Introduction
Delayed neurological deterioration from vasospasm remains the greatest cause of morbidity and mortality after SAH.3) Cerebral hemodynamic abnormality is one of the most common immediate complications of aneurysmal clipping or coiling. The major causes of cerebral hemodynamic abnormality are vessel injury, operation induced vasospasm, and vessel occlusion caused by thrombus formation. Prompt diagnosis and adequate treatment using hyperdynamic therapy (3H therapy)22) is necessary due to its close relationship to patient outcome.35) Diagnostic tools used are positron emission tomography(PET),33) single-photon emission computer tomography (SPECT),25) xenon-enhanced CT,9) transcranial doppler sonography(TCD),18) and magnetic resonance imaging (MRI).2) Recently, relatively easy access and adequate cerebral perfusion imaging of CTP using multi-channel computed tomography has prompted greater use of this imaging modality. We analyzed the maps of CTP studies in evaluating postoperative cerebral blood flow defects, and infarction.
Material & Methods
1. Patients 24 patients who were diagnosed and treated for an aneurysmal subarachnoid hemorrhage (SAH)from March, 2004 to March, 2005 were included in this study. 7 were male and 17 were female. Mean age was 56 years (26~76). 15 patients received surgical clipping and 9 received endovascular coiling (Table 1). A standardized treatment plan was used in all patients: after admission to the neurosurgical ntensive care unit, neurological examination was performed every 2 hours, and intravenous hydration, nimodipine infusion, and phenytoin injection were performed through a central venous catheter. CTP and angiography was done immediately after operation, and follow up CTP was performed every 2 weeks thereafter if patient condition was stable. TCD was done every other day starting from postoperative day 1 to evaluate cerebral vasospasm. Laboratory work was performed daily. However, the studies such as CTP, TCD and etc, were performed immediately when any signs of decreased mentality or neurological deficit was seen, and immediate initiation of hyperdynamic therapy was done if any abnormalities were found.
2. CT perfusion All patients underwent conventional CT with CTP. A multi-slice spiral CT scanner (Light speed: GE Medical Systems, Milwaukee, Wisconsin, U.S.A)was used for CTP imaging. CTP was performed in 2 consecutive 40 second sessions every 5 minutes. Adjacent 10mm slices 5mm thick were made at the point were the basal ganglia is most easily seen on conventional CT. After waiting for 5 minutes for the serum concentration of the contrast dye to return to the basal level, two more image at a higher level was made using the same technique, to create a total of 4 perfusion images. At each stage, 50ml of nonionic contrast dye, Ultravist (Schering, Germany), was injected at 4ml/sec into the cephalic vein using an injection pump (Medrad, U.S.A). Cerebral blood volume(ml/100ml of brain tissue), Cerebral blood flow(ml/100ml of brain tissue/min), and Mean transit time(sec)was calculated using built in software (GE Medical Systems, Milwaukee, Wisconsin, U.S.A).
3. Comparison of different CTP factors and clinical evaluation Conventional CT and CTP were performed immediately after operation and 2 weeks thereafter if patient condition was stable. Abnormalities in CBV, CBF, and MTT on CTP were evaluated by a single radiologist. Clinical evaluation of each patient was done by initial GCS and GOS at discharge.
4. Statistical Analysis The CBV, CBF, and MTT of CTP maging were divided into normal and abnormal. Initial GCS and GOS at discharge were expressed by the mean and standard deviation. Each factor was analyzed using the Chi Square test and a P value of less than 0.05 was identified as statistically significant. All statistical data was calculated using the SPSS 10.0 version for windows.
Results
CTP images immediately after operation and two weeks after operation were taken in all 24 patients (Table 2). Of the 24 patients, 11 patients (45.8%)showed abnormal CTP findings after operation. All 11 patients received hyperdynamic therapy. Of these 11 patients, 9 patients revealed infarction on follow up CT, and only 2 patients revealed normal radiological findings on follow up CT. All 13 patients (54.2%) who exhibited normal immediate postoperative CTP findings also revealed no evidence of cerebral infarct on follow up CT. A statistically significance correlation (p<0.05)was seen between the normal and abnormal CTP groups, and the sensitivity of CTP imaging was 100%. The abnormal CTP group was further divided into the CBF, CBV, MTT (+/+/+)group and the CBF, CBV, MTT (+/-/+)group (Table 3). All 11 patients who showed abnormal immediate postoperative CTP findings received hyperdynamic therapy. However, all patients in the CBF, CBV, MTT (+/+/+)group (8 patients)showed infarction on follow up CT. 1 out of 3 patients in the CBF, CBV, MTT (+/-/+)group showed infarction. The positive predictable value(PPV)of CBF, CBV and MTT were 81.8%, 100%and 81.8%, respectively. Postoperative CTP and initial GCS were compared in all 24 patients (Table 4). 13 patients with normal postoperative CTP findings showed an initial GCS of 13.08 ±2.50, while 11 patients with abnormal postoperative CTP findings showed an initial GCS of 11.82 ±2.89. No statistical significance was seen between the two groups (p>0.05). Postoperative CTP and GOS at discharge were compared in all 24 patients (Table 5). 13 patients with normal postoperative CTP findings showed a GOS at discharge of 4.85 ±0.38, while 11 patients with abnormal postoperative CTP findings showed a GOS at discharge of 2.82 ±1.60. A statistical significance was seen between the two groups(p<0.05).
Illustrative cases
1. Patient 2 A 64-year-old woman was sent to our hospital after complaining of a severe headache and in a lethargic state. A CT scan showed SAH (Fig. 1A). An angiogram showed a left middle cerebral artery (MCA)aneurysm, and she underwent clipping of the aneurysm. Postoperative CTP study was performed (Fig. 1B), which showed normal perfusion lesions on CBF (Fig. 1C), CBV (Fig. 1D) and MTT maps (Fig. 1E). One day after operation, her neurological status improved. On posthemorrhage Day 8, TCD velocity in the left MCA was 128 cm/sec. Mild vasospasm was suspected. but no additional treatment was performed. On posthemorrhage day 9, her mental status returned to normal. Her neurological status remained stable for the duration of the hospitalization, and she was discharged on posthemorrhage day 33 (Fig. 1F).
2. Patient 9 A 58-year-old-man presented to a community hospital emergency room complaining of a severe headache. He was transferred to our nstitution. A CT scan demonstrated SAH (Fig. 2A). An angiogram showed an anterior communicating artery (ACA)aneurysm, for which he underwent clipping of the aneurysm. After the operation, he remained stuporous. Postoperative CTP study was obtained (Fig. 2B), which showed abnormal perfusion lesions on CBF (Fig. 2C), CBV (Fig. 2D)and MTT maps (Fig. 2E). Routine postoperative angiography showed cerebral vasospasm. He was treated with ntra-arterial papaverine infusion (300 mg). An aggressive course of hyperdynamic therapy was pursued. The systolic pressure was maintained between 160 and 180 mmHg. But the patient 's neurological status depressed, changing from withdrawal to noxious stimulation to irresponsive to noxious stimulation. A follow-up CT scan performed 5 days after the operation showed widespread infarction on both hemispheres (Fig. 2F). He died on post hemorrhage day 9.
3. Patient 19 A 76-year-old woman with a history of clipping of the left posterior communicating artery 1 year ago presented to an emergency room at a community hospital complaining of a severe headache. She was transferred to our institution. A CT scan informed SAH (Fig. 3A). An angiogram showed de novo aneurysm at the left posterior communicating artery, for which she underwent clipping of the aneurysm. After the operation, the patient responded to noxious stimulation but not to commands. Postoperative CTP was performed (Fig. 3B), which showed abnormal perfusion lesions on CBF (Fig. 3C) and MTT maps (Fig. 3D), but a normal CBV map (Fig. 3E). So hyperdynamic treatment was executed. On postoperative day 1, follow-up CT scan was performed, which showed a subdural hematoma on left side. A decompressive craniectomy and evacuation of hematoma was performed. Postoperative 3 week follow-up CT scan showed progressive clearing of the subarachnoid blood and no significant infarction (Fig. 3F). On postoperative day 24, her mental status improved to lethargic. Her mental status remained drowsy for the duration of the hospitalization, and she was transferred to the Department of Rehabilitation on postoperative Day 30.
Discusesion
Vasospasm caused by a cerebral aneurysm was first described by Ecker and Reimenschneider in 1951.12) Later, many more studies revealed that vasospasm is one of the most important complications of SAH caused by aneurysmal rupture, and that it may be detrimental to the patients ' prognosis.1)8) Delayed ischemic deficit caused by vasospasm is a major cause of morbidity and mortality after aneurysmal SAH. Therefore, mmediate diagnosis and adequate treatment is essential for a better patient prognosis. Fisher et al., revealed that vasospasm occurs 4~12 days after initial rupture an aneurysm.21) No correlation was seen between the location of the aneurysm and prevalence of vasopasm.7) The total amount of subarachnoid blood seen on an initial CT scan is a well-established predictor of infarction caused by vasospasm.4)17) Also, the number and amount of hemorrhage in the cisterns correlates with prevalence of vasospasm.24) Even with vigorous removal of the subarachnoid blood clots in the surgical clipping group, there is no statistical differences n the incidence of cerebral vasospasm between the aneurysmal clipping and coiling treatment.32) CTP has several advantages in the monitoring of patients with SAH. MRI and SPECT are more sensitive in detecting areas of vasospasm-related ischemia and decreased blood flow and perfusion, respectively.36) However, although these techniques are more sensitive than CT imaging, they are not as widely available and cannot be as easily obtained compared with CT imaging. SPECT and MRI15)37) has limited use as an imaging modality in the clinical setting due to its high cost and limited availability.28) Studies with xenon CT have indicated that patients are at risk of ischemia or infarction if CBF decreases below 18~20 mL/100g/min, while a PET study found CBF values of less than 12 mL/100 g/min to be a good predictor of subsequent infarction.30) However, limited availability of these modalities has restricted their clinical use to specially equipped centers. Also, many radiological modalities have been studied for early detection of abnormal cerebral blood flow, but studies directed at the effectiveness of CTP in evaluating ruptured aneurysms has been rarely seen. CTP is a method that has been shown to overcome many of the limitations of other CBF technologies. It provides direct anatomic correlation, directly calculates the partition coefficient, and provides relatively high-resolution, quantitative, reproducible CBF information.23) In addition, CTP can provide early, highly accurate delineation of ischemic tissue, allowing the underlying hemodynamic disturbances of vasospasm to be further analyzed. Because CTP image can assess physiolosical parameters such as CBF, CBV, MTT, it offers additional data that can be useful in detecting and characterizing tumors, infection, inflammation, and infarction. It is a non-invasive technique that can obtain an accurate information of mass effect and vascular hemodynamic status quickly and inexpensively. TCD is a commonly used technique to measure blood flow velocities in intracranial vessels. Although perhaps the implest and least invasive method to detect changes in CBF in patients with SAH, this technique is associated with poor sensitivity and specificity21) and is operator dependent, can not quantify CBF at the tissue level, and may not be specific enough by itself to guide therapy.8)30) Therefore, CTP can evaluate a patient more objectively and diversely than the TCD, which in turn can help a physician when to initiate hyperdynamic therapy. SAH leads to a progressive decline in CBF for up to 3 weeks.14) CBV may remain unchanged5) or increase significantly, particularly in poor-grade patients and inpatients with cerebral ischemia.16)20) An increase in CBV in the presence of reduced CBF caused by large-artery vasospasm may result from compensatory dilatation of intraparenchymal vessels.16) A variety of mechanism can contribute to a reduction in CBF after SAH.27) Within hours after the hemorrhage, a generalized reduction in cerebral oxidative metabolism occurs.5) Angiographically apparent cerebral vasospasm occurs in up to 70% of patients with SAH and is associated with decreased regional CBF.6)11) Alterations in CBF can also occur because of impariment of cerebrovascular autoregulation.10) In addition, microcirculatory changes,31) microemboli,34) metabloic changes,5) and inflammatory mechanisms13) may also contribute to alterations n CBF after SAH. Nabavi et al, revealed that CTP had a close relationship to location of ischemia. CBF data correlated well with the location of ischemia, and infarction was seen when cerebral blood flow was less than 10 ml/100g/min.29) MTT data were especially more sensitive to early stage ischemia,29) because increased MTT reflects the velocity of the contrast dye when passing the capillaries of the brain parenchyme, thus reflecting the perfusion pressure of the obstructed distal vessels. Although MTT is sensitive to early ischemic changes, it is less specific than CBF.38) Also, when a vessel is completely occluded, the fate of the ischemic area is dependent on the patency of the CBF. And the reversibility of the ischemic area surrounding the irreversible infarction area is controlled by the formation of collateral vessels. When CBF decreases, vasodilatation occurs leading to increased CBV, and when CBV decreases, it leads to cerebral infarction. Therefore, the nfarction area is seen when both CBV and CBF decreases, but the reversible ischemic area is seen when CBV is restored.19) Through these findings, we can see that CBV has a moderate value in detecting potentially salvageable brain tissue.29) Grubb et al. showed markedly increased CBV in patients with vasospasm due to ischemia-related activation of autoregulation resulting in dilation of resistance vessels.16) The same group reported series of patients with SAH with severely impaired autoregulation.39) Through this study, we revealed that CBF, CBV, and MTT in postoperative CTP were very sensitive in detecting minimal changes in cerebral blood perfusion. However, due to the limited time and personnel, we constructed a analysis using only the abnormality of CBF, CBV and MTT rather than a quantitative one. We divided the abnormal postoperative CTP group into the CBF, CBV, MTT (+/+/+) group and the CBF, CBV, MTT (+/-/+)group. In the first group, all patients(8)revealed infarction on follow up CT even after hyperdynamic treatment, but 2 out of 3 patients in the latter group revealed normal follow up findings. We found that patients with abnormal postoperative CTP findings had a lower GOS at discharge compared to the normal group. However, follow up CT were normal in many case when the CTP and CBV were normal, while CBF and MTT were abnormal, as was shown in the case of patient 19. Moreover, the results of Table 2 showed that CBV was the most important PPV, and of all the CTP para
|