Improvement after treatment of hydrocephalus in aneurysmal subarachnoid haemorrhage: implications for grading and prognosis

Summary Two patients with aneurysmal subarachnoid haemorrhage and hydrocephalus are presented. On admission they scored E1M4V1 and E1M3Vtube on the Glasgow Coma Scale. The first patient recovered to E3M5Vtube after treatment of hydrocpehalus by extraventricular drainage. The second recovered to E2M5Vtube and later E4M6V4 after treatment of hydrocephalus with lumbar drainage. Based on the literature it is argued that these cases are no exception as to the improvement after treatment of hydrocephalus. The prognosis of patients with hydrocephalus after a subarachnoid haemorrhage, improves in parallel with the Glasgow Coma Scale after treatment of hydrocephalus. Therefore decision making on whether or not to treat a patient with a subarachnoid haemorrhage should be postponed until after treatment of hydrocephalus, if present.     

Regional differences in outcome from subarachnoid haemorrhage

Summary Background. Surgeons are increasingly placed under pressure to accept publication of their results and to abide by recommendations to change practice which others derive. Considerable concern exists about misinterpretation of such data. The issue is well illustrated by this study.Method. Data on outcome following treatment for subarachnoid haemorrhage were prospectively collected from 1993–1998 in two centres in the British Isles: Newcastle and Nottingham.Findings. Initial examination of this data suggest a substantial difference in the performance favouring Nottingham over Newcastle. The odds of a poor outcome was 1:1.86 in Newcastle compared with 1:4.26 in Nottingham giving an odds ratio of 2.3 in favour of Nottingham and this difference was highly significant with p<0.00001. On a more detailed examination taking account of confounding variables, this difference disappeared entirely. Newcastle was able to operate a less selective admissions policy than Nottingham because of the deficiency of beds at the latter unit. A summary of these results has been published elsewhere.Interpretation. These results illustrate the dangers of applying statistical tools developed for simpler situations such as industrial process control to complex medical problems. We conclude that comprehensive and accurate data on all factors likely to influence the outcome for a particular treatment should be collected as an absolute prerequisite to any judgments being made on apparent statistical differences between the performances of differing units.     

ECG abnormalities in predicting secondary cerebral ischemia after subarachnoid haemorrhage

Summary Background. Electrocardiographic (ECG) abnormalities frequently occur after subarachnoid haemorrhage (SAH), and have been linked with poor outcome. The pathogenesis behind this relation is unclear. We hypothesized that cardiac dysfunction may contribute to the development of delayed cerebral ischemia (DCI) and investigated if electrocardiographic repolarization abnormalities on admission, representing this cardiac dysfunction, are related to DCI. We also assessed the additional value of ECG characteristics to establish prognosticators for clinical outcome (WFNS, age and Hijdra score). Method. In a series of 121 consecutive patients with aneurysmal SAH we related individual repolarization-like ECG changes (ST and T-wave changes, QTc prolongation, a U-wave) to the occurrence of DCI by means of Cox proportional hazard modelling and to poor outcome (death or dependence) with logistic regression analysis. We used ROC curves to assess the additional prognostic value of the most important ECG characteristics to established prognosticators. Findings. Only ST segment depression had a statistically significant relationship with the occurrence of DCI (HR 2.4 [95%CI 1.2–4.9]) in univariate analysis. In a similar analysis ST-elevation (OR 4.9; [95%CI 0.99–24.0]), ST-depression (OR 10.6; [95%CI 2.3–48.8]), T-wave inversion (OR 2.5; [95%CI 1.1–5.5]) and ischemic like ECG abnormalities (OR 8.3; [95%CI 3.0–22.2]) were significantly related to poor outcome. In multivariate models with extension of these ECG characteristics for establishing prognosticators the AUC of the ROC improved from 0.81 to 0.84. Conclusions. ECG abnormalities did not contribute to the prediction of DCI and have limited value in prognosticating poor outcome. The occurrence of DCI is not the explanation of this relationship between ECG characteristics and outcome.     

Prognostic factors on hospital admission after spontaneous subarachnoid haemorrhage

BACKGROUND AND OBJECTIVE: Factors related to prognosis after subarachnoid haemorrhage (SAH) have been mainly extracted from surgical series, and only few authors have considered these factors in total management or population series. Though the level of consciousness is a major determinant of outcome after subarachnoid haemorrhage, there is not a consensus about which classification should be used to define it. The objective of this study was twofold. Firstly to find which factors recorded on hospital admission relate to outcome determining their relative importance in a non-selected series of patients suffering from aneurysmal SAH admitted to our centre, and secondly to assess the validity of the WFNS clinical scale for predicting the final result. METHODS: A series of 294 patients consecutively admitted to Hospital 12 de Octubre Madrid between January 1990 and June 2000 with the diagnosis of aneurysmal SAH were retrospectively reviewed. All factors possibly related to prognosis were recorded on hospital admission. Outcome was measured by means of the Glasgow Outcome Scale measured one month after hospital discharge. Relationship between factors and outcome was evaluated by univariate and logistic regression multivariate analysis. RESULTS: Although several factors, appeared related to prognosis in the univariate analysis, only the age. the level of consciousness defined by the WFNS scale and the presence of global brain hypodensity on the initial CT scan had a significant prognostic influence in the logistic regression model. Global brain hypodensity was strongly related to mortality. Since a number of factors associated with poor outcome in the univariate analysis are related to age, their influence could be explained by the difficulty of recovery of the ageing brain. The WFNS grading scale failed to predict significant differences in outcome between some of its grades. CONCLUSIONS: Age and clinical grade on admission are the most important factors influencing the final outcome of patients suffering aneurysmal SAH. A reappraisal of the WFNS grading scale should be considered as no significant differences in outcome were found between some of its grades.     

A simple scoring system for accurate prediction of outcome within four days of a subarachnoid haemorrhage

Summary This study was designed to examine the consistency of a number of easily identifiable predictive factors in assessing outcome within four days of a subarachnoid haemorrhage. Patients with a proven subarachnoid haemorrhage, aged between 15–65, of any neurological grade who had bled within 72 hours of admission, and who had undergone a CT scan within 96 hours of the ictus, were included.Three groups of patients were studied prospectively. The studies were separated in time and place. The series were similar overall but there were some variations between the three groups of patients because of alterations in referral patterns and management strategies between the series. There were significant differences in the patients' ages, grades on admission, timing of angiography, negative angiography rate and timing of operation. This did not affect overall outcome; 57%, 61% and 59% of the patients in series 1, 2 and 3 respectively making a good recovery. The proportion of patients with a poor outcome was also similar.To identify the level of risk of an individual patient within the first few days of haemorrhage, we considered a number of early predicitive factors. Two emerged as strong predictors of outcome; the early neurological grade and the distribution of blood on the CT scan. We developed a simple scoring system from the first series, based on these findings, designed to predict outcome at three months. The scoring system was calculated on the basis of the distribution of blood seen on the CT scan and the patients' neurological grade on admission. Two points each were scored for interhemispheric, intraventricular, basal or intracerebral blood (excluding blood in the sylvian fissures). Patients in grade 1–3 scored –1, grade 4 scored 0, grades 5&6 scored +5. The scan score and grade score were summated to give the overall score. Patients were placed in risk groups (low, score –1; medium, score 0–2; high, score 3+). The scoring system was then applied prospectively to the two subsequent groups of patients. In each of the three series there was a clear correlation between the patients' scores and their outcomes but more importantly the probability of each outcome for each risk group was considered. In both the second and third series the probability of a full recovery in the low risk group was very likely –P=0.000. In the second series, given a high risk category, there some indication that death was the likely outcome (P=0.085), while in the third series death was significantly the most likely outcome (P=0.001) in the risk category.This study demonstrates that outcome is determined at the time of initial haemorrhage and is reflected by the early neurological grade and the CT distribution of subarachnoid haemorrhage. Other variables, including age, systemic blood pressure, the use of nimodipine or -blockers, and the timing of operation do not alter the risk grouping of patients, i.e., do not move a patient from high to medium or low risk groups.     

Prognostic value of evoked potentials and clinical grading in primary subarachnoid haemorrhage

Summary In a retrospective study of 64 patients suffering from primary subarachnoid haemorrhage (SAH), the clinical grading according to Hunt and Hess as well as the initial findings of brainstem auditory evoked potentials (BAEP) and median-nerve somatosensory potentials (SEP) were correlated with each other and with disease outcome to determine the prognostic value of evoked potential testing in comparison to the initial clinical grading according to Hunt and Hess.All patients were treated in a neurological intensive care unit. Normal evoked potentials usually indicate a favourable course. Alterations of SEP and BAEP increase in parallel with the severity of clinical findings. Unilateral or bilateral loss of SEP or BAEP indicates a poor prognosis. Clinical and electrophysiological findings show a close correlation, but only BAEP provide prognostic information beyond Hunt/Hess grading.In SAH patients, clinical grading was well as evoked potentials correlate significantly with outcome. Use of both clinical and EP rating improves prognostic accuracy.     

Assessment of the consequences of subarachnoid haemorrhage

Summary The management of patients with subarachnoid haemorrhage depends greatly on assessment of the patient's clinical condition. Difficulty in applying currently used grading systems prompted us to conduct studies of observer variability and to attempt to identify sources of inconsistency. Observers graded 15 patients from the Hunt and Hess and Nishioka systems. Kappa statistics were used to evaluate the data. Marked observer variability was found, this being greatest when Grade 3 was selected, irrespective of the system used. When observers graded clinical summaries, similar variability was found, indicating that this was due to difficulty in matching patients' clinical states with specific levels within the grading system. The study shows that a simple and more reliable grading system is required.     

Magnesium therapy after aneurysmal subarachnoid haemorrhage a dose-finding study for long term treatment

Summary.  Background: Magnesium is a neuroprotective agent which might prevent or reverse delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (SAH). Although the dosage for short-term magnesium therapy is well established, there is lack of knowledge on the dosage for extended use of magnesium. Our aim was to find a dosage schedule of magnesium sulphate to maintain a serum magnesium level of 1.0–2.0 mmol/L for 14 days to cover the period of DCI.  Methods: We prospectively studied 14 patients admitted within 48 hours after aneurysmal subarachnoid haemorrhage (SAH) to our hospital. Magnesium sulphate was administrated intravenously for 14 days, using 3 different dosage schedules. Group A (n=3) received a bolus injection of 16 mmol magnesium sulphate followed by a continuous infusion of 16 mmol/dayly; group B (n=6) a continuous infusion of 30 mmol/dayly; and group C (n=5) a continuous infusion of 64 mmol/dayly. Serum magnesium was measured at least every two days and all patients were under continuous observation during magnesium treatment. Renal magnesium excretion was measured only in group C.  Findings: In treatment group A the mean serum magnesium level during treatment was 1.03±0.14 (range 0.82–1.34) mmol/L, in group B 1.10±0.15 (range 0.87–1.43) mmol/L, and in group C 1.38±0.18 (range 1.11–1.98) mmol/L. The renal magnesium excretion in group C was equal to the administrated doses within 48 hours after treatment had started. All patients in group A reported a flushing sensation during the bolus injection; no other side effects were noted.  Interpretation: With a continuous intravenous dosage of 64 mmol/L per day, serum magnesium levels maintained within the range of 1.0–2.0 mmol/L for 14 days. Published online March 3, 2003 Acknowledgments  We gratefully acknowledge the Netherlands Heart Foundation (grant 99.107) and the Schumacher-Kramer Foundation, for financially supporting this study. Dr. Rinkel is clinically established investigator of the Netherlands Heart Foundation (grant D98.014).  Correspondence: W. M. van den Bergh, M.D., Department of Neurosurgery, Room G03.124, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.     

Extent of atherosclerosis and prognosis of patients with aneurysmal subarachnoid haemorrhage

Summary Background and purpose. Atherosclerosis impairs the endothelial dependent vasodilatation and may change the diameter and plasticity of cerebral vessels. The aim of this study was to investigate if an index of the occurrence of atherosclerosis is associated with the risk of delayed cerebral ischemia or poor outcome after subarachnoid haemorrhage. Methods. To assess the likelihood of atherosclerosis we used a modified version of the Framingham Heart Study Coronary Heart Disease Prediction Chart. The relation of this index to the occurrence of delayed cerebral ischemia was studied by means of survival analysis and to poor outcome by regression analysis. A multivariate analysis was used to investigate the independent contribution of the atherosclerosis index. Results. Three hundred and twenty three patients were retrieved from our database from the period 1997 to 2004. The index of atherosclerosis related to a good clinical condition on admission (p = 0.01). A high risk of atherosclerosis independently predicted poor outcome (OR 4.3; 95%CI 1.6–12). This was not caused by an increase in the occurrence of delayed cerebral ischemia (HR 1.1; 95%CI 0.6–2.1), but, in part, by a marked decrease in recurrent bleeding in patients with no or minor atherosclerosis. Conclusions. An index of the occurrence of atherosclerosis is related to prognosis after subarachnoid haemorrhage. The use of the score may focus attention on patients at risk for poor outcome after subarachnoid haemorrhage.     

Cardiac arrhythmias in subarachnoid haemorrhage

Summary In this prospective study 52 patients with spontaneous subarachnoid haemorrhage were examined with respect to cardiac arrhythmias and their relationship to cerebral lesions. A continuous ECG was registered over an average of five days. Sinus tachycardia was the most frequently recorded arrhythmia, followed by multifocal ventricular extrasystoles, couplets, frequent supraventricular extrasystoles, non-sustained ventricular tachycardia, asystolia and sinus arrhythmia. A significant correlation was found between the clinical manifestation of a midbrain syndrome and sinus arrhythmia, and multifocal ventricular extrasystoles. This correlation points to the autonomic cardiovascular centres as the structures involved.     

Is there a difference in cognitive deficits after aneurysmal subarachnoid haemorrhage and subarachnoid haemorrhage of unknown origin?

Summary In a retrospective follow-up study 38 patients with aneurysmal subarachnoid haemorrhage (SAH) and 20 patients without an angiographically proven source of SAH were tested neuropsychologically one to five years after the acute event. All patients were operated on early within 72 hours if an aneursym was proven angiographically and all were treated with nimodipine.Both patient groups had comparable cognitive deficits in spite of the less severe SAH of non-aneurysmal origin. Only in two cognitive functions the groups differed significantly. The patients after non-aneurysmal SAH had a significantly lower mean in the IQ subtest similarities finding (p<0.05), while the patients after aneurysmal SAH had a significantly lower mean in a test of visual cognition (p<0.05).A more detailed analysis with clinically homogenous subgroups was additionally performed. The results showed in the subgroup with poor clinical grades that patients with aneurysmal SAH were significantly more disturbed in focal cognitive functions like short- and long-term memory and word-finding capacity, while patients with SAH of unknown origin scored significantly worse in a neuropsychological test related to attention, which can be regarded as a more diffuse cognitive function.     

Polarization microscopic investigation of subarachnoid fibrosis after subarachnoid haemorrhage

Summary The author used the polarization microscope and topo-optical reactions such as phenol reaction, collagen-specific sulphation, and picrosirius red F 3 BA staining to investigate the nature of subarachnoid fibrosis after experimental subarachnoid haemorrhage. It is strongly suggested that the subarachnoid fibrotic deposits—which here analysed in a previous study by scanning electronmicroscopy—contain a high amount of collagen as a main component both three weeks and three months after the SAH.     

Clinical and long-term follow-up study in patients with spontaneous subarachnoid haemorrhage of unknown aetiology

Summary Clinical characteristics and the outcomes of 50 patients with confirmed subarachnoid haemorrhage (SAH) of unknown aetiology were evaluated. Twenty-nine of these patients were interviewed with a mean follow-up of 7.7 years. Seven patients experienced early rebleeding during hospitalization, and one patient experienced late rebleeding during the follow-up period.On admission to the hospital the consciousness level was clear in 43 of the patients, drowsy in 6, and semicomatose in only 1. Of 10 patients who underwent computerized tomography (CT) within 3 days after SAH, 6 showed no abnormal CT findings and 3 had mild subarachnoid blood. Another patient showed severe SAH. Neurological deficit due to symptomatic vasospasm persisted in only 1 case.Two patients died after re-bleeding during hospitalization, and two others died during the follow-up, thereby representing an overall mortality rate of 8%. Of the latter cases, one died of an unrelated disease, and the other died suddenly from an unknown cause. The remaining forty-six patients (92%) had a good outcome. These results confirm previously reported clinical characteristics, namely that the symptoms of the majority of such cases are mild, the incidence of symptomatic vasospasm is rare, the risk of late re-bleeding is very low (less than 1% per year), and the prognosis is good. The CT findings suggest that some of these features resulted from only mild SAH. Thus, SAH of unknown aetiology seems to be a disease entity with a good prognosis.     

Histochemical evaluation of the glycosaminoglycans in vasoconstricted human cerebral arteries after subarachnoid haemorrhage

Summary Sixteen patients dying after subarachnoid haemorrhage (SAH) were investigated with regard to the presence of angiographic vasoconstriction and of glycosaminoglycans in samples from the main cerebral arteries. All patients had a statistically significant (p < 0.001) vasoconstriction at angiography performed before death. At morphological examination, the vessels of all patients showed signs of intimai thickening, necrosis of the media and leucocyte infiltration of the adventitia. The presence of glycosaminoglycans was determined semiquantitatively and did not differ from the values obtained from presumably normal controls. It is suggested that the angiographically verified vasoconstriction found after SAH as well as the morphological changes of the cerebral arteries are not related to a concentration increase of glycosaminoglycans.     

Fibrinolytic activity after subarachnoid haemorrhage and the effect of tranexamic acid

Summary 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.     

Grading and outcome prediction of cases of aneurysmal subarachnoid haemorrhage by bedside xenon cerebral blood flowmetry

Summary Ninety-six patients with aneurysmal subarachnoid haemorrhage underwent serial measurement of regional cerebral blood flow throughout the period of their treatment over the period of 5 years (1983 to 1988). A portable bedside xenon cerebral blood flow machine was used in this study and the initial slope index (ISI) values showed a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. Furthermore, serial measurements showed a statistically significant relationship between drop of cerebral blood flow, at anytime during the course of the disease, and fatal or less than satisfactory outcome.     

Impaired utilization of exogenous amino acids after surgery for subarachnoid haemorrhage

Summary We studied the metabolic response to acute aneurysm surgery and its modification by parenteral nutrition. Forty-eight patients receiving perioperative corticosteroid treatment were randomly assigned to receive glucose alone (7.2 kcal/day, D5W+C), glucose and a conventional amino acid solution (7.2 kcal/day and 0.15gN/ day, CAA+C) or glucose and branched chain amino acid enriched solution (7.2 kcal/day and 0.14 gN/day, BCAA+C). Twenty patients without corticosteroid treatment received either glucose alone (7.2 kcal/day, D5W) or glucose and a conventional amino acid solution (7.2 kcal/day and 0.14gN/day, CAA). Poor nitrogen utilization was indicated by strongly negative nitrogen balance in all groups and a failure of the infused amino acids to improve nitrogen balance. (Day0; D5W+C: –9.3±3.6g/day and CAA+C: – 8.2±9.7g/ day vs CAA: –2.6±4.9g/day, p<0.05,Day 1; D5W+C: –14.9 ±9g/day vs CAA:–7.7±6.5g/day, p<0.05, MANOVA). We conclude that subarachnoid haemorrhage and its surgical treatment induce a catabolic response and impaired utilization of exogenous nitrogen, further amplified by perioperative corticosteroids, which is in sharp contrast to the response to surgery not involving the central nervous system.     

Magnetic resonance imaging in experimental subarachnoid haemorrhage

Summary Background. We developed an MRI protocol to measure cerebrovascular diameter and blood flow velocity, and if we could detect cerebrovascular alterations after SAH and their impact on cerebral ischaemia.Method. SAH was induced in 15 Wistar rats by means of the endovascular filament method; 6 other rats served as control. MRI measurements were performed on a 4.7T NMR spectrometer 1 and 48 hours after SAH and 9 days thereafter. Diffusion-weighted and T₂-weighted images were acquired to detect cerebral ischaemia. The arterial spin labelling method was used to measure CBF. MR angiography was used to measure vessel diameter and blood flow velocity, from which the arterial blood flow was calculated.Findings. The ischemic lesion volume increased between 1 and 48 hours after SAH from 0.039 to 0.26 ml (P = 0.003). CBF decreased from 53.6 to 39.1 ml/100 g/min. The vessel diameter had narrowed, the blood flow velocity diminished as did the arterial blood flow in most vessels, but only the vasoconstriction in the right proximal ICA reached significance (0.49 mm to 0.43 mm, P = 0.016). Baseline values were restored at day 9.Conclusions. We showed that it is feasible to detect alterations of in-vivo vessel diameter and blood flow velocities and their consequences for brain damage after experimental SAH in the rat. The growth of the infarct volume between day 0 and 2 after SAH and the parallel vasoconstriction suggest that delayed cerebral ischaemia after SAH occurs in rats and that this may be caused by vasoconstriction.     

Rehabilitation implications of non-traumatic subarachnoid haemorrhage

Objective: Subarachnoid haemorrhage (SAH) remains an important cause of stroke in the rehabilitation population, whose incidence has not been changed by pre-morbid medical treatment. The understanding of the pathophysiological changes that occur after SAH has been more clearly defined, therefore the treatment and outcomes of these patients have undergone drastic changes over the past few years. The purpose of this review is to update and familiarize the rehabilitation professional on the state of the art treatment and common complications associated with this disease and how this may affect the rehabilitation programme. Also, the current literature on the outcomes of these patients will be reviewed to help advise the rehabilitation professional on potential predictors.

Data sources: Literature review.

Study selection: Articles of relevance to the current management of SAH.

Data extraction: Information that was deemed significant in the understanding of the pathophysiology, treatment and results of outcomes in patients with SAH.

Data synthesis: Subarachnoid haemorrhage (SAH) is the one sub-type of stroke whose incidence has not declined. Due to advances in medical care, mortality rate is on the decline. Outcomes data was analysed to look for common predictors for this patient population.

Conclusions: While the incidence of SAH has not declined, improving medical treatment has reduced mortality. The rehabilitation professional should be familiar with the latest advances, potential complications and likely outcomes in order to plan the most appropriate therapy course for these patients.     

Sequential changes of cerebral blood flow after aneurysmal subarachnoid haemorrhage

Summary A total of 226 measurements of cerebral blood flow (CBF) were performed in 96 postoperative patients with aneurysmal subarachnoid haemorrhage (SAH). The global CBF was significantly reduced in the first week after SAH, and the extent of the CBF reduction was less in the patients with good outcome than in those with fair/ poor outcome. The good outcome patients showed a progressive increase in CBF in the following 3 weeks. Although the CBF decreased further in the second week in some of those patients, it turned to a steady increase thereafter. On the other hand, in the fair/poor outcome patients CBF remained far below the normal control value for at least 3 months after SAH. When looking into the effect of age on CBF in the patients with good outcome, those in their thirties and forties had a significantly reduced CBF during the first 2 weeks, whereas in those in their fifties and sixties a significant reduction persisted for 3 months to 1 year after SAH. Management of the older patients needs special attention even if they are apparently in good clinical condition, since the CBF threshold to ischaemia is diminished.