Background: Leukoaraiosis (ILA) is believed to be ischaemic in origin due to its similar location as that of lacunar infarctions and its association with cerebrovascular risk factors. However, its pathophysiology is not well understood. The ischaemic injuries may be a result of increased pulsatility or cerebral hypo-perfusion. We used carotid duplex ultrasound to prove that the underlying mechanism is hypo-perfusion. Methods: We compared 55 ILA patients to 44 risk factor-matched controls with normal magnetic resonance imaging (MRI) of the head. ILA diagnosis was based on MRI and was further categorised according to the Fazekas scale. We measured carotid artery blood flow velocity and diameter and calculated carotid blood flow and resistance indexes. Results: Blood flow velocities and blood flows were significantly lower in the ILA group, including diastolic, systolic and mean pressures (p ≤ 0.05). The resistance indices were higher in the ILA group, but the differences were not statistically significant. All the velocities and blood flows showed a decreasing trend with higher Fazekas score, whereas resistance indexes showed an increasing trend. Conclusions: Lower blood flow and higher resistance of carotid arteries are consistent with the hypo-perfusion theory of ILA. Carotid ultrasound could have a diagnostic and prognostic role in ILA patients.

1.
Poggesi A, Pantoni L, Inzitari D, Fazekas F, Ferro J, O'Brien J, Hennerici M, Scheltens P, Erkinjuntti T, Visser M, Langhorne P, Chabriat H, Waldemar G, Wallin A, Wahlund A; The LADIS Study Group: A decade of the LADIS (leukoaraiosis and disability) study: what have we learned about white matter changes and small-vessel disease? Cerebrovasc Dis 2011;32:577-588.
2.
Pantoni L: Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010;9:689-701.
3.
Poels MM, Zaccai K, Verwoert GC, Vernooij MW, Hofman A, van der Lugt A, Witteman JC, Breteler MM, Mattace-Raso FU, Ikram MA: Arterial stiffness and cerebral small vessel disease: the Rotterdam scan study. Stroke 2012;43:2637-2642.
4.
Mitchell GF, van Buchem MA, Sigurdsson S, Gotal JD, Jonsdottir MK, Kjartansson Ó, Garcia M, Aspelund T, Harris TB, Gudnason V, Launer LJ: Arterial stiffness, pressure and flow pulsatility and brain structure and function: the age, gene/environment susceptibility - Reykjavik study. Brain 2011;134:3398-3407.
5.
Webb AJ, Simoni M, Mazzucco S, Kuker W, Schulz U, Rothwell PM: Increased cerebral arterial pulsatility in patients with leukoaraiosis: arterial stiffness enhances transmission of aortic pulsatility. Stroke 2012;43:2631-2636.
6.
Brisset M, Boutouyrie P, Pico F, Zhu Y, Zureik M, Schilling S, Dufouil C, Mazoyer B, Laurent S, Tzourio C, Debette S: Large-vessel correlates of cerebral small-vessel disease. Neurology 2013;80:662-669.
7.
Kearney-Schwartz A, Rossignol P, Bracard S, Felblinger J, Fay R, Boivin JM, Lecompte T, Lacolley P, Benetos A, Zannad F: Vascular structure and function is correlated to cognitive performance and white matter hyperintensities in older hypertensive patients with subjective memory complaints. Stroke 2009;40:1229-1236.
8.
van Elderen SG, Brandts A, Westenberg JJ, van der Grond J, Tamsma JT, van Buchem MA, Romijn JA, Kroft LJ, Smit JW, de Roos A: Aortic stiffness is associated with cardiac function and cerebral small vessel disease in patients with type 1 diabetes mellitus: assessment by magnetic resonance imaging. Eur Radiol 2010;20:1132-1138.
9.
Henskens LH, Kroon AA, van Oostenbrugge RJ, Gronenschild EH, Fuss-Lejeune MM, Hofman PA, Lodder J, de Leeuw PW: Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients. Hypertension 2008;52:1120-1126.
10.
Hatanaka R, Obara T, Watabe D, Ishikawa T, Kondo T, Ishikura K, Aikawa T, Aono Y, Hara A, Metoki H, Asayama K, Kikuya M, Mano N, Ohkubo T, Izumi S, Imai Y: Association of arterial stiffness with silent cerebrovascular lesions: the Ohasama study. Cerebrovasc Dis 2011;31:329-337.
11.
Kim DH, Choi JH, Moon JS, Kim HJ, Cha JK: Association between the severity of cerebral small vessel disease, pulsatility of cerebral arteries, and brachial ankle pulse wave velocity in patients with lacunar infarction. Eur Neurol 2010;64:247-252.
12.
O'Rourke MF, Safar ME: Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension 2005;46:200-204.
13.
Tanaka T, Shimizu T, Fukuhara T: The relationship between leukoaraiosis volume and parameters of carotid artery duplex ultrasonographic scanning in asymptomatic diabetic patients. Comput Med Imaging Graph 2009;33:489-493.
14.
Aribisala BS, Morris Z, Eadie E, Thomas A, Gow A, Valdés Hernández MC, Royle NA, Bastin ME, Starr J, Deary IJ, Wardlaw JM: Blood pressure, internal carotid artery flow parameters, and age - related white matter hyperintensities. Hypertension 2014;63:1011-1018.
15.
Harris AD, Coutts SB, Frayne R: Diffusion and perfusion MR imaging of acute ischemic stroke. Magn Reson Imaging Clin N Am 2009;17:291-313.
16.
Heliopoulos I, Artemis D, Vadikolias K, Tripsianis G, Piperidou C, Tsivgoulis G: Association of ultrasonographic parameters with subclinical white-matter hyperintensities in hypertensive patients. Cardiovasc Psychiatry Neurol 2012;2012:616572.
17.
Jokinen H, Kalska H, Ylikoski R, Madureira S, Verdelho A, van der Flier WM, Scheltens P, Barkhof F, Visser MC, Fazekas F, Schmidt R, O'Brien J, Waldemar G, Wallin A, Chabriat H, Pantoni L, Inzitari D, Erkinjuntti T; LADIS group: Longitudinal cognitive decline in subcortical ischemic vascular disease - the LADIS study. Cerebrovasc Dis 2009;27:384-391.
18.
Appelman AP, Exalto LG, van der Graaf Y, Biessels GJ, Mali WP, Geerlings MI: White matter lesions and brain atrophy: more than shared risk factors? A systematic review. Cerebrovasc Dis 2009;28:227-242.
19.
Muller M, Appelman AP, van der Graaf Y, Vincken KL, Mali WP, Geerlings MI: Brain atrophy and cognition: interaction with cerebrovascular pathology? Neurobiol Aging 2011;32:885-893.
20.
Appelman AP, van der Graaf Y, Vincken KL, Mali WP, Geerlings MI: Combined effect of cerebral hypoperfusion and white matter lesions on executive functioning - the SMART-MR study. Dement Geriatr Cogn Disord 2010;29:240-247.
21.
Appelman AP, van der Graaf Y, Vincken KL, Tiehuis AM, Witkamp TD, Mali WP, Geerlings MI; SMART Study Group: Total cerebral blood flow, white matter lesions and brain atrophy: the SMART-MR study. J Cereb Blood Flow Metab 2008;28:633-639.
22.
Muller M, van der Graaf Y, Visseren FL, Vlek AL, Mali WP, Geerlings MI; SMART Study Group: Blood pressure, cerebral blood flow, and brain volumes. The SMART-MR study. J Hypertens 2010;28:1498-1505.
23.
Fernando MS, Simpson JE, Matthews F, Brayne C, Lewis CE, Barber R, Kalaria RN, Forster G, Esteves F, Wharton SB, Shaw PJ, O'Brien JT, Ince PG; MRC Cognitive Function and Ageing Neuropathology Study Group: White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury. Stroke 2006;37:1391-1398.
24.
Ryan DJ, Byrne S, Dunne R, Harmon M, Harbison J: White matter disease and an incomplete circle of Willis. Int J Stroke 2013, DOI: 10.1111/ijs.12042.
25.
Markus HS, Lythgoe DJ, Ostegaard L, O'Sullivan M, Williams SC: Reduced cerebral blood flow in white matter in ischaemic leukoaraiosis demonstrated using quantitative exogenous contrast based perfusion MRI. J Neurol Neurosurg Psychiatry 2000;69:48-53.
26.
O'Sullivan M, Lythgoe DJ, Pereira AC, Summers PE, Jarosz JM, Williams SC, Markus HS: Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis. Neurology 2002;59:321-326.
27.
Bastos-Leite AJ, Kuijer JP, Rombouts SA, Sanz-Arigita E, van Straaten EC, Gouw AA, van der Flier WM, Scheltens P, Barkhof F: Cerebral blood flow by using pulsed arterial spin-labeling in elderly subjects with white matter hyperintensities. AJNR Am J Neuroradiol 2008;29:1296-1301.
28.
Xu TY, Staessen JA, Wei FF, Xu J, Li FH, Fan WX, Gao PJ, Wang JG, Li Y: Blood flow pattern in the middle cerebral artery in relation to indices of arterial stiffness in the systemic circulation. Am J Hypertens 2012;25:319-324.
29.
Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-Invasive Investigation of Large Arteries: Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 2006;27:2588-2605.
30.
Sutera SP, Skalak R: The history of Poiseuille's law. Annu Rev Fluid Mech 1993;25:1-20.
31.
Mitchell GF: Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol (1985) 2008;105:1652-1660.
32.
Baker AR, Evans DH, Prytherch DR, Morton DB, Bentley S, Asher MJ, Bell PR: Some failings of pulsatility index and damping factor. Ultrasound Med Biol 1986;12:875-881.
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