2026 年 13 巻 p. 201-207
Anti-neutrophil cytoplasmic antibody-associated vasculitis is an autoimmune disorder characterized by inflammation of small vessels, with potential for multi-organ involvement. Anti-neutrophil cytoplasmic antibody-associated vasculitis can affect blood vessels throughout the body, but involvement of cerebral vessels is relatively rare. We report a case of anti-neutrophil cytoplasmic antibody-associated vasculitis complicated by a subarachnoid hemorrhage due to the rupture of a cerebral artery pseudoaneurysm, which was successfully managed with endovascular intervention. A 61-year-old man presented with headache, purpura on the extremities, profound fatigue, and diffuse myalgia. Computed tomography revealed subarachnoid hemorrhage. Based on clinical, laboratory, brain magnetic resonance imaging, and cerebral angiography findings, the patient was diagnosed with anti-neutrophil cytoplasmic antibody-associated vasculitis and subarachnoid hemorrhage secondary to the rupture of pseudoaneurysm formed in perforating branch arising from the vertebral artery. Parent artery occlusion of the vertebral artery resulted in the complete obliteration of the aneurysm and no rebleeding occurred during the course. Despite intensive care management, the patient developed renal and putaminal hemorrhages, resulting in a fatal outcome. Anti-neutrophil cytoplasmic antibody-associated vasculitis may involve the cerebral vessels, and in cases complicated by ruptured aneurysms, implementing appropriate re-rupture prevention alongside adequate treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis may help improve clinical outcomes.
Anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV) is an autoimmune disease that includes 3 distinct types: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA (EGPA).1) Anti-neutrophil cytoplasmic antibodies cause inflammation in the capillaries and small arteries, resulting in multi-organ damage. The prognosis of AAV is poor, with high mortality and morbidity rates.2,3)
AAV primarily affects small vessels, and it is uncommon for it to present with neurological symptoms.4,5) Peripheral neuropathy is common in AAV cases; however, the frequency of central nervous system involvement is 11 times higher than that in the general population.6)
We present a case of AAV with subarachnoid hemorrhage due to a ruptured cerebral aneurysm and intracerebral hematoma, along with a review of the relevant literature.
A 61-year-old man with a history of appendicitis only presented to a primary hospital with fever and lower-limb edema 32 days before admission to our hospital. He was treated with diuretics, which led to improvement of the edema. He had been discharged from the primary hospital 5 days before admission to our hospital. However, after discharge, he continued to experience fatigue and subsequently returned to the primary hospital with complaints of headache. Computed tomography (CT) revealed a cerebral intraventricular hematoma, prompting transfer to our hospital.
On arrival, his Glasgow Coma Scale score was 15, and no neurological abnormalities were observed; however, he reported a persistent severe headache. Physical examination revealed purpura on the extremities, along with severe generalized fatigue and generalized myalgia. Head CT demonstrated subarachnoid hemorrhages anterior to the brainstem and in the medial cortex of the right parietal lobe, and an intraventricular hematoma extending from the fourth ventricle to the foramen of Luschka. Initial magnetic resonance imaging (MRI) confirmed these findings (Figure 1a); however, the source of bleeding was not identified (Figure 1b). Blood tests revealed elevated inflammatory markers and signs of renal dysfunction, including a white blood cell count of 16,300/μL, C-reactive protein level of 17.41 mg/dL, fibrinogen level of 900 mg/dL, blood urea nitrogen of 50.8 mg/dL, and creatinine level of 2.71 mg/dL. Contrast-enhanced imaging was withheld because of renal dysfunction.
MRI on the day of admission (a) (b). (a) FLAIR imaging demonstrates subarachnoid hemorrhage in the prepontine cistern and intraventricular hematoma within the fourth ventricle (arrow). (b) MRA shows no identifiable source of bleeding. (c) Head CT on the 4th day of hospitalization reveals a newly developed left thalamic hemorrhage with intraventricular hemorrhage. (d) Follow-up head MRA on the 5th day of hospitalization shows findings suggestive of an aneurysm near the left vertebral artery (arrow).
CT: computed tomography; FLAIR: fluid-attenuated inversion recovery; MRA: magnetic resonance angiography; MRI: magnetic resonance imaging
The patient was hospitalized, his blood pressure was controlled, and the cause of the intracranial hemorrhage was investigated. On the third day, head CT revealed a new hemorrhage in the left thalamus (Figure 1c), and blood tests showed worsening inflammation and renal dysfunction. Infection, particularly infective endocarditis (IE), and collagen diseases were considered as differential diagnoses. IE was ruled out by transesophageal echocardiography. On the fourth day, myeloperoxidase (MPO) -ANCA positivity was confirmed (116 IU/mL). Although a skin biopsy of the purpuric lesions revealed no pathological evidence of leucocytoclastic vasculitis and no apparent pulmonary lesions were detected, inflammatory cell infiltration around the blood vessels was evident. AAV was diagnosed and steroid pulse therapy was then initiated.
The second MRI suggested aneurysms near the left vertebral artery (VA) (Figure 1d). On the eighth day, the patient developed hemorrhagic shock due to rupture of the right kidney, and emergency arterial embolization was performed (Figure 2a-c). Following embolization, cerebral angiography was performed to investigate the aneurysm responsible for the subarachnoid hemorrhage, and an aneurysm was identified near the left VA (Figure 3a). On the same day, the patient's renal function deteriorated, necessitating dialysis. Because the use of contrast media was no longer restricted, angiography and endovascular surgery for the aneurysm near the left VA were performed on the tenth day.
(a) Contrast-enhanced CT showing right renal rupture (b) Angiography revealing aneurysm formation in the lower pole of the kidney with contrast extravasation from the tip (arrow) (c) Extravasation disappeared after embolization with N-butyl- 2-cyanoacrylate. (d) Head CT shows right putaminal hemorrhage. (e) Post-craniotomy, hematoma was removed.
CT: computed tomography
(a) An aneurysm is noted adjacent to the left VA (arrow). (b) Schema: Three possible arterial inflows to the aneurysm were suspected: (i) the AICA-PICA common trunk, (ii) perforating branches of the VA, and (iii) the C2 segmental artery. Microcatheters were inserted into all of these branches and none of them were involved in supplying the aneurysm. (c) The AICA-PICA common trunk (arrowhead) appears to be supplying the aneurysm (arrow). (d) However, on selective angiography, the aneurysm was not visualized. The same result was obtained for other two arteries. (e) Magnified vertebral artery angiography revealed that the aneurysm was directly supplied by the VA (arrow). (f) Schema: Balloon occlusion of the vertebral artery near the aneurysm resulted in disappearance of the aneurysmal filling, suggesting that parent artery occlusion at this site was feasible. (g, h) Parent artery occlusion of the VA was performed.
AICA: anterior inferior cerebellar artery; PICA: posterior inferior cerebellar artery; VA: vertebral artery
Under general anesthesia, a 6 Fr long sheath was inserted into the right femoral artery, and a 6 Fr Roadmaster MPDA (90 cm; Goodman, Nagoya, Aichi, Japan) was positioned in the left VA. Additionally, a 4 Fr long sheath was inserted into the left femoral artery, and a 4 Fr catheter was placed in the right VA for diagnostic imaging. Selective angiography was performed because the aneurysm was suspected to have formed in the distal portion of the anterior inferior cerebellar artery-posterior inferior cerebellar artery (AICA-PICA) common trunk, VA perforator, or C2 segmental artery (Figure 3b). A Guidepost catheter (Tokai Medical, Kasugai, Aichi, Japan) was inserted into the V4 segment of the VA, and a Marathon microcatheter (Covidien, Minneapolis, MN, USA) was navigated with a CHIKAI microwire X 0.010 (Asahi-Intec, Nagoya, Aichi, Japan) to selectively obtain angiograms of each branch. However, none of the angiograms revealed the presence of an aneurysm (Figure 3c and d). An angiogram from the Guidepost placed near the aneurysm appeared to demonstrate direct supply from the VA (Figure 3e). The aneurysm was suspected to be a pseudoaneurysm because of its delayed contrast enhancement and washout during the venous phase. A balloon occlusion test was planned to determine whether the aneurysm would disappear following temporary occlusion of the suspected inflow site. The Guidepost was replaced with a 4.2 Fr FUBUKI catheter (Asahi-Intec), and a TransForm 4/7 mm balloon catheter (Stryker, Kalamazoo, MI, USA) was guided to the suspected branching site of the inflow vessel using a CHIKAI 0.014 microwire (Asahi-Intec). Antegrade and retrograde angiography performed during balloon inflation showed no visualization of the aneurysm (Figure 3f). Based on these findings, parent vessel occlusion was selected as the treatment strategy. An SL-10 microcatheter (Stryker, Kalamazoo, MI, USA) with a CHIKAI 0.014 microwire was used to occlude the VA from the distal to proximal segments of the inflow vessel with 14 coils (Figure 3g), including a Target coil (Stryker). Post-procedural imaging confirmed disappearance of the aneurysm, as observed during balloon inflation, with preservation of the branch vessels (Figure 3h).
The following day, MRI demonstrated occlusion of the left VA without new ischemic complications related to the treatment. Rituximab was initiated as adjunctive therapy for AAV but was discontinued after the development of agranulocytosis. On the 18th day of hospitalization, CT revealed a right putaminal hematoma measuring 80 mL, which was subsequently evacuated (Figure 2d and e). The patient developed left hemiplegia and impaired consciousness, necessitating tracheotomy on the 30th day. Because AAV remained uncontrolled, plasma exchange therapy was initiated on the 28th day. However, his general condition deteriorated, and he died on the 48th day of hospitalization.
This case provides 2 important insights. First, AAV can potentially involve the cerebral vasculature as a target of vasculitis and may be associated with the development of pseudoaneurysms. Second, detailed assessment of the vascular architecture using a microcatheter enabled us to determine the treatment strategy and safely prevent re-rupture.
Among the AAV subtypes, MPA is most frequently associated with MPO-ANCA positivity and primarily affects the lungs and kidneys without granuloma formation. GPA is characterized by necrotizing granulomatous inflammation of the respiratory tract with concomitant renal involvement and is commonly associated with proteinase 3-ANCA positivity. In contrast, EGPA is distinguished by marked eosinophilia and asthma, accompanied by eosinophilic granuloma formation. Peripheral neuropathy is also common, and the rate of ANCA positivity is approximately 30%-40%.1,2,7) Epidemiologically, the relative proportions of MPA and GPA vary considerably among regions, with MPA predominating in Japan.2) In this case, MPO-ANCA positivity was confirmed, and a rapidly progressive renal inflammatory syndrome was observed. Although the skin biopsy demonstrated only inflammatory cell infiltration around the vessels and no obvious pulmonary lesions were detected, the patient was diagnosed with MPA based on MPO-ANCA positivity and the rapid progressive deterioration of renal function. On pathological examination at autopsy, necrotizing vasculitis of the interlobular arteries was identified in the kidney, which was considered compatible with AAV (Figure 4).
Pathological findings of the left kidney (a, b) and the right kidney (c) EMG stain showed features of necrotizing vasculitis with inflammatory cell accumulation (a: ×100) or organized vasculitis with fibrous intimal thickening and rupture of the internal elastic lamina of the interlobular artery (b: ×100). (c) EMG stain demonstrated transmural fibrinoid necrosis of the interlobular artery with luminal dilatation (×40).
EMG: Elastica Masson Goldner
Time course.
CNS: central nervous system; CT: computed tomography; DSA: digital subtraction angiography; IE: infective endocarditis; IVH: intraventricular hemorrhage; MPO-ANCA: myeloperoxidase anti-neutrophil cytoplasmic antibody; MRI: magnetic resonance imaging; PAO: parent artery occlusion; SAH: subarachnoid hemorrhage; TAE: transcatheter arterial embolization; TEE: transesophageal echocardiography; VA: vertebral artery
In general, ANCA-associated vasculitis predominantly affects small vessels; therefore, central nervous system (CNS) involvement is rare in AAV (<15 %).5) Achkar et al.8) reviewed 47 cases of AAV-associated intracranial hemorrhage and reported that intraparenchymal hemorrhage was the most common type (55.3%), followed by subarachnoid hemorrhage (29.8%). Among AAV subtypes, EGPA was the most prevalent (48.9%), whereas MPA was the least common (14.9%).8) Xie et al.9) reviewed 34 cases of AAV-associated SAH and found that EGPA was also the most common subtype (55.9%), while MPA was the least common (17.6%). According to a report by Ma et al.,10) among 325 patients with MPA, CNS involvement was observed only in 25 cases (7.7%). Several reports have described CNS involvement associated with MPA.9,11-14) The mortality rate of AAV complicated by intracranial hemorrhage exceeds 30%, which is higher than that reported in the general epidemiology of AAV.8,9,15) Ichikawa et al.16) reported 13 cases of ruptured aneurysms associated with AAV, of which 6 were dissecting aneurysms, suggesting cerebrovascular structural damage caused by vasculitis. The rupture sites involved various cerebral vessels, and the treatment strategies varied, including open surgical clipping, endovascular treatment, and conservative management.16) In the literature review, only 3 cases treated with endovascular therapy have been reported,16-18) and all of them, including the present case, involved the posterior circulation.
The pseudoaneurysm arising from perforating branches of the VA is classified as small-sized vessels, whereas aneurysms formed in the renal artery occur at the level of the interlobar arteries and are, therefore, classified as medium-sized vessels. In the present case, it is clear that atypical medium-sized vessel involvement for MPA was present. In addition, with respect to the cerebral vasculature, the possibility that the parent VA itself was affected cannot be excluded. The Chapel Hill Consensus Conference classification describes the possibility of necrotizing arteritis involving small and medium arteries in MPA.1) Pathological series have reported lesions involving medium-sized renal arteries in approximately 23% of MPA cases.19) In the present case, aneurysms developed not only in the cerebral circulation but also in a renal artery, resulting in fatal hemorrhage.
The mechanism of aneurysm formation in AAV remains unknown, but vasculitis is believed to cause necrotic changes in blood vessels, rendering the vessel walls vulnerable.14) Therefore, some reports recommend examination of the cerebral vasculature in patients diagnosed with MPA.13,14) In this case, the aneurysm was suspected to be a pseudoaneurysm. Direct blood flow from the left VA to the aneurysm was observed, and following a detailed anatomical consideration, parent artery occlusion was successfully performed at the same site. Even in severe cases such as this, appropriate management of the bleeding source in combination with multidisciplinary care may improve the chances of survival.
We report a case of AAV presenting with diverse hemorrhagic complications, including subarachnoid hemorrhage due to a pseudoaneurysm formed in a perforating branch arising from the VA, putaminal hemorrhage and rupture of a renal artery aneurysm. As for the cerebral pseudoaneurysm, detailed assessment of the vascular anatomy enabled us to determine the treatment strategy. Appropriate control of disease activity in AAV and prevention of rebleeding may contribute to improved clinical outcomes.
All authors have no conflict of interest.
Informed consent for publication of this case report, including all clinical information and images, was obtained from the patient's wife.
