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ARTICLES: R. Delgado-Mederos, M. Ribo, A. Rovira, M. Rubiera, J. Munuera, E. Santamarina, P. Delgado, O. Maisterra, J. Alvarez-Sabin, and C. A. Molina Prognostic significance of blood pressure variability after thrombolysis in acute stroke Neurology 2008; 71: 552-558 [Abstract] [Full text] [PDF]

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Reply from the Author/ ONLINE ONLY CORRESPONDENCE

Raquel Delgado-Mederos, M.D., PhD   (5 June 2009)

Prognostic significance of blood pressure variability after thrombolysis in acute stroke

Archit C. Bhatt MD,MPH, Muhammad U. Farooq, MD   (21 November 2008)

Prognostic significance of blood pressure variability after thrombolysis in acute stroke

Marek Sykora, Jennifer Diedler, and Thorsten Steiner   (15 August 2008)

Reply from the authors

Raquel Delgado-Mederos, Carlos A. Molina   (15 August 2008)

Reply from the Author/ ONLINE ONLY CORRESPONDENCE 5 June 2009
Raquel Delgado-Mederos, M.D., PhD Barcelona, Spain. Send Correspondence to journal: Re: Reply from the Author/ ONLINE ONLY CORRESPONDENCE 3706rdm{at}comb.cat Raquel Delgado-Mederos, M.D., PhD	We thank Dr. Bhatt et al. for their published comments on our study. [1] They point out the possible influence of initial perfusion-weighted imaging (PWI) on the association between blood pressure (BP) variability and diffusion-weighted imaging (DWI) lesion growth. We agree that a larger baseline PWI volume might have affected the prognostic value of BP variability in the nonrecanalization group. On the other hand, BP may induce changes in the volume of hypoperfusion on PWI. [2] We could hypothesize that excessive BP fluctuations may result in a more severe hemodynamic compromise in the setting of cerebral autoregulation failure and result in a larger perfusion deficit, as a possible mechanism for the increase in the conversion of the ischemic tissue into infarction. However, as they mention, the differences in PWI volume or PWI-DWI mismatch were not significant. Moreover, we showed that BP variability predicted diffusion-weighted imaging (DWI) lesion growth in nonrecanalized patients independently of possible confounders, including initial perfusion-weighted imaging (PWI) and DWI lesion volume and PWI–DWI mismatch. Randomized clinical trials will be necessary to assess the role of BP variability in the management of acute ischemic stroke. Reference 1. Bhatt AC, Farooq MU. Prognostic significance of blood pressure variability after thrombolysis in acute stroke (Correspondence) Neurology, May 2009; 72: 1793. 2. Hillis AE, Ulatowski JA, Barker PB, et al. A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke. Cerebrovasc Dis 2003;16:236-246. Disclosure: Dr. Delgado-Mederos was funded by a Spanish Society of Neurology grant and was sponsored by Sanofi-Aventis to attend the XVI European Stroke conference.
Prognostic significance of blood pressure variability after thrombolysis in acute stroke 21 November 2008
Archit C. Bhatt MD,MPH, Michigan State University, Department of Neurology and Ophthalmology 138 Service Rd., East Lansing, MI 38824, Muhammad U. Farooq, MD Send Correspondence to journal: Re: Prognostic significance of blood pressure variability after thrombolysis in acute stroke archit.bhatt{at}ht.msu.edu Archit C. Bhatt MD,MPH, et al.	Delgado-Mederos et al. consider the issue of blood pressure regulation in acute hemispheric ischemic stroke and effectively demonstrate the difference in blood pressure variability in non-recanalized patients with low and high physical morbidity. [1] The authors also show that blood pressure variability is independently associated with DWI lesion growth and clinical course. However, in non-recanalized patients, the baseline perfusion was different in both groups but not statistically significant (Table 2). It has been shown that low hemispheric perfusion demonstrated by perfusion weighted imaging correlates with the penumbra and the future infarct size. [2] While this PWI-DWI mismatch might be statistically insignificant, it is clinically relevant in this case. These patients might be inherently vulnerable and blood pressure variability might increase the infarct size. References 1. Delgado-Mederos R, Ribo M, Rovira A, et al. Prognostic significance of blood pressure variability after thrombolysis in acute stroke. Neurology 2008;71:552-558. 2. Lubya, Waracha S. Reliability of MR Perfusion-Weighted and Diffusion-Weighted Imaging Mismatch Measurement Methods. American Journal of Neuroradiology 2007;28:1674-1678. Editor’s Note: The authors of the article were offered the opportunity to respond but declined. Disclosure: The authors report no disclosures.
Prognostic significance of blood pressure variability after thrombolysis in acute stroke 15 August 2008
Marek Sykora, Dept. of Neurology, University Heidelberg Im Neuenheimer Feld 400, 69120 Heidelberg, Germany, Jennifer Diedler, and Thorsten Steiner Send Correspondence to journal: Re: Prognostic significance of blood pressure variability after thrombolysis in acute stroke mareksykora{at}yahoo.com Marek Sykora, et al.	We read the article by Delgado et al. with great interest. [1] The authors present an independent association between blood pressure (BP) variability and DWI lesion growth in ischemic stroke due to MCA occlusion. The authors hypothesize that systemic BP fluctuations may negatively influence the ischemic penumbra in non-recanalized MCA occlusions. This association was not observed in patients who recanalized after rtPA. We would like to consider several issues. In most complete MCA occlusions, insular involvement is present due to the direct supply from the main MCA trunk. Unfortunately, the authors have not recorded the insular injury. Lesions within the insular cortex are crucial in the pathogenesis of autonomic dysfunction in acute stroke including baroreflex impairment and sympathetic overdrive activation. This may result in increased BP variability. [2] Furthermore, strokes affecting the insular cortex may be more prone to growth apart from initial lesion volume. [3] In the resulting autonomic imbalance, risks include pro-inflammatory cytokine production, elevated body temperature, hyperglycemia and increased blood-brain barrier permeability. [4] It is possible that BP variability is associated with insular lesions and reflects an underlying complex autonomic impairment which may contribute to infarct size growth. Recent data showed that beta blocker use was associated with less severe stroke implying that modulation of stroke-related autonomic dysfunction with beta blockers may reduce stroke size. [5] We agree that increased BP variability in MCA occlusions with insular involvement may influence the stroke growth. However, other mechanisms should be considered. In addition, the issue of what should be considered causal and what can be considered an association remains unclear. References 1. Delgado-Mederos R, Ribo M, Rovira A, et al. Prognostic significance of blood pressure variability after thrombolysis in acute stroke. Neurology. 2008 01.wnl.0000318294.36223.69v1 (e-Pub Ahead of print) 2. Sykora M, Diedler J, Rupp A, Turcani P, Steiner T. Impaired baroreceptor reflex sensitivity in acute stroke is associated with insular involvement, but not with carotid atherosclerosis. Stroke(in press). 3. Ay H, Arsava EM, Koroshetz WJ, Sorensen AG. Middle cerebral artery infarcts encompassing the insula are more prone to growth. Stroke 2008;39:373-378. 4. Emsley HC, Smith CJ, Tyrrell PJ, Hopkins SJ. Inflammation in acute ischemic stroke and its relevance to stroke critical care. Neurocrit Care. December 18 2007 (e-Pub Ahead of Print). 5. Laowattana S, Oppenheimer SM. Protective effects of beta-blockers in cerebrovascular disease. Neurology 2007;68:509-514. Disclosures: The authors report no disclosures
Reply from the authors 15 August 2008
Raquel Delgado-Mederos, Neurovascular Unit. Department of Neurology. Hospital Vall d´Hebron-Barcelona Passeig Vall d´Hebron 119-129 b08035 Barcelona, Spain, Carlos A. Molina Send Correspondence to journal: Re: Reply from the authors 3706rdm{at}comb.es Raquel Delgado-Mederos, et al.	We thank Dr. Sykora et al. for their interest on our recent article evaluating the prognostic relevance of blood pressure (BP) variability on diffusion-weighted imaging (DWI) lesion growth and clinical outcome in acute stroke patients after thrombolysis. [1] They consider the role of insular cortex infarction and abnormal autonomic activity in the pathophysiology of BP variability and ischemic lesion growth. The investigation of the pathophysiological mechanisms underlying BP variability in acute stroke was beyond the scope of this study. Our goal was to explore the impact of BP variability on ischemic lesion growth in relation to the occurrence of recanalization, not the causes of BP variability in acute stroke. The occlusion of a cerebral artery and its course is considered the first link in the pathogenic chain of BP changes. [6] Various pathophysiological mechanisms have been proposed to explain this phenomenon, including central autonomic dysautoregulation secondary to insular cortex damage after middle cerebral artery (MCA) territory stroke. [7] The insula is particularly vulnerable to ischemia after M1 or M2 MCA occlusion due to the lack of pial collateral supply and has been associated with larger infarct size. [8] Unfortunately, we do not have information on the presence and extent of insular involvement in our patients. Because all patients had a documented MCA occlusion, we expect insular ischemia to be initially present in similar proportion in both recanalization and non-recanalization groups. Although non-recanalized patients had a slightly higher DWI volume on admission, the relationship between BP variability and DWI lesion growth was independent of baseline infarct size. However, we could hypothesize that the impact of BP fluctuations on DWI-lesion growth might be affected by an increased insular damage in the setting of a persisting MCA occlusion, resulting in more profound and lasting hemodynamic instability. The non-recanalization group had higher BP variability compared to the recanalization group. We agree with Sykora and colleagues that there may be additional dysautonomic-related mechanisms secondary to insula infarction contributing to infarct growth. Whether acute BP variability is associated with increased infarct progression itself or is simply a marker of a more complex catecholamine-based dysfunction is still unclear. References 6. Mattle HP, Kappeler L, Arnold M, et al. Blood pressure and vessel recanalization in the first hours after ischemic stroke. Stroke 2005;36:264–268. 7. Meyer S, Strittmatter M, Fischer C, Georg T, Schmitz B. Lateralization in autonomic dysfunction in ischemic stroke involving the insular cortex. Neuroreport 2004;15:357–361. 8. Fink JN, Selim MH, Kumar S, Voetsch B, Fong WC, Caplan LR. Insular cortex infarction in acute middle cerebral artery territory stroke: predictor of stroke severity and vascular lesion. Arch Neurol 2005;62:1081–1085. Disclosures: The authors report no disclosures.