Value of transcranial Doppler examination in the diagnosis of cerebral vasospasm after subarachnoid hemorrhage

In 21 patients with subarachnoid hemorrhage secondary to ruptured intracranial aneurysms, we performed serial neurological evaluations, transcranial Doppler examinations, and cerebral blood flow (CBF) determinations. We classified 8 patients as having vasospasm (delayed neurological deterioration, appropriate reduction of CBF) and 13 patients as having no spasm on the basis of this information. Transcranial Doppler flow velocities in the middle cerebral artery and the anterior cerebral artery were significantly elevated for the group with vasospasm on posthemorrhage Days 4 through 12. Elevation of transcranial Doppler velocities preceded clinical signs of cerebral ischemia. The maximal transcranial Doppler flow velocities achieved were compared on the basis of the extent of clot on early computed tomographic (CT) scans. The mean anterior cerebral artery flow velocities were significantly different between CT Grades II and III. The initial transcranial Doppler flow velocities were compared on the basis of the patient's Hunt and Hess grade upon admission. The flow velocities for Grade V patients were significantly lower than those for Grade IV patients. Transcranial Doppler flow velocities were compared with arteriographically observed anterior cerebral artery and middle cerebral artery radii in 12 instances. The correlation was poor, but the data should be interpreted cautiously in view of the small number of arteriograms. We conclude that transcranial Doppler examination has considerable potential in the early diagnosis of delayed ischemic neurological deficit (clinical vasospasm) in patients with subarachnoid hemorrhage.     

Transcranial Doppler in the evaluation of vasospasm after subarachnoid hemorrhage

Flow velocities (F.V.) in 65 patients admitted for subarachnoid hemorrhage (S.A.H.) were measured 4-7 times a week by Transcranial Doppler (T.C.D.). Patients were classified into 4 T.C.D. groups according to the highest mean flow velocity recorded in the M.C.A. during hospitalization: Group 1 (18 patients) with F.V. below 100 cm/s (normal), group 2 (19 patients) with F.V. between 100-150 cm/s (starting spasm), group 3 (23 patients) with F.V. between 150-200 cm/s (major spasm) and group 4 (5 patients) with F.V. over 200 cm/s (critical spasm). Based on clinical, radiological and ultrasound data as well as patient outcome (good results with no specific problems or with transient deficit, permanent deficit and pre- or postoperative death), the authors analyse the value of T.C.D. in the evaluation of vasospasms following S.A.H. The review involves 49 patients with surgically treated aneurysms (including two associated A.V.M.s), 9 patients who had suffered a S.A.H. of unknown origin and 7 patients who had died prior to surgery. T.C.D. is a non-invasive method of following post-S.A.H. spasms and the close correlation between the angiography and the T.C.D. makes pre-operative control angiographies unnecessary. A correlation between clinical status and T.C.D. was only observed in extreme cases where F.V. exceeded 200 cm/s or increased by 100 cm/s or more within 3 days (6 patients out of 65). M.C.A. spasm can, however, be underestimated by the T.C.D. approach in cases where there is an associated spasm of the infraclinoidal carotid artery. In these cases, classical Doppler evaluation of the cervical portion of the I.C.A. is indicated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of angiographic vasospasm after subarachnoid hemorrhage: implications for diagnosis by transcranial Doppler ultrasonography

A study was undertaken to determine how frequently angiographic vasospasm occurs outside the normal access range of transcranial Doppler ultrasound in patients who have suffered a subarachnoid hemorrhage. Vasospasm located in the basal vessels is readily identifiable using transcranial Doppler ultrasound whereas spasm affecting the more distal, vertically oriented arteries is outside the standard detection range. It is therefore speculated that the sensitivity of the technique would be adversely affected by a high incidence of distal vasospasm. A total of 136 angiograms performed on 68 patients after a subarachnoid hemorrhage from anterior circulation aneurysms were reviewed to determine the typical distribution of vasospasm. Of the 40 cases that showed greater than or equal to 25% vessel narrowing, 50.0% had spasm restricted to the basal vessels, 42.5% had spasm involving both basal and distal segments, and 7.5% had spasm of the distal segments only. None of the patients with distal vasospasm alone developed delayed ischemic deficits. It is concluded that most patients with anterior circulation aneurysms who develop vasospasm will have involvement of the basal vessels, but a small number of patients may develop vasospasm only in distal vessels.     

HLA-type of cerebral vasospasm patients after aneurysmal subarachnoid hemorrhage

We studied human lymphocyte antigen (HLA) types in a group of 45 patients who had aneurysmal subarachnoid hemorrhage (SAH). A significantly increased frequency of HLA antigen A31 and a significantly decreased frequency of HLA antigen B40 were found. In patients with delayed ischemic neurological deficit (DIND) following aneurysmal SAH and HLA typing, HLA-Bw60 antigen showed significant increases; in patients who did not develop HLA-Aw33 and-Cw4 antigens showed significant. Among the patients with Fisher's Group 3 on CT, in particular, these antigens significantly increased when compared with controls from the same geographic area. These results suggest that HLA-Bw60 antigen plays a role as a predisposing factor of DIND resulting from vasospasm following aneurysmal SAH, and that HLA-Aw33 and-Cw4 exert protective influence against DIND.     

Vasospasm probability index: a combination of transcranial doppler velocities, cerebral blood flow, and clinical risk factors to predict cerebral vasospasm after aneurysmal subarachnoid hemorrhage

OBJECT: The goal in this study was to create an index (vasospasm probability index [VPI]) to improve diagnostic accuracy for vasospasm after subarachnoid hemorrhage (SAH). METHODS: Seven hundred ninety-five patients in whom aneurysmal SAH was demonstrated by computed tomography, and in whom one or more intracranial aneurysms had been diagnosed, underwent transcranial Doppler (TCD) studies between April 1998 and January 2000. In 154 patients angiography was performed within 24 hours of the TCD examination, and in 75 133Xe cerebral blood flow (CBF) studies were obtained the same day. Seven cases were excluded because of a limited sonographic window. Forty-one women (60.3%) and 27 men (39.7%) between the ages of 35 and 84 years (58.0 +/- 13.2 years [mean +/- standard deviation]) were included. Clinical characteristics analyzed included age, sex, Hunt and Hess grade, Fisher grade, days after SAH, day of treatment, type of treatment (coil embolization, surgical clip occlusion, or conservative treatment), smoking history, and hypertension history. Lindegaard ratios and spasm indexes (TCD velocities/hemispheric CBF) were calculated bilaterally. Digital subtraction angiography images were measured at specific points of interest. Sensitivity, specificity, predictive values, and global accuracy of the different tests were calculated. Logistic regression was used to evaluate the possible predictive factors, and the coefficients of the logistic regression were integrated to create the VPI. RESULTS: In 18 patients (26.5%) symptomatic vasospasm was diagnosed, and 33 (48.5%) had angiographic evidence of vasospasm. For TCD velocities above 120 cm/second at the middle cerebral artery, the global accuracy was 81.1% for the diagnosis of clinical vasospasm and 77.2% for angiographic vasospasm. For a Lindegaard ratio higher than 3.0, the accuracy was 85% for clinical vasospasm and 83.2% for angiographic vasospasm. A spasm index higher than 3.5 had an accuracy of 82.0% for the diagnosis of clinical vasospasm and 81.6% for angiographic vasospasm. The selected model for estimation of clinical vasospasm included Fisher grade, Hunt and Hess grade, and spasm index. The VPI had a global accuracy of 92.9% for clinical vasospasm detection. For diagnosis of angiographic vasospasm, the model included Fisher grade, Hunt and Hess grade, and Lindegaard ratio. The VPI achieved a global accuracy of 89.9% for angiographic vasospasm detection. CONCLUSIONS: The use of TCD velocities, Lindegaard ratio, and spasm index independently is of limited value for the diagnosis of clinical and angiographic vasospasm. The combination of predictive factors associated with the development of vasospasm in the new index reported here has a significantly superior accuracy compared with the independent tests and may become a valuable tool for the clinician to evaluate the individual probability of cerebral vasospasm after aneurysmal SAH.     

Increased cerebral blood flow but no reversal or prevention of vasospasm in response to L-arginine infusion after subarachnoid hemorrhage

OBJECT: The reduction in the level of nitric oxide (NO) is a purported mechanism of delayed vasospasm after subarachnoid hemorrhage (SAH). Evidence in support of a causative role for NO includes the disappearance of nitric oxide synthase (NOS) from the adventitia of vessels in spasm, the destruction of NO by hemoglobin released from the clot into the subarachnoid space, and reversal of vasospasm by intracarotid NO. The authors sought to establish whether administration of L-arginine, the substrate of the NO-producing enzyme NOS, would reverse and/or prevent vasospasm in a primate model of SAH. METHODS: The study was composed of two sets of experiments: one in which L-arginine was infused over a brief period into the carotid artery of monkeys with vasospasm, and the other in which L-arginine was intravenously infused into monkeys over a longer period of time starting at onset of SAH. In the short-term infusion experiment, the effect of a 3-minute intracarotid infusion of L-arginine (intracarotid concentration 10(-6) M) on the degree of vasospasm of the right middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF) was examined in five cynomolgus monkeys. In the long-term infusion experiment, the effect of a 14-day intravenous infusion of saline (control group, five animals) or L-arginine (10(-3) M; six animals) on the occurrence and degree of cerebral vasospasm was examined in monkeys. The degree of vasospasm in all experiments was assessed by cerebral arteriography, which was performed preoperatively and on postoperative Days 7 (short and long-term infusion experiments) and 14 (long-term infusion experiment). In the long-term infusion experiment, plasma levels of L-arginine were measured at these times in the monkeys to confirm L-arginine availability. Vasospasm was not affected by the intracarotid infusion of L-arginine (shown by the reduction in the right MCA area on an anteroposterior arteriogram compared with preoperative values). However, intracarotid L-arginine infusion increased rCBF by 21% (p < 0.015; PCO2 38-42 mm Hg) in all vasospastic monkeys compared with rCBF measured during the saline infusions. In the long-term infusion experiment, vasospasm of the right MCA occurred with similar intensity with or without continuous intravenous administration of L-arginine on Day 7 and had resolved by Day 14. The mean plasma L-arginine level increased during infusion from 12.7+/-4 microg/ml on Day 0 to 21.9+/-13.1 microg/ml on Day 7 and was 18.5+/-3.1 microg/ml on Day 14 (p < 0.05). CONCLUSIONS: Brief intracarotid and continuous intravenous infusion of L-arginine did not influence the incidence or degree of cerebral vasospasm. After SAH, intracarotid infusion of L-arginine markedly increased rCBF in a primate model of SAH. These findings discourage the use of L-arginine as a treatment for vasospasm after SAH.     

细胞凋亡在蛛网膜下腔出血后脑血管痉挛发病中的作用

背景 脑血管痉挛(cerebral vasospasm,CVS)是蛛网膜下腔出血(subarachnoid hemorrhage,SAH)和颅内动脉瘤术后致死或致残的主要并发症之一,如何有效地治疗脑血管痉挛成为防治SAH的主要目标,但其确切机制尚不清楚,新近许多研究表明细胞凋亡可能在SAH后CVS的发病中发挥重要作用....     

Cerebral vasospasm after subarachnoid hemorrhage, and inhibitory effect of nicardipine investigated by means of transcranial Doppler ultrasonography]

Cerebral vasospasm is a major complication associated with subarachnoid hemorrhage (SAH). However, real-time evaluation of vasospasm is very difficult via angiography, CT scan, and cerebral blood flow. In this study, for the evaluation of the arterial narrowing, the flow velocity in the middle cerebral artery (MCAFV) was measured with transcranial Doppler ultrasonography (TCD) in 41 patients with ruptured cerebral aneurysms which were repaired surgically within 48 hours after SAH. MCAFV was measured daily until the 25th day after onset. All patients underwent CT scan, angiography, and neurological assessments upon admission. To clarify the morphological changes of the cerebral vessels due to SAH, angiography was performed again about 10 days after surgery. For evaluation of the efficacy of treatment for vasospasm, 21 out of 41 cases were administered a calcium antagonist (4mg of nicardipine) through the cisternal drain every 12 hours for an average of 10 days. The other 20 cases did not receive nicardipine and served as controls. 15 patients with clinical symptoms had a rapid increase in MCAFV from the 3rd to 6th day after onset, and a high velocity of more than 150cm/sec continued for 7.6 +/- 3.6 days on the average. In marked contrast, 26 patients without clinical symptoms showed only a small increase in MCAFV of less than 110cm/sec. There was a significant correlation between the arterial narrowing of MCA and MCAFV (gamma = 0.72, p less than 0.01) except for 5 cases (12%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early transcranial Doppler after subarachnoid hemorrhage: clinical and radiological correlations

BACKGROUND: The initial decrease in the level of consciousness after subarachnoid hemorrhage (SAH) is commonly considered secondary to cerebral hypoperfusion and metabolic depression. Age, intracranial pressure, and the amount of cisternal blood are closely related to the clinical grade on admission after SAH. Transcranial Doppler (TCD) may partially and indirectly estimate cerebral blood flow through analysis of flow velocity in the middle cerebral artery (MCA). Besides, pulsatility index (PI) can also be considered an indirect estimator of cerebrovascular resistance. The objective of this study was to determine the TCD parameters in the early stage after SAH and to analyze their correlation with the main clinical and radiological variables on admission. METHODS: A series of 52 consecutive patients diagnosed with SAH, with an abnormal computed tomography (CT) scan on admission and a TCD performed in the first 24 hours from the onset of the hemorrhage, were retrospectively reviewed. Age, sex, clinical grade, presence of cisternal blood or hydrocephalus on initial CT scan, and parameters of TCD examination were recorded for every patient. The relationship between sonographic and clinical and radiological variables was evaluated by partial correlation test, Kruskal-Wallis, and Student t test for paired samples. RESULTS: There were no significant differences in blood flow velocities or PIs between the left and right sides. Lower velocities and higher PIs correlated with a worse clinical condition at admission. Lower velocities also correlated with larger amounts of cisternal blood on the initial CT scan. No significant correlation was observed between PI and the amount of blood in the initial CT scan. CONCLUSIONS: A global decrease in blood velocity in the MCA along with a rise in PI is present in the first 24 hours after SAH. These changes correlate with the clinical deterioration and partially with the amount of blood in the initial CT scan. These findings support the hypothesis that low cerebral perfusion caused by high intracranial pressure leads to diffuse ischemic changes in the early phase of SAH.     

Extracranial-intracranial bypass surgery for the management of vasospasm after subarachnoid hemorrhage

A case is presented which demonstrates the potential utility of the extracranial-intracranial bypass procedure for the treatment of vasospasm after subarachnoid hemorrhage. Extracranial-intracranial bypass surgery offers another alternative to the treatment of patients with vasospasm who have failed aggressive medical management.     

Role of computed tomography in the management of vasospasm after subarachnoid hemorrhage

The role of computed tomography (CT) in the management of vasospasm from subarachnoid hemorrhage was evaluated in 242 consecutive cases with CT performed within 7 days after hemorrhage. Only 20% of these cases did not show a detectable subarachnoid hemorrhage on CT. Subsequent angiograms showed vessel narrowing in 56% of the cases; associated clinical deterioration was noted in 34% of the cases. On later CT, clear ischemic areas were detected in 20% of the cases. A strict correlation between the amount of cisternal blood and the subsequent development of vasospasm was observed: although absent or thin cisternal depositions were rarely associated with vasospasm, consistent or thick depositions were frequently linked to vasospasm (72% of the cases) and to ischemic disturbances (51% of the cases), as well as to clear ischemic areas on later CT (30% of the cases). Regarding the morphology of the cisternal blood collection, the risk of developing vasospasm was at its lowest (42%) for depositions only in the frontal interhemispheric fissure and was at its highest (79%) for depositions in multiple cisterns. The site of cisternal deposition corresponded closely to the area of ischemia on later CT. The persistence of subarachnoid blood more than 72 hours after hemorrhage probably increases the risk of vasospasm, although our data are not conclusive. The definition of a CT scan "at risk" for vasospasm--based on the previous findings--gives practical advantages: proper selection of patients in regard to timing of operation, closer observation and the possibility of prophylactic treatment in patients "at risk," and more adequate evaluation of different therapeutic modalities for vasospasm. With regard to the last point, the incidence of vasospasm was not statistically different between two groups of patients uniformly "at risk": the first group submitted to early operation and the second awaiting operation.     

Cerebral vasospasm following subarachnoid hemorrhage: effect of calcitonin gene-related peptide on middle cerebral artery velocities using transcranial Doppler sonography

The case of a middle cerebral artery vasospasm following subarachnoid hemorrhage is discussed. The effectiveness of treating the vasospasm with calcitonin gene-related peptide is illustrated.     

Contribution of Src tyrosine kinase to cerebral vasospasm after subarachnoid hemorrhage

OBJECT: Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm. METHODS: An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2-treated, and Src inhibitor damnacanthal-treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of 18 dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed. Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal. CONCLUSIONS: The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.