References

1. Lee M, Saver JL, Hong KS, et al. Does achieving an intensive ver-sus usual blood pressure level prevent stroke? Ann Neurol 2012;71:133–140.

2. MacMahon S, Sharpe N, Gamble G, et al. Randomized, pla-cebo-controlled trial of the angiotensin-converting enzyme in-hibitor, ramipril, in patients with coronary or other occlusivearterial disease. PART-2 Collaborative Research Group. Preven-tion of Atherosclerosis with Ramipril. J Am Coll Cardiol 2000;36:438–443.

3. Cooper-DeHoff RM, Gong Y, Handberg EM, et al. Tight bloodpressure control and cardiovascular outcomes among hyperten-sive patients with diabetes and coronary artery disease. JAMA2010;304:61–68.

4. Ovbiagele B, Diener HC, Yusuf S, et al. Level of systolic bloodpressure within the normal range and risk of recurrent stroke.JAMA 2011;306:2137–2144.

5. Ovbiagele B. Low-normal systolic blood pressure and secondarystroke risk. J Stroke Cerebrovasc Dis 2012.

DOI: 10.1002/ana.23615

Pathogenesis of Intracranial AtherosclerosisMark Fisher, MD,1 Laszlo Csiba, MD,2

Artak Labadzhyan, MD,3 Jun Zhou,3

Navneet Narula, MD,4 and Jagat Narula, MD5

Using magnetic resonance imaging of middle cerebral ar-

tery, Xu et al report low prevalence of hemorrhage in advanced

atherosclerotic lesions.1 This interesting finding is consistent

with our pathologic analysis of basilar artery atherosclerosis.2 In

that study, we proposed a new model of pathogenesis of basilar

atherosclerosis in which the lesion is relatively benign, com-

pared to extracranial/systemic lesions, due to paucity of neovas-

cularity. The limited neovascularity of the intracranial athero-

sclerotic lesion is likely due to infrequent or absent vasa

vasorum of these vessels.3,4 Reduced prevalence of intraplaque

hemorrhage is a logical consequence of a paucity of plaque neo-

vascularity. Moreover, the recent findings of good outcome for

medically treated patients with intracranial atherosclerosis5 may

well reflect a relatively benign lesion.

Supported by NIH RO1 NS20989.

Potential Conflicts of Interest

Nothing to report.

1Departments of Neurology, Anatomy & Neurobiology, andPathology & Laboratory Medicine, University of California atIrvine School of Medicine, Irvine, CA, 2Department ofNeurology, University of Debrecen, Debrecen,Hungary, 3Department of Medicine, University of California atIrvine School of Medicine, Irvine, CA, 4Department of Pathologyand Laboratory Medicine, Weill Cornell Medical College,New York, NY, and 5Department of Medicine, Mount SinaiSchool of Medicine, New York, NY

References

1. Xu W-H, Li M-L, Gao S, et al. Middle cerebral artery intraplaquehemorrhage: prevalence and clinical relevance. Ann Neurol 2012;71:195–198.

2. Labadzhyan A, Csiba L, Narula N, et al. Histopathologic evalua-tion of basilar artery atherosclerosis. J Neurol Sci 2011;307:97–99.

3. Takaba M, Endo S, Kurimoto M, et al. Vasa vasorum of the intra-cranial arteries. Acta Neurochir (Wien) 1998;140:411–416.

4. Aydin F. Do human in tracranial arteries lack vasa vasorum? Acomparative immunohistochemical study of intracranial and sys-temic arteries. Acta Neuropathol 1998;96:22–28.

5. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versusaggressive medical therapy for intracranial arterial stenosis. NEngl J Med 2011;365:993–1003.

DOI: 10.1002/ana.23617

ReplyWei-Hai Xu, MD

We thank Dr Fisher and colleagues for their comments

on our article. Intraplaque hemorrhage in extracranial athero-

sclerosis is closely related to plaque progression and ischemic

events. The low prevalence of intraplaque hemorrhage in

advanced middle cerebral artery atherosclerosis suggests an

underlying pathophysiology that is distinct from extracranial

atherosclerosis.1 Interestingly, spontaneous dissecting intramural

hematoma is also less frequently reported in intracranial arteries

than in extracranial arteries,2 although the systematic risk fac-

tors, such as hypertension and hypercholesterolemia, involve the

whole arterial tree of the human body. We suspect both of these

phenomena are partly due to the absent vasa vasorum of intra-

cranial arteries. Further investigations are required to confirm

our suspicion.

The characteristic plaque components, such as thin fi-

brous caps, large lipid core, and intraplaque hemorrhage, are

highly suggestive of vulnerable atherosclerosis. Carotid intrapla-

que hemorrhage and increased intraplaque vessel formation are

independently related to clinical outcome and are independent

of clinical risk factors and medication use.3 However, the clini-

cal outcome of intracranial atherosclerosis may have multiple

determinants aside from plaque components, such as stenosis

degree, collaterals, and brain tolerance.4 Plaque distribution

may also play a role, which has been reported recently.5 We

fully agree that the SAMPPRIS study has provided a successful

medical management regimen for intracranial atherosclerosis,

but we believe the medical intervention in the SAMPPRIS

study may affect multiple facets, not only the plaque compo-

nents. This intensive medication regimen has not been applied

in clinical trials of symptomatic carotid atherosclerosis, although

carotid endarterectomy and stenting therapy have been per-

formed widely. Therefore, we are not sure whether intracranial

atherosclerosis lesions are relatively benign or responsive to in-

tensive medical treatments.

July 2012 149

Letter/Replies