This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pfefferkorn, T. Articles by Dichgans, M. Search for Related Content PubMed PubMed Citation Articles by Pfefferkorn, T. Articles by Dichgans, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CARBON DIOXIDE Genetics Home Reference Related Collections Genetics of Stroke Doppler ultrasound, Transcranial Doppler etc. Other Vascular biology

(Stroke. 2001;32:17.)
© 2001 American Heart Association, Inc.

Original Contributions

Reduced Cerebrovascular CO₂ Reactivity in CADASIL

A Transcranial Doppler Sonography Study

Thomas Pfefferkorn, MD; Sebastian von Stuckrad-Barre, MD; Jürgen Herzog, MD; Thomas Gasser, MD; Gerhard F. Hamann, MD Martin Dichgans, MD

From the Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität München.

Correspondence to Dr Martin Dichgans, Department of Neurology, Klinikum Großhadern, Marchioninstr 15, 81377 München, Germany. E-mail mdichgans{at}brain.nefo.med-uni-muenchen.de

Background and Purpose—Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukencephalopathy (CADASIL) is a hereditary angiopathy caused by mutations in Notch3. Cerebral microvessels show an accumulation of granular osmiophilic material in the vicinity of degenerating vascular smooth muscle cells. To study cerebrovascular function in CADASIL, we performed measurements on cerebral hemodynamics by using transcranial Doppler sonography.

Methods—Middle cerebral artery (MCA) mean blood flow velocity (MFV), cerebrovascular CO₂ reactivity, and the resistance index were measured by bilateral transcranial Doppler sonography in 29 CADASIL individuals (mean age, 49.0±2.4 years) and an equal number of age- and sex-matched control subjects.

Results—Compared with control subjects, CO₂ reactivity was reduced in CADASIL (33.4±2.7% versus 45.3±3.0%; P<0.01). This difference remained significant when only nondisabled CADASIL individuals (Rankin=0, n=21) were included in the analysis (P<0.05). CO₂ reactivity was significantly lower in disabled than in nondisabled CADASIL individuals (24.5±2.7% versus 36.8±3.4%; P<0.05). MCA MFV was reduced in CADASIL (45.6±2.2 cm/s versus 54.2±2.4 cm/s; P<0.05) and correlated negatively with age both in affected individuals (r=-0.314; P<0.05) and control subjects (r=-0.339; P<0.05). Resistance index was not significantly altered (59.0±1.0% versus 57.7±1.2%; P=0.42).

Conclusions—In CADASIL, there is a reduction of both CO₂ reactivity and basal MCA MFV. The reduced CO₂ reactivity suggests functional impairment of cerebral vasoreactivity probably related to vascular smooth muscle cell dysfunction. The reduction of CO₂ reactivity in nondisabled CADASIL individuals suggests an early role of impaired cerebral vasoreactivity in the evolution of the disease.

Key Words: CADASIL • carbon dioxide • ultrasonography, Doppler, transcranial

This article has been cited by other articles:

				Y. Yamamoto, M. Ihara, C. Tham, R. W.C. Low, J. Y. Slade, T. Moss, A. E. Oakley, T. Polvikoski, and R. N. Kalaria Neuropathological Correlates of Temporal Pole White Matter Hyperintensities in CADASIL Stroke, June 1, 2009; 40(6): 2004 - 2011. [Abstract] [Full Text] [PDF]

				J.M. Pollock, A.R. Deibler, C.T. Whitlow, H. Tan, R.A. Kraft, J.H. Burdette, and J.A. Maldjian Hypercapnia-Induced Cerebral Hyperperfusion: An Underrecognized Clinical Entity AJNR Am. J. Neuroradiol., February 1, 2009; 30(2): 378 - 385. [Abstract] [Full Text] [PDF]

				A. Stenborg, H. Kalimo, M. Viitanen, A. Terent, and L. Lind Impaired Endothelial Function of Forearm Resistance Arteries in CADASIL Patients Stroke, October 1, 2007; 38(10): 2692 - 2697. [Abstract] [Full Text] [PDF]

				A. Viswanathan, J.-P. Guichard, A. Gschwendtner, F. Buffon, R. Cumurcuic, C. Boutron, E. Vicaut, M. Holtmannspotter, C. Pachai, M.-G. Bousser, et al. Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study Brain, September 1, 2006; 129(9): 2375 - 2383. [Abstract] [Full Text] [PDF]

				P. Lacombe, C. Oligo, V. Domenga, E. Tournier-Lasserve, and A. Joutel Impaired Cerebral Vasoreactivity in a Transgenic Mouse Model of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Arteriopathy Stroke, May 1, 2005; 36(5): 1053 - 1058. [Abstract] [Full Text] [PDF]

				C. Dubroca, P. Lacombe, V. Domenga, J. Maciazek, B. Levy, E. Tournier-Lasserve, A. Joutel, and D. Henrion Impaired Vascular Mechanotransduction in a Transgenic Mouse Model of CADASIL Arteriopathy Stroke, January 1, 2005; 36(1): 113 - 117. [Abstract] [Full Text] [PDF]

				S. Singhal, S. Bevan, T. Barrick, P. Rich, and H. S. Markus The influence of genetic and cardiovascular risk factors on the CADASIL phenotype Brain, September 1, 2004; 127(9): 2031 - 2038. [Abstract] [Full Text] [PDF]

				M. B. Hussain, S. Singhal, H. S. Markus, and D. R.J. Singer Abnormal Vasoconstrictor Responses to Angiotensin II and Noradrenaline in Isolated Small Arteries From Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Stroke, April 1, 2004; 35(4): 853 - 858. [Abstract] [Full Text] [PDF]

				J. H. Dieu and F. Veyckemans Perioperative management of a CADASIL type arteriopathy patient Br. J. Anaesth., September 1, 2003; 91(3): 442 - 444. [Abstract] [Full Text] [PDF]

				K. Tatsch, W. Koch, R. Linke, G. Poepperl, N. Peters, M. Holtmannspoetter, and M. Dichgans Cortical Hypometabolism and Crossed Cerebellar Diaschisis Suggest Subcortically Induced Disconnection in CADASIL: An 18F-FDG PET Study J. Nucl. Med., June 1, 2003; 44(6): 862 - 869. [Abstract] [Full Text] [PDF]

				C. Zimmermann and R.L. Haberl L-Arginine Improves Diminished Cerebral CO2 Reactivity in Patients Stroke, March 1, 2003; 34(3): 643 - 647. [Abstract] [Full Text] [PDF]

				S. T. Engelter, S. Rueegg, E. C. Kirsch, F. Fluri, A. Probst, A. J. Steck, and P. A. Lyrer CADASIL Mimicking Primary Angiitis of the Central Nervous System Arch Neurol, September 1, 2002; 59(9): 1480 - 1483. [Abstract] [Full Text] [PDF]

				M. Liebetrau, J. Herzog, C. U.A. Kloss, G. F. Hamann, and M. Dichgans Prolonged Cerebral Transit Time in CADASIL: A Transcranial Ultrasound Study Stroke, February 1, 2002; 33(2): 509 - 512. [Abstract] [Full Text] [PDF]

				A. M. Forteza, B. Brozman, A. A. Rabinstein, J. G. Romano, and W. G. Bradley Acetazolamide for the treatment of migraine with aura in CADASIL Neurology, December 11, 2001; 57(11): 2144 - 2145. [Full Text] [PDF]