Beruflich Dokumente
Kultur Dokumente
a
Department of Neurology, University of Freiburg, Germany
b
Department of Neurology, Park Klinikum, Bad Krozingen, Germany
KEYWORDS Summary Cerebral autoregulation is particularly challenged in acute ischemic stroke. In this
Cerebral review we summarize the data of our previous studies on autoregulation regarding the effect of
autoregulation; rtPA on autoregulation after stroke. A pooled analysis of two studies (45 patients) has shown a
Acute cerebral worsening of the autoregulatory index Mx between an early (rst 48 h) and late (days 57) mea-
ischemia; surement. This increase was more pronounced on affected sides than on unaffected sides. Poor
Transcranial Doppler ipsilateral Mx was associated with a greater volume of MCA infarction at a late measurement
sonography and related to poor clinical outcome. Overall, autoregulatory impairment tends to increase
mainly in large infarction and generalize to the contralateral side during the rst days after
ischemic stroke. As a limitation, transcranial Doppler sonography does not allow to detect focal
areas of dysautoregulation in smaller strokes. To better understand the temporal and spatial
dynamics of dysautoregulation in acute stroke in relation to the type and size of infarction, new
bedside hemodynamic monitoring techniques (like multi-channel near-infrared spectroscopy)
are needed.
2012 Elsevier GmbH. Open access under CC BY-NC-ND license.
Methods
Corresponding author at: Department of Neurology, Univer-
sity of Freiburg, Neurocenter, Breisacherstr. 64, D-79106 Freiburg,
Germany. This review comprises a total of 45 patients from two
E-mail address: matthias.reinhard@uniklinik-freiburg.de previous studies [4,5]. Patients were admitted with acute
(M. Reinhard). ischemic stroke in the middle cerebral artery (MCA) territory
Results
Figure 1 Cerebral autoregulation after ischemic stroke. Signicant oncrease of Mx on ipsi- and contralateral sides between the
early (rst 48 h) and late (days 57) measurement after stroke onset [7]. Separate analysis of patients with poor outcome and large
infarction (62 21% of MCA territory) [5]. Controls refer to 71 age-matched healthy persons (64 9 years).
196 M. Reinhard et al.
outcome. A separate detrimental effect of rtPA treatment days after ischemic stroke. Studies in which autoregula-
on autoregulation after stroke was not found [5]. tion in the MCA was measured once within four days of
MCA- or non-MCA-territory stroke onset found a bilateral
reduction in dynamic autoregulatory capacity independent
Discussion of infarct type and vascular risk factors [9,10]. Such changes
were not detectable for static autoregulation, leading to the
The main ndings of our studies so far is that dynamic assumption that dynamic autoregulatory measures are more
autoregulation in acute stroke detected by TCD worsens sensitive to general vascular dysfunction in acute stroke
over the rst days after stroke onset (more on affected [10]. The reason for this general impairment, which seems
than unaffected sides) and that this worsening of autoreg- to be limited to dynamic autoregulation, is not clear. Pre-
ulation associates with a larger MCA infarct size and poorer existing endothelial dysfunction may exacerbate within an
outcome. acute phase response shortly after cortical ischemic stroke
Various other studies have generally shown mild to mod- [12], when inammatory or autonomic changes addition-
erate impairment of dynamic autoregulation affecting the ally affect the cerebral vasculature. In a further study,
MCA ipsi- and contralateral to the ischemic stroke [8,9]. we found that secondary impairment of autoregulation in
Previous TCD studies on autoregulation in stroke did not the subacute stage after stroke was associated with alter-
consider the actual size of infarction [9,10]. ations in the neurovascular coupling mechanism outside the
When using TCD for measuring dynamic autoregula- infarcted area using functional magnetic resonance imaging
tion in acute ischemic stroke, two mechanisms need to [13]. This underlines the assumption of a secondary endothe-
be considered: 1. Local dysautoregulation related to the lial dysfunction leading to both impaired autoregulation and
affected stroke territory. Within the infarction core, cere- impaired neurovascular coupling. A general autoregulatory
bral autoregulation is probably severely disturbed in the dysfunction could thus potentially interfere with functional
early stages. Tissue lactate acidosis leads to local vasoparal- restitution and thus affect the clinical outcome [13].
ysis, compromising the autoregulatory mechanism in both We have indeed found an association between impaired
the ischemic core and the direct periinfarct region [11]. Such autoregulation after ischemic stroke and clinical outcome.
a presumed early impairment is, however, not univocally The association between autoregulation and outcome might,
detected by the index Mx in larger strokes in our studies. The however, be linked via the size of MCA infarction. How-
Mx value rather indicated a secondary decline in autoregu- ever, the infarction size in the current cohort of patients
lation after reperfusion mainly in large infarcts. This means was mainly derived from demarcated lesions visualized by
that either autoregulation in the area of large infarction follow-up imaging. Dysautoregulation could still have con-
becomes worse, or that additional areas within the territory tributed to the nal size of infarction.
become involved. Such a pattern of secondary deterioration A main methodological problem of the studies reported
was also reported in a study using invasive autoregulation here is the low spatial resolution of TCD. A small infarct
monitoring of malignant MCA stroke [11]. A vicious cycle of within the MCA territory could also lead to severe focal
reperfusion, producing inammatory vasotoxic substances, dysautoregulation without a clear autoregulatory impair-
dysautoregulation, edema and further ischemia has been ment in the main stem of the MCA. To better understand
discussed [5,11]. Whether such a mechanism also exists for the spatial characteristics of impaired autoregulation in
smaller MCA infarctions cannot be determined by transcra- ischemic stroke (focal versus global dysautoregulation) we
nial Doppler sonography. However, an impairment within need new bedside hemodynamic monitoring techniques
large areas of the MCA territory seems unlikely in this situ- with a high spatial resolution. One promising but tech-
ation, because TCD recordings in the MCA should then have nically demanding method is multi-channel near-infrared
produced clearly pathological results. spectroscopy. A rst example of noninvasive autoregula-
There seems to occur a milder and more global autoreg- tion mapping with this technology in a patient with severe
ulatory dysfunction which probably evolves during the rst carotid stenosis is illustrated in Fig. 3 [14].
Figure 3 Spatially resolved autoregulation mapping with multi-channel near infrared spectroscopy. Example of a 68-year-old
patient with near occlusion of left internal carotid artery [14]. Dynamic autoregulation is graded from the phase shift between
respiratory-induced 0.1 Hz oscillations in ABP and oxy-hemoglobin. Autoregulation is impaired on the side ipsilateral to the stenosis
and this is most prominent in the borderzone between middle cerebal and anterior cerebral artery.
Cerebral autoregulation in acute ischemic stroke 197