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September 13, 2016; 87 (11) Article

Role of atherosclerosis, clot extent, and penumbra volume in headache during ischemic stroke

Hendrikus J.A. van Os, Inge A. Mulder, Irene C. van der Schaaf, L. Jaap Kappelle, Birgitta K. Velthuis, Alexander Broersen, Jan A. Vos, Gisela M. Terwindt, Wouter Schonewille, Michel D. Ferrari, Ale Algra, Marianne A.A. van Walderveen, Marieke J.H. Wermer
First published August 17, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003092
Hendrikus J.A. van Os
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Inge A. Mulder
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Irene C. van der Schaaf
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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L. Jaap Kappelle
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Birgitta K. Velthuis
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Alexander Broersen
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Jan A. Vos
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Gisela M. Terwindt
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Wouter Schonewille
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Michel D. Ferrari
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Ale Algra
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Marianne A.A. van Walderveen
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Marieke J.H. Wermer
From the Department of Neurology (H.J.A.v.O., I.A.M., G.M.T., M.D.F., M.J.H.W.) and Department of Radiology (M.A.A.v.W.), Division of Image Processing (A.B.), Leiden University Medical Center; Departments of Radiology (I.C.v.d.S., B.K.V.) and Neurology (L.J.K.), Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus (A.A.), and Julius Center for Health Sciences and Primary Care (A.A.), University Medical Center Utrecht; and Department of Neurology (J.A.V., W.S.), St Antonius Hospital, Nieuwegein, Netherlands.
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Full PDF
Citation
Role of atherosclerosis, clot extent, and penumbra volume in headache during ischemic stroke
Hendrikus J.A. van Os, Inge A. Mulder, Irene C. van der Schaaf, L. Jaap Kappelle, Birgitta K. Velthuis, Alexander Broersen, Jan A. Vos, Gisela M. Terwindt, Wouter Schonewille, Michel D. Ferrari, Ale Algra, Marianne A.A. van Walderveen, Marieke J.H. Wermer
Neurology Sep 2016, 87 (11) 1124-1130; DOI: 10.1212/WNL.0000000000003092

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Abstract

Objective: To investigate the role of large vessel atherosclerosis, blood clot extent, and penumbra volume in relation to headache in ischemic stroke patients.

Methods: In this cross-sectional study, we performed noncontrast CT, CT angiography (CTA), and CT perfusion (CTP) in 284 participants from the Dutch Acute Stroke Study and Leiden Stroke Cohort within 9 hours after ischemic stroke onset. We collected headache characteristics prospectively using a semi-structured questionnaire. Atherosclerosis was assessed by evaluating presence of plaques in extracranial and intracranial vessels and by quantifying intracranial carotid artery calcifications. Clot extent was estimated by the clot burden score on CTA and penumbra volume by CTP. We calculated risk ratios (RRs) with adjustments (aRR) for possible confounders using multivariable Poisson regression.

Results: Headache during stroke was reported in 109/284 (38%) participants. Headache was less prevalent in patients with than in patients without atherosclerosis in the extracranial anterior circulation (35% vs 48%; RR 0.72; 95% confidence interval [CI] 0.54–0.97). Atherosclerosis in the intracranial arteries was also associated with less headache, but this association was not statistically significant. Penumbra volume (aRR 1.08; 95% CI 0.63–1.85) and clot extent (aRR 1.02; 95% CI 0.86–1.20) were not related with headache.

Conclusions: Headache in the early phase of ischemic stroke tends to occur less often in patients with atherosclerosis than in patients without atherosclerosis in the large cerebral arteries. This finding lends support to the hypothesis that vessel wall elasticity is a necessary contributing factor in the occurrence of headache during acute ischemic stroke.

GLOSSARY

aRR=
adjusted risk ratio;
ASPECTS=
Alberta Stroke Program Early CT Score;
CBS=
clot burden score;
CBV=
cerebral blood volume;
CI=
confidence interval;
CTA=
CT angiography;
CTP=
CT perfusion;
DUST=
Dutch Acute Stroke Study;
ICA=
internal carotid artery;
LUMC=
Leiden University Medical Center;
mRS=
modified Rankin Scale;
MTT=
mean transit time;
NCCT=
noncontrast CT;
NIHSS=
NIH Stroke Scale;
RR=
risk ratio;
SDs=
spreading depolarizations

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • ↵* These authors contributed equally to this work.

  • Supplemental data at Neurology.org

  • Received January 26, 2016.
  • Accepted in final form June 1, 2016.
  • © 2016 American Academy of Neurology
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