(Stroke. 1997;28:2479-2482.)
© 1997 American Heart Association, Inc.
Articles |
Cerebrovascular Reserve Capacity Many Years After Vasospasm Due to Aneurysmal Subarachnoid Hemorrhage
A Transcranial Doppler Study With Acetazolamide Test
From the Departments of Neurosurgery (S.S., L.N., L.R.) and Neurology (A.F.), Medical School University of Debrecen (Hungary).
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Abstract |
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Background and Purpose Vasospasm in aneurysmal subarachnoid hemorrhage results in proliferative vasculopathy. Systemic hypertension also causes vascular hypertrophy. Both of these histological changes can lead to rigidity of the cerebrovascular system, reducing its autoregulatory capacity.
Methods Blood flow velocity (BFV) in the middle cerebral artery at rest and cerebrovascular reserve capacity (CVRC) (percent rise in BFV after acetazolamide stimulation) measured by means of transcranial Doppler sonography were studied many years after aneurysmal subarachnoid hemorrhage in patients with proven cerebral vasospasm (mean BFV >160 cm/s). The BFV under resting conditions and the CVRC values of the ipsilateral and the contralateral hemispheres were measured in 29 patients (mean age, 43 years; mean follow-up, 4.6 years) and compared with those of control subjects.
Results Persistent high BFV (>120 cm/s) was found in three patients in the peripheral branch of the ipsilateral middle cerebral artery. In the main trunks of the arteries of the anterior circle of Willis, BFV was normal in all cases. CVRC was normal in all patients (ipsilateral, 52±21%; contralateral, 56±17%); values did not differ significantly from each other or from the control value (45±18%). The higher value of CVRC on the contralateral side was found to be statistically significant in selected groups (hypertensive patients and patients with residual infarct on late CT).
Conclusions Proliferative vasculopathy developed at the time of vasospasm must have resolved and did not reduce late vasoreactivity. Comorbidity with hypertension also did not seem to influence the late vasoreactivity toward normalization.
Key Words: acetazolamide • Doppler • subarachnoid hemorrhage • vasospasm
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Introduction |
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Vasospasm in aneurysmal subarachnoid hemorrhage results in histological changes in the vessel wall designated as proliferative vasculopathy.1 It is questionable whether this proliferative vasculopathy resolves with time.2 Nevertheless, systemic hypertension affecting approximately 50% of aneurysmal patients also causes vascular hypertrophy.3 4 Both of these vascular changes may lead to definitive stenosis of the vessels and can result in rigidity of the cerebrovascular system, reducing its autoregulatory capacity.
TCD has been proven to be a valid method to evaluate vasospasm. The increase in BFV after acetazolamide injection defined as CVRC is a relevant marker of cerebrovascular integrity. In the literature no data were available regarding TCD findings several years after the aneurysmal vasospasm.
If the histopathological changes in a vasospastic artery were irreversible, then the resting value of BFV would still be high as a result of stenosis. On the other hand, we hypothesized that both vasospasm and hypertension may lead to permanent changes in the arteries, which may lead to impaired CVRC.
We examined BFV at rest and CVRC after acetazolamide provocation in patients with documented vasospasm many years after subarachnoid hemorrhage. We investigated whether there was any persisting high BFV under resting conditions reflecting definitive stenosis of the vessels and whether the histological changes that occur during vasospasm (and in hypertension) influence CVRC.
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Subjects and Methods |
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Two hundred thirty-four aneurysmal patients were monitored preoperatively and postoperatively by TCD between 1987 and 1994. Vasospasm in each case was graded according to the highest mean BFV during the entire clinical course (grade 1, 120 to 160 cm/s; grade 2, 160 to 200 cm/s; grade 3, >200 cm/s) measured in the MCA.
Of 42 patients who had proven vasospasm grade 2 or grade 3, 29 responded and gave their informed consent to perform the test. Two patients were excluded from the acetazolamide test because of side effects, resulting in a total of 27 patients (age range, 18 to 56 years; mean age, 43 years; 18 women, 9 men). The mean follow-up was 4.6 years (range, 1 to 8 years). Seventeen patients had been classified with vasospasm grade 2 and 10 with grade 3. Data on hypertension, the patient's condition at admission according to Hunt-Hess grade, timing of surgery, severity of hemorrhage according to Fisher grade, and outcome according to Glasgow Outcome Scale were collected from the patient's chart retrospectively.
TCD investigation was performed by means of TCD 2 EME 64 equipment with the use of a 2-MHz probe and the temporal window. A thorough examination of all major vessels and their branches was performed at rest to identify any residual high BFV reflecting any stenosis. We defined the most reproducible insonation of the MCA, and 1 g of acetazolamide (Diamox, Lederle) was slowly injected intravenously within 1 minute. TCD was performed every 5 minutes for 20 minutes on both sides after injection. Sides were defined as ipsilateral (according to the site of aneurysm or in the case of communicating artery aneurysm according to the side of surgical procedure) and as contralateral. Blood pressure and heart rate were monitored continuously, and blood gas parameters were controlled before and after the examination. All the readings occurred in a semi-lighted room. Eleven patients underwent a CT examination to search for any evidence of infarcts.
The baseline mean BFV and the highest BFV after acetazolamide stimulation were determined. The rise in BFV, expressed as a percentage, was defined as CVRC.
Values of 14 age- and sex-matched lumbar disc patients without hypertension served as control values. Data were entered into the computer with the use of an Excel 5.0 database. ANOVA and unpaired Student's t test were used for statistical analysis.
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Results |
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TCD Findings at Rest
Twenty-nine patients were examined under resting conditions. In all patients the mean BFV was found to be normal (42 to 86 cm/s) in the major basal arteries of the anterior circle of Willis. However, in 3 cases we found residual high BFV (120 to 130 cm/s) in small peripheral arteries registered at a depth of 35 to 40 mm, corresponding to a peripheral branch of the MCA distal from the bifurcation. Of these 3 patients, 2 had high BFV recorded on the ipsilateral side where the aneurysm (at the bifurcation of the MCA) was clipped, and in 1 patient the aneurysm was on the anterior communicating artery. The residual high BFV in this case was on the side of the surgery.
Acetazolamide Vasoreactivity
TCD and the acetazolamide provocation test were
performed in 27 patients. All had a significant increase of BFV
compared with the baseline value (P<.001). CVRC ranged
between 21% and 91% (mean, 52±21% on the ipsilateral and 56±17%
on the contralateral side); all were within normal limits. The CVRC of
the control subjects was 45±18%.
We investigated whether there was any statistically significant
difference between the CVRC of the ipsilateral and the contralateral
hemispheres and the control values (Table 1
). The highest mean BFV in the
contralateral hemisphere was significantly greater than that in either
the ipsilateral side or the control subjects. However, the CVRC did not
differ significantly in the patient group compared with the control
subjects.
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In the next step we defined subgroups of patients who were exposed to
an even greater risk of vascular changes and therefore must have a more
compromised CVRC. The following subgroups were identified: group 1
(n=10), patients with severe vasospasm (grade 3, BFV >200 cm/s); group
2 (n=13), patients with hypertension for at least 5 years before
subarachnoid hemorrhage; group 3 (n=13), acutely
operated patients; and group 4 (n=7), those with late control CT proof
of some residual infarct or brain damage related to either primary
hemorrhage or vasospasm or surgical trauma (Tables 2 through 5)
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To summarize, the following results can be deduced from the tables.
When the results between the contralateral and the ipsilateral
hemispheres were compared, there was a tendency for the highest mean
BFV and the CVRC to be greater on the contralateral side. This
difference was significant in the group with severe vasospasm and in
the acutely operated patients (Tables 2
and 4). When the data of the
patients and the control subjects were compared, there was a
statistically significance increase in CVRC in both hemispheres in the
hypertensive patients (Table 3). In the group of patients with
morphological brain damage, the baseline BFV, highest BFV, and CVRC
were significantly greater than those in control subjects (Table 5).
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Discussion |
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At least 20% to 25% of the aneurysmal patient population is exposed to the danger of vasospasm, and approximately 50% of the patients are hypertensive.5 6 7 Potentially any of these can be a serious cerebrovascular risk factor.
Prolonged spasm leads to degenerative changes in the vessel wall.8 9 The vessel wall becomes rigid and loses compliance to elastic expansion.10 Chronic vasospasm leads to reduced contractility, increased rigidity of the arterial wall, increased collagen deposition in the media,11 12 and increased active muscle tone.13 The term for these histological changes, noted first by Crompton14 and subsequently confirmed by others,8 15 16 is proliferative vasculopathy. It is not known whether proliferative vasculopathy resolves in survivors. Experiments suggest that the fibrosis does not disappear, but rather the luminal diameter restores itself as a result of passive stretching produced by normal arterial blood pressure.2
In our study we found only three patients of the 29 who still had existing high BFV in a small peripheral branch of the MCA distal from the bifurcation, reflecting residual stenosis. This finding can also be interpreted as mechanical narrowing after clipping or as an accidental atherosclerotic stenosis; however, this finding was not registered preoperatively, it was noticed in the postoperative period, and the depth of registration was 35 mm, measured distally from the clip position. These arguments suggest that the persisting high velocity in these peripheral vessels resulted from vasospasm. Normal BFV was found in all cases in the main trunks of the basal arteries of the anterior circle of Willis. This supports the hypothesis that proliferative vasculopathy in most of the vasospastic arteries must have resolved.
In addition to vasospasm, the cerebrovascular system of aneurysmal patients is also affected by chronic arterial hypertension. In hypertension vascular hypertrophy develops that mainly affects the middle-sized vessels6 7 ; supposedly the larger vessels are spared,5 but some authors suggest that small capillaries are often involved.17 Impaired18 19 or preserved20 21 cerebrovascular reactivity in hypertension has been variously reported, but recent publications refer to impaired cerebrovascular reactivity in hypertensive patients.22 23 24
Assessment of BFV after increasing blood CO2 or by acetazolamide reactivity in arteries is a valid method for the estimation of CVRC.25 26 27 This has been confirmed in internal carotid artery stenosis28 29 30 31 in the acute phase of aneurysmal hemorrhage and vasospasm.32 33 The normal range of CVRC evaluated by the acetazolamide test is 38±15%.25 34 35 36 Recent evidence concerning the pathophysiology of cerebral ischemia identified a subgroup of patients with a "hemodynamic" type of stroke. Characteristically, these patients demonstrated impaired CVRC due to occlusive disease and insufficient collateral blood supply. CTs either were normal or showed evidence of border-zone infarction37 38 in these cases.
In our study CVRC many years after severe vasospasm was still normal. We were not able to demonstrate reduced CVRC even in subgroups of patients definitely exposed to a greater risk of cerebrovascular morbidity. Although long-standing hypertension leads to small-vessel disease and therefore to reduced CVRC39 and increased risk for stroke,38 in our patient population concomitant hypertension with severe vasospasm did not result in reduced CVRC. Reactivity that was not only normal but was even slightly increased was found on the contralateral side in particular, which was most remarkable in the group of patients with residual infarct on late CT scans. Within all subgroups of patients, the contralateral side had a higher reactivity toward acetazolamide compared with control subjects.
In summary, normalization of BFV at rest and CVRC many years after aneurysmal vasospasm supports the hypothesis that proliferative vasculopathy resolves with time and does not influence late vasodilatory capacity.
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Selected Abbreviations and Acronyms |
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Footnotes |
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Corrrespondence to Sandor Szabo, MD, Department of Neurosurgery, Medical School University of Debrecen, 98 Nagyerdei krt, PO Box 31, Debrecen 4012, Hungary.
Received July 4, 1997; revision received August 29, 1997; accepted September 12, 1997.
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