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SHORT REPORT

Tissue at risk concept for endovascular treatment of severe
vasospasm after aneurysmal subarachnoid haemorrhage
J Beck, A Raabe, H Lanfermann, V Seifert, S Weidauer
...............................................................................................................................
J Neurol Neurosurg Psychiatry 2004;75:1779–1781. doi: 10.1136/jnnp.2004.036921

Objective: To report a case of severe vasospasm after
subarachnoid haemorrhage (SAH) where ‘‘tissue at risk’’
was identified by magnetic resonance imaging (MRI), and to
demonstrate the haemodynamic consequences with either
resolution of the perfusion–diffusion mismatch by balloon
angioplasty or evolution of an infarct.
Methods: A 45 year old women with SAH underwent
surgical treatment of a ruptured middle cerebral artery
(MCA) aneurysm. On day 3 she became obtunded and
developed a right hemiparesis. Diffusion weighted (DWI)
and perfusion weighted (PWI) imaging were done before
and after transluminal balloon angioplasty (TBA) of multifocal proximal vasospasm.
Results: The initial MRI revealed no DWI lesion but PWI
showed a severe perfusion deficit of 6.7 to 16.4 seconds in
the complete left MCA territory. Digital subtraction angiography confirmed severe segmental narrowing of left C1 and
M1. The spastic segments were successfully dilated by TBA.
Follow up MRI showed that the PWI2DWI mismatch resolved
in the anterior and middle MCA territory with no tissue
infarction, whereas in the terminal dorsal MCA territory a
severe mismatch remained and cerebral infarction evolved.
Conclusions: PWI/DWI can identify tissue at risk for infarction in severe vasospasm following SAH. This may allow
selection of patients for angioplasty and the monitoring of
treatment effects.

D

espite much effort and progress the early diagnosis of
cerebral ischaemia from vasospasm after subarachnoid
haemorrhage remains a serious obstacle in the treatment of patients with ruptured intracranial aneurysms.1 With
a combination of perfusion weighted (PWI) and diffusion
weighted (DWI) imaging it is possible to detect areas with a
perfusion–diffusion mismatch—that is, areas of misery
perfusion where the tissue is ischaemic but not yet infarcted.2
This ‘‘tissue at risk’’ concept derives from studies of
ischaemic stroke, grossly identifies the ischaemic penumbra,
and has proved to be a valuable tool for selecting patients for
intravenous or intra-arterial thrombolysis.3
We hypothesise that the tissue at risk concept for cerebral
infarction also applies to patients with vasospasm after
subarachnoid haemorrhage and we present a case where a
PWI–DWI mismatch was identified. Segmental arterial
narrowing was thought to have been the cause for misery
perfusion and was treated with transluminal balloon
angioplasty (TBA). Follow up magnetic resonance imaging
(MRI) revealed areas of resolution of the mismatch with no
infarction and areas with remaining mismatch where an
infarct developed. This case indicates that the tissue at risk
concept may also apply to misery perfusion caused by
vasospasm after subarachnoid haemorrhage.

CASE REPORT
A 45 year old women was admitted to the department of
neurosurgery of the University Hospital Frankfurt, Germany,
with subarachnoid haemorrhage and a small intracerebral
haemorrhage from a ruptured left middle cerebral artery
(MCA). Clinically she was graded as Hunt and Hess grade 3.
Owing to the aneurysm morphology, endovascular coiling
was not undertaken and the aneurysm was clipped 23 hours
after the ictus. The initial postoperative period was uneventful until she became obtunded and developed a right
hemiparesis on day 3. MRI with PWI and DWI was carried
out. DWI showed no hyperintense signal changes (fig 1,
panels A and B). Measurement of time to peak (TTP), mean
transit time (MTT), relative regional cerebral blood volume
(rrCBV), and relative regional cerebral blood flow (rrCBF)
showed a severe perfusion deficit in the complete left MCA
territory (fig 1C). On the affected left side, rrCBF was reduced
to 0.47 (frontal MCA territory) and to 0.32 (dorsal MCA
territory) compared with the contralateral side. Relative
regional CBV was 0.69 and 0.30 on the left side compared
with the right in the frontal and dorsal MCA territories,
respectively. Digital subtraction angiography was undertaken
immediately after MRI and confirmed severe proximal focal
vasospasm in the left C1 and M1 segments (fig 1D).
Following TBA, which was done two hours after MRI, there
was impressive widening of the C1 and M1 segments (fig 2D),
and follow up MRI 70 hours after TBA showed resolution of
PWI–DWI mismatch with exception of the terminal dorsal
MCA territory (fig 2C). In this area there were hyperintense
signal changes in DWI, indicating tissue infarction (fig 2B).
In the anterior and middle MCA territory there were,
however, no signs of infarction and PWI showed nearly
complete normalisation of the initial perfusion deficit, with
only 1.2 to 1.8 seconds delay compared with the contralateral
regions of interest. Likewise the rrCBF (rrCBV) increased to
0.80 (0.84) in the left frontal but only to 0.39 (0.40) in the
terminal dorsal MCA territory.
During the remaining hospital stay the patient recovered
and was discharged into a rehabilitation centre. At follow up
examination six months after the ictus the patient was
graded 2 on the modified Rankin scale.

DISCUSSION
In this case of severe vasospasm after subarachnoid
haemorrhage, MRI identified a large area—that is, the
complete left MCA territory—with a PWI–DWI mismatch.
There was a delay of MTT of 6.7 to 16.4 seconds caused by
vasospastic narrowing of the ipsilateral proximal M1 and C1
Abbreviations: DWI, diffusion weighted imaging; MCA, middle
cerebral artery; MTT, mean transit time; PWI, perfusion weighted
imaging; rrCBF, relative regional cerebral blood flow; rrCBV, relative
regional cerebral blood volume; SAH, subarachnoid haemorrhage;
TBA, transluminal balloon angioplasty; TCD, transcranial Doppler; TTP,
time to peak

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1780

Beck, Raabe, Lanfermann, et al

Figure 1 T2 (A) and diffusion weighted (B) images before transluminal balloon angioplasty showed no structural abnormality due to ischaemic
infarction. However, on perfusion weighted imaging (C), the MTT (TTP) delay, as quantified between regions of interest (ROI) 1 and 2, was 6.7 seconds
(5.9), and 16.4 seconds (16.1) between ROI 3 and 4. Digital subtraction angiography (D), carried out two hours later, revealed severe segmental
vasospasm of the C1 and M1 segments.

segments, as detected by digital subtraction angiography. The
stenoses could be successfully dilated by TBA, the patient
recovered, and follow up MRI examination 70 hours after
TBA showed that angioplasty not only had lasting haemodynamic effects but also prevented infarction of the complete
MCA territory. Moreover the MCA territories with normalisation of the perfusion deficits did not undergo infarction, in
contrast to the small area where the delay of MTT was
reduced though still as long as 11.4 seconds compared with
the contralateral side.
MRI including DWI and PWI sequences is very promising
in subarachnoid haemorrhage to assess ischaemia and brain
damage.4–8 Review of the literature yielded one report of the
use of PWI/DWI to select for angioplasty in severe vasospasm.
The investigators assessed qualitatively a large perfusion
deficit in the setting of a small lesion on DWI, and this area of
oligaemia was reversed by angioplasty combined with a
papaverine infusion, resulting in prevention of infarction and
a good outcome.9 In the current study we additionally tried to
quantify the perfusion deficit as well as the treatment effects
of TBA.
The diagnosis and pathophysiology of cerebral ischaemia
caused by vasospasm in subarachnoid haemorrhage is
challenging.1 Angiographic measurement of vessel diameter detects anatomical narrowing of cerebral arteries in

up to 70% which may be asymptomatic.10 Transcranial
Doppler (TCD) is routinely used to detect vasospasm but
has a very low predictive value, and even in patients who
develop delayed neurological deficits TCD indices do not
reflect cerebral perfusion.1 11 In our patient, TCD was not
diagnostic for vasospasm and correlated with neither the
clinical nor the radiological findings. Measurement of rCBF
by a thermodilution probe is promising and yields absolute
values of CBF but may miss the territory of misery
perfusion.12
The appeal of the tissue at risk concept in vasospasm is that
it allows one to determine whether vasospasm is symptomatic—that is, that it leads to tissue ischaemia—as compared
with other regions of interest. Furthermore, with this tool
one can recognise whether the ischaemic tissue is still
salvageable, potentially widening the window of opportunity
for TBA.13 Thus the decision to institute invasive and
potentially harmful treatments such as TBA or triple-H
therapy may be based on the results of MRI.14 15 To reject
angioplasty or triple-H therapy if tissue is already infarcted
could reduce the side effects and complications by further
improving the efficacy of these treatments.16–18 Once such
measures are applied in a patient, the efficacy as well as the
possible complications can be monitored by follow up MRI
investigations.

Figure 2 T2 (A) and diffusion weighted (B) images after transluminal balloon angioplasty show small hyperintense lesions due to infarction in the
terminal dorsal middle cerebral artery (MCA) territory. Additional perfusion weighted imaging (C) 70 hours after dilatation of the left M1 and C1
segments (D) now showed normalisation of perfusion in the anterior and middle MCA territory with a reduction in the MTT (TTP) delay from 9.4 seconds
(8.8) in the initial study to 1.8 seconds (1.2) between regions of interest (ROI) 1 and 2. The exception was an area in the terminal dorsal MCA territory
which still had an MTT (TTP) delay of 11.4 seconds (10.8) as assessed between ROI 3 and 4. This area is recognised as infarcted tissue on diffusion
weighted imaging (B).

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Tissue at risk in vasospasm

In ischaemic stroke the tissue at risk concept is well
established and PWI/DWI studies are part of the clinical
routine before systemic or intra-arterial lysis.3 In acute
ischaemic stroke a perfusion deficit of more than six seconds
in the mismatch region is followed by expansion of tissue
infarction if it is not rapidly reversed.19 20 Even a less severe
perfusion deficit of 2.0 to 2.5 seconds may represent
dysfunctional and potentially salvageable tissue rather than
oligaemia with no risk for infarction.21 These thresholds may
not apply to the scenario in vasospasm after subarachnoid
haemorrhage. In contrast to embolic or thrombotic ischaemic
stroke, the development of misery perfusion is presumably
not a sudden event but rather evolves over hours or days. On
the one hand this time allows for some collateralisation to
develop; on the other hand a less severe reduction in
perfusion, if of long enough duration, can also lead to
infarction.22 In the current case of severe vasospasm we do
not know for certain whether that part of the MCA territory
with deficits of 6.7 and 9.4 seconds would have been
infarcted without TBA or not. Although it is very likely that
infarction would have occurred without TBA more research
will have to be done to clarify the thresholds for tissue
infarction in vasospasm and the sensitivity and specificity of
PWI/DWI. The best time for undertaking a PWI/DWI
investigation after subarachnoid haemorrhage, and whether
the method can detect a mismatch in clinically asymptomatic
patients, remain to be determined. A drawback of all relative
perfusion measurements in different regions of interest is
that global changes—that is, changes in both hemispheres—
may not be detected.23
Conclusions
PWI/DWI imaging could be used on a routine basis to
monitor patients with subarachnoid haemorrhage for tissue
at risk, even in sedated patients where clinical surveillance is
not possible. We believe that the tissue at risk concept is a
promising tool in the detection of cerebral vasospasm as well
as in monitoring the effects of TBA. However, the concept
requires further development, especially in patients with
higher grading on the Hunt and Hess scale.
.....................

Authors’ affiliations

J Beck, A Raabe, V Seifert, Department of Neurosurgery, Johann
Wolfgang Goethe-University, Frankfurt am Main, Germany
H Lanfermann, S Weidauer, Institute of Neuroradiology, Johann
Wolfgang Goethe-University
Competing interests: none declared
Correspondence to: Dr Jürgen Beck, Department of Neurosurgery,
Johann Wolfgang Goethe-University Frankfurt am Main, Schleusenweg
2-16, 60528 Frankfurt am Main, Germany; J.Beck@em.uni-frankfurt.de
Received 16 January 2004
In revised form 25 March 2004
Accepted 31 March 2004

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