Cerebral proliferative angiopathy
- 1Department of Radiology and Neurosurgery, Stanford University School of Medicine, Stanford, California, USA
- 2Department of Neurosurgery, Stanford University, Stanford, California, USA
- Correspondence to Dr M P Marks, Department of Radiology and Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Room s-047, Stanford, CA 94305, USA;
- Received 14 March 2011
- Revised 2 August 2011
- Accepted 24 August 2011
- Published Online First 20 September 2011
Cerebral proliferative angiopathy is a rare lesion marked by diffuse intravascular shunting, which should be differentiated from brain arteriovenous malformations. A patient is presented with cerebral proliferative angiopathy and documented progressive development of hypervascular shunting involving extensive portions of the left hemisphere. The patient had angiographic and laboratory evidence of angiogenesis and a progressive neurologic deterioration which corresponded to the development of her lesion. This is the first case which documents the progressive proliferative changes seen with this abnormality.
Cerebral proliferative angiopathy (CPA) is an unusual hypervascular entity marked by a diffuse network of arteriovenous shunting. It is distinguished from cerebral arteriovenous malformations (AVMs) in that normal brain is interspersed with abnormal vascular channels.1 The CPA ‘nidus’ frequently exceeds 6 cm. The transdural supply is commonly encountered. Prior reports of this rare entity have suggested there may be angiogenetic activity but there has not been any description of progression or change seen in these lesions over time. We report a case of a CPA patient with striking progressive clinical and imaging changes.
A patient in their early 30s was seen at our medical center with progressive headaches, right-sided weakness and aphasia. Six years prior, in the spring of 2000, the patient experienced left suboccipital headaches. Workup demonstrated a left ninth cranial nerve schwannoma. The patient underwent a retromastoid craniotomy to resect the tumor in December 2000.
Surgery was uncomplicated and the patient was neurologically normal until the fall of 2004 when the patient began developing left frontal headaches and was concerned about possible right-sided weakness and trouble with word finding. An MRI was carried out in October of 2004 as a follow-up evaluation of the schwannoma resection. A prior MRI from October 2002 was available for comparison. The 2004 MRI demonstrated proliferation of pial vessels in the temporal and parietal lobes of the left hemisphere. In retrospect, the MRI from 2002 showed mild vascular asymmetry between the right and left hemispheres but the left hemispheric hypervascularity had become far more pronounced by 2004 (figure 1A,B). An angiogram in November 2004 showed hypervascularity in these regions with evidence of arteriovenous shunting (figure 2A,B). The arterial supply came from the left anterior cerebral artery, middle cerebral artery and posterior cerebral artery circulations. Very slight dural supply was seen from the left middle meningeal artery.
Right-sided weakness and word finding difficulty were progressive, and in March 2005 the patient was seen at another institution. The patient was noted to have a right visual field deficit, intermittent difficulty with speech and language comprehension, and new right-sided facial weakness. An MRI and angiography showed progressive changes since 2004 in the extent of territory involved (figure 1C) and more pronounced shunting (figure 2C,D). Workup included evaluation of vascular growth factors in plasma and CSF. The patient was found to have a markedly elevated level of vascular endothelial growth factor (VEGF) in the CSF (827.5, control normal 17.61) with normal plasma levels. The patient also had elevated CSF levels of thrombospondin (978.6, control normal 41.98) and basic fibroblast growth factor (2.06, control normal 1.84). No treatment was recommended at the time.
In the fall of 2005, the patient was seen at our institution with continued progression of symptoms and severe unrelenting left-sided headaches. Speech was noted to be slow and dysarthric, with significant word finding difficulties. The patient had a right facial droop and mild right upper and lower extremity weakness along with a right homonymous hemianopsia. An angiogram showed continued shunt vascularity from the left-sided hypervascular process. The dural supply from branches of the external carotid artery was more prominent than previously (figure 3A–C). It was decided to perform partial embolization targeted to the external carotid artery supply and the pial supply to the occipital lobe to reduce the shunt vascularity. The patient had some relief of headache symptoms but these returned after several weeks. The patient was not felt to be a candidate for surgical or radiosurgical treatment. The patient continued to decline neurologically and the headaches could not be controlled. Several months later the patient was started on a course of bevacizumab in the hope that it would alter the vascular proliferation process. Six cycles were planned, but the course was discontinued after four cycles as the patient did not feel the drug was having an impact. The patient died after a short febrile illness in December 2006. A post mortem was not obtained.
This is the first case of CPA which documents progressive changes, in this case occurring over a relatively short period. CPA is a rare entity. There have been a few scattered case reports2–4 and one series of 49 cases coming from a large referral center reporting cases collected over 17 years.1 The authors of the series chose the term ‘proliferative’ because they felt that there were features on the angiogram (such as meningeal contribution) which suggested ‘the formation of new blood vessels’. However, they did not document angiogenesis or present any cases demonstrating these lesions underwent progressive growth or enlargement. In our case, there was a fulminatory course to the patient's clinical symptoms accompanied by a relentless progression of angiographic findings. This case may be an example of more rapid progression in the spectrum of patients with CPA.
Our patient fits the described profile of CPA.1 The disease is more commonly manifest in young females. Seizures and disabling headaches are the most common symptom. The angiographic appearance of a large poorly circumscribed ‘nidus’ (often >6 cm) with relatively slow flow shunting and prominent dural supply was present in this case. Hemorrhage can occur and patients can present with neurologic deficits in the absence of hemorrhage. This is thought to be due to ischemia based on MR perfusion studies which have demonstrated hypoperfusion beyond the confines of the nidus.1 ,5
One reason this entity may be rarely described is possible confusion with CPA and brain AVMs. Chin et al described 12 cases of a ‘Diffuse AVM’ as an atypical AVM with ‘AVM vessels interspersed among normal neurons and white matter’ in contradistinction to the accepted pathologic appearance of AVMs in parenchyma which is highly gliotic or absent.6 The behavior of our case strongly suggests that CPA is indeed a different entity then the classic AVM.
We performed targeted partial embolization hoping we might temporize the patient's progressive symptoms. This did not prove successful and other options, microsurgery or radiosurgery were not considered good options here. In addition to the observed changes on MRI and angiography, the patient had laboratory evidence of ongoing angiogenesis with elevated levels of VEGF and basic fibroblast growth factor in CSF. Angiogenesis, the formation of new vessels from existing vessels, has been found to be promoted by these factors. These proteins have been found to induce endothelial replication, migration, and differentiation and maturation.7 They are thought to be implicated in the angiogenesis occurring in brain AVMs.7 ,8 The patient was started on a course of bevacizumab, a monoclonal antibody which binds to VEGF, used to inhibit angiogenesis in cancer patients. This was started late in the course of the disease and stopped prematurely so it is not clear if such a therapeutic approach could be of benefit in CPA.
In conclusion, we have presented a patient with CPA who had documented angiographic changes occurring over a 3 year period, with angiographic and laboratory evidence of angiogenesis and a corresponding clinical deterioration consisting of gradual neurologic deficits. This is the first documented evidence of the progressive course CPA may assume.
Detail has been removed from this case description to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.