COMMENTARIES

Intracranial Atherosclerosis: An Underdiagnosed Disease?

Mikael Mazighi and Pierre Amarenco, Service de Neurologie et Centre d'Accueil et de Traitement de l'Attaque Cérébrale, Unité INSERM 698: Recherche Clinique en Athérothrombose, Groupe Hospitalier Bichat Claude Bernard, 46, rue Henri Huchard, 75877 Paris Cedex 18, Tel: (+44) 01 40 25 87 25, Fax: (+44) 01 40 25 71 98

Intracranial atherosclerosis is considered to be a severe but rare condition, occurring more frequently in Asian, Afro-American, or Hispanic populations [1]. Overall, intracranial atherosclerosis is considered to account for 5% to 10% of ischemic strokes [1] and is associated with a high risk of recurrent ischemic events as high as 22% per year [2,3]. The severity of intracranial atherosclerosis warrants an accurate diagnostic work-up and a correct knowledge of the natural history of the disease. Among the available imaging modalities, x-ray angiography, MRA, CT angiography, and transcranial Doppler ultrasonography, only image the residual lumen of intracranial arteries and may fail to detect culprit intracranial plaques. Only high-resolution MRI has proven capable of imaging the arterial wall and detects symptomatic stenosis of intracranial arteries, such as the middle cerebral artery (MCA) and basilar artery [4]. These results suggest that intracranial atherosclerosis prevalence is potentially underestimated due to lack of appropriate diagnostic procedures. Recent data on autopsies of fatal stroke patients emphasizes this hypothesis.

          Today, because of the dramatic decline in post-mortem studies, large autopsy studies are rare. For this reason, extensive and thoroughly studied autopsy material is unique. A systematic analysis of intra- and extracranial arteries, the aortic arch, and the heart in 339 consecutive autopsies of fatal stroke patients was conducted in La Salpêtrière hospital in Paris [5]. Clinical history, risk factors, imaging data, and general autopsy reports were analyzed. In this autopsy series of mostly white patients, intracranial atherosclerosis was highly prevalent in patients with brain infarction (BI) and 2 to 4 times more frequent than in the brain hemorrhage (BH) control group [5]. This case control autopsy study of intracranial atherosclerosis in stroke patients was the first to show that intracranial stenoses < 75% may be causally related with ischemic stroke. Intracranial plaques and stenoses occurred in 62.2% (95% CI, 56.3 to 68.1) and 43.2% (95% CI, 37.2 to 49.3) of patients with BI, respectively, compared with 48.8% (P < 0.05) and 17.5% (P < 0.001) of patients with BH, respectively. In the 43% of patients with BI with at least one intracranial plaque inducing luminal stenosis graded > 30%, the stenosis was considered to be causal in 5.8% of cases because of superimposed clot on ulcerated plaques. Interestingly, history of myocardial infarction was significantly associated with intracranial plaques and previous stroke was associated with the presence of intracranial stenosis.

          In multivariate analyses, diabetes and male sex were significantly associated with intracranial atherosclerosis. Based on these findings, intracranial atherosclerosis may be highly represented in Caucasian populations with diffuse atherosclerosis. The independent association between either male sex or diabetes and intracranial atherosclerosis favors this hypothesis. It is worth noting that diabetes appeared to be positively related to the degree of stenosis, a relationship not described previously. Obviously, these findings can only be applied to fatal strokes because autopsy studies are not representative of the whole spectrum of strokes. Patients who died were more likely to have had the most severe strokes, accounting for the high prevalence of cardioembolic strokes and low prevalence of lacunar strokes observed in this study. These results need to be confirmed using modern imaging of the arterial wall of intracranial arteries in series of patients with nonfatal stroke.

These data bring new insights compared with early pathological studies, which supported the rarity of intracranial atherosclerosis. Some decades earlier, in a necropsy series of 200 stroke patients, Fisher [6] failed to identify a single MCA thrombosis. Whereas, 15 years later, in a necropsy study of a predominantly Afro-American population performed in 142 patients with recent BI, Moossy [7] identified the presence of intracranial thrombi in 55%. The ethnic disparity, between the studied populations, was considered to be the main explanatory factor for the increase in intracranial lesion incidence; and atherosclerosis as the cause for intracranial lesions was even debated. Beyond the abundant literature on intracranial lesions in Asian, Afro-American, and Hispanic populations, some groups have argued that the increased prevalence of intracranial atherosclerosis was not related to ethnicity but to a higher prevalence of vascular risk factors [1].

Intracranial atherosclerosis may be underdiagnosed and responsible for a higher proportion of ischemic strokes than is currently accepted, particularly if stenosis > 30% to 75% are identified. In large registries, such patients are probably classified as having had a stroke of unknown cause. New arterial wall imaging techniques should be used to reevaluate the frequency and role of intracranial artery plaques in living patients with stroke. The use of accurate arterial wall imaging of intracranial arteries with, for example, high resolution MRI, should prompt a reappraisal of the frequency of intracranial atherosclerosis in nonfatal strokes patients. These findings emphasize the importance of identifying intracranial atherosclerosis in ischemic stroke patients and may impact on the management of intracranial lesions.

References

  1.    Sacco RL, Kargman DE, Gu Q, Zamanillo MC. 1995. Race-ethnicity and determinants of intracranial atherosclerotic cerebral infarction. The Northern Manhattan Stroke Study. Stroke 26: 14-20.
  2.    Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. 2005. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med 352: 1305-16.
  3.    Mazighi M, Tanasescu R, Ducrocq X, et al. 2006. Prospective study of symptomatic atherothrombotic intracranial stenoses: the Gesica study. Neurology 66: 1187-91.
  4.    Klein IF, Lavallee PC, Schouman-Claeys E, Amarenco P. 2005. High resolution MRI identifies basilar artery plaques in paramedian pontine infarct. Neurology 64: 551-52.
  5.    Mazighi M, Labreuche J, Gongora-Rivera F, Duyckaerts C, Amarenco P. 2008. Autopsy prevalence of intracranial atherosclerosis in patients with fatal stroke. Stroke 39: 1142-47.
  6.    Fisher M. 1951. Occlusion of the internal carotid artery. AMA Arch Neurol Psychiatry 65: 346-77.
  7.    Moossy J. 1966. Cerebral infarction and intracranial arterial thrombosis. Necropsy studies and clinical implications. Arch Neurol 14: 119-23.

 

 

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