Metaanalysis of trials of tirilazad mesylate in aneurysmal SAH.
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Adult↗
Biomedical subjects
N W Dorsch
Publications and source records attributed to N W Dorsch.
Intracranial aneurysms: evaluation in 200 patients with spiral CT angiography.
The goal of this study was to assess the usefulness of spiral CT angiography (CTA) with three- dimensional reconstructions in defining intracranial aneurysms, particularly around the Circle of Willis. Two hundred consecutive patients with angiographic and/or surgical correlation were studied between 1993 and 1998, with CTA performed on a GE HiSpeed unit and Windows workstation. The following clinical situations were evaluated: conventional CT suspicion of an aneurysm; follow-up of treated aneurysm remnants or of untreated aneurysms; subarachnoid haemorrhage (SAH) and negative angiography; family or past aneurysm history; and for improved definition of aneurysm anatomy. Spiral CTA detected 140 of 144 aneurysms, and an overall sensitivity of 97%, including 30 of 32 aneurysms 3 mm or less in size. In 38 patients with SAH and negative angiography, CTA found six of the seven aneurysms finally diagnosed. There was no significant artefact in 17 of 23 patients (74%) with clips. The specificity of CTA was 86% with 8 false-positive cases. Spiral CTA is very useful in demonstrating intracranial aneurysms.
Adolescent↗
Unruptured aneurysms should generally be clipped.
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Cerebral Arteries↗
Aggressive management of aneurysmal subarachnoid haemorrhage based on a papaverine angioplasty protocol.
The aim of this study was to analyse the results of intensive therapy unit management of aneurysmal subarachnoid haemorrhage incorporating angioplasty in the protocol. Two hundred consecutive patients were treated using a detailed protocol that included nimodipine, early aneurysm repair, and surveillance angiography. Angiography was performed on days 5 to 7 (or when the clinical state suggested the presence of vasospasm). If angiographic vasospasm was identified, irrespective of whether clinical vasospasm was present or absent, papaverine was selectively administered. In patients with vasospasm blood pressure was elevated to 160-180 mmHg and selective papaverine administration was repeated daily until vasospasm resolved. In cases requiring more frequent administration of papaverine, or in whom papaverine failed to adequately reverse spasm, balloon angioplasty was considered and for clinically refractory cases barbiturate coma was introduced. 43% of patients underwent papaverine administration and of these the average number of separate papaverine procedures was four (maximum 23). 26% of patients developed neurological deficits though to be due to vasospasm whilst 17% underwent papaverine angioplasty without clinical signs of vasospasm. Twelve patients (6%) were entered into barbiturate coma. There was a 5.5% mortality and no difference in outcome between patients who developed angiographic vasospasm and those who did not. For those developing clinical vasospasm, 71% were independent and 10% were dead at follow up compared with 84% reaching independent grades and 4% dead in those not developing clinical vasospasm. These differences failed to reach a significant difference. The average Intensive Therapy Unit stay for aneurysmal subarachnoid haemorrhage patients was 13.1 days with a mean cost to the hospital of $AUD 24,379. This protocol appears to be both a clinically and cost effective method of managing aneurysmal subarachnoid haemorrhage.
Angioplasty, Balloon↗
Pitfalls in the use of spiral CT for identification of intracranial aneurysms.
We describe problems encountered in our first 136 patients, with 95 aneurysms, who underwent spiral CT for investigation of possible aneurysms involving the circle of Willis and adjacent major vessels, and who had surgical and/or angiographic confirmation. There were seven false-positive cases, of which the first three could be explained by operator inexperience. There were four false negatives, all small aneurysms; two were not seen because of operator error and two were hidden by an adjacent larger aneurysm. Clip artefacts prevented diagnostic studies in six of 21 postoperative studies. One aneurysm was outside the CT field of view, being on a pericallosal artery. One basilar artery tip aneurysm was excluded from the field of the CT study because of a planning error. Inspection of the axial source images is critical if the diagnosis of small or thrombosed aneurysms is to be made. Close attention to image acquisition and computer modelling is required to reduce errors in spiral CT angiography of intracranial aneurysms.
Adolescent↗
Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I. A cooperative study in Europe, Australia, New Zealand, and South Africa.
OBJECT: Findings from previous multicenter clinical trials have suggested that tirilazad mesylate, a synthetic nonhormonal 21-aminosteroid, might be effective in preventing delayed cerebral ischemia following subarachnoid hemorrhage (SAH). This beneficial effect, however, was greater in males than females, possibly because of gender-related pharmacokinetic differences. The authors sought to assess the effects of administering a larger dose of tirilazad in women with SAH. METHODS: To test the efficacy of a higher tirilazad mesylate dose in female patients, a prospective randomized, double-blind, vehicle-controlled trial was conducted at 56 neurosurgical centers in Europe, Australia, New Zealand, and South Africa. Eight hundred nineteen patients were randomly assigned to receive either 15 mg/kg/day of tirilazad mesylate or a placebo containing the citrate vehicle. The two groups were similar in prognostic factors for delayed cerebral ischemia and overall outcome. High-dose tirilazad appeared to be well tolerated because no differences in the incidence of untoward medical events were noted between the two groups. Medical and surgical interventions were no different in the two treatment groups except for hyperdynamic therapy (intentional hypervolemia, induced hypertension, and/or hemodilution), which was more often used in the placebo-treated group to counteract symptomatic vasospasm (24% of patients given placebo compared with 18% of patients given tirilazad, p = 0.02). Mortality rates and overall outcome, assessed using the Glasgow Outcome Scale at 3 months post-SAH, were not different between the two groups, despite a significantly lower incidence of delayed cerebral ischemia in patients given tirilazad. Post hoc subgroup analysis by neurological grade also did not reveal significant differences in outcome, although a trend toward a lower mortality rate favoring the study drug was present in patients with neurological Grade IV and V at admission (32% compared with 37%). Symptomatic vasospasm occurred in 33.7% of the placebo-treated patients as opposed to 24.8% of the patients who were given tirilazad (p = 0.005). The severity of symptomatic vasospasm was also attenuated by administration of the study drug (severe symptomatic vasospasm was reported in 11% of the placebo-treated patients compared with 6% of patients in the tirilazad-treated group (p = 0.008). Clinical cerebral infarction from vasospasm was also reduced from 13% in the vehicle-treated group to 8% in the tirilazad-treated group (p < 0.04). CONCLUSIONS: The authors conclude that high-dose tirilazad mesylate is well tolerated in women with aneurysmal SAH. Although a significant reduction in the incidence of symptomatic vasospasm was observed in the treatment group, the primary end point (mortality rate at 3 months post-SAH) was not affected by the study drug. The use of other potentially effective rescue therapies (that is, hypervolemia, hemodilution, and induced hypertension) to counteract vasospasm may have been responsible for these contrasting observations between the two groups.
Dose-Response Relationship, Drug↗
Spiral CT scanning in the detection and evaluation of aneurysms of the Circle of Willis.
PURPOSE: To assess the utility of spiral computed tomography (CT) with three-dimensional reconstruction in defining aneurysms of the Circle of Willis. METHODS: Eighty-one patients with angiographic or surgical correlation were studied between 1993 and 1995, with surface rendered reconstructions of the arteries of the Circle of Willis. RESULTS: Spiral CT was useful in six clinical situations: further assessment in cases with CT suspicion of an aneurysm, follow-up of known untreated aneurysms or aneurysm remnants, subarachnoid hemorrhage (SAH) with negative angiography, a past or family history of aneurysms, and improved definition of aneurysm anatomy. Ten of fifteen patients with previous surgery had no significant artifacts on the spiral study. In 66 other patients studied in search of aneurysms, the sensitivity of detection was 95% and specificity 74%. Seventeen of nineteen aneurysms 3 mm or less in size and 38 of 39 larger were detected by spiral CT. Four of thirteen patients with SAH and previous negative angiography had aneurysms identified, which were confirmed at surgery. CONCLUSIONS: There is great promise in the use of spiral CT in demonstrating aneurysms of the Circle of Willis, including very small ones. Careful detailing of scan protocols and meticulous examination of multiplanar images are needed for maximum accuracy.
Adolescent↗
The effect and management of delayed vasospasm after aneurysmal subarachnoid hemorrhage.
Delayed cerebral vasospasm after aneurysm rupture is one of the major complications of subarachnoid hemorrhage. The purpose of this review was to determine the true incidence of vasospasm. All literature on cerebral aneurysms from 1960 onwards was reviewed, and the figures extracted from publications that mentioned vasospasm. Angiographic vasospasm, where patients were studied at the time of peak incidence, was reported in about two thirds of cases. Symptomatic vasospasm or delayed ischemia affects about one third. Untreated, nearly a third of those with ischemic deficits die and a similar proportion are left permanently disabled. Variations of Triple-H (hypervolemia, hypertension, hemodilution) therapy, used early after hemorrhage for prophylaxis of vasospasm, are associated with a decrease of nearly half in the incidence of delayed ischemia. When used as therapy outcome also appears better, with a reduction particularly in the death rate. Calcium antagonists have been widely used, especially nimodipine. In several controlled trials the incidence of delayed ischemia was significantly reduced. More importantly, the overall outcome of all subarachnoid hemorrhage patients was better with nimodipine prophylaxis. The 21-aminosteroid tirilazad mesylate has been the subject of several trials. In one the overall outcome of all patients was improved, but the effect was essentially in males only. Further studies with larger doses in females are being analyzed.
Aneurysm, Ruptured↗
Haemorrhagic stroke. Intracerebral and subarachnoid haemorrhage.
A proportion of strokes are due to intracranial haemorrhage. Their characteristics and treatment are different from ischaemic stroke-surgery is often necessary and thrombolytic or anticoagulant treatment contraindicated. Most intracerebral haematomas (ICH) are hypertensive in origin. Small haematomas are treated with blood pressure control and rehabilitation. Larger ones often need surgery. Treatment must be tailored to the patient's circumstances, taking into account age, general and neurological health, location of haematoma etc. Subarachnoid haemorrhage (SAH) affects younger people and is classically due to aneurysm rupture, requiring urgent neurosurgical referral. Another cause is arteriovenous malformations (AVM), also treated surgically. A major problem is failure to diagnose less severe bleeds, which often precede major haemorrhages.
Age Factors↗
Cervical spine degenerative diseases: an evaluation of clinical and imaging features in surgical decisions.
In clinically severe cervical spondylosis, imaging plays a vital role in surgical decisions. A prime factor is acquired canal stenosis with cord compression. To validate this concept, the clinical and imaging features of 20 patients with spondylotic myelopathy and 24 with radiculopathy were retrospectively reviewed. All had computed tomographic myelography (CTM) as part of their clinical work-up. The patients' clinical severity was graded as mild, moderate and severe; the age, length of illness and a history of eventual surgery or otherwise were recorded. At the level of maximum compression the following parameters were obtained from the axial CTM images: surface area and ratio of the anteroposterior to the transverse diameter of the cord; subarachnoid space and vertebral canal areas. Data were statistically analysed. A significant association exists between surgery and increasing severity of symptoms (P = 0.04), and advancing age (P = 0.01). These associations hold true for myelopathy and radiculopathy. A strong association is present between surgery and the surface area of the cord (P = 0.01), being applicable to myelopathy only. The other parameters show no association with surgical decisions. It is concluded that with myelopathy a narrow cord area at the level of maximum compression, and moderate--severe functional impairment are indicators for surgical intervention.
Case-Control Studies↗
A review of the radiological features of intracranial meningiomas.
To evaluate the role of radiological imaging of meningiomas in confirming the diagnosis and as a neuroanatomical aid to surgical planning, 115 patients with surgically excised meningiomas between 1990 and 1993 were studied. Computed tomography (CT), magnetic resonance imaging (MRI) (on a 0.5 T unit) and angiography were reviewed, and compared with histopathology (when available). Seventy-eight CT, 89 MRI and 85 angiographic studies were reviewed, and correlated with histopathology in 67 cases. In 48 cases, the surgical specimens could not be pathologically classified. The most common lesion sites were the cerebral convexities, falx and sphenoidal ridges. True demarcation of cleavage planes was seen on 73% of MRI and 10% of CT studies. Computed tomography showed hyperostosis in 27% and MRI in 7% of studies. Tumours enhanced strongly with contrast in 98% of CT scans. On MRI there were variable signal intensities on different sequences, and no correlation between signal intensities and histological subtype was found. Oedema was present in 59% of CT and 66% of MRI studies, and was most pronounced in lesions > 3 cm in diameter. Tumour calcification was seen in 62% of CT and 8% of MRI studies. Vascular abnormalities were seen on 65% of MRI, 21% of CT and 84% of angiogram studies. Angiographic tumour vascularity did not correlate with histologic subtype. All three imaging modalities have management roles: CT for bony changes and calcification, MRI for multiplanar and vessel anatomy imaging, and angiography for vessel delineation and embolization if required.
Aged↗
Incidence and effects of increased cerebral blood flow velocity after severe head injury: a transcranial Doppler ultrasound study I. Prediction of post-traumatic vasospasm and hyperemia.
Cerebral blood flow velocity was monitored in 50 patients with severe head injury (GCS 8 or less) within 24 h of injury and at least once daily thereafter, using transcranial Doppler ultrasonography (TCD). Delayed post-traumatic vasospasm occurred in 20, and cerebral hyperemia in another 15. Doppler velocities were higher in vasospasm, which also lasted significantly longer than hyperemia. The presence of visible blood on an early CT scan was of some value in predicting vasospasm only (accuracy 59%). Xenon-133 cerebral blood flow (CBF) was also measured within 24 h of injury. An abnormal early cerebral blood flow level, either above or below a narrow central range, was more effective than CT in predicting vasospasm or hyperemia (accuracy 80%), while the combination of an abnormal blood flow and hemorrhagic findings on CT scan helped to determine which of these would occur later. Patients with an abnormal early cerebral blood flow and hemorrhagic findings on CT were more likely to develop vasospasm--accuracy for prediction of vasospasm 73%. This distinction may be of great importance, since these different groups of patients may well need different management.
Adolescent↗
Incidence and effects of increased cerebral blood flow velocity after severe head injury: a transcranial Doppler ultrasound study II. Effect of vasospasm and hyperemia on outcome.
Cerebral blood flow velocities were measured in 50 severely head injured (Glasgow Coma Scale (GCS) 8 or less) patients using transcranial Doppler ultrasonography (TCD). Abnormally high TCD velocities were recorded in 35 patients; in 20 this was deemed to be due to vasospasm and in the other 15 to hyperemia. Patients who developed hyperemia also had the highest intracranial pressure (ICP) and the lowest cerebral perfusion pressure (CPP) of the three groups. Outcome was assessed at six months after injury using the Glasgow outcome scale and the disability rating scale. In the normal velocity group 87% of patients had a good outcome, compared with 47% of those with hyperemia and 40% of those with vasospasm. The highest velocity (HVEL), GCS, age, ICP and CPP were entered into a logistic regression analysis. HVEL, age and CPP were found to be the most significant predictors of outcome (chi 2 = 29.5; p < 0.0001). These factors predicted outcome with 82% accuracy, 86% sensitivity and 76% specificity. Routine monitoring of TCD velocity may be useful in detecting hyperemia and vasospasm after severe head injury, allowing appropriate treatment to be started as early as possible.
Adolescent↗
The significance of traumatic intraventricular haemorrhage in severe head injury.
Since the advent of computed tomography (CT) traumatic intraventricular haemorrhage (IVH) has been diagnosed more often. It has reportedly been associated with a poor prognosis, but pure or solitary IVH is rare, suggesting that other lesions occurring concurrently with it may contribute to the poor outcome. In a series of 65 patients with severe head injury (GCS < or = 8), 14 (22%) had IVH on initial CT. Death rate in these 14 was 21%, not significantly different from that in patients without IVH (14%), although a significantly higher proportion of patients without IVH had a good outcome. These results suggest that mortality is related to other lesions associated with IVH rather than to IVH alone and that the presence of IVH does not necessarily lead to a poor outcome.
Acute Disease↗
Cerebral arterial spasm--a clinical review.
A review of the literature on cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH) has shown that angiographic vasospasm occurs in 67.3% of cases when angiography is timed for the highest likelihood, and delayed ischaemic deficit or symptomatic vasospasm in 32.6%. The presence of vasospasm has a marked effect on overall outcome of SAH, and the outcome of delayed ischaemia itself is in about one-third death and in one-third permanent deficit. Management with fluid loading or induced hypertension and with calcium antagonists has been reported widely for both prevention and treatment, and can reduce the incidence and improve the outcome of vasospasm. Other forms of treatment including tissue plasminogen activator, aminosteroids and transluminal angioplasty also appear useful. In spite of these improved therapeutic possibilities, large numbers of patients are still being reported in whom no specific treatment is used.
Angioplasty, Balloon↗
Early experience with spiral CT in the diagnosis of intracranial aneurysms.
We report experience with 16 patients undergoing spiral CT Scans for the evaluation of cerebral aneurysms. There were 10 females and six males, aged between 36 and 73 years. The three-dimensional scanning was useful in five situations: (i) Suspicion of aneurysm on conventional scan. An aneurysm was found in one of four patients and later confirmed by angiography, and two showed arterial ectasia with no saccular aneurysm; the fourth again appeared to have an aneurysm, but this was not shown on angiography. (ii) Follow-up of previously detected aneurysms not planned for surgery. This has been done in three patients, the spiral CT findings correlating well with previous angiography. (iii) Follow-up of aneurysm remnants after surgery (three cases); findings correlate well with previous angiography, and clips cause no artefact problems. (iv) Detection of ruptured aneurysms. In two cases, small aneurysms were found that had been missed on angiography, and in a third, with doubtful angiographic findings, spiral CT was useful. (v) Investigation of patients with past treated aneurysms, or of relatives. Three subjects have been screened so far for that purpose; in one a small aneurysm has been found, and confirmed angiographically.
Adult↗
Treatment of symptomatic vasospasm with nimodipine.
Over a seven-year period, 130 patients with delayed ischaemia after cerebral aneurysm haemorrhage were treated with intravenous nimodipine. The delay from the last haemorrhage to the appearance of ischaemic symptoms was one to 18 days, and vasospasm was confirmed in most cases. Nimodipine treatment was started within three days of delayed ischaemic deficit (DID) onset, at a low dose increased quickly to 30-45 ug/kg/hr, and reduced gradually over the last day or two of the course. The duration of treatment was one to 27 days. Side effects were minor, and serious complications few. Hypotension occurred in 35 cases. During treatment, there were highly significant improvements in both clinical grade and Glasgow Coma Score. The final outcome was 98 good (Glasgow Outcome Score 1), 18 permanent deficits (eight GOS 2, ten GOS 3), and 14 dead. Ischaemia was directly involved in only half the deaths. These results are much better than the natural history (about 1/3 dead and 1/3 disabled), and a considerable improvement over fluid and hypertensive treatment (17% dead, 29% deficits), calculated from a literature review. Nimodipine is also safer than induced hypertension, especially pre-operatively.
Adolescent↗
Cerebral aneurysms and subarachnoid haemorrhage.
Up to 2000 Australians each year rupture a cerebral aneurysm. This is immediately fatal in some, and others remain disabled. The main risks after a first haemorrhage are recurrent bleeding, prevented by early surgery, and delayed cerebral ischaemia due to vasospasm. This is minimised by keeping a good fluid balance, calcium antagonists, and possibly newer treatments such as aminosteroids or plasminogen activator. An important problem is that of the missed haemorrhage, which often leads to delay in treatment and a fatal or disabling recurrence.
Humans↗