Technical considerations on intra-arterial papaverine hydrochloride for cerebral vasospasm

Intra-arterial infusion of papaverine hydrochloride for subarachnoid hemorrhage-induced cerebral vasospasm has become an adjunctive endovascular therapy along with cerebral angioplasty. Our knowledge concerning the mechanism of action, method of administration and potential side effects of this therapeutic alternative are reviewed. Received: 6 October 1995 Accepted: 4 March 1996     

Restenosis after balloon angioplasty for cerebral vasospasm

Transluminal balloon dilatation for symptomatic vasospasm after subarachnoid hemorrhage is effective, and clinical studies have shown that it achieves long-lasting dilatation of spastic cerebral arteries. Delayed arterial renarrowing has not been reported. Here we report the case of a 58-year-old woman who presented asymptomatic and permanent restenosis after angioplasty for cerebral vasospasm.     

Three-dimensional CT angiography of intracranial vasospasm following subarachnoid haemorrhage

We evaluated the usefulness of three-dimensional CT angiography (3D-CTA) in the diagnosis of intracranial vasospasm following subarachnoid haemorrhage (SAH) in 13 patients suspected of having vasospasm on clinical grounds. The intracranial vessels were clearly shown by 3D-CTA in 12 patients. 3D-CTA revealed spasm in the vessels of nine patients. Catheter angiography performed in seven of these patients immediately after 3D-CTA confirmed vasospasm. A low-attenuation area was seen on CT in the other two patients, representing an ischaemic lesion due to the spasm. In nine patients, a second 3D-CTA was performed using the same technique 1 week after the first, showing no vasospasm. Initial 3D-CTA revealed no vasospasm change in three patients. Following 3D-CTA, one of these had conventional angiography, which also demonstrated no spasm.     

Efficacy of intra-arterial nimodipine in the treatment of cerebral vasospasm complicating subarachnoid haemorrhage

AIM: To examine the efficacy and safety of nimodipine as an alternative to papaverine for the treatment of cerebral vasospasm following subarachnoid haemorrhage. METHODS: We retrospectively reviewed the procedure reports, anaesthetic records, clinical charts and CT and angiographic images of 9 patients who had received intra-arterial nimodipine; 1 of these patients received both nimodipine and papaverine. The difference in arterial luminal diameter before and after treatment was calculated as a percentage change. RESULTS: The average dose of nimodipine administered per vessel was 3.3mg. The mean increase in arterial diameter was 66.6% in the vasospastic segment. There was no significant change in blood pressure of any of the subjects during endovascular treatment of vasospasm. CONCLUSION: Intra-arterial nimodipine is effective in improving angiographic vasospasm complicating subarachnoid haemorrhage. Further studies aimed at examining the clinical benefits of nimodipine are warranted, particularly in view of the low risk of adverse side effects of nimopidine when compared with papaverine.     

New angiographic measurement tool for analysis of small cerebral vessels: application to a subarachnoid haemorrhage model in the rat

Introduction Exact quantification of vasospasm by angiography is known to be difficult especially in small vessels. The purpose of the study was to develop a new method for computerized analysis of small arteries and to demonstrate feasibility on cerebral angiographies of rats acquired on a clinical angiography unit. Methods A new software tool analysing grey values and subtracting background noise was validated on a vessel model. It was tested in practice in animals with subarachnoid haemorrhage (SAH). A total of 28 rats were divided into four groups: SAH untreated, SAH treated with local calcium antagonist, SAH treated with placebo, and sham-operated. The diameters of segments of the internal carotid, caudal cerebral, middle cerebral, rostral cerebral and the stapedial arteries were measured and compared to direct measurements of the diameters on magnified images. Results There was a direct correlation between the cross-sectional area of vessels measured in a phantom and the measurements acquired using the new image analysis method. The spread of repeated measurements with the new software was small compared to the spread of direct measurements of vessel diameters on magnified images. Application of the measurement tool to experimental SAH in rats showed a statistically significant reduction of vasospasm in the SAH groups treated with nimodipine-releasing pellets in comparison to all the other groups combined. Conclusion The presented computerized method for analysis of small intracranial vessels is a new method allowing precise relative measurements. Nimodipine-releasing subarachnoidal pellets reduce vasospasm, but further testing with larger numbers is necessary. The tool can be applied to human angiography without modification and offers the promise of substantial progress in the diagnosis of vasospasm after SAH.     

Prediction of delayed neurological deficit after subarachnoid haemorrhage: a CT blood load and Doppler velocity approach

The predictive value of cranial computed tomography (CT) blood load and serial transcranial Doppler sonography for the development of delayed ischaemic neurological deficit was assessed in 121 patients following subarachnoid haemorrhage. Of the 121 patients, 81 (67%) had thick layers of blood or haematoma, including intraventricular bleeding. The proportion of patients who developed delayed deficit was higher with increasing amounts of subarachnoid blood on the admission CT (51% of 53 cases in Fisher grade 3; 35% of 33 cases in grade 2; 28% of 7 cases in grade 1,P<0.01). Doppler velocities obtained from readings at least every 2 days following admission were higher in patients with delayed neurological deficit (peak velocity for grade 3 patients 176±6 cm/s (mean±SE), versus grade 2: 164±7 cm/s; grade 4 149±9, bothP=0.04, Mann-Whitney). Peak velocity and maximal 24-h rise tended to be higher within different CT grades in patients with a deficit than in those without; this difference was significant for grade 3 patients (P<0.01). We conclude that a combined approach with CT and Doppler sonography provides greater predictive value for the development of delayed ischaemic neurological deficit than either test considered independently. The value of Doppler sonography may be greatest for patients with Fisher grade 3 blood, in whom the risk of delayed ischaemia is greatest.     

The negative angiogram in subarachnoid haemorrhage

Our purpose was to review the incidence of negative cerebral panangiography in acute nontraumatic subarachnoid haemorrhage (SAH); to document the amount and distribution of subarachnoid blood on CT and determine its relationship to findings on repeat angiography; and to study the outcome of these patients from the time of presentation to hospital discharge. From 1983 to 1992, 295 patients underwent cerebral angiography for acute SAH at our institution. The CT, angiographic and MRI findings and clinical course of patients with initially negative angiograms were reviewed retrospectively. The overall incidence of negative cerebral panangiography was 31% (92/295). An aneurysm was disclosed on a second angiogram in 4 cases, and on a third angiogram in 1, giving a total false negative rate of 5%. In 55% of cases, only a small amount of SAH was present on CT. The distribution of the subarachnoid blood was nonspecific and resembled the pattern seen in aneurysmal SAH. Ninetyfour percent, of the patients presented in Hunt-Hess grades I and II. The complications of conservative treatment were few: a rebleed rate of 4%, delayed cerebral ischemia in 4%, cerebral infarcts in 8% and hydrocephalus requiring shunting in 3%. On discharge, 93% of patients had recovered completely and the others were left with moderate disability. There were two deaths related to massive rebleeding. Patients with perimesencephalic SAH (35%) fared particularly well; none developed complications during their hospital stay and repeat angiograms never revealed an underlying aneurysm. In such cases, further angiographic investigations do not seem warranted.     

Postoperative assessment of cerebral blood flow in subarachnoid haemorrhage by means of99mTc-HMPAO tomography

Regional hypoperfusion is a very frequent complication of subarachnoid haemorrhage (SAH), being related to vasospasm in the majority of cases. Twenty-six patients who were admitted for SAH underwent follow-up with technetium-99m hexamethylpropylene amine oxime single photon emission tomography (SPECT) 3 and 8 days after surgery. Fifteen patients of these had one more examination 15 days after surgery. The degree of hypoperfusion was quantified using an index of asymmetry which allow the comparison of two symmetrical regions of interest (ROIs) on the transaxial slice which presented the greatest perfusion defect. Comparison of CT data, transcranial Doppler data and clinical signs with the perfusion as quantified by^99mTc-HMPAO SPECT indicates that a difference in counts of less than 10% between the two symmetrical ROIs is of no diagnostic value. Follow-up of the brain perfusion clearly shows that the most pronounced hypoperfusion was observed just after surgery, with progressive normalization at 8 and 15 days after surgery.^99mTc-HMPAO SPECT performed 8 days after surgery allows prediction of the clinical outcome. For these reasons,^99mTc-HMPAO SPECT, which is the only method for follow-up of cerebral perfusion in routine clinical practice, should be the first examination to be performed after surgery in patients with SAH.     

Intraarterial papaverine infusion for cerebral vasospasm after subarachnoid hemorrhage.

PURPOSETo evaluate the techniques and efficacy of intracranial intraarterial papaverine infusion for symptomatic vasospasm after subarachnoid hemorrhage caused by aneurysm rupture.METHODSPapaverine was infused on 19 occasions in 14 patients, 6 hours to 2 days after spasm became apparent clinically. Sixty vascular territories were treated. Infusion was made into the supraclinoid internal carotid artery 20 times, cavernous internal carotid artery once, selective A1 anterior cerebral artery 8 times, M1 middle cerebral artery 7 times, and basilar artery 3 times. Papaverine doses ranged from 150 to 600 mg and exceeded 400 mg on 8 occasions.RESULTSAngiographic improvement occurred in 18 (95%) of the 19 treatment sessions: results were excellent in 3 sessions, moderate in 8, and mild in 7. The best angiographic results often were obtained with superselective infusion, although angiographic results did not always correlate with clinical response. Seven (50%) of the 14 treated patients showed dramatic acute clinical improvement within 24 hours of papaverine therapy, and there was no clinical evidence of recurrent vasospasm in these patients. Recurrence of angiographic vasoconstriction was demonstrated in three patients; one showed marked clinical improvement after a second treatment. There were no episodes of systemic hypotension in any of the cases. Monocular blindness developed in one patient because of papaverine infusion near the ophthalmic artery.CONCLUSIONSPapaverine was effective in dilating narrowed arteries in most patients with symptomatic vasospasm caused by subarachnoid hemorrhage. This series showed encouraging clinical results with no recurrence of neurologic deterioration in those patients who responded well to papaverine. Superselective infusion appears to be indicated in some cases for adequate papaverine delivery.     

The need for repeat angiography in subarachnoid haemorrhage

This study was designed to assess the necessity for a second angiogram study in patients in whom initial angiography after primary subarachnoid haemorrhage (SAH) was negative. During a 12-year period, 122 of 694 patients (17.5 %) had negative initial angiograms. CT, available for 98 patients, showed a preponderance of subarachnoid blood in the perimesencephalic cisterns in 50 of 73 patients (68.5 %) in whom blood was visible on CT. Angiography, repeated in 67 patients, revealed an aneurysm in 4 (6 %): 2 had an aneurysm of the anterior communicating artery, 1 of the posterior inferior cerebellar artery, and 1 of the P2 segment of the posterior cerebral artery. CT showed subarachnoid blood in the interpeduncular and ambient cisterns in this last case, and a preponderance of subarachnoid blood outside the perimesencephalic cisterns in the remaining 3 patients. Received: 14 March 1997 Accepted: 2 May 1997     

硫酸镁对兔蛛网膜下腔出血后血管痉挛的防治效果

目的探讨药物硫酸镁对蛛网膜下腔出血后血管痉挛的影响。方法新西兰大白兔12只,枕大池二次注血法建立蛛网膜下腔出血模型,经TCD检测筛选出发生血管痉挛8只,随机分为硫酸镁组（MgSO4组）与生理盐水组（NaCl组）,按时间点再分为1d、3d、5d、7d、14d,5亚组（n=4）,观察各亚组实验兔神经行为学评分变化,运用经颅多普勒（TCD）对各亚组实验兔基底动脉（BA）血流速率进行检测。结果 3d起MgSO4组较NaCl组神经行为学测定评分减轻（P〈0.05）,硫酸镁组的BA平均速率3d起较生理盐水组减轻（P〈0.05）,7d时最具显著性（P〈0.01）。结论硫酸镁药物可缓解蛛网膜下腔出血后血管痉挛。     

Current diagnostic approaches to subarachnoid haemorrhage

Over the past decade, significant advances have been made in the field of subarachnoid haemorrhage (SAH). Prompt diagnosis with high-resolution CT and intensive critical care support remain key aspects of good patient management. Early identification and definitive treatment of underlying ruptured aneurysms is generally advocated to reduce the risk of re-bleeding, a complication with high mortality and morbidity. Although intra-arterial digital subtraction angiography (DSA) is still considered the gold standard for sourcing aneurysms, CT angiography, especially with the evolution of multi-slice technology, is slowly gaining acceptance as a rapid, accessible and minimally invasive method which appears likely to replace DSA as first-line modality in the future. Furthermore, the advent of Guglielmi detachable coils and the ISAT trial have revolutionised the treatment of ruptured aneurysms, with a significant trend towards endovascular coiling away from operative clipping. Improvements in clinical experience, coiling technology and assistive devices now allow interventionalists to potentially treat the majority of aneurysms, including wide-necked or complex lesions. The uncertain long-term results of coiling, however, still fuel strong debate and controversy. This review summarises current diagnostic approaches to SAH from a radiological perspective, with an emphasis on aneurysmal SAH and an evidence-based approach to the role of imaging and interventional radiology in diagnosis, treatment and follow-up.     

The source of haemorrhage in traumatic basal subarachnoid haemorrhage

Traumatic basal subarachnoid haemorrhage (TBSH) following trauma to the head, face or neck is well-established as a cause of death; however it remains a heavily disputed topic as the site of vascular injury is difficult to identify. Whilst many regions within the vasculature of the head and neck have been proposed as more susceptible to rupture, the vertebral artery remains the focal point of many investigations. We present a retrospective case review of TBSH in our forensic centre at Forensic and Scientific Services in Brisbane, Australia, from 2003 to 2011. Thirteen cases of TBSH were found, one case excluded due to vasculopathy. All decedents were male, the majority of which were involved in an altercation receiving blows to the head, face, or neck and were unconscious at the scene. All victims were under the influence of alcohol, drugs, or a combination thereof. External examination revealed injuries to the head, face, and neck in all cases. Various combinations of further examination techniques were used during the post-mortem examination including brain and/or cervical spine retention, CT imaging, and angiography. Vascular injury was identified in eight of the twelve cases, all of which occurred intracranially, with seven involving the vertebral artery. Histology was most reliable in identifying the rupture site and angiography failed to reveal a rupture site. The added benefits of histology over angiography are the ability to identify the microscopic architecture of the tear and to diagnose vasculopathy that may have rendered the individual more susceptible to TBSH.     

Intraarterial injection of colforsin daropate hydrochloride for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage: preliminary report of two cases

We describe two patients with symptomatic vasospasms after aneurysmal subarachnoid hemorrhage who were successfully treated with intraarterial injection of colforsin daropate hydrochloride (HCl). Colforsin daropate HCl is capable of directly stimulating adenylate cyclase, which in turn causes vasorelaxation via elevated intracellular concentrations of cyclic adenosine monophosphate. We suggest that colforsin daropate HCl might be a useful therapeutic tool in treating cerebral vasospasm.     

Perfusion-weighted MRI to evaluate cerebral autoregulation in aneurysmal subarachnoid haemorrhage

Introduction  The aim of this study was to evaluate autoregulatory mechanisms in different vascular territories within the first week after aneurysmal subarachnoid haemorrhage (SAH) by perfusion-weighted magnetic resonance imaging (PW-MRI). For this purpose, regional cerebral blood flow and volume (rCVF and rCBV) were measured in relation to different degrees of angiographically visible cerebral vasospasm (CVS). Materials and methods  In 51 SAH patients, PW-MRI and digital subtraction angiography were performed about 5 days after onset of SAH. Regional CBF and rCBV were analysed in the territories of the anterior cerebral artery (ACA), the middle cerebral artery (MCA) and the basal ganglia of each hemisphere in relationship to the degree of CVS in the particular territory. Correlations between rCBF, rCBV and CVS were analysed. Results  CVS was found in 22 out of 51 patients in at least one territory. In all territories, rCBV decreased with increasing degree of CVS, correlated with a decrease of rCBF. In the ACA territories, SAH patients with severe CVS had significantly lower rCBF compared to healthy subjects and to SAH patients without CVS. In the basal ganglia, rCBF and rCBV of the control group were significantly higher compared to the patients without and with moderate vasospasms. Conclusion  PW-MRI showed simultaneous decrease of rCBF and rCBV in patients with SAH. The fact that rCBV did not increase in territories with CVS to maintain rCBF reveals dysfunctional vascular autoregulation. Vasospasms in the microvasculature are most evident in the basal ganglia, showing decreased rCBV and rCBF even in SAH patients without CVS.     

MRI in acute subarachnoid haemorrhage; findings with a standardised stroke protocol

There is doubt as to whether acute haemorrhage is visible on MRI. We carried out MRI within 6 h of symptom onset on five patients with minor (low Hunt and Hess grades 1 or 2) subarachnoid haemorrhage (SAH) diagnosed by CT to search for any specific pattern. We used our standard stroke MRI protocol, including multiecho proton density (PD)- and T2-weighted images, echoplanar (EPI) diffusion- (DWI) and perfusion- (PWI) weighted imaging, and MRA. In all cases SAH was clearly visible on PD-weighted images with a short TE. In four patients it caused a low-signal rim on the T2*-weighted source images of PWI, and DWI revealed high signal in SAH. In the fifth patient SAH was perimesencephalic; susceptibility effects from the skull base made it impossible to detect SAH on EPI DWI and T2*-weighted images. Perfusion maps were normal in all cases. MRA and conventional angiography revealed an aneurysm in only one patient. Stroke MRI within 6 h of SAH thus shows a characteristic pattern.     

Dilatation of the temporal horn in subarachnoid haemorrhage

Summary CT studies of 50 patients with spontaneous subarachnoid haemorrhage (SAH) and 100 randomly selected patients were reviewed with regard to the size of the frontal and temporal horns of the lateral ventricles. The temporal horn was classified into four grades, based on the size of its posterior portion at the level of the midbrain. The horn was clearly visible in 66% of patients with SAH, but in only 2% of controls. In the SAH group, the temporal horn tended to dilate sooner than the frontal horn after haemorrhage and could be seen clearly in a larger proportion of patients. Thus, assessment of the size of the temporal horn appears to be a simple and sensitive method for assessing ventricular dilatation. In addition, dilatation of the temporal horn may prove to be an important indirect sign suggesting SAH in patients in whom no high density clot is seen on CT.     

CT angiography and perfusion imaging in patients with subarachnoid hemorrhage: correlation of vasospasm to perfusion abnormality

INTRODUCTION: We retrospectively evaluated computed tomography angiography (CTA) and perfusion imaging (CTP) of patients with aneurysmal subarachnoid hemorrhage (SAH) for any correlation between degree of vasospasm and perfusion deficit. MATERIALS AND METHODS: Sequentially performed CTP and CTA of 41 patients at least at the third day of postbleeding were reviewed for vasospasm and perfusion deficit throughout the anterior and middle cerebral arteries and corresponding territories. Vasospasm was noted comparing the contralateral normal ones or extradural components of the vessel itself and graded to negative, mild, moderate, and severe as luminal narrowing none, <25%, between 25% and 50%, and >/=50%, respectively. CTP abnormality was noted using cerebral blood flow and volume and mean transit time maps. RESULTS: Of 41 patients, 20 had no vasospasm; 15 had mild to moderate and six had severe vasospasm. Three of 20 patients with no vasospasm (15%), four of 15 patients with mild to moderate vasospasm (26%), and five of six patients with severe vasospasm (83%) had perfusion abnormality. Perfusion abnormalities noted were ischemia, infarction, and hyperperfusion. Perfusion abnormality without vasospasm was observed in the watershed areas and adjacent to sulcal clots. CONCLUSION: In SAH patients, if there is a macrovascular vasospasm with luminal narrowing >/=50%, there is a high likelihood (83%) of perfusion abnormality in the territory of the vasospastic vessel. There may also be perfusion abnormality without macrovascular vasospasm in the watershed areas or in the vicinity of sulcal clots.     

Endovascular treatment of cerebral vasospasm: assessment of treatment effect by cerebral angiography and transcranial colour Doppler sonography

In a retrospective study of 30 consecutive patients with symptomatic vasospasm the mean degree of narrowing as compared to the initial angiogram was 35 % (± 24 %) in 12 intradural internal carotid arteries (ICA), 42 % (± 17 %) in 42 proximal middle cerebral (MCA) and 38 % (± 19 %) in 27 anterior cerebral arteries (ACA). The corresponding increase in mean flow velocities from baseline values obtained by transcranial colour Doppler sonography (TCD) within 12 h of the first angiogram to the time of clinical vasospasm was considerably higher, with 49 % (± 34 %) in the ICA, 119 % (± 92 %) in the MCA and 147 % (± 170 %) in the ACA. Following superselective intra-arterial papaverine application in 66 arteries and balloon angioplasty of 15 arteries, 78 (96.3 %) of 81 dilated. Sustained clinical improvement was achieved in 22 patients (73.3 %). The mean reversal of angiographic vasospasm was 71 % for the ICA (range 10–100 %), 81 % for the MCA (range 9–100 %) and 82 % (range 0–100 %) for the A1 segment. The mean reduction of flow velocities after treatment was much less with 23 % (± 21 %) in the ICA, 32 % (± 24 %) in the MCA and 25 % (± 22 %) in the A1 segment. Received: 10 November 1998 Accepted: 1 December 1998     

Acute subarachnoid Haemorrhage: 3D time-of-flight MR angiography versus intra-arterial digital angiography

To evaluate the efficacy and reliability of 3D time-of-flight MR angiography (TOF MRA) as a noninvasive procedure, 27 patients with acute subarachnoid haemorrhage (SAH) were studied with MRA immediately before or after intra-arterial digital subtraction angiography (DSA). 3DTOF MRA was performed with an axial slab of 60 mm centred on the circle of Willis and isotropic voxels. DSA showed 22 aneurysms and 1 dural arteriovenous fistula in 21 patients; the aneurysms ranged in size from 2 to 8 mm. MRA failed to show 2 small aneurysms, at the origin of the posterior and anterior communicating arteries. The 3D display of the intracranial vessels obtained with maximum intensity projection (MIP) or targetted MIP sometimes rendered the aneurysms better than DSA. However, due to its high spatial resolution, DSA more clearly defined the overall anatomy of the walls of the normal and abnormal vessels.1992 Scientific Award of the ESNR