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

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

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

4. 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

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

6. 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

7. 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

8. 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

9. 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.

10. 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

11. 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

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

13. Transdural blood supply
Intermingled normal brain parenchyma

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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

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

21. 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.

22. 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.

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

24. 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.

25. 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.

26. 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 Mar: 1-8.

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

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

29. 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).

30. 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.

31. 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

32. 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.

33. 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.

34. 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.

35. References
Scott R. et al. Moyamoya Disease and Moyamoya Syndrome. NEJM 2009;360:
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 Mar: 1-8.
Paolo Tortori-Donati, Andrea Rossi, C. Raybaud. Pediatric Neuroradiology: Brain, Head , Neck, and Spine. Springer Berlin Heidelberg New York
Lasjaunias P, Ter Brugge K.G., Berenstein A. Surgical Neuroangiography. Volume 3: Clinical and Interventioal Aspects in Children. Springer. 2006:
Zanation 68852