Recent Subarachnoid Hemorrhage Research Articles

The detection and management of unruptured intracranial aneurysms.

The incidence of subarachnoid haemorrhage (SAH) is 6-8 per 100 000 person years, peaking in the sixth decade. SAH, mostly due to rupture of an intracranial aneurysm, accounts for a quarter of cerebrovascular deaths. Aneurysms increase in frequency with age beyond the third decade, are 1.6 times more common in women and are associated with a number of genetic conditions. Prospective autopsy and angiographic studies indicate that between 3.6 and 6% of the population harbour an intracranial aneurysm. Studies have found an increased rate of SAH in first degree relatives of SAH patients (relative risk 3.7-6.6). In affected families, the most frequent relationship between sufferers is sibling to sibling. The rupture rate of asymptomatic aneurysms was thought to be 1-2% per annum, but the recent International Study of Unruptured Intracranial Aneurysms found that the rupture rate of small aneurysms was only 0.05% per annum in patients with no prior SAH, and 0.5% per annum for large (>10 mm diameter) aneurysms and for all aneurysms in patients with previous SAH. Non-invasive tests such as magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and transcranial Doppler (TCD) have been advocated as alternatives to intra-arterial digital subtraction angiography to screen for aneurysms. Although all are promising techniques, the quality of data testing their accuracy is limited. Overall reported sensitivity for CTA and MRA (TCD is poorer) was 76-98% and specificity was 85-100%, but many subjects had an aneurysm or recent SAH, which could overestimate accuracy. CTA and MRA are much poorer methods for the detection of aneurysms <5 mm diameter, which account for up to one-third of unruptured aneurysms. Elective surgical clipping of asymptomatic aneurysms has a morbidity of 10.9% and mortality of 3. 8%. Treatment of aneurysms by Guglielmi coils, for which there is less long-term follow-up available, has a 4% morbidity and 1% mortality, but only achieves complete aneurysm occlusion in 52-78% of cases. There has been interest in screening for aneurysms, but the indication for, and cost effectiveness of screening are unclear because aneurysm prevalence varies, rupture rate is low, non-invasive imaging tests are not yet accurate enough to exclude small aneurysms and the morbidity and mortality for elective surgical treatment of unruptured aneurysms is high. There may be a limited role for investigation of high risk subgroups. Ideally, screening in such subgroups should be tested in a randomized trial. The avoidance of risk factors for aneurysms such as smoking, hypertension and hypercholesterolaemia should be part of the management of at-risk subjects.

Detection of meningeal fibrosis after subarachnoid haemorrhage by assaying procollagen propeptides in cerebrospinal fluid

OBJECTIVETo study whether meningeal collagen synthesis under normal conditions is reflected in the CSF and whether a meningeal fibroproliferative reaction or fibrosis after subarachnoid haemorrhage can be detected by measuring...

Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage.

To analyze the influence of extracerebral organ system dysfunction after aneurysmal subarachnoid hemorrhage (SAH) on mortality and neurologic outcome. Observational study with retrospective data extraction. Neurosurgical intensive care unit (NICU) at a primary level university hospital, supervised and staffed by both members of the Clinic of Neurosurgery and the Clinic of Anesthesiology and General Intensive Care. Two hundred forty-two patients treated for intracranial aneurysm rupture within 7 days of the most recent SAH. Routine neurosurgical interventions for obliteration of the ruptured aneurysm (microsurgery, Guglielmi Detachable Coils embolization) and for treatment of posthemorrhagic hydrocephalus (ventriculostomy, cerebrospinal fluid shunt implantation). Respiratory, renal, hepatic, cardiovascular, and hematologic organ system functions were evaluated both individually and in aggregate by using a modified version of the Multiple Organ Dysfunction (mMOD) score. Of 1,452 organ system functions assessed in 242 patients during their NICU stay, 714 organ system functions were intact (cerebral: 0, extracerebral: 714), 556 organ systems had mild-to-moderate dysfunctions (mMOD scoremax 1-2 for the affected organ system; cerebral: 153, extracerebral: 403), and 182 organ systems failed (mMOD scoremax 3 for the affected organ system; cerebral: 89, extracerebral: 93). Severity of extracerebral organ system dysfunctions correlated with the degree of neurologic impairment (Hunt and Hess [H&H] score) in a graded fashion. Similarly, the chance to develop systemic inflammatory response syndrome (SIRS) during the NICU stay increased with increasing admission H&H grade. The incidence of SIRS and septic shock was 29% and 10.3%, respectively. The mortality rate was 40.2% in patients with SIRS and 80% for patients suffering septic shock. Seventy-seven percent of extracerebral organ system failures (OSFs) occurred in conjunction with SIRS: 51% of respiratory OSFs, 97% of renal OSFs, 100% of hepatic OSFs, 96% of cardiovascular OSFs, and 73% of hematopoietic OSFs. Both CNS dysfunction and extracerebral organ system dysfunctions were significantly related to neurologic outcome. The probability of unfavorable neurologic outcome significantly increased with both decreasing cerebral perfusion pressure (CPP) and increasing severity of extracerebral organ dysfunction. Aneurysmal SAH and its neurologic sequelae accounted for the principal morbidity and mortality in the current series. Development of extracerebral organ system dysfunction was associated with a higher probability of unfavorable neurologic outcome. Systemic inflammation (SIRS) and secondary organ dysfunction were the principal non-neurologic causes of death.

The role of transcranial Doppler in the management of patients with subarachnoid haemorrhage--a review.

Introduced 15 years ago, transcranial Doppler (TCD) recordings of blood-velocity in patients with recent subarachnoid haemorrhage (SAH) have two objectives: to detect elevated blood velocities suggesting cerebral vasospasm (VSP) and to identify patients at risk for delayed cerebral ischemic deficits (DID). The pathophysiological cascade causing DID is complex. Discrepancies between blood velocities and DID (presuming that there actually is an "ischemic threshold" for blood velocity in absolute terms, which seems most unlikely) have been demonstrated, particularly in patients with elevated intracranial pressure (ICP) levels. Furthermore, the vessel showing the highest blood velocity is not always the one perfusing the area where ischemic symptoms arise, nor does the site of the greatest subarachnoid blood clot always relate to the ischemic brain region. Moreover, it is probable that the complex haemodynamic changes following SAH and the subsequent development of VSP may be underestimated if only considering the crude intracranial artery blood velocities. Cerebral blood flow measurements combined with TCD to assess both flow and velocity have emphasised this point. Despite these findings and ignoring the basic principles of cerebral haemodynamics, cerebral vasospasm is still being assessed from the intracranial velocity measurement alone. The addition of at least a careful measurement from the extracranial internal carotid artery--using the same TCD equipment and taking only a few short minutes to perform--allows a much more accurate assessment of the degree and the effects of vasospasm. This probably explains why the clinical value of TCD is still debated. There is still uncertainty as to the best method to prevent and to treat VSP, and the overall outcome after SAH depends on so many factors besides VSP. Conclusive evidence may therefore be hard to obtain, and it appears sound to conclude that even with advanced investigation technology available, proper selection, pre- peri- and postoperative care and timing of surgery remain cornerstones in the management of these patients,--equal in importance to their treatment in the operating room or in the interventional angiography suite.

Abstracts of literature

Abstracts of literature

Is routine transcranial Doppler ultrasound useful in the management of subarachnoid hemorrhage?

In this prospective observational study, the authors assess the impact of routine transcranial Doppler (TCD) ultrasound monitoring on the diagnosis, management, and outcome of delayed ischemic neurological deficit complicating subarachnoid hemorrhage (SAH). Over a 10-month period 186 patients admitted to a regional neurosciences center were included in the study. Three times a week, routine TCD examinations performed by neuroradiographers made an important positive contribution to the diagnosis of delayed ischemic neurological deficit in 72% of patients with this complication and altered management for the benefit of the patient in 43%. In 9% of patients with recent SAH, it was believed that the outcome might have been better if the TCD result had been acted upon appropriately. The TCD results did not adversely influence management or outcome and were accurate when compared with those obtained on angiography. The authors conclude that a routine TCD service provided by neuroradiographers is accurate and useful in diagnosing and managing elevated blood velocities and ischemic neurological deficit following SAH. In addition, it is possible that if the information gleened from TCD findings was used more often in patient management, outcome might be improved; however, a randomized controlled trial is necessary to assess this definitively.

Family history of subarachnoid haemorrhage: supplemental value of scrutinizing all relatives.

OBJECTIVE AND METHODS: To assess the validity of the family history obtained at the bedside of patients with recent subarachnoid haemorrhage by subsequently contacting all first and second degree relatives,...

Case Report. Active Hemorrhage of Intracranial Aneurysms: Diagnosis by CT Angiography

Two cases of active hemorrhage from an intracranial aneurysm demonstrated by CT angiography are presented. In each case, extraluminal opacified blood was seen entering a recent hemorrhage surrounding the aneurysm, simulating a vascular structure. This is a potential pitfall in the interpretation of CT angiograms in patients with recent subarachnoid hemorrhage.

Magnetic resonance angiography in the management of aneurysmal subarachnoid haemorrhage: a study of 51 cases.

We report preliminary experience with the use of magnetic resonance angiography (MRA) in the assessment of intracranial aneurysms. The aims of the study were to confirm that aneurysms could be detected and to assess the quality of the images with a view to early surgery if clinically indicated. We studied 51 patients with recent spontaneous subarachnoid haemorrhage with MRA, using a three-dimensional time-of-flight technique. The results of MRA were subsequently confirmed on intra-arterial digital subtraction angiography (IA-DSA) for anatomical correlation, and were considered satisfactory in 38 patients (74.5%). In 20 patients early surgical obliteration of their aneurysm was possible on the MRA results without recourse to IA-DSA. A total of 37 aneurysms were identified in 32 patients, while the remaining 6 patients did not have an aneurysm. MRA was misinterpreted in 4 patients (7.9%), and in 9 other patients (17.6%) MRA was unsatisfactory due to movement artefacts.

Color transcranial “power” Doppler ultrasound of intracranial aneurysms

"Color Doppler energy" (or "power Doppler"), a new color Doppler ultrasound technique that is independent of flow direction and very sensitive to movement, was assessed for its use in the identification of intracranial aneurysms in patients with recent subarachnoid hemorrhage immediately prior to using cerebral angiography. Features that identified aneurysms using this technique included the appearance of abnormal color where no normal artery was expected, abnormal bulging of an artery, and greater "expansibility" of the aneurysm in comparison to an adjacent normal vessel. In this exploratory study, 30 of 33 aneurysms were correctly identified in 35 patients with a good bone window. Color Doppler energy is considerably more sensitive to intracranial blood flow than conventional color Doppler imaging. Color Doppler energy is a useful research tool; if these preliminary results are verified in larger series, in addition to examination for vasospasm, the technique could be used for identification and follow up of aneurysms.

The nasal route of cerebrospinal fluid drainage in man. A light–microscope study

The drainage routes from the subarachnoid space to the nasal mucosa were investigated in autopsy material. Indian ink, applied post-mortem to the olfactory groove, promptly filled the perineurial spaces around the olfactory nerve branches in the dura, the lamina cribrosa and the submucosal tissue in the nose. In a case of recent subarachnoid haemorrhage, the perineurial spaces even around the most distal olfactory nerve branches were congested with blood and there was an abundant accumulation of red corpuscles in the apical part of the nasal mucosa. Iron-containing pigment was found in the perineurial spaces of proximal and distal olfactory nerve branches as well as in the nasal mucosal stroma in cases with older haemorrhagic lesions. The findings show that the perineurial spaces provide an efficient drainage route from the subarachnoid space to the nasal mucosa in cases with haemorrhagic cerebral lesions. A complementary drainage route for the cerebrospinal fluid was indicated by the presence of indian ink, red corpuscles and iron pigment in arachnoid villi, which penetrated the lamina cribrosa and ended in the nasal submucosal tissue. Iron in the deep cervical lymph nodes should not be taken as evidence of transport from the CNS, since iron pigment was also found in cases without intracranial haemorrhage.

Cerebrospinal fluid dynamics in infants evaluated with echographic color-coded flow imaging.

To use color Doppler flow ultrasonography (US) for investigation of rapid regional motion of cerebrospinal fluid (CSF) in infants with subarachnoid hemorrhage or meningitis. Sixty-four transfontanellar and transcranial color Doppler US scans of the cerebral aqueduct, ventricles, and basal cerebral and spinal subarachnoid spaces were obtained in 19 infants (12 male and seven female infants, aged 1-81 days). Abdominal palpation or periods of straining or crying were used to increase velocity of CSF motion. In all 19 infants, rapid to-and-fro color CSF flow was observed in the aqueduct. Color-coded CSF flow signals were seen in the aqueduct in 19 infants, in the third (n = 17 with jetlike flow) and fourth (n = 7 with jets) ventricles in 17, at the foramen of Magendie in 11 (n = 4 with jets), and in the spinal compartment in 14. In the presence of scattering particles or cells, regional CSF flow can be investigated with transfontanellar, transcranial, and spinal color flow imaging. Results of regional echographic CSF flow investigation can indicate recent subarachnoid hemorrhage or exclude obstruction. Jetlike CSF flow might stimulate new concepts of rapid CSF dynamics.

Acute headache of recent onset and subarachnoid hemorrhage: a prospective study.

Twenty-seven patients with acute severe headache of recent onset were prospectively recruited in the Emergency Room. Mean duration of headache was 61 hours. CT scan disclosed subarachnoid bleeding in 4 patients and spinal tap revealed subarachnoid hemorrhage (SAH) in 5 patients with normal CT scan. In most SAH cases pain was bilateral, very intense and involving the occipital region. Four of these patients had doubtful or no nuchal rigidity and in one, pain improved while in the Emergency Room. In every case with an intense acute severe headache of recent onset CT scan and (if normal) a lumbar puncture are warranted to help rule out a SAH.

A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results

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.

Angiographic and Doppler diagnosis of cerebral artery vasospasm following subarachnoid haemorrhage

Angiographic middle and anterior cerebral artery diameter and transcranial ultrasound flow velocity measurements were performed within 24 h of each other in 102 patients with recent aneurysmal subarachnoid haemorrhage. There was a significant inverse correlation between middle cerebral artery diameter and flow velocity (r = -0.54, p < 0.001). No such correlation was seen for anterior cerebral arteries (r = -0.25). The ratio of middle cerebral artery to extracranial internal carotid artery velocities, which is an index of vasospasm, did not show improved correlation with arteriographic diameters, compared with uncorrected middle cerebral artery readings. Middle and anterior cerebral artery velocities and diameters both began to show significant changes indicative of vasospasm from day 4-5 onwards, suggesting that an increase in Doppler velocity is a good indicator of middle cerebral artery diameter, as shown by angiography. These studies indicate that transcranial Doppler is a useful non-invasive monitor for the development of delayed vasospasm following subarachnoid haemorrhage.

Management of giant intracranial aneurysms

Based on an own material of 64 cases a survey is given on the management of giant intracranial aneurysms. Essential investigations are as well CT and Magnetic Resonance Scanning as detailed angiographic studies. With regard to the operative handling the following questions are discussed: approach; use of temporary vascular occlusion and related monitoring; preparation of the aneurysm neck for occlusion. In cases without recent subarachnoid haemorrhage morbidity and mortality were less than 10%. It was 15% in cases where recent haemorrhage had occurred.

Factors affecting outcome after surgery for intracranial aneurysm in Glasgow

Two-hundred and ninety-five patients with angiographically demonstrated intracranial aneurysms presented to the Institute of Neurological Sciences, Glasgow over a 3-year period (1986-88). We have reviewed this group to assess the effect of changing patterns of management upon outcome. The overall mortality rate was 9.4%, and the surgical mortality rate was 4% in this selected series. Factors significantly associated with a poor outcome were: WFNS grades III-V on admission, presence of a haematoma on the first CT scan, delayed ischaemic deficit, and development of a post-operative haematoma. Seventy-six per cent of the patients who developed a delayed ischaemic deficit (nearly a third of those with recent subarachnoid haemorrhage) made a good recovery, in contrast to previous studies, and over two-thirds of those accepted in grades IV and V (28 patients) made a good recovery after surgery. Active management of patients in grades IV and V, and those with delayed ischaemia, together with prophylactic Nimodipine therapy and selective early surgery, offers the best prospect for further improvement in outcome after aneurysmal subarachnoid haemorrhage.

Fibrinolytic activity after subarachnoid haemorrhage and the effect of tranexamic acid

Seventy-four patients with recent subarachnoid haemorrhage were randomly allocated to placebo or tranexamic acid treatment. Fibrinolytic activity in the blood and cerebrospinal fluid was assessed before treatment, one week later and two weeks later. The natural history of fibrinolysis following subarachnoid haemorrhage was obtained from analysis of the placebo group. Following subarachnoid haemorrhage, fibrin degradation products and plasminogen activity in the cerebrospinal fluid were elevated. Subsequently, fibrin degradation products in the cerebrospinal fluid fell progressively over the following 2 weeks. Changes in cerebrospinal fluid plasminogen activity correlated with those of blood plasminogen activity. Complications such as rebleeding, hydrocephalus or cerebral thrombosis could not be predicted from analysis of fibrinolytic activity. Tranexamic acid treatment resulted in a reduction in cerebrospinal fluid and blood plasminogen activity. The relevance of fibrinolysis in cerebrospinal fluid and blood to the management of subarachnoid haemorrhage is discussed.

Cerebrospinal fluid factors following subarachnoid haemorrhage accelerate collagen lattice contraction by fibroblasts

Proliferation in the intimal layer and medial necrosis are the most consistent findings in the cerebral artery following subarachnoid haemorrhage (SAH) in man. Recently, SEM studies from our laboratory have also shown marked endothelial injury as demonstrated by a profuse platelet carpet. Myofibroblasts proliferate in response to the platelet derived growth factor (PDGF), and abundant collagen is present in the vessel wall. We have employed experiments using fibroblast-populated collagen lattices to study cerebrospinal fluid (CSF) from patients with recent SAH. Isolated rat tail collagen and cultured human dermal fibroblasts are mixed together, placed in 35 mm Petri dishes, and allowed to gel. CSF samples are placed on the surface of the collagen lattice, using 0.2 ml saline for control. The collagen lattices are then incubated and daily measurements recorded. We found that CSF samples from patients with recently ruptured aneurysms significantly accelerate contraction of the collagen lattice. The factor in CSF is heat stable and has a molecular weight of less than 6000.

Plasma atrial natriuretic factor and subarachnoid hemorrhage.

Hyponatremia is common following aneurysmal subarachnoid hemorrhage and has been linked to the syndrome of inappropriate secretion of antidiuretic hormone. However, the demonstration of volume depletion and natriuresis in some patients has suggested that salt wasting is a more likely etiology. Atrial natriuretic factor appears to play a role in both central and peripheral regulation of sodium homeostasis. To investigate the behavior of circulating atrial natriuretic factor following subarachnoid hemorrhage, we studied 25 patients with intracranial aneurysms: 21 after acute subarachnoid hemorrhage and four without evidence of recent rupture. Atrial natriuretic factor was measured by radioimmunoassay of extracted plasma (normal value, 20.8 +/- 24.6, mean +/- 3 SD). Mean +/- SEM plasma atrial natriuretic factor concentration was elevated to 84 +/- 25 pg/ml on Day 1, rose to 134 +/- 29 pg/ml on Day 3, and fell to 86 +/- 17 pg/ml by Day 7 after subarachnoid hemorrhage (p less than 0.01). In two patients (9.5%) who developed hyponatremia after aneurysm rupture, plasma concentrations were no different from that in the group as a whole; concentrations in patients with no evidence of recent subarachnoid hemorrhage were not elevated. Neither fluid administration nor timing of surgery could account for the elevated concentrations. We conclude that concentrations of circulating atrial natriuretic factor are elevated after subarachnoid hemorrhage but do not solely account for the accompanying hyponatremia.