BOLD cerebrovascular reactivity as a novel marker for crossed cerebellar diaschisis
Abstract
Objective
To study blood oxygen level–dependent cerebrovascular reactivity (BOLD-CVR) as a surrogate imaging marker for crossed cerebellar diaschisis (CCD).
Methods
Twenty-five participants with symptomatic unilateral cerebrovascular steno-occlusive disease underwent a BOLD-CVR and an acetazolamide challenged (15O)-H2O-PET study. CCD and cerebellar asymmetry index were determined from PET and compared to BOLD-CVR quantitative values. Neurologic status at admission and outcome after 3 months were determined with NIH Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores.
Results
For both the BOLD-CVR and PET examination, a significant cerebellar asymmetry index was found for participants exhibiting CCD (CCD+ vs CCD−: for BOLD-CVR 13.11 ± 9.46 vs 1.52 ± 4.97, p < 0.001; and for PET 7.31 ± 2.75 vs 1.68 ± 2.98, p < 0.001). The area under the curve for BOLD-CVR was 0.89 (95% confidence interval: 0.75–1.0) with 0.91 sensitivity and 0.81 specificity to detect CCD. Participants exhibiting CCD were in poorer clinical condition at baseline (CCD+ vs CCD−: NIHSS 7 vs 1, p = 0.003; mRS 3 vs 1, p = 0.001) and after 3-month follow-up (NIHSS 2 vs 0, p = 0.02; mRS 1 vs 0, p = 0.04). Worse performance on both scores showed an agreement with a larger BOLD-CVR cerebellar asymmetry index. This was not found for PET.
Conclusions
BOLD-CVR demonstrates similar sensitivity to detect CCD as compared to (15O)-H2O-PET in patients with symptomatic unilateral cerebrovascular steno-occlusive disease. Furthermore, participants exhibiting CCD had a poorer baseline neurologic performance and neurologic outcome at 3 months.
Classification of evidence
This study provides Class II evidence that BOLD-CVR identifies CCD in patients with symptomatic unilateral cerebrovascular steno-occlusive disease.
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Publication history
Received by Neurology March 1, 2018. Accepted in final form July 2, 2018.
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Information & Authors
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Copyright
© 2018 American Academy of Neurology.
Publication History
Received: March 1, 2018
Accepted: July 2, 2018
Published online: September 5, 2018
Published in print: October 2, 2018
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Study Funding
This work was funded by 2 personal grants obtained by Dr. Jorn Fierstra (Zurich University Forschungskredit; Postdoc 2016, FK-16-040 & Swiss Cancer League, KFS-3975-08-2016-R).
Authors
Author Contributions
Dr. Sebök: study concept and design, acquisition of data, analysis and interpretation, constructed the manuscript. Dr. van Niftrik: patient selection, study concept and design, acquisition of data, analysis and interpretation, constructed the manuscript. Dr. Piccirelli: acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. Dr. Bozinov: patient selection, critical revision of the manuscript for important intellectual content, study supervision. Prof. Wegener: critical revision of the manuscript for important intellectual content. Dr. Esposito: critical revision of the manuscript for important intellectual content. Dr. Pangalu: analysis and interpretation, critical revision of the manuscript for important intellectual content. Prof. Valavanis: critical revision of the manuscript for important intellectual content. Prof. Buck: acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. Prof. Luft: critical revision of the manuscript for important intellectual content. Prof. Regli: patient selection, critical revision of the manuscript for important intellectual content, study supervision. Dr. Fierstra: patient selection, study concept and design, acquisition of data, analysis and interpretation, study supervision.
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We kindly thank Drs. Reidler and Kunz for their insightful comments regarding our paper.1 The main objective was to study BOLD-CVR for CCD detection. In this regard, worse clinical outcome in the CCD(+) group should indeed be interpreted with caution. Ideally, this association needs to be further investigated in a uniform stroke cohort with sequential follow-up studies.
We deliberately did not comment on supratentorial stroke volume, since it is an inexact measurement and does not say anything about the infarct location.2 Besides, the concept that stroke volume is highly associated with presence of CCD in the acute phase remains debatable, as the studies mentioned in the readers’ comment appeared to be in disagreement.3,4 Nevertheless, we agree that stroke location would be a better variable for an adjusted analysis.
The statement made by Drs. Reidler and Kunz about "inferior cerebrovascular response indicating more severe supratentorial lesions" is, however, erroneous. We have only shown the presence of more impaired supratentorial BOLD-CVR in the CCD(+) group. This finding has led us to believe that hemodynamic alterations may also cause CCD rather than a functional disruption alone. In general, BOLD imaging enables investigations on resting-state functional connectivity and the influence of CCD-induced altered metabolism in stroke patients.5
References
Footnote
For disclosures, please contact the editorial office at [email protected].
We read with great interest the article by Sebök et al. on the detection of crossed cerebellar diaschisis (CCD) in subacute and chronic stroke using BOLD-MRI. [1] They observed that patients with signs of CCD had poorer neurologic function at baseline and at 3 months. However, as adjusted analysis is lacking, it remains unclear whether CCD was the cause or consequence of poor outcomes.
The phenomenon of CCD, especially in the acute phase, is highly associated with large-volume supratentorial stroke. [2,3] Acute CCD had no independent impact on outcome and may be an epiphenomenon of large-volume strokes. [2] Correlations of chronic CCD with worse outcome have been reported, yet adjustments were not made for confounders. [4,5] In the current study, inferior cerebrovascular response indicated more severe supratentorial lesions in the CCD+ group, yet lesion volumes were not specified. [1] As lesion volume and distribution affect outcome, group comparisons should be interpreted with caution concerning a CCD-outcome relationship. The final infarct size and location would provide additional insight on this matter.
Interestingly, CCD has been linked to BOLD signal change, a measure of neuronal metabolism and activity. This is encouraging for future studies relating resting state functional connectivity and CCD status.
For disclosures, please contact the editorial office at [email protected].