left vertebral arteriovenous fistula arising from the left vertebral artery and an epidural haematoma. Angiography demonstrated maintained blood flow through the branches of the left vertebral artery, which had not been completely occluded after coiling, right vertebral artery and left internal carotid artery (figure 3). The fistula point was located at the C2-3 level. The drainage route consisted of the epidural and perimedullary veins. Bleeding appeared to have occurred from the left vertebral arteriovenous fistula with epidural and perimedullary venous drainage. In this case, the incomplete occlusion of the feeder of the previous fistula, which was embolised 8 years prior, resulted in new vertebral arteriovenous fistula, complicating the endovascular treatment. Therefore, she underwent emergent direct surgery to identify the lesion.

Figure 3.

Figure 3

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(A) Left vertebral angiogram demonstrated the left vertebral arteriovenous fistula fed by the branches of the left vertebral artery, which had not been completely occluded after coiling. (B) Left carotid angiogram revealed the feeder from left internal carotid artery. (C) Right vertebral angiogram showed the feeder from the right vertebral artery.

Differential diagnosis

The differential diagnosis of non-aneurysmal SAH includes perimesencephalic haemorrhage, intracranial or spinal vascular malformations, intracranial or vertebral arterial dissection and other causes. In this case, the CT findings were not consistent with perimesencephalic haemorrhage. CT angiography did not show any intracranial vascular malformation or any arterial dissection, but revealed a left vertebral arteriovenous fistula. Angiography demonstrated that bleeding appeared to have occurred from the left vertebral arteriovenous fistula. The direct surgery confirmed that in this case, SAH was caused by the bleeding from the left vertebral arteriovenous fistula with epidural and perimedullary venous drainage.

Outcome and follow-up

The patient tolerated the surgical procedure. She was discharged with an uneventful postoperative period. However, she presented with mild memory impairment and was diagnosed with normal pressure hydrocephalus 1 month after discharge. After she was treated with ventriculoperitoneal shunt, she had no neurologic deficits. At the 3-month follow-up, she had no neck pain, radiculopathy, radiculomyelopathy or cervical bruit.

Discussion

NF1 is an autosomal dominant genetic disorder caused by mutations in the NF1 gene on the long arm of chromosome 17.1 These mutations cause dysplastic disorders affecting the vascular system. Patients with NF1 present with a spectrum of vascular lesions ranging from occlusive disease to acute haemorrhage.5

The literature was reviewed using the PubMed database. We identified 40 cases of vertebral arteriovenous fistula associated with NF1 (table 1).5–37 The majority of these cases were reported in Asia. The mean age at diagnosis of the vertebral arteriovenous fistula was 39.8 years. The majority of fistulae occurred on the left side (65%) and in women (75%). Patients with vertebral arteriovenous fistula typically present with neck pain (40%), radiculopathy (30%) and radiculomyelopathy (28%). On physical examination, >50% of the patients experienced cervical bruit. After direct surgery or endovascular coil embolisation, the bruit resolved in all cases of successful treatment.

Table 1.

Literature review of cases of vertebral arteriovenous fistula associated with NF-15–37

Reference Country Age Sex Side Symptoms
Su et al6 China 33 Female Left Neck pain
Maki et al7 Japan 59 NR Left Coma
Rai et al8 USA 39 Female Right Difficulty walking
Uneda et al9 Japan 35 Female Right Neck pain, shoulder pain, radiculopathy
Gao et al10 China 24 Female Left Neck pain
Gao et al10 China 46 Female Left Neck mass, neck pain
Hughes and Alleyne 11 USA 29 Female Left Difficulty walking, spasticity, neck pain, radiculopathy
Takegami et al12 Japan 28 Male Left Neck pain, radiculopathy
Ng et al13 Germany 37 Male Left Radiculopathy, neck pain, numbness
Higa et al14 USA 60 Female Left Neck pain, swelling, difficulty breathing
Patro et al15 India 29 Female Left Tinnitus, radiculopathy, radiculomyelopathy, bruit
Paolini et al16 Italy 26 Male Left Sensory disturbances, weakness of all limbs
Guzel et al17 Turkey 36 Male Right Arm and leg weakness, arm pain, hoarseness
Hauck and Nauta5 USA 51 Female Left Tinnitus, radiculomyelopathy, bruit
Siddhartha et al18 India 36 Female Bilateral Radiculopathy, radiculomyelopathy, neck pain
Tanaka et al19 Japan 20 Male Left Neck mass
Maheshwari et al20 Canada 30 Female NR Neck pain, loss of bowel/bladder control, radiculomyelopathy
Kāhārā et al21 Finland 38 Male Right Neck pain, numbness, muscular weakness
Benndorf et al22 Germany 59 Male Right Neck mass, neck pain, bruit
Hori et al23 Japan 41 Female Right Tinnitus, bruit
Hori et al23 Japan 51 Female Left Bruit, tinnitus
Hori et al23 Japan 29 Female Left Bruit, radiculopathy
Hori et al23 Japan 66 Female Left Bruit
Hori et al23 Japan 51 Female Right Radiculopathy, radiculomyelopathy, bruit
Roth et al24 USA 36 Female Left Shoulder pain, radiculopathy, radiculomyelopathy, neck mass
Ma et al25 USA 32 Female Left Radiculomyelopathy, neck pain, loss of bladder control, bruit
Sampei et al26 Japan 41 Male Left Headache, neck pain
Ushikoshi et al27 Japan 40 Female Left Bruit, occipitalgia, cervical haematoma
Murayama et al28 Japan 27 Female Right Bruit, radiculopathy
Koenigsberg et al29 USA 34 Female Right Neck pain, radiculopathy, difficulty walking, loss of bladder control
Anegawa et al30 Japan 54 Female Left Radiculomyelopathy, loss of bowel/bladder control
Schievink and Piepgras31 USA 28 Female Right Bruit, neck swelling
Johnson et al32 USA 11 Female Right Bruit, tinnitus
Wada et al33 Japan 24 Female Left Radiculopathy, radiculomyelopathy, bruit
Hasegawa et al34 Japan 47 Male Right Suboccipital pain, bruit, myelopathy
Parkinson and Hay35 Canada 54 Female Left Bruit, tinnitus
Kamiyama et al36 Japan 58 Female Left Bruit, tinnitus
Deans et al37 USA 53 Female Left Myelopathy, numbness, bruit
Deans et al37 USA 45 Female Left Bruit, neck pain, shoulder pain
Deans et al37 USA 58 Female Left Neck pain, neck mass, bruit
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NF-1, neurofibromatosis type 1; NR, not reported.

The clinical symptoms caused by vertebral arteriovenous fistula are variable,5–37 but only one case of SAH related to vertebral arteriovenous fistula in a patient with NF1 has been reported.7 In this previous case, SAH was caused by epidural drainage of the vertebral arteriovenous fistula, but SAH is typically caused by perimedullary drainage of the fistula.38 Maki et al suggested that haemodynamic stress to the epidural drainage system and tissue fragility of the dura due to NF1 could have caused the SAH in their case.7 Our current case is considered to be the first case of SAH caused by perimedullary drainage of an NF1-associated vertebral arteriovenous fistula.

There are two possible mechanisms underlying NF1-associated arteriovenous fistula.33 First, dysplastic smooth muscle in the blood wall might lead to aneurysm formation, leakage and rupture into adjacent veins. Second, arteriovenous malformation could arise congenitally as a mesodermal dysplasia. In our patient, the incomplete occlusion of the feeder of the previous fistula, which was embolised 8 years prior, likely resulted in flow redistribution and abnormal arterial flow. This could have led to mural weakening, leakage perforation and rupture into the adjacent vein, which resulted in the formation of new fistulae.10

Clinicians should consider vertebral arteriovenous fistula and auscultate cervical bruits in patients with NF1, particularly on the left side in female patients. The presence of a cervical bruit in patients with NF1 who present with neurologic symptoms should prompt further vascular imaging.

Patient’s perspective.

Patient’s husband: I am grateful for the help of all doctors at various hospitals. I was surprised to learn that she is at risk of developing a vertebral arteriovenous fistula because of neurofibromatosis type 1. I hope that people around the world will know this fact, which contribute to medicine. I want to trust that nothing will happen to my wife in the future.

Learning points.

  • Patients with vertebral arteriovenous fistula typically present with neck pain, radiculopathy and radiculomyelopathy.

  • Clinicians should auscultate the cervical bruits in patients with neurofibromatosis type 1 (NF1), particularly on the left side in female patients.

  • Vertebral arteriovenous fistula related to NF1 is relatively rare; however, it could cause subarachnoid haemorrhage, as in this case.

Acknowledgments

The authors would like to thank Toyota Kosei Hospital, Toyota, Aichi, Japan, for taking care of the patient and for providing clinical information and images.

Footnotes

Contributors: TN took care of the patient and wrote the report. TN and TT reviewed 40 cases of vertebral arteriovenous fistula associated with neurofibromatosis type 1 in a literature search. YT and YO read and approved the final version of the report.

Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests: None declared.

Patient consent for publication: Obtained.

Provenance and peer review: Not commissioned; externally peer reviewed.

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