Neuroradiologic diagnosis and treatment of vasospasm

For survivors of aneurysmal subarachnoid hemorrhage, cerebral vasospasm significantly contributes to its morbidity and mortality by causing delayed ischemic neurological deficit. Noninvasive evaluation with computed tomography, transcranial doppler and single photon emission computerized tomography helps guide clinical decisions. Endovascular therapy of symptomatic vasospasm with balloon angioplasty and to a lesser extent with intraarterial papaverine infusion has emerged as an important treatment adjunct to neurosurgical medical and operative management. Early and aggressive treatment with balloon angioplasty has resulted in sustained clinical improvement in about two-thirds of patients suffering from neurological deficits attributable to vasospasm. Encouraging long-term clinical and transcranial artery damage following angioplasty. Despite balloon angioplasty's 2% to 5% peri-procedure mortality rate, it remains under used.     

The protective effects of ipratropium bromide and terbutaline on distilled water-induced bronchoconstriction

Subarachnoid hemorrhage (SAH) was produced in rabbits by four subarachnoid injections of blood (n = 7) or saline (n = 6); a control group (n = 6) had no injections. Basilar artery vasospasm was assessed by serial angiograms. Resting CBF (microspheres) and CBF reactivity to hypercapnia (65 and 85 mm Hg) and hypoxia (fractions of inspired oxygen of 0.15 and 0.10) were determined. Basilar artery vasospasm was seen with SAH. Resting CBF was reduced by 31% (SAH 43 +/- 12, saline 65 +/- 17, control 60 +/- 21 ml 100 g-1 min-1), and resting cerebrovascular resistance was increased (SAH 1.84 +/- 0.30, saline 1.31 +/- 0.49, control 1.39 +/- 0.25 mm Hg ml-1 100 g-1 min-1) after SAH. CBF rose to a similar degree in all three groups in response to hypercarbia and hypoxia. We conclude that resting CBF is reduced in this model of SAH, but vascular reactivity remains intact.     

Prenatal diagnosis of 22q11 microdeletion

It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm. A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically. Mean cisternal CSF level of SOD in 12 control cases (12.99 +/- 2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44 +/- 0.7 U/ml) and in 40 patients treated by delayed surgery (7.64 +/- 0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23 +/- 1.86 U/ml; in 27 cases without vasospasm mean level was 5.43 +/- 0.7 U/ml (p < 001). The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.     

Intra-aortic balloon counterpulsation augments cerebral blood flow in the patient with cerebral vasospasm: a xenon-enhanced computed tomography study

OBJECTIVE: We previously established the ability of intra-aortic balloon counterpulsation (IABC) to improve cerebral blood flow (CBF) significantly in a canine model of cerebral vasospasm. This study was performed to assess the efficacy of IABC in a patient with cardiac dysfunction and severe cerebral vasospasm that was refractory to traditional treatment measures. METHODS: We report our experience with the clinical use of IABC to treat cerebral vasospasm in a patient who suffered subarachnoid hemorrhage and concomitant myocardial infarction. Hypertensive, hypervolemic, hemodilution therapy was ineffective, and IABC was instituted. Xenon-enhanced computed tomography (Xe-CT) was utilized to obtain serial measurements of CBF with and without IABC over a 4-day period. RESULTS: IABC dramatically improved cardiac function in this patient, and Xe-CT demonstrated significant improvement in CBF with IABC. The average global CBF was 20.5 +/- 4.4 ml/100g/min before versus 34.7 +/- 3.8 ml/100g/min after IABC (p < 0.0001, paired student's t-test). The lower the CBF before IABC, the greater the improvement with IABC (correlation coefficient r = 0.83, p = 0.0007). CBF improvement ranged from 33% to 161% above baseline, average 69.3%. No complications of IABC were observed. CONCLUSIONS: This is the first report demonstrating the ability of IABC to improve CBF in a patient with vasospasm. We suggest that IABC is a rational treatment option in select patients with refractory cerebral vasospasm who do not respond to traditional treatment measures.     

Effectiveness of intra-arterially infused papaverine solutions of various concentrations for the treatment of cerebral vasospasm

We evaluated the effect of intra-arterially infused papaverine solutions of various concentrations on cerebral vasospasm following subarachnoid haemorrhage. A total of 90 vascular territories in 46 patients with symptomatic cerebral vasospasm after subarachnoid haemorrhage were treated with intra-arterial infusions of papaverine. In all patients, papaverine was infused at the top of the internal carotid artery (ICA). Of the 90 vascular territories, 30 vascular territories in 14 patients were treated with an infusion of 0.1-0.2% (weight/volume) papaverine (Group 1), 30 vascular territories in 16 patients were treated with a 0.4% (w/v) papaverine infusion (Group 2), and 30 vascular territories in 16 patients were treated with an infusion of 0.8-2.0% (w/v) papaverine (Group 3). Among the three groups, we compared the vasodilatory effects of papaverine by assessing the angiographical and clinical improvements following the treatment. When 0.4% (w/v) papaverine was infused, 24 vascular territories (80%) were successfully dilated and 7 patients (44%) showed a marked reversal of neurological deficits due to vasospasm. Therefore, 80 mg/20 ml (0.4% (w/v)) papaverine infused over a 10-minute period proved to be a beneficial concentration. Transient focal neurological deficits due to the infusion of papaverine occurred in 1 Group 1 patient (7%), 1 Group 2 patient (6%), and 7 Group 3 patients (44%). Highly concentrated papaverine had a higher risk of temporary deterioration. In conclusion, the papaverine concentration of 0.4% (w/v) infused at the top of the ICA was a safe and adequate concentration for treating cerebral vasospasm.     

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO[2]) and cerebral metabolic rate of oxygen (CMRO[2]). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF calculated from cerebral clearance curves integrated to 15 minutes (mean CBF 32.3 +/- 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean V[MCA] 56.7 +/- 2.9 cm/second), normal hemispheric index ([HI], mean HI 1.67 +/- 0.11), and normal AVDO(2) (mean AVDO[2] 5.4 +/- 0.5 vol%). The CMRO, is approximately 50% of normal (mean CMRO(2) 1.77 +/- 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 +/- 3 ml/100 g/minute), AVDO(2) falls (3.8 +/- 0.1 vol%), V(MCA) rises (86 +/- 3.7 cm/second), and the HI remains less than 3 (2.41 +/- 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 +/- 3.8 ml/100 g/minute), a further increase in V(MCA) (96.7 +/- 6.3 cm/second), and a pronounced rise in the HI (2.87 +/- 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.     

Cerebral blood flow as a predictor of outcome following traumatic brain injury

As part of a prospective study of the cerebrovascular effects of head injury, 54 moderate and severely injured patients underwent 184 133Xe-cerebral blood flow (CBF) studies to determine the relationship between the period of maximum blood flow and outcome. The lowest blood flows were observed on the day of injury (Day 0) and the highest CBFs were documented on postinjury Days 1 to 5. Patients were divided into three groups based on CBF values obtained during this period of maximum flow: Group 1 (seven patients), CBF less than 33 ml/100 g/minute on all determinations; Group 2 (13 patients), CBF both less than and greater than or equal to 33 ml/100 g/minute; and Group 3 (34 patients), CBF greater than or equal to 33 ml/100 g/minute on all measurements. For Groups 1, 2, and 3, mean CBF during Days 1 to 5 postinjury was 25.7 +/- 4, 36.5 +/- 4.2, and 49.4 +/- 9.3 ml/100 g/minute, respectively, and PaCO2 at the time of the CBF study was 31.4 +/- 6, 32.7 +/- 2.9, and 33.4 +/- 4.7 mm Hg, respectively. There were significant differences across Groups 1, 2, and 3 regarding mean age, percentage of individuals younger than 35 years of age (42.9%, 23.1%, and 76.5%, respectively), incidence of patients requiring evacuation of intradural hematomas (57.1%, 38.5%, and 17.6%, respectively) and incidence of abnormal pupils (57.1%, 61.5%, and 32.4%, respectively). Favorable neurological outcome at 6 months postinjury in Groups 1, 2, and 3 was 0%, 46.2%, and 58.8%, respectively (p < 0.05). Further analysis of patients in Group 3 revealed that of 14 with poor outcomes, six had one or more episodes of hyperemia-associated intracranial hypertension (simultaneous CBF > 55 ml/100 g/minute and ICP > 20 mm Hg). These six patients were unique in having the highest CBFs for postinjury Days 1 to 5 (mean 59.8 ml/100 g/minute) and the most severe degree of intracranial hypertension and reduced cerebral perfusion pressure (p < 0.0001). These results indicate that a phasic elevation in CBF acutely after head injury is a necessary condition for achieving functional recovery. It is postulated that for the majority of patients, this rise in blood flow results from an increase in metabolic demands in the setting of intact vasoreactivity. In a minority of individuals, however, the constellation of supranormal CBF, severe intracranial hypertension, and poor outcome indicates a state of grossly impaired vasoreactivity with uncoupling between blood flow and metabolism.     

Cerebral blood flow and the response to acetazolamide during the acute, subacute, and chronic stages of aneurysmal subarachnoid hemorrhage

Cerebral blood flow (CBF) and response to acetazolamide were measured during the acute, subacute, and chronic stages after aneurysmal subarachnoid hemorrhage and correlated with symptomatic vasospasm and clinical outcome in 45 patients who underwent early clipping of ruptured cerebral aneurysms, of whom 18 had symptomatic vasospasm and 27 did not. Xenon-enhanced computed tomography was used to measure CBF in both groups during the acute, subacute, and chronic stages, defined as days 0-4, 5-20, and > or = 21, respectively. Vasoresponse was assessed by the CBF increase in response to 1 g of acetazolamide administered after the baseline CBF study, except in the subacute stage of patients with symptomatic vasospasm. Outcome was scored based on activities of daily living 2-3 months after subarachnoid hemorrhage. CBF values and the response to acetazolamide were preserved during the acute stage but CBF values fell considerably below control values during the subacute stage in patients with vasospasm. The regions with flow values below 15 ml/100 g/min subsequently converted to infarction and the regions with those above 19 ml/100 g/min remained intact without infarction. During the chronic stage, low CBF persisted, but the response to acetazolamide was higher than that of the control group. Outcome scores were good and fair. CBF values were normal during all stages in patients without vasospasm. The response to acetazolamide fell transiently during the subacute stage. All outcome scores were excellent. In conclusion, the CBF informations soon after the onset of symptomatic vasospasm are useful to predict a reversibility of ischemic brain tissue and a final outcome. We suggest that vasospasm may cause a pathological or ischemic insult to brain tissue during the subacute stage, and the brain may remain metabolically depressed thereafter, leading to a poor outcome. Even clinically asymptomatic patients may suffer mildly vasospastic or ischemic conditions during the subacute stage.     

Intracranial pressure monitoring during intraarterial papaverine infusion for cerebral vasospasm

PURPOSE: Intraarterial papaverine infusions are performed to reverse cerebral arterial vasospasm resulting from subarachnoid hemorrhage, but such infusions may lead to increases in intracranial pressure (ICP). This study was undertaken to determine when ICP monitoring is indicated during papaverine treatment. METHODS: Seventy-eight vessels were treated in 51 sessions in 28 patients with symptomatic vasospasm. ICP, papaverine doses, and infusion rates were recorded during treatment sessions. The procedural data, Hunt and Hess scores, Fisher grades, Glasgow Coma Scale scores, and ages for all subjects were reviewed and analyzed retrospectively. RESULTS: Baseline ICP ranged from 0 to 34 mm Hg. With typical papaverine doses of 300 mg per territory and infusion times ranging from 5 to 60 minutes per vessel, ICP increases above baseline during papaverine infusion ranged from 0 to 60 mm Hg. Significant (> or = 20 mm Hg) ICP increases during therapy were observed even in patients with low baseline ICP and with papaverine infused at the slowest rate. Patients with a baseline ICP of more than 15 mm Hg were much more likely to have significant ICP increases than were patients with a baseline ICP of 0 to 15 mm Hg. Hunt and Hess scores, Fisher grades, age, and Glasgow Coma Scale scores on admission and immediately before treatment did not correlate with ICP increases during papaverine infusion. Patients with ICP increases of more than 10 mm Hg during therapy were more likely to experience adverse clinical events than were patients with ICP increases of < or = 10 mm Hg. Reduction in the rate of papaverine infusion, or termination of infusion, resulted in reversal of drug-induced ICP elevation. CONCLUSION: ICP monitoring during intraarterial papaverine infusions for cerebral vasospasm is recommended for all patients and is particularly important for patients with elevated baseline ICP. Continuous ICP monitoring facilitates safe and time-efficient drug delivery.     

Net efflux of cysteine, glutathione and related metabolites from rat hippocampal slices during oxygen/glucose deprivation: dependence on gamma-glutamyl transpeptidase

BACKGROUND: Effect of clot removal and surgical manipulation on cerebral blood flow (CBF) and delayed vasospasm was studied in early aneurysm surgery for subarachnoid hemorrhage (SAH). METHODS: Thirty-two patients in this study fulfilled the following criteria: ruptured anterior communicating aneurysms, computed tomography (CT) within 2 days and unilateral pterional approach within 3 days after the ictus, bilaterally symmetrical clots without intracerebral hematoma, no postoperative complication, and CBF studies with single photon emission computed tomography (SPECT) with 123I-IMP. RESULTS: Postoperative regional hypoperfusion due to brain retraction was frequently recognized on 123I-IMP-SPECT without infarction. The regional CBF (rCBF) showed a continuous fall during the first 4 weeks after the ictus, followed by improvement. The rCBF in the vicinity of the surgical route was significantly lower, especially in the acute stage (Day 3-7). A significant association between decrease of cisternal blood after surgery and the degree of local vasospasm and local CBF values during spasm stage was observed in the interhemispheric cisterns, A2 and medial frontal cortex, but not in the sylvian fissure or insular cisterns, M1 or M2, and frontal watershed and temporal cortex. CONCLUSIONS: The present study provides evidence for the effectiveness of direct clot removal by early surgery for SAH on local vasospasm and CBF reduction. However, a potential improvement in local CBF with clot removal could be masked by brain retraction, which was demonstrated to affect rCBF adversely. Therefore, it is critical to perform brain retraction as gently as possible.     

Oxidative stress in the human brain after subarachnoid hemorrhage

OBJECT: The aim of this study was to verify the patterns of antioxidant enzymatic activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the human brain after subarachnoid hemorrhage (SAH) to verify whether an "oxidative stress situation" characterizes the brain response to subarachnoid bleeding. METHODS: Forty samples of gyrus rectus or temporal operculum that were obtained during a surgical approach to anterior circulation aneurysms were used for this study. The activity of total SOD, GSH-Px, and the SOD/GSH/Px ratio (which expresses the balance between the production of hydrogen peroxides by dismutation of superoxide radicals and the scavenging potential) were calculated in each case. Twelve samples were obtained from patients who underwent surgery for unruptured aneurysms (control group); 13 samples were obtained during surgical procedures performed within 72 hours of SAH; and 15 samples were obtained during delayed surgical procedures (> 10 days post-SAH). Ten patients presented with clinical deterioration caused by arterial vasospasm. In both SAH groups, the mean total SOD activity was significantly higher than in the control group (p=0.029). The mean activity of GSH-Px did not differ significantly between the SAH and control groups (p=0.731). There was a significant increase in the SOD/GSH-Px ratio in both SAH groups, as compared with controls (p < 0.05). There was a significant correlation between the enzymatic activity and the clinical severity of the hemorrhage, with findings of lower values of SOD and, mainly, of the SOD/GSH-Px ratio in the poor-grade patients. The SOD/GSH-Px ratio was 2.14+/-0.44 in patients who presented with clinical vasospasm and 1.24+/-0.2 in cases without vasospasm. CONCLUSIONS: The results of this study show an imbalance of the antioxidant enzymatic activities in the human brain after SAH. which is linked to the severity of the initial bleeding and possibly modified by the development of arterial vasospasm.     

Diagnostic value of nasal provocation testing and rhinomanometry in allergic rhinitis

Assessment of the hemodynamic and anatomic results following balloon angioplasty of discrete native coarctation of the aorta, with particular attention to "remodeling," has required repeat cardiac catheterization and angiography, which is invasive and has limited resolution. Eight patients with hypertension and discrete native coarctation with an otherwise normally developed aortic arch underwent angioplasty at 5.0 +/- 6.8 years of age. Angiographic cross-sectional areas of the aorta indexed to body surface area at the isthmus (I), coarctation site (C), and 1 cm distal to the coarctation site (Cd) pre- and postangioplasty were compared with MRI-indexed cross-sectional areas 18 +/- 10 months (MRI-1) and 35 +/- 11 months (MRI-2) postangioplasty. From preangioplasty to MRI-2, the isthmus was smaller (149 +/- 22 versus 127 +/- 27 mm2/m2; p < 0. 05). The coarctation site was larger postangioplasty (25 +/- 9 versus 116 +/- 40 mm2/m2; p < 0.001) with continued growth at latest follow-up (116 +/- 40 versus 164 +/- 36 mm2/m2; p < 0.01). The segment 1 cm distal to the coarctation site continued to decrease in area at latest follow-up (267 +/- 78 versus 163 +/- 38 mm2/m2; p < 0. 001). I versus C versus Cd at MRI-2 were similar, whereas postangioplasty and MRI-1 cross-sectional area measurements were significantly different. Following angioplasty of discrete native coarctation, the aorta becomes more uniform or undergoes "remodeling." Noninvasive MRI is an effective means of evaluating the anatomic result following balloon angioplasty, obviating the need for repeated invasive cardiac catheterizations.     

Recurrent abrupt occlusion after transluminal angioplasty for basilar artery stenosis: case report

OBJECTIVE AND IMPORTANCE: Angioplasty for basilar artery stenosis is often complicated by recurrent abrupt vessel closure. The clinical results can be catastrophic. In this case report, we assess the effects of intra-arterial papaverine (American Regent Laboratories Inc., Shirley, NJ) on rebound occlusion. CLINICAL PRESENTATION: The patient presented with crescendo transient ischemic attacks from atherosclerotic narrowing of the midbasilar artery despite maximal medical treatment. INTERVENTION: Angioplasty of the midbasilar artery was performed with serial balloon inflations. The patient was treated successfully with intra-arterial papaverine and achieved a nearly full recovery, with only mild dysarthria, by the time of the 7-month follow-up examination. CONCLUSION: Using intra-arterial papaverine, we were able to reverse the effects of this potentially life-threatening complication of basilar artery angioplasty.     

Adult daycare: an entrepreneurial opportunity for nursing

We described the techniques and efficacy of intra-arterial papaverine hydrochloride infusion (IA-PAP) for symptomatic vasospasm due to aneurysmal subarachnoid hemorrhage based on our experience and review of the literature. Angiographic improvement occurred almost always, but only 50% of patients who presented with acute symptoms showed remarkable clinical improvement after the first, second, or third IA-PAP. Recurrent vasospasm after IA-PAP frequently occurred and this seems to be an apparent source of controversy regarding its efficacy. Review of the literature indicates that IA-PAP may be most effective in combination with percutaneous transluminal angioplasty. Further controlled studies should be conducted regarding papaverine's true efficacy including most effective papaverine concentration and rate of infusion, maximum total dose, site of infusion, timing of treatment, and selection of patients.     

Transluminal angioplasty and intra-arterial papaverine for the treatment of cerebral vasospasm after ruptured arteriovenous malformations

BACKGROUND: This is the first report on the use of intra-arterial papaverine and percutaneous transluminal angioplasty in two patients with severe, symptomatic cerebral vasospasm who suffered ruptured arteriovenous malformations (AVMs). CASE DESCRIPTIONS: The source of hemorrhage was a venous aneurysm in the first case and a pedicular aneurysm of the distal posterior inferior cerebellar artery in the second case. In both cases, the AVMs were located in the superior vermis and there was minimal subarachnoid hemorrhage. The first patient underwent removal of the AVM before the period of cerebral vasospasm and the second patient underwent removal of the AVM after the cerebral vasospasm had resolved. The outcome was excellent in the first patient and poor in the second patient. CONCLUSION: Arteriovenous malformation with ruptured aneurysms may be at high risk for cerebral vasospasm even when there is minimal subarachnoid hemorrhage. We recommend early treatment of AVMs with ruptured pedicular, intranidal, or venous aneurysms to avoid rebleeding and to allow for aggressive treatment of cerebral vasospasm. The management of cerebral vasospasm after AVM rupture is discussed.     

A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study

Calcium antagonist drugs were proposed for use in patients with recent aneurysmal subarachnoid hemorrhage (SAH) because of their ability to block the effects of a wide variety of vasoconstrictor substances on cerebral arteries in vitro. It was suggested that these agents might, therefore, be useful in ameliorating cerebral vasospasm and its ischemic consequences which frequently complicate SAH. This hypothesis was tested in an arm of a randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine in patients with recently ruptured aneurysms. Participating investigators were required to send selected copies of all admission and follow-up angiograms obtained between Days 7 and 11 following hemorrhage (the peak period of risk for vasospasm) to the Central Registry of the Cooperative Aneurysm Study for blinded interpretation and review for the presence and severity of angiographic vasospasm. In centers with transcranial Doppler ultrasound (TCD) capabilities, middle cerebral artery (MCA) mean flow velocities were measured and recorded. Angiograms obtained between Days 7 and 11 were available for 103 (23%) of 449 patients receiving nicardipine and 121 (26%) of 457 receiving placebo. There was a balance of prognostic factors for vasospasm between the groups. Fifty-one percent of placebo-treated patients had moderate or severe vasospasm on "Day 7-11 angiograms" compared to 33% of nicardipine-treated patients. This difference is statistically significant (p < 0.01). Sixty-seven (49%) of 137 placebo-treated patients examined with TCD between Days 7 and 11 had mean MCA flow velocities exceeding 120 cm/sec compared to 26 (23%) of 112 nicardipine-treated patients (significant difference, p < 0.001). These data suggest that high-dose intravenous nicardipine reduces the incidence and severity of delayed cerebral arterial narrowing in patients following aneurysmal SAH.     

Amount of subarachnoid blood and vasospasm: current aspects. A transcranial Doppler study

Subsequent to admission after aneurysmal subarachnoid haemorrhage (SAH), 120 patients (74 women and 46 men) underwent microsurgical clipping of a total of 158 cerebral aneurysms within 96 hours after the bleed. Their mean age was 46 (20-91) years. Computed tomography (CT) findings were graded according to the modified Fisher scale and all patients had daily transcranial doppler (TCD) recordings of their basal cerebral arteries. In 19% of SAH was grade I on CT, in 44% grade II and in 37% grade III. The rate of patients who developed severe vasospasm as documented by TCD (mean blood flow velocities exceeding 160 cm/s on 2 or more consecutive days) was 39% for grade I patients, 26% for grade II patients and 34% for patients with SAH grade III on the initial CT. There was no difference in the rate of occurrence of severe vasospasm, when the patients were split into 2 groups according to the time of performance of the initial CT scan-within 24 hours, and 48-80 hours after SAH, respectively. It is concluded that the amount of subarachnoid blood on the initial CT scan should no longer be used as the indicator for occurrence and severity of the multifactorial entity vasospasm.     

Combination of serine protease inhibitor FUT-175 and thromboxane synthetase inhibitor OKY-046 decreases cerebral vasospasm in patients with subarachnoid hemorrhage

The preventive effect of the serine protease inhibitor FUT-175 (nafamostat mesilate), a potent inhibitor of the complement system, against vasospasm was evaluated in 34 high risk patients with thick and diffuse subarachnoid hemorrhage (SAH) demonstrated by computed tomography corresponding to Fisher group 3. All patients underwent surgery within 96 hours following SAH and received the thromboxane A2 synthetase inhibitor, OKY-046, as part of standard care. FUT-175 (40-160 mg/day) was administered during the initial 4 days following surgery. 455 patients treated without FUT-175 in the Nagasaki SAH Data Bank (non-FUT group) formed the control group. FUT-175 significantly decreased the incidence of symptomatic vasospasm in patients with severe neurological grade (Hunt and Hess grade 3, p < 0.02; Hunt and Hess grade 4, p < 0.02). The incidence of favorable outcome was 76.5% in the FUT group and 60.4% in the non-FUT group, but not statistically different. However, when patients of Hunt and Hess grade 5 were excluded, the FUT group had a significantly improved outcome (p < 0.05). This study suggests that FUT-175 has an additive effect to OKY-046 in preventing vasospasm in high risk patients with severe SAH.     

Prophylactic effect of papaverine prolonged-release pellets on cerebral vasospasm in dogs

OBJECTIVE: A drug delivery system using copoly(lactic/glycolic acid) was developed for the intracranial administration of papaverine. A rod-shaped implant prepared by a heat compression method was tested to determine its efficacy in preventing cerebral vasospasm in dogs. METHODS: Sixteen dogs were randomly assigned to one of two groups, i.e., placebo or papaverine. Control angiography was performed, followed by right craniectomy and the induction of subarachnoid hemorrhage by the placement of a clot in the Sylvian fissure. Two pellets, containing either 25 mg of papaverine or no papaverine, were placed in the cistern. In in vitro studies, 56% of the actual papaverine loading was released in the first 4 days and 78% within 8 days. On Day 7, angiography was repeated and the animals were killed. A similar experiment using low-dose pellets containing 5 mg of papaverine, half of which was released within 7 days, was performed with 16 mongrel dogs. RESULTS: There were significant differences between the papaverine- and placebo-treated groups in the reductions of vessel diameters of the internal carotid, middle cerebral, and anterior cerebral arteries on the clot side. The mean concentration of papaverine in the clot was 4.5 x 10(-4) mol/L. The low-dose pellet failed to prevent cerebral vasospasm, although the mean concentration of papaverine in the clot was 2.3 x 10(-5) mol/L. CONCLUSION: A prolonged-release preparation of papaverine that could be implanted intracranially at the time of surgery prevented vasospasm significantly while maintaining an appropriate concentration of papaverine in the cistern.     

CO2 reactivity in patients after subarachnoid haemorrhage

CO2 reactivity was tested in patients with transcranial Doppler sonography (TCD) and endtidal CO2 measurements after an average time interval of ten months after subarachnoid haemorrhage (SAH). After deliberately changing breathing there was a significant change in endtidal CO2 and in flow velocities in all three examination groups. Comparing 27 patients with SAH and 5 patients treated for incidental aneurysms and 20 patients without cerebrovascular disease there were no significant differences in CO2 reactivity. Furthermore, there were no right to left differences. In 12 patients with vasospasm, two of them treated by percutaneous transluminal angioplasty for delayed ischaemic deficits, CO2 reactivity was normal at the time of investigation. Furthermore, normal CO2 reactivity was found in patients after SAH and surgery for ruptured aneurysms regardless of the severity of the SAH.