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Erschienen in: Journal of Neurology 7/2019

26.04.2019 | Original Communication

Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

verfasst von: Andrea Jokumsen-Cabral, Ana Aires, Susana Ferreira, Elsa Azevedo, Pedro Castro

Erschienen in: Journal of Neurology | Ausgabe 7/2019

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Abstract

Background

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent monogenic cause of cerebral ischemia, but reliable biomarkers to monitor the disease are lacking.

Aims and objectives

To evaluate cerebral autoregulation (CA), vasoreactivity (VR), and neurovascular coupling (NVC) in CADASIL patients through a battery of dynamic transcranial Doppler tests.

Methods

We screened our database for all pre-dementia CADASIL cases. We monitored cerebral blood flow velocity (CBFV) with transcranial Doppler, blood pressure, and expiratory carbon dioxide (CO2) non-invasively. CA was assessed by transfer function from the spontaneous oscillations of blood pressure to CBFV, VR with inhalation of CO2 at 5%, and hyperventilation and NVC by the CBFV response to visual stimulation.

Results

We included 27 CADASIL patients and 20 healthy controls with similar age and sexes. CA and VR were similar between groups. However, NVC was significantly affected in CADASIL patients, with lower magnitudes of CBFV upsurge (overshoot 19 ± 5 vs 26 ± 6%, p = 0.013; gain 12 ± 7 vs 17 ± 5%, p = 0.003) and altered time behavior during visual stimulation (natural frequency 0.18 ± 0.06 vs 0.24 ± 0.06 Hz, p = 0.005; rate time 0.7 ± 1.7 vs 2.7 ± 3.5 s, p = 0.025).

Conclusion

Our results express a primary and selective involvement of the neurovascular unit in CADASIL rather than a generalized cerebral vasomotor disturbance. Functional cerebrovascular testing could be useful in patient evaluation and monitoring.
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Literatur
1.
Zurück zum Zitat Arboix A, Font A, Garro C, Garcia-Eroles L, Comes E, Massons J (2007) Recurrent lacunar infarction following a previous lacunar stroke: a clinical study of 122 patients. J Neurol Neurosurg Psychiatry 78:1392–1394CrossRefPubMedPubMedCentral Arboix A, Font A, Garro C, Garcia-Eroles L, Comes E, Massons J (2007) Recurrent lacunar infarction following a previous lacunar stroke: a clinical study of 122 patients. J Neurol Neurosurg Psychiatry 78:1392–1394CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Azevedo E, Castro P, Santos R, Freitas J, Coelho T, Rosengarten B, Panerai R (2011) Autonomic dysfunction affects cerebral neurovascular coupling. Clin Auton Res 21:395–403CrossRefPubMed Azevedo E, Castro P, Santos R, Freitas J, Coelho T, Rosengarten B, Panerai R (2011) Autonomic dysfunction affects cerebral neurovascular coupling. Clin Auton Res 21:395–403CrossRefPubMed
3.
Zurück zum Zitat Azevedo E, Mendes A, Seixas D, Santos R, Castro P, Ayres-Basto M, Rosengarten B, Oliveira JP (2012) Functional transcranial Doppler: presymptomatic changes in Fabry disease. Eur Neurol 67:331–337CrossRefPubMed Azevedo E, Mendes A, Seixas D, Santos R, Castro P, Ayres-Basto M, Rosengarten B, Oliveira JP (2012) Functional transcranial Doppler: presymptomatic changes in Fabry disease. Eur Neurol 67:331–337CrossRefPubMed
4.
Zurück zum Zitat Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG (2009) Cadasil. Lancet Neurol 8:643–653CrossRef Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser MG (2009) Cadasil. Lancet Neurol 8:643–653CrossRef
5.
Zurück zum Zitat Cheema I, Switzer AR, McCreary CR, Hill MD, Frayne R, Goodyear BG, Smith EE (2017) Functional magnetic resonance imaging responses in CADASIL. J Neurol Sci 375:248–254CrossRefPubMed Cheema I, Switzer AR, McCreary CR, Hill MD, Frayne R, Goodyear BG, Smith EE (2017) Functional magnetic resonance imaging responses in CADASIL. J Neurol Sci 375:248–254CrossRefPubMed
6.
Zurück zum Zitat Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB (2016) Transfer function analysis of dynamic cerebral autoregulation: a white paper from the international cerebral autoregulation research network. J Cereb Blood Flow Metab 36:665–680CrossRefPubMedPubMedCentral Claassen JA, Meel-van den Abeelen AS, Simpson DM, Panerai RB (2016) Transfer function analysis of dynamic cerebral autoregulation: a white paper from the international cerebral autoregulation research network. J Cereb Blood Flow Metab 36:665–680CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Dabertrand F, Kroigaard C, Bonev AD, Cognat E, Dalsgaard T, Domenga-Denier V, Hill-Eubanks DC, Brayden JE, Joutel A, Nelson MT (2015) Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease. Proc Natl Acad Sci USA 112:E796–805CrossRefPubMed Dabertrand F, Kroigaard C, Bonev AD, Cognat E, Dalsgaard T, Domenga-Denier V, Hill-Eubanks DC, Brayden JE, Joutel A, Nelson MT (2015) Potassium channelopathy-like defect underlies early-stage cerebrovascular dysfunction in a genetic model of small vessel disease. Proc Natl Acad Sci USA 112:E796–805CrossRefPubMed
8.
Zurück zum Zitat Freitas S, Simoes MR, Alves L, Santana I (2011) Montreal cognitive assessment (MoCA): normative study for the Portuguese population. J Clin Exp Neuropsychol 33:989–996CrossRefPubMed Freitas S, Simoes MR, Alves L, Santana I (2011) Montreal cognitive assessment (MoCA): normative study for the Portuguese population. J Clin Exp Neuropsychol 33:989–996CrossRefPubMed
9.
Zurück zum Zitat Freitas S, Simoes MR, Alves L, Vicente M, Santana I (2012) Montreal cognitive assessment (MoCA): validation study for vascular dementia. J Int Neuropsychol Soc 18:1031–1040CrossRefPubMed Freitas S, Simoes MR, Alves L, Vicente M, Santana I (2012) Montreal cognitive assessment (MoCA): validation study for vascular dementia. J Int Neuropsychol Soc 18:1031–1040CrossRefPubMed
10.
Zurück zum Zitat Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N (2015) Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 78:887–900CrossRef Ghosh M, Balbi M, Hellal F, Dichgans M, Lindauer U, Plesnila N (2015) Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Ann Neurol 78:887–900CrossRef
11.
Zurück zum Zitat Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 100:328–335CrossRefPubMed Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 100:328–335CrossRefPubMed
12.
Zurück zum Zitat Hamel E (2006) Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 100:1059–1064CrossRefPubMed Hamel E (2006) Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 100:1059–1064CrossRefPubMed
13.
Zurück zum Zitat Hao Q, Wong LK, Lin WH, Leung TW, Kaps M, Rosengarten B (2010) Ethnic influences on neurovascular coupling: a pilot study in whites and Asians. Stroke 41:383–384CrossRefPubMed Hao Q, Wong LK, Lin WH, Leung TW, Kaps M, Rosengarten B (2010) Ethnic influences on neurovascular coupling: a pilot study in whites and Asians. Stroke 41:383–384CrossRefPubMed
14.
Zurück zum Zitat Joutel A, Monet-Lepretre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, Lemaire-Carrette B, Domenga V, Schedl A, Lacombe P, Hubner N (2010) Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Investig 120:433–445CrossRef Joutel A, Monet-Lepretre M, Gosele C, Baron-Menguy C, Hammes A, Schmidt S, Lemaire-Carrette B, Domenga V, Schedl A, Lacombe P, Hubner N (2010) Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease. J Clin Investig 120:433–445CrossRef
15.
Zurück zum Zitat Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186CrossRefPubMed Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186CrossRefPubMed
16.
Zurück zum Zitat Lin WH, Hao Q, Rosengarten B, Leung WH, Wong KS (2011) Impaired neurovascular coupling in ischaemic stroke patients with large or small vessel disease. Eur J Neurol 18:731–736CrossRefPubMed Lin WH, Hao Q, Rosengarten B, Leung WH, Wong KS (2011) Impaired neurovascular coupling in ischaemic stroke patients with large or small vessel disease. Eur J Neurol 18:731–736CrossRefPubMed
17.
Zurück zum Zitat Madureira J, Castro P, Azevedo E (2017) Demographic and systemic hemodynamic influences in mechanisms of cerebrovascular regulation in healthy adults. J Stroke Cerebrovasc Dis 26:500–508CrossRefPubMed Madureira J, Castro P, Azevedo E (2017) Demographic and systemic hemodynamic influences in mechanisms of cerebrovascular regulation in healthy adults. J Stroke Cerebrovasc Dis 26:500–508CrossRefPubMed
18.
Zurück zum Zitat Malojcic B, Giannakopoulos P, Sorond FA, Azevedo E, Diomedi M, Oblak JP, Carraro N, Boban M, Olah L, Schreiber SJ, Pavlovic A, Garami Z, Bornstein NM, Rosengarten B (2017) Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimers’s disease. BMC Med 15:27CrossRefPubMedPubMedCentral Malojcic B, Giannakopoulos P, Sorond FA, Azevedo E, Diomedi M, Oblak JP, Carraro N, Boban M, Olah L, Schreiber SJ, Pavlovic A, Garami Z, Bornstein NM, Rosengarten B (2017) Ultrasound and dynamic functional imaging in vascular cognitive impairment and Alzheimers’s disease. BMC Med 15:27CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Pfefferkorn T, von Stuckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M (2001) Reduced cerebrovascular CO(2) reactivity in CADASIL: a transcranial Doppler sonography study. Stroke 32:17–21CrossRefPubMed Pfefferkorn T, von Stuckrad-Barre S, Herzog J, Gasser T, Hamann GF, Dichgans M (2001) Reduced cerebrovascular CO(2) reactivity in CADASIL: a transcranial Doppler sonography study. Stroke 32:17–21CrossRefPubMed
21.
Zurück zum Zitat Rosengarten B, Aldinger C, Kaufmann A, Kaps M (2001) Comparison of visually evoked peak systolic and end diastolic blood flow velocity using a control system approach. Ultrasound Med Biol 27:1499–1503CrossRefPubMed Rosengarten B, Aldinger C, Kaufmann A, Kaps M (2001) Comparison of visually evoked peak systolic and end diastolic blood flow velocity using a control system approach. Ultrasound Med Biol 27:1499–1503CrossRefPubMed
22.
Zurück zum Zitat Rosengarten B, Budden C, Osthaus S, Kaps M (2003) Effect of heart rate on regulative features of the cortical activity-flow coupling. Cerebrovasc Dis 16:47–52CrossRefPubMed Rosengarten B, Budden C, Osthaus S, Kaps M (2003) Effect of heart rate on regulative features of the cortical activity-flow coupling. Cerebrovasc Dis 16:47–52CrossRefPubMed
23.
Zurück zum Zitat Rosengarten B, Huwendiek O, Kaps M (2001) Neurovascular coupling in terms of a control system: validation of a second-order linear system model. Ultrasound Med Biol 27:631–635CrossRefPubMed Rosengarten B, Huwendiek O, Kaps M (2001) Neurovascular coupling in terms of a control system: validation of a second-order linear system model. Ultrasound Med Biol 27:631–635CrossRefPubMed
24.
Zurück zum Zitat Rosengarten B, Sperner J, Gorgen-Pauly U, Kaps M (2003) Cerebrovascular reactivity in adolescents with migraine and tension-type headache during headache-free interval and attack. Headache 43:458–463CrossRefPubMed Rosengarten B, Sperner J, Gorgen-Pauly U, Kaps M (2003) Cerebrovascular reactivity in adolescents with migraine and tension-type headache during headache-free interval and attack. Headache 43:458–463CrossRefPubMed
25.
Zurück zum Zitat Singhal S, Markus HS (2005) Cerebrovascular reactivity and dynamic autoregulation in nondemented patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). J Neurol 252:163–167CrossRefPubMed Singhal S, Markus HS (2005) Cerebrovascular reactivity and dynamic autoregulation in nondemented patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). J Neurol 252:163–167CrossRefPubMed
26.
Zurück zum Zitat Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322CrossRef Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjogren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322CrossRef
27.
Zurück zum Zitat Willie CK, Colino FL, Bailey DM, Tzeng YC, Binsted G, Jones LW, Haykowsky MJ, Bellapart J, Ogoh S, Smith KJ, Smirl JD, Day TA, Lucas SJ, Eller LK, Ainslie PN (2011) Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function. J Neurosci Methods 196:221–237CrossRef Willie CK, Colino FL, Bailey DM, Tzeng YC, Binsted G, Jones LW, Haykowsky MJ, Bellapart J, Ogoh S, Smith KJ, Smirl JD, Day TA, Lucas SJ, Eller LK, Ainslie PN (2011) Utility of transcranial Doppler ultrasound for the integrative assessment of cerebrovascular function. J Neurosci Methods 196:221–237CrossRef
Metadaten
Titel
Primary involvement of neurovascular coupling in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy
verfasst von
Andrea Jokumsen-Cabral
Ana Aires
Susana Ferreira
Elsa Azevedo
Pedro Castro
Publikationsdatum
26.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 7/2019
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-019-09331-y

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