Recurrent periventricular hemorrhage in cerebral proliferative angiopathy: Case report

Abstract

Cerebral proliferative angiopathy (CPA) is a rare vascular lesion. Bleeding from CPA is uncommon, but the risk of rebleeding is high once it bleeds. We describe a case of CPA with multiple intra- and periventricular hemorrhages during 30-year follow-up. Recurrent bleeding in these areas are common in moyamoya disease. These lesions may share the cause of bleeding: proliferation of the periventricular vessels functioning as collateral pathways. Revascularization surgery for CPA may attenuate the vascular proliferation in the vicinity of the ventricle, which may prevent rebleeding.

Introduction

Cerebral proliferative angiopathy (CPA) is a rare vascular disease characterized by abnormal proliferation of ectatic capillaries without overt fistulous arteriovenous shunting, which differs from brain arteriovenous malformation (AVM).¹ Although recurrent bleeding in CPA was reported in four patients within a case series,¹ none of them were reported in clinical or angiomorphological detail. In addition, there is no report describing recurrence of hemorrhage in CPA. Here, we present a case of CPA with multiple hemorrhages over 30 years, and try to elucidate features associated with hemorrhagic presentation in this patient population.

Case report

A 12-year-old girl presented with intractable headaches occurring once per week. Her headaches became more frequent with time. Six years later, she started suffering from seizures. MRI demonstrated extensive flow voids within the sulci, gyri, and white matter of the lefttemporo-occipito-parietal region (Figure 1(a)). No compact nidus to suggest an AVM was identified. A postgadolinium T1 weighted image showed contrast enhancement within the abnormal vessels (Figure 1(b)). Cerebral angiogram performed elsewhere demonstrated a large vascular network (Figure 1(c) to (d)), and the diagnosis of AVM was made. Considering the size and location of the lesion, she was conservatively followed with antiepileptic treatment. A couple of years later, ventriculoperitoneal shunt was carried out at another hospital for gradually worsening hydrocephalus. Although the cause of hydrocephalus could be attributable to venous hypertension caused by the vascular lesion, it remained unclear.

Figure 1.

(a) and (b) MRI at 18 years old (a: T2 weighted image, b: contrast enhanced T1 weighted image). (c) and (d) Left internal carotid angiography, lateral projection (c: arterial phase, d: late capillary phase).

Figure 2.

CT at 33 (a), 35 (b), 37 (c), and 38 (d) years.

The patient experienced her first intracerebral bleeding in the left temporal lobe at 24 years of age, followed by intracerebral hemorrhages in the left thalamus, cingulate gyrus, and left temporoparietal lobe and two intraventricular hemorrhages at 33, 35, 36, 37, and 38 years old, respectively (Figure 2(a) to (d)). When she was referred to us, review of the angiogram revealed capillary ectasias with delayed washout of contrast within the poorly delineated vascular network. Although the arteries contributing to the lesion were enlarged, there was neither a dominant feeding artery nor too early filling of enlarged veins. Based on these findings, we diagnosed the lesion as CPA. However, as no bleeding point was identified, a conservative treatment was adopted. Stenosis in the left internal carotid and middle cerebral artery was not evident at this time. She developed gradually worsening right hemiparesis. MRI at age 39 redemonstrated the known vascular network with increased density of intraparenchymal flow voids. Parenchymal signal change on T2 weighted image was noted in the atrophic left temporo-occipital lobe (Figure 3(a) and (b)). An angiogram demonstrated left supraclinoid internal carotid artery stenosis and transdural supply to the left occipital and posterior parietal regions, which were no longer supplied by the posterior or middle cerebral artery. The frontoparietal cortical draining veins were enlarged possibly due to increased blood flow into the network (Figure 3(c) to (e)). Multiple intralesional small calcifications were noted on CT (Figure 2). These changes indicated progression of the disease. Since no possible source of bleeding such as a microaneurysm was identified, no intervention was performed. The patient was followed conservatively thereafter. She was diagnosed with advanced lung cancer afterwards. She died of unknown cause at home when she was 43 years old.

Figure 3.

(a)–(c) MRI at 39 years old. T2 weighted (a, b) and contrast enhanced T1-weighted image (c). (d)–(f) Angiography at 39 years old. Injection of the left internal carotid artery, anteroposterior (d) and lateral projection (e). Left external carotid artery injection, lateral projection (f).

Discussion

The diagnosis of CPA is based on radiological findings: absence of high-flow shunting, evidence of high angiogenetic activity, such as transdural supply, extensive capillary proliferation, and stenosis of feeding arteries, and intermingled brain parenchyma within the lesion.¹ Although CPA angiographically resembles so-called diffuse AVM, the nature of these lesions is considered different: CPA is characterized by proliferation of vessels, while AVM is an arteriovenous fistula with an intervening nidus devoid of capillary network.^1,2 The proliferation of vessels in CPA is considered angiogenesis in response to ischemia.¹ This hypothesis was supported by perfusion MRI study demonstrating hypoperfusion in the affected brain and elevated level of angiogenetic molecules in the cerebrospinal fluid.^1,3

Patients with CPA classically present with seizures, headaches, and neurological deficits. These symptoms may be attributable to ischemia.¹ On the other hand, hemorrhage is rare and only 10 cases have been reported.^1,4–7 In the largest case series including 49 patients, 6 had hemorrhage, 4 experienced recurrence, and 1 died of a rebleeding.¹ Unfortunately, the authors described none of these cases in detail. However, no case of CPA with recurrent bleeding has been reported elsewhere. The clinical course of this CPA case over 30 years time is of great importance in the literature.

If bleeding occurs, recurrence appears to be common (4/6 cases, 67%) in CPA. Fragile vessels induced by angiogenesis are considered responsible for bleeding in CPA.¹ Another pathology characterized by cerebral ischemia and recurrent hemorrhage is moyamoya disease.⁸ In moyamoya disease, collateral vessels develop as proximal steno-occlusive changes progress in response to cerebral ischemia. These vessels are vulnerable to increased hemodynamic stress and are the supposed culprit of bleeding.⁸ Hemorrhagic presentation in moyamoya disease is rare in children but more frequent in adults.⁸ This suggests that long-term hemodynamic stress in the collateral vessels aggravates vulnerability of these vessels and finally leads to bleeding.⁹ This might be applicable to CPA. If so, the frequency of hemorrhage in CPA may be underestimated in the above-mentioned case series, because of the short follow-up period (mean 3 years).¹

In moyamoya disease, in which rebleeding is common in the adult populations, thalamic and intraventricular hemorrhage and proliferation of periventricular collateral vessels are considered as risk factors for rebleeding.^8,9 Our patient experienced three hemorrhages: one thalamic and two intraventricular hemorrhages. Therefore, involvement of periventricular area may be a risk factor for rebleeding in CPA similar to moyamoya disease.

The treatment option for ruptured CPA includes embolization of fragile structure such as intralesional aneurysms.¹ In moyamoya disease, revascularization surgery is effective to prevent rebleeding.⁸ Whether this is the case in CPA is unclear, since revascularization surgery aiming at prevention of rebleeding has not been reported for CPA patients. In one CPA case burr hole surgery inhibited progression of the disease,¹⁰ suggesting that revascularization surgery may prevent progression of CPA. More CPA cases are needed to elucidate the pathomechanism and frequency of bleeding, and to establish management.

In conclusion, we described a CPA patient who experience recurrent hemorrhages over 30 years of follow-up. All the bleedings occurred in the periventricular region, similar to moyamoya disease. Revascularlization surgery may inhibit rehemorrhage.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.