Abstract

Background: Cerebral proliferative angiopathy (CPA) is a rare vascular disease characterized by nonfocal angiogenic activity. Numerous case reports have been published; however, despite there are a few reported cases of infratentorial CPA (or cerebellar proliferative angiopathy), no comprehensive review of this condition has been conducted.

Case Description: We report two cases of infratentorial CPA, and both of them presented intracranial hemorrhage. The first case was a 48-year-old woman with an incidentally detected vascular abnormality in the cerebellum, which remained stable for 11 years before presenting with subarachnoid hemorrhage. The second case was a 5-year-old girl who presented with a sudden headache and decreased consciousness. Digital subtraction angiography was performed in both cases, but the source of hemorrhage remained unidentified, and conservative management was chosen.

Conclusion: A review of previously reported infratentorial CPA cases suggests that infratentorial CPA has a significantly higher risk of hemorrhage than supratentorial CPA. However, the risk of rebleeding appears to be low. Our findings highlight the need for further research to determine the optimal management strategies for this rare entity.

Keywords: Cerebral proliferative angiopathy, Intracranial hemorrhages, Vascular disease

INTRODUCTION

Cerebral proliferative angiopathy (CPA) is a rare vascular brain abnormality distinct from classical arteriovenous malformations (AVMs).[ 3 , 6 , 7 , 9 ] Transdural supply, stenosis of feeding arteries, and the absence of dominant feeders or drainers in the large abnormal angioarchitecture are distinct features of CPA.[ 6 ] Normal brain parenchyma is intermingled with the abnormal angioarchitecture.[ 6 ] According to previous studies, the main symptoms of CPA are headaches and seizures, while hemorrhagic events are relatively rare.[ 3 , 6 , 7 , 9 ] Most of these studies are based on supratentorial CPAs, and no comprehensive reports have examined infratentorial CPAs. In this report, we present two extremely rare cases of infratentorial CPA, both of which resulted in hemorrhage. One patient had the longest follow-up period, whereas the other was the youngest reported case of hemorrhagic CPA.

CASE REPORT

Patient 1

A 48-year-old woman underwent a routine brain health check-up, during which magnetic resonance imaging (MRI) incidentally detected abnormal angioarchitecture in the cerebellum [ Figure 1a ]. She was asymptomatic and remained under observation. Eleven years later, the patient presented to our hospital with a worsening headache. Computed tomography (CT) revealed a subarachnoid hemorrhage in the posterior fossa [ Figure 1b ]. MRI revealed no significant changes in the vascular structure compared to images acquired 11 years earlier [ Figure 1c ]. An abnormal vascular network was observed throughout the entire left cerebellar hemisphere, with involvement of the normal cerebellar parenchyma. Digital subtraction angiography (DSA) showed diffusely proliferated vessels in the left cerebellum and numerous small feeders arising from the left posterior cerebral artery, superior cerebellar artery (SCA), posterior inferior cerebellar artery (PICA), and transdural supply [ Figures 2a and b ]. Compared to the large size of the lesion, the caliber of the feeding arteries was disproportionately small. Moderately dilated and tortuous venous drainage was clearly visualized; however, there was no high-flow arteriovenous shunt, and the lesion was composed of diffusely proliferated feeding arteries that had formed a clustered network [ Figure 2c ]. Based on these DSA findings, the case was diagnosed as infratentorial CPA. The source of the hemorrhage could not be identified; therefore, the patient was managed conservatively. The patient has been stable for 8 years, with no neurological deficits or rebleeding.

Figure 1:

(a) Initial magnetic resonance imaging (MRI) obtained when patient 1 was 48 years old revealed abnormal vascular proliferation in the left cerebellar hemisphere. The MRI also showed dilation of the draining vein into the great vein of Galen. (b) Computed tomography performed 11 years later, following a severe headache episode, revealed a subarachnoid hemorrhage. (c) MRI at the time of subarachnoid hemorrhage. Vascular structures showed no significant changes compared to the findings 11 years earlier.

Figure 2:

(a) Left vertebral angiogram revealed densely proliferated abnormal vessels throughout the left cerebellar hemisphere, draining into an enlarged great vein of Galen. No dominant feeder was identified. (b) Left external carotid angiogram demonstrated transdural supply from the occipital and middle meningeal arteries. (c) Posterior oblique view of three-dimensional rotational angiography revealed no aneurysms or dissections. Numerous abnormal vessels were observed in the left cerebellar hemisphere.

Patient 2

A 5-year-old girl presented to our hospital with a sudden headache and deteriorating consciousness. CT revealed a left cerebellar hemorrhage [ Figure 3a ]. An emergency craniectomy was performed, and her level of consciousness gradually improved. MRI showed abnormal angioarchitecture in the left cerebellum with intermingled cerebellar parenchyma [ Figure 3b ]. DSA revealed numerous small feeders proliferating from the SCA and PICA [ Figure 4a ], with no obvious arteriovenous shunts, aneurysms, or arterial dissections. Despite performing three-dimensional rotational angiography, the source of bleeding could not be identified [ Figure 4b ]. Based on these findings, conservative management was chosen. One month after the onset, she was discharged from our hospital with mild motor ataxia.

Figure 3:

(a) Initial computed tomography of patient 2 revealed a 3 cm hematoma in the left cerebellum. (b) Contrast-enhanced magnetic resonance imaging revealed extensive abnormal vascular networks within the left cerebellar parenchyma.

Figure 4:

(a) Digital subtraction angiography of patient 2 showed numerous small feeders originating from the left superior cerebellar artery and posterior inferior cerebellar artery with no identifiable dominant feeder or draining vein. (b) Three-dimensional rotational angiography was performed to identify the source of bleeding, but no clear evidence of an aneurysm or dissection was observed.

DISCUSSION

Numerous case reports and reviews on CPA have been published. According to the latest systematic review, which primarily included supratentorial CPA, the mean age of discovery of CPA was 26.9 years, with 58% of cases occurring in females, indicating a higher prevalence in young women.[ 9 ] Regarding the location of CPA, no particular cerebral lobe has been identified as a predominant site; however, the majority of reported cases are located in the supratentorial area.[ 9 ] The most common symptoms are headaches and seizures; however, hemorrhage is considered relatively rare, with a reported risk of 24%.[ 9 ] Moreover, a CPA that has caused hemorrhage once is likely to rebleed.[ 6 ] Among infratentorial CPA cases, only nine reported cases, including our two cases, had available follow-up information[ 1 , 2 , 4 , 5 , 7 , 8 , 10 ] [ Table 1 ]. The mean age of discovery of CPA was 25.3 years (range, 5–66 years), with 66.7% of patients being female. This higher prevalence among young women is consistent with CPA overall. Remarkably, seven of the nine patients (77.8%) experienced hemorrhage, yet none experienced rebleeding.[ 1 , 4 , 5 , 8 , 10 ] These findings suggest that infratentorial CPAs may have a significantly higher risk of hemorrhage but not a high risk of rebleeding.

Table 1:

Reported cases of infratentorial CPAs with available follow-up information.

CPA is thought to be caused by reactive angiogenesis in response to ischemia.[ 6 , 9 , 11 ] A distinct feature is the presence of nonfocal angiogenetic activity. Differentiation from diffuse AVMs can be challenging; however, several distinguishing features have been reported. Despite the large size of the lesion, major feeders are absent, stenosis of feeding arteries is observed, and flow-related aneurysms are typically not observed in CPA. Lasjaunias et al. reported that a major difference between AVM and CPA is the presence of normal brain tissue within the vascular lesion in CPA.[ 6 ]

Among our two cases, the 48-year-old female patient is particularly significant because of the exceptionally long follow-up period of 19 years, providing valuable insights into the clinical course before and after hemorrhage. Hemorrhage occurred 11 years after the initial detection, with no re-bleeding observed over the subsequent 8 years. This case represents the longest observation period for hemorrhagic infratentorial CPA and suggests that hemorrhage may occur several years after initial detection. Furthermore, a review of previously reported cases suggests that hemorrhage in infratentorial CPA can occur across a wide range of age groups. The 5-year-old patient represents the youngest reported case of infratentorial CPA presenting with hemorrhage. These findings highlight the importance of recognizing the risk of hemorrhage regardless of age.

Various treatment approaches, including endovascular therapy, surgical resection, radiosurgery, revascularization, and conservative management, have been used for CPA.[ 3 , 9 , 11 ] However, due to diffuse vascular abnormalities intermingled with normal brain parenchyma and the risks associated with surgical intervention, conservative management remains the primary treatment method.[ 3 , 9 ] A review of all previously reported cases of infratentorial CPA (n = 9) revealed that most cases (4/9) were managed conservatively.[ 1 , 5 , 7 ] Two patients underwent decompressive craniectomy following hemorrhage.[ 10 ] One patient received selective endovascular therapy,[ 4 ] another underwent surgical resection,[ 8 ] and one was treated with a combination of endovascular therapy and radiation therapy, initially diagnosed and managed as an AVM.[ 2 ] In cases of hemorrhagic infratentorial CPA, the bleeding source was identified in only one case, where an aneurysm was detected within the CPA and treated with targeted embolization. In all other cases, the exact source of hemorrhage remained unidentified. Given the seemingly low risk of rebleeding in hemorrhagic infratentorial CPA, the need for resection or endovascular therapy should be carefully evaluated.

CONCLUSION

Our findings suggest that infratentorial CPA may have a distinct natural history compared to supratentorial CPA, with a significantly higher risk of hemorrhage but a low risk of rebleeding. Further research is needed to elucidate the underlying causes of hemorrhage and develop effective treatment strategies.

Ethical approval:

Institutional Review Board approval is not required.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that they have used artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript or image creations.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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