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Acta Neurol Scand.

, 1986:74:439-451

Key words: stroke; CBF; xenon-133; inhalation tomography

Cerebral blood flow in acute and chronic ischemic


stroke using xenon- 133 inhalation tomography
S. Vorstrup, 0. B. Paulson, N. A. Lassen
The Department of Neurology, Rigshospitalet,
Copenhagen, Denmark

ABSTRACT - Serial measurements of cerebral blood flow (CBF) were performed in 12 pa-
tients with acute symptoms of ischemic cerebrovascular disease. CBF was measured by xen-
on-133 inhalation and single photon emission computer tomography. Six patients had severe
strokes and large infarcts on the CT scan. They showed in the acute phase (Days 1-3) very
large low-flow areas, larger than the hypodense areas seen on the CT scan. The cerebral va-
soconstrictor and vasodilator capacity was tested in the acute phase following aminophylline
and acetazolamide, respectively. A preserved but reduced reactivity was seen at both tests in
all 6 cases in the infarct and the peri-infarct areas. On Days 5-25,4 of the patients had trans-
itory increases (59- 108%) of CBF, probably corresponding to lysis of an intracerebral em-
bolic occlusion. The other 2 patients showed on Days 7-15 only a moderate CBF increase
(appr. 20%),both had occlusion of the relevant internal carotid artery. In all 6 patients, CBF
studies at 2 and 6 months resembled the acute phase, showing large areas with reduced flow.
At the 6 months follow-up, the vasodilatory stress test was repeated, and all but one showed
a preserved but reduced vasoreactivity in the infarct and peri-infarct tissue. Of the remaining
6 patients, one had a pontine infarct and one had no lesions on the CT scan, both having nor-
mal angiograms and CBF maps. Four patients had small deep or subcortical Cr lesions, and
showed a slight, but persistent CBF reduction of about 6 4 % in the parietal region on the af-
fected side. No changes in the flow pattern were seen at the vasoreactive studies. A likely ex-
planation for the finding of superjacent low-flow areas is an intrahemispheric uncrossed dias-
chisis. This interpretation is discussed in relation to the peri-infarct low-flow area seen in the
6 cases with large infarcts.

Accepted for publication July 11, 1986

Following a moderate to severe ischemic stroke, hy- nized that often more complex neurological symp-
podense lesions are seen on the CT scan within 24- toms are associated with these lesions (7,8). In ad-
48 h in the majority of cases in regions correspond- dition to these diverse structural changes, angiogra-
ing to the neurological symptoms (1).In the chronic phical studies in the acute and chronic phase of an
phase, these lesions are taken to represent complete ischemic stroke have shown a wide spectrum of vas-
cerebral infarction (2,3) and a correlation between cular lesions, which range from occlusion of the
the size of the lesion and the clinical symptoms have major extracranial or intracerebral arteries to nor-
been established. But, despite rather severe clinical mal findings (9-12).
symptoms, some patients have only small CT-le- Studies of the patho-physiological changes, i.e.
sions, and some have only lacunar infarcts or no le- cerebral blood flow (CBF) and the cerebral meta-
sion at all (4). Lacunes were originally described as bolic rate for oxygen (CMRO,) in ischemic stroke
post mortem findings in patients with pure motor or have recently become possible by use of positron
sensory symptoms (5,6). As lacunes now can be emission tomography (PET) (13-16). In patients
identified in vivo using CT scans, it has been recog- with larger cerebral infarcts, the studies have shown
440 VORSTRUP

that potentially viable brain tissue may be present were performed, ranging from 8-12 studies in the
within the first days after a stroke, such regions be- individual patient.
ing defined as low-flow areas having an increased Cerebral vasoreactivity was tested in conjunction
oxygen extraction ratio with a preserved CMRO,. with the CBF measurement in the acute phase fol-
Patients studied later than Day 3 invariably showed lowing intravenous injections of aminophylline and
a low oxygen extraction associated with either a re- acetazolamide (DiamoxcR)). The effect of amino-
duced, a normal or even an increased CBF (16). In phylline is analoguous to a reduction of Pa CO,,
the chronic phase, CBF and CMRO, are coupled normally causing constriction of the cerebral vessels
again, i.e. CBF reflects as in normal tissue the meta- and inducing slight hyperventilation (18,19). Dia-
bolic demand (15). Rougemont et al. (17) mea- moxR increases CBF by an effect corresponding to
sured CBF and CMRO, by PET in 7 patients with inhalation of hypercapnic air. Both drugs leave
symptoms of a moderate to severe stroke, having a CMRO, unchanged (20,21). After the first baseline
normal CT scan or a lacunar infarct. They were measurement, 220 mg of aminophylline was inject-
studied in the acute or in the chronic phase. In none ed over 5 min, and CBF was measured 10 min later.
of these cases were significant changes of CBF or Following this study, 1 gram of DiamoxR dissolved
CMRO, observed. Thus, the patho-anatomical and in sterile water was injected over 30 s, and CBF
-physiological findings differ considerably in pa- measured 20 min later. In the chronic phase at the
tients with cerebral ischemic stroke. 6-months follow-up vasoreactivity was tested 20
To study the time course of CBF changes in a ty- min after an intravenous injection of 1 g of Dia-
pical stroke population to obtain a guidance for la- moxR.
ter series on therapeutic interventions, CBF was X-ray transmission (CT) scanning was per-
measured in 12 consecutive patients with clinical formed within the first week after admission to ex-
symptoms of an acute ischemic stroke. CBF was clude a hematoma or a hemorrhagic infarct, and it
studied by xenon- 133 inhalation and single-photon was repeated 8 weeks later for determination of the
emission computer tomography (SPECT) allowing definitive CT lesion. Angiography was performed
sequential measurements of CBF at much lower in 11 of the 12 patients by direct puncture of the
cost than PET. In patients with larger infarcts our relevant internal carotid artery in 9 patients, 5-10
studies show the same phases as the PET obser- days (in average 7 days) after onset of the symp-
vations. In patients with smaller infarcts or lacunes toms. In 2 patients the angiographical studies were
areas of slightly reduced flow located at a distance performed 4 and 6 weeks after onset; in one of
of the lesion could be ascertained by the sequence these patients (Case 2) 4-vessel angiography with a
of CBF tomograms obtained in each patient. cranial series was performed.
A clinical neurological examination was per-
formed in connection with every CBF measure-
Material and methods ment. The clinical symptoms of paresis were graded
Serial measurements were performed in a consecu- as: none, slight (25% reduction), moderate (50%
tive series of 12 patients, suffering their first ische- reduction), severe (movement on couch only) or
mic stroke with symptoms referable to the cerebral paralysis. One-step changes in these motor func-
hemispheres. The age limits were set from 20-75 tions in either arm, hand, leg or foot was considered
years. All patients had a hemiparesis, and most had an improvement. The acute neurological findings
other focal symptoms as well. The series comprised and the clinical course, the findings on the %week
4 women and 8 men, with an age ranging from 32- CT scan, and the angiographical findings are pre-
66 years, mean 61 years. The first CBF studies were sented in Table 1.
performed as soon as possible after onset, in 11 pa- Only one patient had a history of previous neu-
tients by Day 2, and in one patient by Day 3 after rological symptoms. This patient (Case 12) had suf-
onset (acute phase). Subsequent CBF studies were fered approximately 10 transient ischemic attacks
then performed 1-3 times within the first 2 weeks with paresthesia of the left hand (the same brain
(subacute phase) and repeated 2 and 6 months later areas subsequently involved in stroke). These
(chronic phase). A total of 112 CBF measurements symptoms occurred unrelated to postural changes,
CBF IN ISCHEMIC STROKE 441

Table 1
Patient Presenting clinical Clinical course of Size (in cc) and location Angiographical findmgs
age, sex signs motor disturbances of infarct on CT scan (time since infarction)
2 months 6 months
1 73M Global aphasia Unchanged Unchanged 26 L basal ganglia Not performed
R hemiparalysis, and insula
hemiparesthesia and DCA
homonymous hemianopia
2 32F global aphasia Unchanged Unchanged 45 L temporo-parietal Normal (4 weeks)
R paralysis of arm and (Aphasia region
moderate paresis of leg improved)
Facial palsy
3 72F Severe L hemiparesis Unchanged Unchanged 48 R temporo-parietal R ICA occluded
and hemiparesthesia region R MCA stenosed (7 days)
4 70 F L hemiparalysis Unchanged Improved 6 1 R temporo-parietal R intracranial ICA and
hemiparesthesia and region MCA severely stenosed
homonymous hemianopia Severe DCA (6 weeks)
5 60M Severe L hemiparesis Improved Unchanged 39 R temporo-parietal R ICA occluded
and hemiparesthesia region - DCA (10 days)
6 57M Global aphasia severe R Unchanged Unchanged 91 L temporo-parietal L ICA severely stenosed
hemiparesis, hemiparesthesia region Poor filling of MCA-
and homonymous hemianopia Severe DCA territory (9 days)
7 55 M Moderate L hemiparesis Improved Unchanged Normal Normal (6 days)
8 34 M L hemiparalysis Improved Unchanged 8 R middle part of pons Normal (5 days)
9 74M Slight L paresis of arm Improved Unchanged 25 R temporo-occipital Normal
and leg region - Severe DCA (6 days)
10 69 M Slight R hemiparesis Improved Unchanged 7 L parietal lobe Stenosis of L ICA
Moderate DCA Normal intracranial
filling (7 days)
I1 69F R paralysis of arm and Unchanged Improved 0.5 L internal capsule Diffuse arteriosclerotic
severe paresis of leg changes - Normal
intracranial filling
(7 days)
12 6 2 M Slight L paresis of arm Unchanged Improved 0.5 R internal capsule Normal
and leg Severe DCA (7 days)
. ,

Abbreviations: M = male, F = female. R = right, L = left. ICA = internal carotid artery, MCA = middle cerebral artery,
DCA = diffuse cortical atrophy

and had always subsided in less than 12 h. One pa- photomultiplier tubes to constitute a total of 192
tient had arterial hypertension, and one had cardiac detectors. These detectors are equipped with a sen-
insufficiency, symptoms that in both cases were well sitive collimator. Measurements of the isotope con-
controlled by appropriate therapy. A third patient centration during the rotation of the detectors
(Case 2) had a congenital heart disease (see case yields the isotope uptake, distribution, and wash-
history). out from 3 slices of brain tissue simultaneously.
The study was approved by the Copenhagen Dis- Each slice is 2 cm thick, and separated by an inter-
trict Ethical Committee. track distance of 2 cm. The resolution is 1.5-1.7 cm
in the horizontal plane and 2,O cm in the axial
CBF measurement and CT scanning plane, when measured as full width half maximum
For measurement of CBF, xenon-133 inhalation using a line source. CBF is determined from a series
was used combined with a single-photon emission of isotope concentration pictures using a modified
computer tomograph (Tomomatic 64, Medimatic filtered back-projection algorithm (23).
Inc., Hellerup, Denmark) previously described The patients were studied resting in a supine po-
(22). The detector device consists of 64 NaI crys- sition in most cases with eyes closed. No speaking
tals, which are placed in 4 banks, and covered by was allowed during the studies. The patient’s head
442 VORSTRUP

was carefully positioned in the aperture of the in- the CT lesions were either small (less than 25cc) or
strument, so that the slices were oriented in parallel it was not possible to detect hypodense lesions in
to the orbitomeatal (OM) plane, and centered 1 the supratentorial brain tissue. In 4 of these cases,
cm, 5 cm, and 9 cm above it by use of an inflatable rather extensive areas with slightly reduced flow
cuff. Correct symmetrical positioning of the pa- were observed in the early studies in the diseased
tient’s head could be ascertained by comparing the hemisphere. This region was found in either Slice
localization of the low flow areas corresponding to 2 or 3, and the time courses of these flow
the petrous bones on the lowest slice (Slice 1). changes were analyzed.
End-tidal p C 0 , was measured before, during the Finally, CBF was calculated in the cerebellar
third minute, and immediately after the CBF study hemispheres in all 12 patients.
using a spectroscopic infrared analyzer. Blood pres- The degree of side-to-side asymmetry was evalu-
sure was measured by ausculation at the end of eve- ated by an asymmetry index: the difference of CBF
ry CBF measurement. in the symmetrical ROIs calculated as a percentage
The CT scans were performed using either a of the higher CBF value.
EM1 1010 Head Scanner or a Siemens Somatom.
The size of the hypodense lesion was calculated on Controls. For comparison, mean cerebral and re-
the CT scan performed 2 months after onset as the gional flow values were obtained from a normal
product of the 2 largest diameters at a right angle to material of 9 elderly controls without symptoms of
each other, and the height of the lesion estimated cerebrovascular disease with a mean age of 63 years
from the number of slices. For the 6 patients having (range from 57-69 years). Regional CBF values
large infarcts, this value was then divided by 4 to were calculated from the territories of arterial sup-
yield a more correct value for a spherical lesion. ply, i.e. the territory of the anterior cerebral artery,
the cortical part of the middle cerebral artery and
the posterior cerebral artery (24). The mean values
Data analysis of the left to right side difference as a percentage of
Calculation of the average CBF in a given region the highest side, ranged from 1.2% * 1.4% (SD)
was performed by the computer after encircling the (posterior cerebral territory) to 4.8% _+ 2.6% (cor-
region. This yielded the average flow value in the tical part of the middle cerebral artery territory).
region of interest (ROI), as well as the average flow The size of these areas ranged from 15.7 cm2 to
value in a symmetrically placed region in the con- 27.2 cm2. Based on these results a significant
tralateral hemisphere. In this way, mean hemisphe- asymmetry was defined when the side-to-side diffe-
ric flow values were obtained from Slices 2 and 3, rence taken as a percentage of the higher value (the
and in every ROI. Positioning of the ROI was per- asymmetry index) was equal to or exceeded 10%.
formed on the flow map from the acute study, and CBF was repeated 20 min after an intravenous dose
CBF values from the similar ROIs were then calcu- of 1 g DiamoxR. Mean CBF increased by 13% to
lated from all successive CBF studies. The size of 46%, in average by 31%. Calculation of the
the ROI ranged from 10-36cm2. changes in side-to-side asymmetry after DiamoxR
When the 8-week CT scan showed large hypo- for the same vascular regions as descibed above was
dense lesions (6 patients), delineation of the region performed, and enhancement of the side-to-side
of complete infarction on the flow map was made asymmetry by 10% or more by DiamoxR indicated
by comparing the corresponding levels of the CT a significant change in the flow pattern ( ~ ~ 0 . 0 5 ) .
scan and the CBF tomogram. This region was in all To evaluate the time course changes of the de-
+
cases largest on Slice 2 (OM 5 cm). Calculations gree of side-to-side asymmetry for a ROI as used in
of CBF were also performed in the low-flow areas the 4 patients having small CT lesions and supeja-
surrounding the region corresponding to the com- cent low-flow areas, calculations were performed in
plete infarct, in the following referred to as the peri- a normal material of 10 persons, (mean age 43
infarct areas. The size of these ROIs were in the years) where CBF had been measured 3 times one
same order as descibed above, and the areas chosen week apart. This material has previously been de-
from either Slice 2 or 3. In the remaining patients, scribed (24). Only 1 of the 10 controls showed a
CBF IN ISCHEMIC STROKE 443

COMPLETE INFARCTION showed a moderate stenosis of the MCA, whereas


the other had a normal angiogram.
_/.-. In the remaining 2 patients with large infarcts
(Cases 5,6), flow increases of about 20% were seen
in the regions of complete infarction in the studies
from Days 7-14. In the pen-infarct low-flow regions
.-. in the same hemisphere, no increase was seen (Figs.
-
.. .* 1,2). These patients were angiographed on Days 7
8oi and 10, and both showed an occlusion of the ipsila-
teral internal carotid artery.
At the 2-month study, as well as in the 6-month
1 3 5 7 9 11 13 16 17 19 2 6 Time
from onset, follow-up, a large area with very low
days rnonlhr
flow values, much like the acute CBF studies, were
seen in all 6 patients. However, the low-flow areas
Fig. 1. Six stroke cases with large infarcts on C
T scan.
tended to be somewhat larger and more sharply
The graphs show the time course of CBF changes in
the region corresponding to the infarcted area as evi- demarcated.
denced by the 8-week CT scan. The values are ex- The time course changes in the non-affected
pressed as percentages of the first CBF study. Hyper- hemisphere were also studied. In the acute phase,
emia was not observed in the acute studies, but trans- Days 7-10, 2 months and 6 months after onset the
ition through a hyperemic phase was seen in 4 patients, mean hemispheric flow values were 56 f 5 ml/
most likely due to lysis of an intracerebral embolus. 100g/min (SD), 49 f 4 m1/100g/min (ASD), 53 f
3 m1/100g/min (ASD), and 56 f 5 mI/lOOg/min
(ASD), respectively. ASD indicates the standard de-
flow pattern where the flow in the ROI was lowest viation of the CBF change from the acute study. For
in the same hemisphere during 3 consecutive mea- the ROI located symmetrically to the area of com-
surements one week apart. The values of the side- plete infarction, the same values were 59 i 7 ml/
to-side asymmetry for this patient were 2%, 2%, lOOg/min (SD), 52 f 5 m1/100g/min (ASD), 55 f
and 6%. 3 m1/100g/min (ASD), and 57 f 3 m1/100g/min
(ASD); a two-way analysis of variance followed by
a Dunnett test was applied to these data (26). Using
ResuIts
CBF changes with large infarcts on CT (6 pa- INCOMPLETE INFARCTlON
tients)
Time course changes. The 6 patients (cases 1-6)
with large infarcts (26-91 cc) on the %week CT 180
scan all showed even more extensive areas with de-

--
160
creased CBF in the acute phase, Days 1-3.
F m of these 6 patients (Cases 1-4) showed on
Days 5-9 a marked increase in CBF in regions
corresponding to the CT lesions. The increases
ranges from 59-108%, taken as a percentage of the
CBF value in the acute flow study (Fig. 1). In the
peri-infarct low-flow areas more modest increases
"1 1 3 5 7 9 11 13 15 17 19
*

2
I.

6 Time
of about 30% were seen on Days 5-25 in 2 of the aoys mO"lhl

patients, whereas the other 2 showed no such in-


Fig. 2. Six stroke cases with large infarcts on CT scan.
creases (Fig. 2). Three patients were angiographed: The graphs show the time course of CBF changes ex-
one study (on Day 9) showed an occlusion of the pressed as percentages of the value in the first CBF
middle cerebral artery (MCA). In 2 other studies study in the peri-infarct regions. Only moderate CBF
performed 4 and 6 weeks after onset, one patient changes with increases of about 20% are seen.
444 VORSTRUP

COMPLETE INFARCTION INCOMPLETE INFARCTION

oj , 0’ I

B A D B A D

/:
!/. 504
Asymmetry

I*/

OJ I

B A D
Fig. 3. Vasoreactive studies in 6 stroke cases with large infarcts on C T scan, studied in the acute (Days 1-3) and
chronic (6 months) phase. B = baseline study, A = aminophylline, D = DiamoxR,all performed in the acute phase.
B, = baseline study and D, = DiamoxKtest performed in the chronic phase. Following aminophylline, a decrease
in side-to-side asymmetry was seen in all cases, both in the infarct and the peri-infarct tissue, whereas DiamoxRen-
hanced the asymmetry anew. In the chronic phase, a significant change in flow distribution was noted, in the peri-
infarct areas in one patient, but the finding of a CBF increase indicated a preserved vasodilational capacity.

the acute-flow study as reference value, a significant decreased in all cases. After DiamoxK, the flow
CBF decrease in the ROI was observed at Days asymmetry worsened again. The cases who showed
7-10. a CBF increase in the ROI after aminophylline all
All 6 patients with large hemispheric CT lesions showed a CBF decrease after DiamoxR, and vice
showed a significant reduction of CBF in the con- versa. One patient showed improvement in motor
tralateral cerebellar hemisphere, present through- function after aminophylline. No changes were seen
out the whole study period. in the clinical symptoms after DiamoxR.
The DiamoxR test was repeated at the 6-month
Vasoreactive studies in the acute and chronicphases. follow up. At this point, enhanced side-to-side as-
Aminophylline caused a reduction of CBF in both symmetry was seen in all cases in the area of com-
hemispheres in all cases, but variable changes were plete infarction. In the pen-infarct area, a signifi-
seen in the infarct and peri-infarct areas (Fig. 3). cant change in flow-distribution was seen in one
The degree of side-to side asymmetry, however, case (the asymmetry was enhanced from 28% at

Fig. 4. Stroke case with large CT lesion (Case 2). This patient suffered sudden onset of a severe right-sided hemi-
paresis and global aphasia. Corresponding levels of the 8-week CT scan and the flow maps are presented, placed 5
and 9 cm above the orbito-meatal (OM) plane (Slices 2 and 3, respectively). The scale ranges from 0 - 96 ml/
100g/min, and white indicates the highest flow value. The right hemisphere is oriented to the right, nose upward.
The CT scan shows a well-demarcated hypodense lesion the temporal lobe of the left hemisphere. No lesion was
seen above OM+7 cm. In the acute phase, the flow pictures showed a severely hypoperfused area present on both
Slices 2 and 3. Hyperemia in the area of infarction was seen on Day 7. In the chronic phase, the large low-flow
areas reappeared. A 4-vessel angiogram including cerebral series performed 6 weeks after onset was normal.
CBF IN ISCHEMIC STROKE 445
446 VORSTRUP

the baseline study to 40% after DiamoxR),indicat- lesions of the extracranial neck vessels, and normal fill-
ing a limited vasodilational capacity in this one case ing of the intracranial vessels which indicated that no
only. vascular obstructions were present any longer.

Case 2 history CBF changes with small or absent CT-lesions


This patient, a 32-year-old woman, suffered an acute (6 patients).
stroke with a right-sided facial palsy and a severe hemi- Time course changes. Two patients in this group
paresis, slight hemiparesthesia, and global aphasia. She (Cases 7,8) had no C T lesions in the cerebral hem-
had a congenital heart disease, a patent ductus arterio- ispheres; in one case, however, the repeated CT
sus and coarctation of the aorta with pulmonary hyper- scan revealed a hemi pontine infarct explaining the
tension. At admission, atrial fibrillation was present. severe hemiparesis. Significant focal changes or
The patient received digoxin and diuretics, but she was
persistence of an asymmetrical flow pattern were
not being treated with anticoagulants. Embolism from
the heart was considered the pathogenetic factor in this not seen in these 2 patients. Both had normal an-
patient. giograms.
The acute CBF study performed on Day 1 showed a Four patients showed minor CT lesions. Cases 9
large hypoperfused area confined to the territory of the and 10 showed small subcortical infarcts of about 6
anterior part of the MCA (Fig. 4). This was taken as and 2 cc on the 8-week CT scan. In one case, the
evidence of embolism to the anterior branches of the infarct was seen only on the C T level 3 cm above
MCA. On Day 7, the CBF study focal hyperemia in the the orbito-meatal plane, and the infarct was there-
previous low-flow area in Slice 2, suggesting lysis of the fore between the planes normally used for CBF
embolus. CT showed a large infarct in Slice 2, but no
studies. However, large regions with a marginally
hypodensities were seen above the level of OM 7cm. + decreased flow were seen in the ipsilateral hemis-
The late CBF studies performed approximately 2
and 6 months later showed large low-flow areas corre- phere in both 2 and 3 in the early as well as in the
sponding to the CI-lesion. However, in rather wide pe- chronic phase (Table 2). The angiogram showed
ri-infarct regions which almost comprised the entire left normal intracranical filling. Case 10 had a subcorti-
hemisphere, very low flow values were now present. In cal infarct in the parietal region. In this region, and
this patient, the angiogram was performed 6 weeks af- the overlying areas variable CBF changes were seen
ter the acute episode. This showed no atherosclerotic in the early phase, but in the chronic phase a low
flow was seen. Also this case had a normal intra-
Table 2 cerebral angiogram.
Time course of the degree of side-to-side asymmetry ("6)in patients
with small infarcts.
Two patients (Cases 11,12) showed lacunar in-
~ ~ ~ ~~~ ~~

farcts of less than 0.5 cc on the CT scan, in both


Flow no. Case 9 Case 10 Case I1 Case 12
cases located to the internal capsule (5-6 cm above
1 Acute phase 8/12 2 12 8
the OM plane). The CBF map showed no abnor-
2 Aminophylline test 15 2 I I
3 Diamox" test 7 6 6 13 mality at the site of the CT lesion or in the immedi-
4 Subacute phase - 6 -13 12 11 ate surroundings. Surprisingly, a slight CBF reduc-
5 Subacute phase -10 0 8 tion was seen in both patients in the posterior part
6 Subacute phase 10 6 5 of the parietal lobe in Slices 2 and 3 ipsilateral to
7 2 months 9 8 6 9
8 6 months I 9 6 18
the lacunar infarction, but a significant side-to-side
9 Diamox" test 5 10 4 17 asymmetry exceeding the 10% level was obtained
Positive values = decreased, negative values = increased flow in dis-
only in some of the individual studies. However, the
eased side compared to the symmetrical region in the contralateral repeated CBF studies allowed for the recognition of
hemisphere. this slight but persisting flow reduction (Table 2).
Fig. 5. Stroke case with lacunar infarct (Case 11). This patient suffered a severe right-sided hemiparesis. Corre-
sponding levels of the 8-week Cr scan and the flow maps are presented, both placed 5 and 9 cm above the orbi-
tomeatal plane, representing Slices, 2 and 3, respectively.The scale ranges from 0 - 96 ml/lOOg/min. The CT scan
showed a small lacunar infarct in the left hemisphere. The CBF studies showed a rather large area with slightly re-
duced flow in the posterior part of Slice 3 as demarcated by the dotted line. This moderate change was seen
throughout all successive CBF measurements. The carotid angiogram was normal.
CBF IN ISCHEMIC STROKE 447
448 VORSTRUP

The angiographical studies were normal. having a diameter of 5 cm, an activity of about 55%
A transient, crossed cerebellar diaschisis was seen of the surrounding could be measured (28).
on Days 4 and 9 in the 2 patients with lacunar in-
farcts, i.e. the cerebellar side-to-side asymmetry ex- CBF changes with large CBF lesions
ceeded 10%. In the remaining, no significant chan- Despite the methodological limitations, focal low-
ges were seen. flow areas were easily identified in all stroke pa-
tients who had large CT lesions, but the lowest CBF
Vasoreactive studies in the acute and chronic phase. value recorded even in the most severe case with the
In this group of patients CBF changed in all regions largest low-flow area was about 20-26 m1/100g/
such that there was no change in the flow pattern. min, i.e. in regions where true flow values could be
expected to be much lower.
Case 11 history The vasomotor function in the acute stage. Fol-
This patient, a 69-year-old woman suffered an acute lowing arninophylline, all 6 patients showed a re-
stroke with a moderate, right-sided facial palsy and duced reactivity in the infarct and peri-infarct areas
hemiparesis combined with aphasia. In the following as indicated by the decrease in side-to-side
days, the aphasic symptoms gradually declined, but at asymmetry. Following DiamoxK, redistribution of
the same time her arm became paralysed. For several flow in favour of the healthy hemisphere was seen
years, she had received treatment for arterial hyperten-
with aggravation of the side-to-side asymmetry. The
sion, to keep her blood pressure at about 200/ 100
changes in the absolute CBF values during the va-
mmHg.
The first CBF measurement was performed on Day soactive tests did not permit conclusions. It should
2 after onset of the symptoms and showed a quite large be noted, however, that DiamoxR apparently only
area with reduced flow (12% less than the symmetrical abolished the vasoconstriction produced by amino-
region) in the parietal lobe of Slice 3. This moderate phylline. Nevertheless, these findings demonstrate,
change was seen throughout all successive CBF mea- that although the vasoreactivity is reduced in the is-
surements (Fig. 5). The CT scan showed a lacunar in- chemic tissues, CBF may be modified by vasoactive
+ +
farct on Slices OM 5cm and OM 6cm. The angio- substances. Except for one patient, no changes in
gram showed no lesions. the clinical symptoms were noted. Larger series in
this subgroup, including long term clinical evalua-
tion, will be needed to identify the drugs that in-
Discussion crease CBF in the ischemic areas and thereby im-
Xenon-133 inhalation and SPECT is well suited to prove the clinical outcome.
the performance of serial CBF studies. Measure- The repeated CBF studies in the early phase
ments may be repeated with an interval of 20 rnin, showed a transition through a hyperemic phase with
which is needed to allow the remaining activity an increase of CBF in the area of complete infarc-
from the previous study to decline to acceptable le- tion in 4 of the 6 cases on Days 5-9. The increase in
vels. Analyses of simulated data have shown, that CBF ranges from 59-108%, taken as a percentage
despite the varying and unknown lambda values of the value measured at the first CBF study (Fig.1).
within the brain tissues, the use of a fixed lambda Although neither acute nor serial angiographical
only causes minor errors in the final CBF values studies were possible in the present series, it is most
(27). On the other hand, it is recognized that the likely that the CBF increase was due to fragmenta-
CBF values on the low-flow areas are severly influ- tion and lysis of an embolus with reopening of the
enced by scattered radiation, an effect depending previously occluded vessel, although metabolic der-
on the size and the localization of the low-flow area angements may also occur. This has been described
as well as on the difference between the flow values by several authors (14-16, 29-31), in some relating
in the hypoperfused area and its surroundings. the angiographical findings directly to the changes
Studies have been performed on water filled cylin- in CBF (29,32), Dissolution of an intracerebral em-
drical perspex phantoms containing cold spots of bolus with luxury perfusion may occur within the
varying diameters within hot surroundings. These first days after a stroke, but delayed recanalisation
analyses showed, that in the centre of a cold spot is not an uncommon finding (10,31,33). In the
CBF IN ISCHEMIC STROKE 449

present study, none of our patients showed hyper- enhancement of the side-to-side asymmetry indi-
emia in the acute stage, i.e. Days 1-3 (Fig.1). In the cating a restricted collateral capacity. Thus, in these
2 patients without hyperemia it could be assumed 6 cases we may consider the low-flow CT negative
that the occlusion of the ICA combined with poor areas to represent a final “functional” lesion with
collateral flow caused the cerebral symptoms. A CBF adjusted to the lowered metabolic demands.
permanent occlusion of a major intracerebral artery The pathogenetic lesion causing these low-flow
could also explain these findings as cerebral emboli- areas still remains mostly unsettled, but some au-
sation is a common finding in patients with ICA oc- thors have suggested, that deafferentiation (discon-
clusions (34). nection) due to undercutting of the nerve fibers
Analyses of the time course changes of CBF in could be an explanation (35,38). Also, it could be
the contralateral hemisphere revealed a significant assumed, that in the regions surrounding the in-
decrease in CBF in the mirror locus to the infarct on farcted area direct injury to the most vulnerable tis-
Days 7-10. Hcledt-Rasmussen et a1 originally de- sue component - the nerve cells - could occur
scribed a decreased CBF in the hemisphere contral- (39,40). In either case the reduced flow level repre-
ateral to the ischemic lesion, and denoted this find- sents an adaptation to reduced metabolic demands.
ing a transneuronal depression (35). The pheno- It could have been speculated, that the low-flow
menon was later described by other authors (15). areas in the CT intact regions represented a state of
Other factors such as increased intracranial pressure “chronic penumbra” (41). Astrup and co-workers
owing to brain edema after stroke should, however, (42) coined the term the “acute ischemic penumb-
also be considered as pathogenetic factors (36). ra” to the blood flow range within which the neu-
The finding in the present study of a delayed onset, ronal tissue is structurally intact maintaining the ion
of its transient nature, and the circumscript location homeostasis, but functionally inactive. The tolerat-
of the lesion may support both theories. ed time limits before irreversible ischemic damage
In the chronic phase 2 and 6 months after onset, occurs have yet to be assessed, although experi-
the flow maps were most like the early flow studies mental studies have been performed to extend
with no tendency toward diminuition of the low- these results to the chronic phase (43,44). It is diffi-
flow area. In some cases, even enlargement and cult, however, to conceive that the very narrow
sharper demarcation were seen. Thus, an increase range of perfusion pressure required to keep CBF
in CBF does not accompany the gradual improve- just below the lower limit for neuronal function and
ment noted in most stroke patients. The same con- above the threshold for irreversible ischemic da-
clusions were reached by Demeurisse et a1 (37) who mage can be maintained over longer periods in
measured CBF 15, 30 and 60 days after the acute man. A preserved vasodilatational capacity as indi-
symptoms using xenon- 133 inhalation with station- cated by the DiamoxR test in the present study
ary detectors. Neither mean hemispheric nor re- seems to exclude that the peri-infarct low-flow re-
gional CBF increased contrasting the clinical im- gions observed in our cases reflects a chronic pen-
provement seen in most cases. umbra.
The DiamoxR test was repeated at the 6-month
follow-up. At this point, the collateral flow capacity CBF changes with small or no CT lesions
may be assessed from the regional CBF increase. In Two patients in the present series showed lacunar
regions with a compromised collateral capacity, the lesions on the CT scan, and another 2 showed only
perfusion pressure will decrease but initially the smaller CT lesions. These patients showed quite
cerebral autoregulation maintains CBF by a com- large regions with slight reduced CBF, but the de-
pensatory dilatation of the arterioles. However, gree of side-to-side asymmetry only occasionally
when additional vasodilatory stress (DiamoxR) is reached significant levels. However, as this CBF
applied in such regions, the flow response is res- pattern was seen in nearly all the CBF studies, both
tricted compared with unaffected regions. In the in the early and in the chronic phase, this was taken
present study, an increase in CBF after DiamoxK as suggestive evidence of an intracerebral diaschisis.
was observed in all 6 patients in the peri-infarct Recently, Rougemont et al (17) reported single
areas, although one patient did have a significant measurements of CBF and CMRO, in 7 patients

29
450 VORSTRUP

who had clinical syndromes of lacunar infarction. In References


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