Diffuse proliferative cerebral arterial disorders: similar appearances, different diagnosis. J. Barnwell, H. Alvarez, M. Castillo Division of Neuroradiology UNC, Chapel Hill

Diffuse Proliferative cerebral arterial disorders. Types. Cerebral Proliferative Angiopathy Moyamoya Hemorrhagic Angiopathy

Outline of Presentation Epidemiology Clinical Presentations Pathology, differences between disorders Imaging findings: catheter angiography, CT & MRI findings Treatment Conclusions References

Cerebral Proliferative Angiopathy Epidemiology Cerebral Proliferative Angiopathy Moyamoya Rare subset of AVM’s 3.4% of AVMs Females, 2:1 Age at Dx: Mean: 22 yrs, median: 17.5 yrs Range 10-65 Rare Condition Japan, 3:100,000 Europe, 3:1,000,000 US, 8.6:10,000,000 Asian Americans > African Americans > Caucasians > Hispanics 2 peaks: 5 yrs & 40’s Asian Americans to Caucasians: 4.6 African Americans to Caucasians: 2.2 Hispanics to Caucasians: 0.5

Clinical Features Cerebral Proliferative Angiopathy Moyamoya Seizure: 45% Headache: 41% Focal deficits: 16% Hemorrhages (12%): 33% single -- 67% recurrent Prognosis: poor Infarction: 50-75% TIA: 50-75% Seizures, headaches Hemorrhages Rare: choreiform, cognitive or psychiatric changes Prognosis: variable 33% single -- 67% recurrent vs. 4% in typical AVM If a patient with suspect CPA presents with HEMORRHAGE consider HEMORRHAGIC ANGIOPATHY

More facts about Moyamoya 10-20% associated with sickle cell disease, NF-1, Down Syndrome, previous cranial irradiation <10% associated with congenital cardiac anomalies, renal-artery stenosis, giant cervicofacial hemangiomas, hyperthyroidism Genetic component: 10% of Japanese & 6% of US pts have a 1st degree relative Associated w/abnormalities in chromosomes 3,6,8, & 17 None of these associations are seen with CPA

Cerebral Proliferative Angiopathy Pathology Features Cerebral Proliferative Angiopathy Moyamoya Altered internal elastic lamina & smooth muscle cells Collagenous thickening of veins Intermingled normal neural tissue Smooth muscle hyperplasia Irregular elastic lamina No inflamacion Altered internal elastic lamina reduplicated, interrupted, and/or distorted Altered smooth muscle cells hyperplastic or thinned leading to aneurysms Collagenous thickening of veins increased type IV collagen in the subendothelium Intermingled normal neural tissue

CT Features Cerebral Proliferative Angiopathy Moyamoya Hemorrhage: Areas of dense contrast enhancement which may be focal, lobar or hemispheric Collateral deep perforators & pial vessels (Ivy sign) Cortical Infarcts Calcium in old infarcts Hemorrhage Cerebellum always nl Hemorrhage: Consider Hemorrhagic Angiopathy

Hemorrhagic Angiopathy: CT 5 yo Intracerbral subcortical arterioles May rehemorrhage 3 pts with Hemorrhagic Angiopathy show intraparenchymal bleeds. Hemorrhages are much less common in CPA.

Angiography Features (1) Cerebral Proliferative Angiopathy Moyamoya Intermingled nl brain parenchyma No dominant feeders Fast capillary transit Transdural blood supply Late stenosis (ICA, M1-2, A1-2): 39% Aneurysms (12%) Mildly enlarged draining veins Dilated perforating arteries Generally bilateral Spares posterior circulation arteries Early stenosis of ICA, M1 & A1 Aneurysms CPA proximal aneurysms 10

Angiography Features (2) Cerebral Proliferative Angiopathy Hemorrhagic Angiopathy Intermingled nl brain parenchyma No dominant feeders Fast capillary transit Transdural blood supply Late stenosis Aneurysms (12%) Blush may be focal, lobar or hemispheric Low incidence of bleeds No transdural blood supply No stenoses No aneurysms Small pseudo-tumoral blush; usually subcortical High incidence of bleeds 11

Cerebral Proliferative Angiopathy: Angiography Arterial stenoses Lack of dominant feeders Fast capillary transit

Transdural blood supply Intermingled normal brain parenchyma

Cerebral Proliferative Angiopathy: Angiography 3 frontal angiographic views show arterial proliferation without A-V shunting & filling of multiple moderate dilated veins.

Cerebral Proliferative Angiopathy: Angiography Initial lateral angiogram (left) shows CPA, center shows revascularization obtained via dural branches of the middle meningeal artery after burr holes, follow-up angiogram (right) shows diminished CPA.

Cerebral Proliferative Angiopathy: Angiography Initial lateral angiogram (left) shows CPA, center shows revascularization obtained via dural branches of the middle meningeal artery after burr holes, follow-up angiogram (right) shows diminished CPA.

Hemorrhagic Angiopathy: Angiography Imaging Small pseudo-tumoral blush, usually in the subcortical white matter Normal sized arterial feeders Normal draining veins or a lack of venous shunting Intermingled with normal brain Respond well to radiotherapy Paolo Tortori-Donati, Andrea Rossi, C. Raybaud. Pediatric neuroradiology: brain, head , neck, and spine Angiography demonstrates nl sized arterial feeders with a pseudo tumoral blush & no venous shunting.

Hemorrhagic Angiopathy: Angiography Imaging Small scattered nidus like lesions in the subcortical/white matter areas Arterial feeders are normal in size Drains into normal veins Intermingled with normal brain Respond well to radiotherapy Early arterial phase (left) & late arterial phase (right) demonstrates nl size arterial feeders & slightly early draining veins.

Moyamoya: angiography, different stages Narrowing of ICA, M1, A1 Narrowing of ICA with “Puff-of-Smoke”, diminished cortical flow. Obliteration of ICA, disappearance of Puff-of-Smoke, further reduction of cortical flow.

Cerebral Proliferative Angiopathy : MR & Angiography MR T2WIs & lateral angiogram show focal CPA in the right frontal lobe.

Cerebral Proliferative Angiopathy: MR Source MRA (left) shows multiple hypertrophied arteries, MRA frontal view (center) shows stenosis of left MCA & CPA, T2WI (right) shows abnormal blood vessels & gliosis in left hemisphere.

Cerebral Proliferative Angiopathy: MR MRI studies (different pts) show multiple flow voids on T1WI (left), FLAIR (center) & after Gdt administration (right). Note intermingled normal brain in all pts.

Cerebral Proliferative Angiopathy: MR MR T1WIs (left, center) &T2WI show CPA in left hemisphere including basal ganglia.

Cerebral Proliferative Angiopathy: MR Perfusion CBV CBF MTT MTT, rCBF & rCBV are increased due to capillary & venous ectasia. In classic brain AVMs MTT is decreased due to rapid shunting.

Cerebral Proliferative Angiopathy: MR Perfusion T2 image shows diffuse CPA & gliosis, source MRA image confirms presence of vessels & Gd perfusion rCBF map shows high perfusion.

Cerebral Proliferative Angiopathy: MR Perfusion MRI (T1-weighted postcontrast, time to peak [TTP]), cerebral blood volume (CBV), and cerebral blood flow (CBF) map in a 11-year-old girl with headaches demonstrating a large left frontoparietal nidus with brain parenchyma intermingled between the vascular spaces. Perfusion-weighted MRI demonstrates an increase in cerebral blood volume and flow indicating hypervascularization within the nidus and decreased times to peak in the area surrounding the nidus testifying for the ischemic nature of the disease. T1WI post Gd, TTP, rCBV & rCBF maps in an 11-year-old girl with headaches shows left frontoparietal CPA. MRI demonstrate increase CBV & CVF indicating hypervascularization in lesion & decreased TTP in nidus and surrounding areas suggesting the ischemic nature of the disease. Lasjaunias P. et al. Cerebral proliferative angiopathy, clinical and angiographic description of an entity different from cerebral AVMs. Stroke. 2008 Mar: 1-8.

Hemorrhagic Angiopathy: MR 2 pts presenting with intraparenchymal hemorrhages. (Left) T1WI non-contrast, (Middle) FLAIR, (Right) T2WI.

Moyamoya: MR Leptomeningeal enhancement (leptomeningeal blood vessel engorgement: Ivy sign). Flow Voids in basal ganglia

Moyamoya: MR Might change Different patients: FLAIR shows watershed chronic infarcts (far left) & acute parietal infarct (ctr left). T2WI shows left intraventricular acute hemorrhage (ctr right). T2* shows right temporal acute bleed (far right).

Moyamoya: Vascular MR Different patients: MRA shows stenosis of both MCAs & large perforators (left). Center shows stenosis of left MCA. MR perfusion (right) shows low rCBF in deep regions of both hemispheres.

Cerebral Proliferative Angiopathy Treatment Cerebral Proliferative Angiopathy Moyamoya Targeted embolization Increase cortical blood supply: Synangiogenesis or calvarial burr holes increase cortical blood supply by recruiting additional dural arteries Antiplatelet Tx Calcium channel blockers Surgery: Synangiogenesis or calvarial burr holes Bypass ECA to ischemic zone is feasible CPA Embolization: partial and targeted Surgery: non-targeted Embolization and radiation: Only use if intractable seizures and/or headaches Increase cortical blood supply: Calvarial burr holes increase cortical blood supply by recruiting additional dural arteries Moyamoya Antiplatelet: to prevent emboli CCB (relieve intractable headaches/migraines, also to reduce frequency and severity of TIAs) Surgery: Spares ECA, so bypass ECA to ischemic zone is feasible

Hemorrhagic Angiopathy: Response to Radiation therapy Unlike proliferative angiopathy, hemorrhagic angiopathy tends to present with recurrent intracerebellar hemorrhages as shown in this adult patient and there is no gender predilection. An angiogram shows an almost tumoral blush without enlarged arterial pedicles or venous drainage. This disease responds favorably to radiation therapy as shown in the angiogram to your right. This slide shows hemorrhage in the right occipital lobe of a 14 year old girl. In the center, an angiogram shows the typical appearance of proliferative angiopathy without dilated arteries or veins. . On the right, the control angiogram after radiation shows disappearance of the lesion. Pre Treatment Post Treatment Pre Treatment Post Treatment Pre & Post radiation Tx angiography performed on hemorrhagic angiopathy pts. Pre images demonstrate pseudo tumoral blush at time of ICH with rapid capillary transity. Post Tx images show excellent response to irradiation.

Conclusions Both cerebral proliferative angiopathy & Moyamoya are arterial proliferative conditions leading to stenoses in proximal vessels. Both are ischemic arterial conditions. Proliferative angiopathy and hemorrhagic angiopathy have to be considered as a group of disorders different from classical brain AVMs.

Conclusions Treatment of Moyamoya aims to an improvement in arterial supply by direct (bypass) or indirect (synangiogenesis or calvarial burr holes) revascularization techniques. Proliferative angiopathy pts. can be candidates for arterial revascularisation treatments. In some instances they can benefit from targeted embolizations. Hemorrhagic angiopathy has a rapid response to the radiotherapy.

References Scott R. et al. Moyamoya Disease and Moyamoya Syndrome. NEJM 2009;360:1226-37. Bacigaluppi S, Dehdashti AR, Agid R, Krings T, Tymianski M, Mikulis DJ.Neurosurg The contribution of imaging in diagnosis, preoperative assessment, and follow-up of moyamoya disease: a review. Neurosurg Focus. 2009; 26:E3a Lasjaunias P. et al. Cerebral Proliferative Angiopathy, Clinical and Angiographic Description of an Entity Different From Cerebral AVMs. Stroke. 2008 Mar: 1-8. Paolo Tortori-Donati, Andrea Rossi, C. Raybaud. Pediatric Neuroradiology: Brain, Head , Neck, and Spine. Springer Berlin Heidelberg New York. 2005. 291-297. Lasjaunias P, Ter Brugge K.G., Berenstein A. Surgical Neuroangiography. Volume 3: Clinical and Interventioal Aspects in Children. Springer. 2006: 35-39. Zanation 68852