Neurocrit Care (2015) 23:355–363
DOI 10.1007/s12028-014-0104-7
ORIGINAL ARTICLE
Dynamic Autoregulatory Response After Aneurysmal
Subarachnoid Hemorrhage and Its Relation to Angiographic
Vasospasm and Clinical Outcome
Johann Fontana • Julius Moratin • Gregory Ehrlich • Johann Scharf
Christel Weiß • Kirsten Schmieder • Martin Barth
Published online: 18 March 2015
Ó Springer Science+Business Media New York 2015
Abstract
Background Impaired cerebral autoregulation (CA) is
increasingly recognized to contribute to sequelae after
aneurysmal subarachnoid hemorrhage (SAH). The current
study characterizes the course of the dynamic autoregula-
tion index (ARI) during the first 8 days after SAH and its
coherence with angiographic vasospasm (VS) and clinical
outcome.
Methods Fifty-one patients with SAH were prospectively
included within 48 h after the ictus. The ARI was deter-
mined daily for each hemisphere with the thigh cuff test.
The degree of cerebral VS was evaluated based on a
baseline digital subtraction angiography (DSA) after the
ictus and a follow-up DSA on day 8. The clinical outcome
was determined by the Modified Rankin Scale (mRS), the
J. Fontana
K. Schmieder
M. Barth (&)
Department of Neurosurgery, Knappschafts-Krankenhaus
Bochum, Ruhr-University Bochum, In der Schornau 23-25,
44892 Bochum, Germany
e-mail: martin.barth@kk-bochum.de
J. Fontana
e-mail: johann.fontana@kk-bochum.de
J. Moratin
G. Ehrlich
Department of Neurosurgery, University Medicine Mannheim,
Medical Faculty Mannheim of the University of Heidelberg,
Mannheim, Germany
J. Scharf
Department of Neuroradiology, University Medicine Mannheim,
Medical Faculty Mannheim of the University of Heidelberg,
Mannheim, Germany
C. Weiß
Department of Medical Statistics, University Medicine
Mannheim, Medical Faculty Mannheim of the University of
Heidelberg, Mannheim, Germany
•
Glasgow Outcome Scale Extended (GOSE), and the
National Institute of Health Stroke Scale (NIHSS) at dis-
charge from the intensive care unit.
Results Impaired CA significantly correlated with unfa-
vorable clinical outcome scores (mRS, p = 0.0021; GOSE,
p = 0.0027; NIHSS, p = 0.0091). ARI-values of patients
with a favorable clinical outcome (mRS 0–3) showed a
significant improvement during the first 8 days (+0.1964/
day; p = 0.0148) compared to a significant decrease of
ARI-values in patients with an unfavorable clinical out-
come (–0.2976/day; p = 0.0182). The degree of CA
impairment significantly correlated with the severity of VS
in the middle cerebral artery (p = 0.0184).
Conclusions Early deterioration of CA significantly cor-
relates with unfavorable clinical outcome and severity of
angiographic vasospasm. Dynamic CA measurements
might represent an important tool in stratifying therapy
guidelines in patients after SAH.
Keywords Cerebral autoregulation

Dynamic autoregulation index

Subarachnoid hemorrhage
Cerebral vasospasm
Introduction
The ability of the brain to regulate cerebral blood flow
upon blood pressure variations has been described as
cerebral autoregulation (CA). Previous data demonstrated
an impairment of the CA after a variety of cerebral path-
ologic conditions, such as traumatic brain injury,
intracerebral hemorrhage, stroke, hyperperfusion syn-
drome, and subarachnoid hemorrhage (SAH) [1–5].
In order to quantify the degree of CA disturbance and its
time course, multiple measurement methods have been
123
356
established [6]. These methods use the analysis of spon-
taneous blood pressure variations and its effect on various
variables, such as intracranial pressure, middle cerebral
artery blood flow velocity, cerebral oxygenation, or near-
infrared spectroscopy. Another concept of quantifying the
CA is represented by external stimulus–response tests. The
bilateral thigh cuff deflation test represents one of the most
commonly applied stimulus–response tests. With this test,
the autoregulation index (ARI) is measured which is
derived from reactions of the middle cerebral artery flow
velocity to blood pressure variations induced by bilateral
thigh cuff deflations [7].
However, validity of those different CA measurements
remains unclear since previous studies demonstrated only a
very limited consistency between those methods [8–11].
This implicates that these methods are not interchangeable
when describing the actual status of CA. So far, no con-
sensus exists which measurement approach describes the
degree of CA impairment after SAH most accurately.
Furthermore, most previouslyperformed studies on CA in
SAH-patients used ambiguous variables like for example
increased flow velocities in the middle cerebral artery
determined by transcranial Doppler (TCD) or various cri-
teria for delayed cerebral ischemia to determine cerebral
vasospasm (VS) instead of using the more reliable angio-
graphic variables [12–14].
Therefore, the current study was designed to character-
ize the time course of the well-established and reliable
dynamic ARI during the first 8 days after SAH based on
standardized angiographic and clinical variables.
Materials and Methods
The study was approved by the local Research Ethics
Committee and Institutional Review Board. All consecu-
tive patients admitted with the diagnosis ‘subarachnoid
hemorrhage’ were screened for eligibility and included in
the study following consenting either by themselves or
their relatives. Inclusion criteria consisted of 1. age from 18
to 85 years, 2. initial H&H I-IV, 3. presence of a saccular
aneurysm, 4. diffuse or localized thick subarachnoid clot
on baseline CT scan, 5. onset of aSAH symptoms within
48 h. Exclusion criteria consisted of 1. nonaneurysmal
SAH, 2. onset of aSAH symptoms >48 h, 3. initial H&H
V, 4. other than saccular aneurysms, 5. history of previous
aSAH, 6. no or only thin clot on baseline CT (<20 mm
length), 7. severe concomitant disease including peripheral
artery occlusive disease. The day of aneurysm rupture was
defined as day 0.
Following computed tomography (CT) for diagnosis of
SAH, patients received a baseline digital subtraction
angiography (DSA), if possible. If patients showed a
123
Neurocrit Care (2015) 23:355–363
concomitant intracerebral hematoma, they only received
computed tomography angiography (CTA) prior to treat-
ment. Thereafter, treatment modality was determined in
consensus with the local neuroradiologist (clipping or coil-
embolization of the aneurysm).
Further, patient management was carried out according
to recommendations of the German neurosurgical associ-
ation [15], with the exception that no oral nimodipin was
administered. All patients received an invasive arterial
blood pressure monitoring. Patients were kept under nor-
movolaemia with a central venous pressure of C8 mmHg
and a urinary output C1 ml/kg/h. If clinical data suggested
presence of vasospasm, patients received a control DSA. If
not already performed, all patients received control DSA
on day 8 ± 2. If angiographic vasospasm was confirmed,
hypertensive therapy was initiated with all concomitant
standard medical and pharmacological management of
critically ill patients.
For further analysis, angiographic images were reviewed
by an experienced neuroradiologist (JS) based on the
method used in the Conscious 1 study [16]. Angiographic
vasospasm of the proximal M1 segments of the middle
cerebral artery (MCA) has been determined quantitatively
by measuring bilateral diameters of the C1 and M1 seg-
ments and expressed in percentage change from baseline
(M1 VS [%]). Then, the proximal VS (pVS) was graded as
none (vessel diameter reduction of 0–10 %), mild (vessel
diameter reduction of 11–30 %), moderate (vessel diameter
reduction of 31–70 %), and severe (vessel diameter
reduction >71 %) and termed ‘M1 VS graded’. For esti-
mation of global MCA-VS (gVS), first the vasospasm
severity of the distal MCA vessel segments was qualita-
tively determined using the same classes (none/mild/
moderate/severe) and termed ‘M2 + VS graded’. Second,
global MCA-VS was graded by the most affected section
of both, the proximal and distal MCA sections into the
same classes (none/mild/moderate/severe) and termed
‘MCA-VS graded’ (Fig. 1).
For determination of dynamic pressure autoregulation,
Aaslid’s thigh leg cuff test were performed as described in
the original publication [7]. Prior to that procedure, the
arterial CO2 has been determined to ensure normocapnia.
The thigh leg cuffs were inflated to a pressure
>200 mmHg or at least C20 mmHg above the systolic
blood pressure for 2 min followed by a rapid pressure
release. During that maneuver, bilateral blood flow veloc-
ities in the middle cerebral artery using transcranial
Doppler sonography and the invasively measured arterial
blood pressure signal was recorded. Extraction of the aut-
oregulatory indices (ARI) was performed offline using
software supplied by the manufacturer (DWL, Sipplingen,
Germany). ARI determination was done daily starting after
definitive treatment of the ruptured aneurysm until day 11
Neurocrit Care (2015) 23:355–363
Fig. 1 Illustration of VS-determination: Angiogram shows a quan-
titative vessel diameter reduction of -76.5 % in the M1-section (M1
VS [%]) in the control angiography (b) compared to the baseline
value (a). This represents by definition a severe VS-grade for the
after bleeding and was performed three times for each site
per day. This procedure has been considered as sufficient
based on the results of previous studies [8, 17–20]. Fol-
lowing exclusion of ARI-values calculated with a RR-
decrease B20 mmHg or random values caused by motion
artifacts, correlation analysis of median ARI-values has
been done with quantitative pVS-, graded pVS-, and graded
gVS-values. ARI-scores around five are considered as
physiological [21, 22].
Clinical status was evaluated daily during the acute
phase and at discharge from the intensive care unit using
the modified Rankin Score (mRS), the Glasgow Outcome
Scale Extended (GOSE), and the National Institutes of
Health Stroke Scale (NIHSS).
Statistical Analysis
Statistical analysis was done using the program Statistical
Analysis System (SAS Institute, Cary, North Carolina,
USA). Patient characteristics and clinical outcome vari-
ables are given as n (%), mean values ± standard deviation
(SD), or as min/median/max and were analyzed with the
two-tailed unpaired t test, the Fisher exact test, and the v2
test. The ARI course was analyzed by regression analysis
357
proximal vessel section (M1 VS graded). The degree of VS for the
distal M2-section is also qualified as severe (M2 + VS graded). In
this case both sections are severely affected, thus the degree of global
vessel VS is graded as severe (MCA-VS graded)
and the Cochran-Armitage trend test. A weighted Spear-
man’s ranked correlation analysis was used for correlation
analyses. Differences were considered significant when
p value was <0.05.
Results
Study Population and Clinical Outcome
From June 2009 to July 2010, 97 patients were screened for
eligibility. 46 patients (47.4 %) had to be excluded. Reasons
for exclusion were nonaneurysmal or perimesencephalic
SAH in 14 (14.4 %), traumatic SAH in 11 (11.3 %), onset
of aSAH symptoms >48 h in 9 (9.3 %), aSAH H&H V in 7
(7.2 %), presence of non-saccular aneurysm in 2 (2.1 %),
history of previous aSAH in 2 (2.1 %), and severe con-
comitant disease in 1 patient (1 %). Mean age was
55.6 ± 12.3 years, 35 patients (68.6 %) were female and
the majority were smokers (n = 31, 60.8 %). Patients
showed a significant deterioration of the clinical status from
the initial contact until hospital admission. During the post-
bleeding course, eight patients died (time to death
8.1 ± 2.9 days). However, the mean of the surviving
123
358 Neurocrit Care (2015) 23:355–363

Table 1 Patient characteristics (n = 51)

n (%) Mean (SD) p value Median Min Max

Age 55.6 (12.3) 53 29 83

Female 35 68.6
Smoker 31 60.8
Hypertension 38 74.5
Glasgow Coma Scale
Initial 11.7 (4.2) <0.05 14 3 15
Admission 9.6 (4.9) 11 3 15
Hunt & Hess
Initial 2.6 (0.8) <0.005 2 1 4
Admission 3.3 (1.2) 3 1 5
Aneurysm localization
Anterior communicating artery 21 41.2
Posterior communicating artery 10 19.6
Middle cerebral artery 10 19.6
Internal carotid artery 3 5.9
Pericallosal/choroidal artery 2 3.9
Basilar artery 4 7.8
Posterior inferior cerebellar artery 1 2
Patients with additional A. 7 13.7
Number of additional A. 11
Clip—occlusion 31 60.8
Modified Rankin Scale
Day 11 3.6 (1.9) <0.05 5 0 6
Discharge 2.7 (2.1) 2 0 6
National Institutes of Health Stroke Scale
Day 11 11.7 (11.4) <0.001 8 0 28
Discharge 4.0 (4.6) 4 0 20
Glasgow Outcome Scale Extended
Day 11 5.1 (2.7) <0.05 6 1 8
Discharge 6.1 (2.5) 7 1 8
Demographic and clinical data of 51 patients with aneurysmal SAH. Statistical analysis was performed using the unpaired two-tailed t test, the
Fisher exact test, and the v2 test. p < 0.05 was considered as significant

patients showed a significant clinical improvement during
the post-ictal period. For detailed patient characteristics see
Table 1.
ARI Determination
The ARI could be determined daily in 46 patients from
admission until day 11. Reasons for missing values were
refusal of ARI-maneuver, insufficient unilateral bone
windows, death prior to day 11 after bleeding, or due to the
absence or dysfunction of an invasive arterial blood pres-
sure monitoring. After elimination of ARI-values
calculated with a RR-decrease B20 mmHg, 387 ARI-val-
ues could be processed for further analysis. Patients were
normocapnic with a mean CO2 of 38.4 ± 4.6 mmHg prior
to ARI determination. The median ARI-values of both
hemispheres dropped initially from four on day 1 to 2.5 on
day 7 and started to recover afterward (Fig. 2a).
In order to detect a relationship between the ARI and the
clinical outcome at discharge from the intensive care unit,
the median ARI-values of the observation period were
used. Severe impairment of CA showed a significant cor-
relation with an unfavorable clinical outcome. Thus, low
mRS- and low NIHSS-values were significantly correlated
with high ARI-values (mRS: Spearman correlation index:
-0.44, p = 0.0021; NIHSS: Spearman correlation index:
-0.41, p = 0.0091) and high GOSE-values with high ARI-
values (GOSE: Spearman correlation index: 0.43,
p = 0.0027). For further analysis, the study population was
divided in two groups depending on their clinical outcome
at discharge from the intensive care unit. A mRS of 0–3
was considered as a favorable (group 1, n = 27) and a

123
Neurocrit Care (2015) 23:355–363 359

Fig. 2 a Trend of bilateral

median ARI-values during the
observational period. ARI-
values of the whole population
were relatively normal at day 1
and decreased to 2.5 at day 7
with a recovery thereafter.
b Trend of bilateral median
ARI-values after dividing the
study population in two groups
depending on the clinical
outcome. The favorable
outcome group (mRS 0–3)
showed a significant positive
trend with improvement of
values of 0.1964 per day
compared to the unfavorable
outcome group (mRS 4–6) with
a significant negative trend with
declining values of –0.2976 per
day. Cochran-Armitage Trend
Test analysis showed significant
differences in the day-to-day
analysis on day 2, 3, 5, 7, and 8

mRS of 4–6 as an unfavorable clinical outcome (group 2,
n = 19). Since eight patients of group 2 died between day
9 and 11, the observation period for further analysis was
restricted from day 1 till 8 to prevent an attrition bias.
Regression analysis showed a significant positive trend
(+0.1964/day; p = 0.0148) for group 1 starting from a
median ARI-value of 3.5 increasing to a median ARI-value
of 5 at day 8. In contrast, group 2 showed a significant
negative trend (–0.2976/day; p = 0.0182) starting from a
median ARI-value of four decreasing to a median ARI-
value of two at day 8 (Fig. 2b). The Cochran-Armitage
trend test analysis showed significant differences between
the two groups on day 2, 3, 5, 7, and 8.
similar range of vasospasm severity and likewise showed
no significant differences between hemispheres (Table 2).
For correlation analysis between severity of angio-
graphic vasospasm and median ARI-values, each
hemispheric median ARI-value was correlated with the
quantitatively measured proximal VS (M1 VS [%]), the
graded proximal VS (M1 VS graded) and the graded global
MCA-VS (MCA-VS graded). The correlation analysis
revealed significant correlations with M1 VS [%] (Spear-
man correlation index: 0.35, p = 0.0059), M1 VS graded
(Spearman correlation index: -0.39, p = 0.0023), and
MCA-VS graded (Spearman correlation index: -0.3,
p = 0.0204).

Angiographic Vasospasm
Thirty-seven patients (72.5 %) received a sufficient pair of
DSA. Control DSA has been performed 8.2 ± 0.9 days
after bleeding. The degree of the proximal MCA vaso-
spasm ranged from -82.4 % (severe vasospasm) to a
nearly unchanged vessel diameter of +9 % (no VS). There
were no significant differences between the two hemi-
spheres. The distant MCA sections, termed as ‘M2+’
according to the materials and methods sections, showed a
Discussion
The results of the present study suggest a relationship be-
tween the functional outcome, which was evaluated by
three different clinical outcome scores (mRS, NIHSS, and
GOSE), and the time course of the dynamic ARI in patients
with aneurysmal SAH during the early post-ictal period.
This finding is in line with previous reports although dif-
ferent measurement methods were used to quantify the

123
360 Neurocrit Care (2015) 23:355–363

Table 2 Hemispheric MCA vasospasm and ARI-values

Right Left p value Combined

M1 VS [%]
n 37 36
Mean -19.8 -28.6 -24.1
Standard Deviation 20.6 24.2 NS 22.9
Median -19.9 -24.9 -22.7
Min -67.6 -82.4 -82.4
Max 9 8.9 9
M1 VS graded
Median 2 2 2
Min 1 1 NS 1
Max 3 4 4
M2 + VS graded
Median 2 1 2
Min 1 1 NS 1
Max 4 4 4
MCA-VS graded
Median 2 2 2
Min 1 1 NS 1
Max 4 4 4
ARI
Median 3 3.5 3
Min 1 0 NS 0
Max 8 7 8
The mean percentual reduction of the M1-vessel diameters are shown, followed by grading into four categories (none, mild, moderate, severe).
Grading was done qualitatively for MCA sections distant from M2. Considering proximal and distal sections together, MCA-VS was graded into
the same four categories. Statistical analysis was performed using the unpaired two-tailed t test. p < 0.05 was considered as significant

degree of CA impairment [1, 23, 24]. Patients with an
unfavorable clinical course showed an early deterioration
of ARI-values at day 2 after the initial bleeding with
demonstration of a significant negative trend from day 1
until day 8 with significantly lower ARI-values compared
to the group with a favorable clinical outcome. Addition-
ally, a significant negative correlation between the degree
of angiographic vasospasm on day 8 and the median ARI
were detectable. Thus, a decline of ARI-values during the
first 5 days after SAH seems to represent an early indicator
for an imminent unfavorable clinical and radiological
course.
For a variety of diseases, a relationship has been
established between an impaired pressure autoregulation
and clinical outcome, such as traumatic brain injury,
cerebral ischemia, and obstructive carotid disease [17, 24–
29]. There are also data available which demonstrate an
impairment of CA after SAH [1, 12–14, 30–35]. Although
all studies demonstrated an impairment of the CA at a more
or less early time point, comparability between these
studies is difficult due to significant differences in the study
populations, the use of different measurement methods for
quantification of CA, and different clinical and radiological
outcome variables. Among them, the conclusion of the
most recent study claimed that addition of autoregulatory
variables to clinical and radiographic variables potentially
could identify patients at a high risk for VS and DCI [35].
However, comparability to the present study is limited
since a spontaneous fluctuation method was used, CA was
only determined from day 2 till 4, severity of VS was only
described in a dichotomized manner without differentiating
between proximal and distal VS and clinical outcome
variables were missing.
One key question arises with the choice of the mea-
surement technique for quantification of CA. Although
static and dynamic indices for quantification of the CA
show similar results, the dynamic indices seem to be more
sensitive than the static indices [36].
Among dynamic measurement techniques, stimulus–
response and spontaneous fluctuation methods can be used.
For the present study, a dynamic stimulus–response test
was chosen with an external trigger by thigh cuff deflation
which has been introduced by Aaslid in 1989 [7]. This test
has shown good reliability compared to the static indices

123
Neurocrit Care (2015) 23:355–363
[36, 37] and proofed good reproducibility under physio-
logical and pathophysiological conditions [8, 17–20].
Negative aspects of the test are its time-consuming char-
acter and the discomfort for the patient during the inflation
of the thigh cuffs with pressures of 20 mmHg or more
above the systolic arterial blood pressure (ABP) for at least
2 min. Moreover, external stimuli like the thigh cuff test
can potentially increase sympathetic activity and thereby
lead to changes in cerebral blood flow and modifications of
the upper and lower limits of CA [38]. The discomfort
during the procedure was the major reason for refusing
further participation in the present study.
Alternatively, dynamic cerebral autoregulation can also
be estimated by methods using spontaneous fluctuations of
ABP and CBF-related variables. Those fluctuations may be
analyzed using transfer function methods [39–42] or by
calculating correlation coefficients between paired obser-
vations of the ABP and the intracranial pressure (ICP), the
cerebral perfusion pressure (CPP), the mean systolic flow
velocity in the MCA or the tissue oxygen index from Near-
infrared spectroscopy [1, 13, 14, 26]. Although these
variables are continuously available and CA-analysis does
not affect patient’s comfort, these tests are known to
depend on the signal-to-noise ratio and spectral character-
istics of the input (i.e., ABP). Low signal variability and
limited spectral power in spontaneous ABP fluctuations
have been suggested to be the main reasons behind the
limited reproducibility of such dynamic cerebral autoreg-
ulation indices [8, 43] and poor model performance [44].
Sensitivity and specificity of these CA indices might
probably be improved by externally enhancing spontaneous
fluctuation of the input, which needs to be clarified in
further clinical trials [45].
Although stimulus–response and spontaneous fluctua-
tion methods seem to show similar results in detection of
an impaired CA, several ambiguities remain. Discrepant
information arises from different spontaneous fluctuation
methods as well as from correlation analyses between
spontaneous fluctuation methods and stimulus–response
methods. Thus, some authors were able to detect good
agreement between different measurement methods [46],
the majority of previous studies demonstrated only minor
correlations [8, 10, 47]. However, specificity for predicting
DCI could be enhanced by combining stimulus–response
and spontaneous fluctuation methods obtained from the
same patient, although the time courses of the two indices
showed only a weak correlation [9].
Due to those ambiguities between the time course and
the lack of adequate data for characterization of the dif-
ferent CA indices after SAH, the designation of a method
as ‘‘gold-standard’’ for the quantification of CA impairment
after SAH is currently not possible. Despite those mis-
matches, most studies seem to support the hypothesis that
361
an impaired cerebral CA is related to an unfavorable out-
come in respect to DCI, clinical scores or angiographic
vasospasm as demonstrated in the current study. Our
finding that an impaired CA seems to predict an imminent
clinical deterioration which is in line with the results of a
previously cited study [1], but certainly needs further
confirmation using different approaches in CA-
determination.
Three different outcome scores (mRS, GOSE, NIHSS)
were used for evaluation of the clinical outcome instead of
the in earlier studies proposed criteria for delayed cerebral
ischemia (DCI) [48]. In particular, the mRS consists of
well-defined and easy to understand grades that describe
the whole range of global disability which makes it a valid
and easy tool to describe clinical outcome [49]. In order to
exclude potential confounders, such as medical and car-
diopulmonary complications or sepsis during the acute
phase, we combined the more general outcome scores
(mRS, GOSE) with a very specific neurological outcome
score (NIHSS) and chose the latest possible time point for
examination which was the discharge from intensive care
unit. It must be noted that those scales were used at a very
early time point and must not be misinterpreted as the long-
term outcome of this patient collective. We did not use the
criteria for ‘DCI’ as proposed by Vergouwen [48] since
those criteria are partly very subjective. Especially in situ-
ations when several pathophysiological developments
occur isolated or in combination, no clear criteria exist to
exclude the presence or absence of DCI. Furthermore, it is
very difficult to evaluate the proposed criteria for DCI in
comatose or sedated patients.
In the present patient cohort, a positive correlation could
be demonstrated between the degree of impaired CA and
the degree of VS. Similar to the definition of DCI, the term
vasospasms has been used in the literature in a variable and
ambiguous way, like for example as clinically relevant
vasospasm, TCD-defined, or radiographically defined VS.
We decided to use the angiographic degree of vessel nar-
rowing for VS-determination in order to create objective
and reproducible data. To further enhance reproducibility
and comparability of our data, we used an evaluation
technique similar to the technique which was used in the
CONSCIOUS1-study [16]. In contrast to previous studies
[50], we were able to demonstrate a correlation between
the degree of angiographic vasospasm and an unfavorable
clinical outcome as well as the degree of CA impairment.
Conclusion
This observational study demonstrates that ARI determi-
nation might serve as a powerful diagnostic tool for early
123
362
detection of an imminent clinical and radiological deteri-
oration. However, this relationship needs to be further
characterized by additional clinical trials with larger
numbers of patients. Additionally, further studies using
different measurement methods of CA are indispensable to
verify these results and to determine the most specific CA
index for patients with SAH.
Conflict of interest The authors declare that they have no conflict
of interest.
Funding None.
References
1. Budohoski KP, Czosnyka M, Smielewski P, et al. Impairment of
cerebral autoregulation predicts delayed cerebral ischemia after
subarachnoid hemorrhage: a prospective observational study.
Stroke. 2012;43:3230–7.
2. Diedler J, Sykora M, Rupp A, et al. Impaired cerebral vasomotor
activity in spontaneous intracerebral hemorrhage. Stroke.
2009;40:815–9.
3. Saeed NP, Panerai RB, Horsfield MA, Robinson TG. Does stroke
subtype and measurement technique influence estimation of
cerebral autoregulation in acute ischaemic stroke? Cerebrovasc
Dis. 2013;35:257–61.
4. Buczek J, Karliński M, Kobayashi A, Białek P, Członkowska A.
Hyperperfusion syndrome after carotid endarterectomy and car-
otid stenting. Cerebrovasc Dis. 2013;35:531–7.
5. Atkins ER, Brodie FG, Rafelt SE, Panerai RB, Robinson TG.
Dynamic cerebral autoregulation is compromised acutely fol-
lowing mild ischaemic stroke but not transient ischaemic attack.
Cerebrovasc Dis. 2010;29:228–35.
6. Abstracts of the 18th Meeting of the European Society of Neur-
osonology and Cerebral Hemodynamics (ESNCH) and the 3rd
Meeting of the Cerebral Autoregulation Network (CAR-
Net).Cerebrovasc Dis. 2013;35 Suppl 2:1–77. May 24–27, 2013
Porto, Portugal.
7. Aaslid R, Lindegaard KF, Sorteberg W, Nornes H. Cerebral
autoregulation dynamics in humans. Stroke. 1989;20:45–52.
8. Barth M, Woitzik J, Weiss C, et al. Correlation of clinical out-
come with pressure-, oxygen-, and flow-related indices of
cerebrovascular reactivity in patients following aneurysmal SAH.
Neurocrit Care. 2010;12:234–43.
9. Budohoski KP, Czosnyka M, Smielewski P, et al. Cerebral
autoregulation after subarachnoid hemorrhage: comparison of
three methods. J Cereb Blood Flow Metab. 2013;33:449–56.
10. Christ M, Noack F, Schroeder T, et al. Continuous cerebral
autoregulation monitoring by improved cross-correlation ana-
lysis: comparison with the cuff deflation test. Intensive Care Med.
2007;33:246–54 Epub 2006 Dec 2.
11. Tzeng YC, Ainslie PN, Cooke WH, et al. Assessment of cerebral
autoregulation: the quandary of quantification. Am J Physiol
Heart Circ Physiol. 2012;303:H658–71.
12. Jaeger M, Schuhmann MU, Soehle M, Nagel C, Meixensberger J.
Continuous monitoring of cerebrovascular autoregulation after
subarachnoid hemorrhage by brain tissue oxygen pressure reac-
tivity and its relation to delayed cerebral infarction. Stroke.
2007;38:981–6.
13. Jaeger M, Soehle M, Schuhmann MU, Meixensberger J. Clinical
significance of impaired cerebrovascular autoregulation after
123
Neurocrit Care (2015) 23:355–363
severe aneurysmal subarachnoid hemorrhage. Stroke.
2012;43:2097–101.
14. Soehle M, Czosnyka M, Pickard JD, Kirkpatrick PJ. Continuous
assessment of cerebral autoregulation in subarachnoid hemor-
rhage. Anesth Analg 2004;98:1133–9, table of contents.
15. Raabe A, Beck J, Berkefeld J, et al. Recommendations for the
management of patients with aneurysmal subarachnoid hemor-
rhage. Zentralbl Neurochir. 2005;66:79–91.
16. Macdonald RL, Kassell NF, Mayer S, et al. Clazosentan to
overcome neurological ischemia and infarction occurring after
subarachnoid hemorrhage (CONSCIOUS-1): randomized, dou-
ble-blind, placebo-controlled phase 2 dose-finding trial. Stroke.
2008;39:3015–21.
17. Hlatky R, Furuya Y, Valadka AB, et al. Dynamic autoregulatory
response after severe head injury. J Neurosurg. 2002;97:1054–61.
18. Mahony PJ, Panerai RB, Deverson ST, Hayes PD, Evans DH.
Assessment of the thigh cuff technique for measurement of
dynamic cerebral autoregulation. Stroke. 2000;31:476–80.
19. Park CW, Sturzenegger M, Douville CM, Aaslid R, Newell DW.
Autoregulatory response and CO2 reactivity of the basilar artery.
Stroke. 2003;34:34–9.
20. Vavilala MS, Newell DW, Junger E, et al. Dynamic cerebral
autoregulation in healthy adolescents. Acta Anaesthesiol Scand.
2002;46:393–7.
21. Jünger EC, Newell DW, Grant GA, et al. Cerebral autoregulation
following minor head injury. J Neurosurg. 1997;86:425–32.
22. Engelhard K, Werner C, Mollenberg O, Kochs E. Effects of
remifentanil/propofol in comparison with isoflurane on dynamic
cerebrovascular autoregulation in humans. Acta Anesthesiol
Scand. 2001;45:971–6.
23. Barth M, Moratin B, Dostal M, Kalenka A, Scharf J, Schmieder
K. Correlation of clinical outcome and angiographic vasospasm
with the dynamic autoregulatory response after aneurysmal sub-
arachnoid hemorrhage. Acta Neurochir Suppl. 2012;114:157–60.
24. Jaeger M, Schuhmann MU, Soehle M, Meixensberger J. Con-
tinuous assessment of cerebrovascular autoregulation after
traumatic brain injury using brain tissue oxygen pressure reac-
tivity. Crit Care Med. 2006;34:1783–8.
25. Czosnyka M, Smielewski P, Kirkpatrick P, Laing RJ, Menon D,
Pickard JD. Continuous assessment of the cerebral vasomotor reac-
tivity in head injury. Neurosurgery 1997;41:11–7; discussion 7–9.
26. Czosnyka M, Smielewski P, Kirkpatrick P, Menon DK, Pickard
JD. Monitoring of cerebral autoregulation in head-injured
patients. Stroke. 1996;27:1829–34.
27. Dohmen C, Bosche B, Graf R, et al. Identification and clinical
impact of impaired cerebrovascular autoregulation in patients
with malignant middle cerebral artery infarction. Stroke.
2007;38:56–61.
28. Reinhard M, Gerds TA, Grabiak D, et al. Cerebral dysautoregu-
lation and the risk of ischemic events in occlusive carotid artery
disease. J Neurol. 2008;255:1182–9.
29. Schmieder K, Moller F, Engelhardt M, et al. Dynamic cerebral
autoregulation in patients with ruptured and unruptured aneu-
rysms after induction of general anesthesia. Zentralbl Neurochir.
2006;67:81–7.
30. Frontera JA, Rundek T, Schmidt JM, et al. Cerebrovascular
reactivity and vasospasm after subarachnoid hemorrhage: a pilot
study. Neurology. 2006;66:727–9.
31. Lam JM, Smielewski P, Czosnyka M, Pickard JD, Kirkpatrick PJ.
Predicting delayed ischemic deficits after aneurysmal subarach-
noid hemorrhage using a transient hyperemic response test of
cerebral autoregulation. Neurosurgery. 2000;47:819–25.
32. Lang EW, Diehl RR, Mehdorn HM. Cerebral autoregulation
testing after aneurysmal subarachnoid hemorrhage: the phase
relationship between arterial blood pressure and cerebral blood
flow velocity. Crit Care Med. 2001;29:158–63.
Neurocrit Care (2015) 23:355–363
33. Ratsep T, Asser T. Cerebral hemodynamic impairment after
aneurysmal subarachnoid hemorrhage as evaluated using trans-
cranial doppler ultrasonography: relationship to delayed cerebral
ischemia and clinical outcome. J Neurosurg. 2001;95:393–401.
34. Voldby B, Enevoldsen EM, Jensen FT. Cerebrovascular reac-
tivity in patients with ruptured intracranial aneurysms.
J Neurosurg. 1985;62:59–67.
35. Otite F, Mink S, Tan CO, et al. Impaired cerebral autoregulation
is associated with vasospasm and delayed cerebral ischemia in
subarachnoid hemorrhage. Stroke. 2014;45:677–82.
36. Tiecks FP, Lam AM, Aaslid R, Newell DW. Comparison of static
and dynamic cerebral autoregulation measurements. Stroke.
1995;26:1014–9.
37. Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell
DW. Dynamic and static cerebral autoregulation during isoflu-
rane, desflurane, and propofol anesthesia. Anesthesiology.
1995;83:66–76.
38. van Lieshout JJ, Secher NH. Point:counterpoint: sympathetic
activity does/does not influence cerebral blood flow. Point:
sympathetic activity does influence cerebral blood flow. J Appl
Physiol. 2008;105:1364–6.
39. Diehl RR, Linden D, Lucke D, Berlit P. Phase relationship
between cerebral blood flow velocity and blood pressure. Clinical
test of autoregulation. Stroke. 1995;26:1801–4.
40. Steinmeier R, Bauhuf C, Hubner U, et al. Slow rhythmic oscil-
lations of blood pressure, intracranial pressure, microcirculation,
and cerebral oxygenation. Dynamic interrelation and time course
in humans. Stroke. 1996;27:2236–43.
41. Steinmeier R, Hofmann RP, Bauhuf C, Hubner U, Fahlbusch R.
Continuous cerebral autoregulation monitoring by cross-correla-
tion analysis. J Neurotrauma. 2002;19:1127–38.
42. Périard D, Rey MA, Casagrande D, Vesin JM, Carrera E, Hayoz
D. The effect of valsartan versus non-RAAS treatment on
363
autoregulation of cerebral blood flow. Cerebrovasc Dis.
2012;34:78–85.
43. Brodie FG, Atkins ER, Robinson TG, Panerai RB. Reliability of
dynamic cerebral autoregulation measurement using spontaneous
fluctuations in blood pressure. Clin sci (Lond). 2009;116:513–20.
44. Ramos EG, Simpson DM, Panerai RB, Nadal J, Lopes JM, Evans
DH. Objective selection of signals for assessment of cerebral
blood flow autoregulation in neonates. Physiol Meas.
2006;27:35–49.
45. Katsogridakis E, Bush G, Fan L, et al. Detection of impaired
cerebral autoregulation improves by increasing arterial blood
pressure variability. J Cereb Blood Flow Metab. 2013;33:519–23.
46. Czosnyka M, Smielewski P, Lavinio A, Pickard JD, Panerai RB.
An assessment of dynamic autoregulation from spontaneous
fluctuations of cerebral blood flow velocity: a comparison of two
models, index of autoregulation and mean flow index. Anaesth
Analg. 2008;106:234–9.
47. Piechnik SK, Yang X, Czosnyka M, et al. The continuous
assessment of cerebrovascular reactivity: a validation of the
method in healthy volunteers. Anesth Analg. 1999;89:944–9.
48. Vergouwen MD, Vermeulen M, van Gijn J, et al. Definition of
delayed cerebral ischemia after aneurysmal subarachnoid hem-
orrhage as an outcome event in clinical trials and observational
studies: proposal of a multidisciplinary research group. Stroke.
2010;41:2391–5.
49. Banks JL, Marotta CA. Outcomes validity and reliability of the
modified Rankin scale: implications for stroke clinical trials: a
literature review and synthesis. Stroke. 2007;38:1091–6.
50. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL. Effect
of pharmaceutical treatment on vasospasm, delayed cerebral
ischemia, and clinical outcome in patients with aneurysmal
subarachnoid hemorrhage: a systematic review and meta-ana-
lysis. J Cereb Blood Flow Metab. 2011;31:1443–51.
123