S-100 protein plasma levels after aneurysmal subarachnoid haemorrhage

Summary We investigated the level of S-100 protein in blood as an indicator of brain damage in 71 patients suffering from subarachnoid haemorrhage (SAH) due to ruptured aneurysms.Concentrations of S-100 protein were determined by micro-titre based immunofluorometic assay detecting predominantly S-100_b on blood samples obtained 24 hours, 3 days and 7 days after onset of symptoms in patients with SAH and from 120 healthy control subjects. Neurological status was assessed using the Hunt and Hess (HH) scale on admission and by the Glasgow Outcome Scale (GOS) 6 months later.Mean concentrations of S-100 protein in blood were significantly (p<0.0001) higher in patients 24 hours (0.263±0.387 g/l), 3 days (0.192±0.288 g/l) and 7 days (0.256±0.442 g/l) after onset of SAH symptoms compared to controls (0.050±0.081 g/l). More severe neurological symptoms (higher HH scale scores) on admission correlated with higher S-100 levels on admission (R=0.70) and Day 3 (R=0.66) (p<0.0001). Worse outcome (lower GOS score) 6 months after SAH was also associated with higher plasma concentration of S-100 in the first week after SAH.In summary, this study showed that in patients with SAH due to ruptured aneurysm, S-100 protein levels correlate with early neurological deficit and are as sensitive as HH scores in predicting neurological outcome (GOS scores). Measurement of S-100 protein in blood is a reliable non-invasive method and may be clinically useful to screen for and monitor progression of central nervous system diseases of various origins.     

Non-aneurysmal subarachnoid haemorrhage

A subarachnoid haemorrhage (SAH) is frequent after a severe head injury. Traumatic-SAH is associated with a bad outcome and may induce cerebral vasospasm. There is no agreement on the treatment based on the amount of traumatic-SAH. Non-aneurysmal SAH accounts for 15% of all causes of non-traumatic SAH. There is a risk of cerebral vasospasm, although less frequent than after aneurysmal rupture. The improvement in imaging techniques has decreased the frequency of idiopathic SAH.     

Has plasma renin activity a prognostic significance in subarachnoid haemorrhage?

Summary The possible relationship between plasma renin activity and neurological deficits was examined in ten patients with spontaneous subarachnoid haemorrhage in a prospective clinical study. The patients were examined daily, particular attention being given to signs of brain stem dysfunction. The degree of impaired consciousness was assessed using the Glasgow Coma Score. Plasma renin activity was determined on days 1–5, 7, 9, 11, 13, 15 and 21 after the initial bleeding episode using an Angiotensin-I-radioimmunoassay. Six of seven patients with signs of brain stem dysfunction displayed a marked increase in plasma renin activity. Thus a significant negative correlation between the degree of consciousness and the plasma renin activity resulted. An explanation for this correlation may be found in the localization of the autonomous centres and the high concentrations of renin in the hypothalamus and brain stem. The individual changes in plasma renin activity have prognostic significance, whereas single estimated plasma renin activities show great interindividual differences and have only limited prognostic value.     

Aneurysmal subarachnoid haemorrhage

Spontaneous subarachnoid haemorrhage accounts for only 3–4% of all stroke but the consequences can be devastating. In the present review article, we review the epidemiology, clinical features, investigations and management philosophy in patients with aneurysmal subarachnoid haemorrhage. Oral nimodipine, aneurysmal occlusion and advances in neurointensive care are the keys to improve neurological outcome in patients after aneurysmal subarachnoid haemorrhage. These patients should be managed by a combined team with expertise in microsurgery, endovascular surgery and neurointensive care for optimal management outcome. Early diagnosis and treatment is the key to improve outcome and reduce disability and mortality.     

Management of subarachnoid haemorrhage

Subarachnoid haemorrhage is an acute neurosurgical emergency affecting patients of all ages and with high mortality. It is usually caused by rupture of an aneurysm of an intracranial artery at a point of turbulent blood flow within the circle of Willis. Diagnosis should be made rapidly initially with non-contrast CT of the head. Minimizing secondary neurological injury is the focus of care. Initial stabilization focussing on providing adequate cerebral oxygenation and perfusion should be carried out expediently and this may require intubation and ventilation. Transfer to a specialist neurosciences centre for ongoing management is the next priority. Culprit aneurysms should be secured promptly by endovascular coiling or surgical clipping. Recognition and management of complications is best undertaken in a centre managing high volumes of these patients. Vasospasm is a common and feared complication of subarachnoid haemorrhage. All patients should be given nimodipine for prophylaxis and management of this complication.     

Changes in the subarachnoid space after experimental subarachnoid haemorrhage in the dog: Scanning electron microscopic observation

Summary The possible changes in the subarachnoid space after subarachnoid haemorrhage were studied in animals by using a scanning electron microscope (SEM).About 1 ml/kg of autogenous blood was injected intracisternally in 36 adult mongrel dogs to investigate changes in the subarachnoid space, over periods ranging from immediately after the injection to as long as 6 months.We have come to the conclusion that the injected blood disappears in about one to two weeks; the fibrosis or thickening of the arachnoid membrane appears in one to three weeks, and then returns to normal in a month in instances of rapid recovery, but there are some cases in which fibrosis persists for a long period and becomes chronic. The fact that an increase of fibrous tissue was found in the parietal region, where the injected blood had hardly reached, appears to indicate that the fibrosis is not always limited to the site of the haemorrhage but can occur in remote regions.We also discuss the usefulness of the SEM in the observation of the subarachnoid space, and the finding that vascular specimen preparations can be made by perfusing the brain with 2–10% phosphate-buffered formaldehyde solution.     

Management of subarachnoid haemorrhage

Subarachnoid haemorrhage is an acute life-threatening neurosurgical emergency affecting all ages and causing high mortality and morbidity. The rupture of an aneurysm of an intracranial artery at a point of turbulent blood flow within the circle of Willis usually causes it. Diagnosis begins with a non-contrast CT of the head, followed by more definitive angiography. The focus after diagnosis is to minimize further neurological injury called secondary injury. Initial stabilization with an ABCDEF approach should focus on maintaining adequate cerebral oxygenation and cerebral perfusion pressure (CPP). In emergent cases, this may require intubation and mechanical ventilation. Transfer to a specialist neuroscience centre for ongoing management is the next priority. Culprit aneurysms should be secured promptly by endovascular coiling or surgical clipping. Anaesthesia for either clipping or coiling must be neuroprotective. Recognition and management of complications are best undertaken in a centre managing high volumes of these patients. Vasospasm and delayed cerebral ischaemia are common and feared complications of subarachnoid haemorrhage. All patients should be given nimodipine for prophylaxis and management of these complications. Future research into the pathophysiology of the injured brain in SAH can guide us to novel therapies.     

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.     

Adrenergic blockade in subarachnoid haemorrhage

Summary Over the last 15 years progressive interest has developed in the relationship between subarachnoid haemorrhage, sympathetie nervous system overactivity and the genesis of cerebral artery spasm. Following on from earlier work, vide infra, suggesting that adrenergic blockade might influence the course and prognosis of patients with subarachnoid haemorrhage, two double blind trials have recently been completed in Southampton.The first trial attempted to establish whether or not a single intracarotid injection of phenoxybenzamine improved the mortality and late morbidity of patients with subarachnoid haemorrhage. Results suggested that it did not. The second trial, comprising two groups of 50 patients each, attempted to assess the influence of prolonged treatment with propranolol on the course and prognosis of these subarachnoid haemorrhage patients. Early results suggest that, as with the- blocker, the mortality and severe morbidity was not improved by-adrenergic blockade.     

Activation of the coagulation system in the subarachnoid space after subarachnoid haemorrhage: Serial measurement of fibrinopeptide A and bradykinin of cerebrospinal fluid and plasma in patients with subarachnoid haemorrhage

Summary Fibrinopeptide A (FPA) levels as an indicator of thrombin activity in the cerebrospinal fluid (CSF) and plasma of 25 patients with subarachnoid haemorrhage (SAH) were measured serially by radioimmunoassay (RIA). FPA levels in CSF were extremely high on days 0–1 (1253±269 ng/ml, mean ± standard error) but decreased rapidly (11.3±3.9 ng/ml on days 2–4, 10.7±5.9 ng/ml on days 5–7, and 6.3±1.5 ng/ml on days 8–14). In the controls the FPA concentration in CSF was 1.2±0.9 ng/ml (mean ± standard deviation). Plasma FPA levels in patients with SAH showed no statistically significant changes with time.The bradykinin (BK) concentration in CSF and plasma in 27 patients with SAH was measured serially by RIA. The cocentrations in CSF were 122.7±22.7 pg/ml (mean ± standard error) on day 0, 38.6±6.1 pg/ml on day 1,22.7±6.3 pg/ml on day 2, and 17.1±3.0 pg/ml or less thereafter. Plasma BK levels in patients with SAH were higher than those in the control group, but there was no statistically significant change over time.From the measurement of FPA it was apparent that the coagulation system in the subarachnoid space is strongly activated in the early stage of SAH. The formation of BK in CSF after SAH is thought to be due to the contact activation of Hageman factor (intrinsic factor) in the subarachnoid space. Trabeculae as collagen bundles in the subarachnoid space were considered to have a possible role in activating the Hageman factor of the coagulation system in SAH.     

Treatment-orientated classification of subarachnoid haemorrhage

The prognosis of patients with cerebral aneurysms has improved greatly with modern management, notably hypotensive and steroid therapy and microneurosurgical techniques. A new classification of subarachnoid haemorrhage is discussed to clarify the early management of patients and their referral to specialized units for intensive medical care and curative surgery.     

Cerebrospinal fluid production in subarachnoid haemorrhage

Eight patients with subarachnoid and/or intraventricular haemorrhage underwent continuous extraventricular drainage and cerebrospinal fluid production was estimated by modified open drainage. The patients were in Hunt & Hess grades 2-5 on admission. Drainage was instituted within 24 h after the last bleeding episode in seven patients and the duration of drainage was 3-37 days. The median amount of CSF that was drained in 24 h was 210 ml. CSF production rate was 0.10-0.55 ml/min (median 0.28 ml/min) and there was a great variation within as well as between patients. Thus there was a trend towards a reduction in CSF production compared to reported normal values for CSF production. Three of six surviving patients required a shunt. The possible role of reduction in CSF production rate in the modification of intracranial hypertension and hydrocephalus after subarachnoid haemorrhage is discussed.     

Beta-blockade in acute aneurysmal subarachnoid haemorrhage

Summary The effects of beta-blockade to prevent autonomic disorders after acute aneurysmal subarachnoid haemorrhage were prospectively investigated. 11 patients were treated with the beta-1-selective beta-blocker metoprolol (up to 200 mg/die intravenously). 14 patients received standard therapy as controls. Pulse rate, blood pressure and dosage of the additional antihypertensive medication as signs of sympathetic disturbance were registered. The main result was the normalizing of the pulse rate especially during the first two weeks in contrast to the control group. The patients in the beta-blocker group did not need further antihypertensive medication. This was mainly a result of the reduction in sympathetic activation. No severe side-effects were documented and the survival was better in the treated group. Thus, beta-blockade is able to prevent and reduce autonomic disorders, especially activation of the sympathetic tone, in subarachnoid haemorrhage. Metoprolol as a so called cardioselective beta-blocker seems to be one of the suitable agents and is considered superior to the non-selective agents.     

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.     

Computertomography in subarachnoid haemorrhage and aneurysm

Summary 59 patients with SAH and an aneurysm were investigated by CT and angiography. In the 59 patients 67 aneurysms were found. The mean interval between SAH and CT was 8 days, between SAH and angiography 11 days. Blood in the CSF space was visualized up to the 9th day in the patients and 67% of those investigated showed blood in the CSF-space in the CT. In 31% of the patients an aneurysm, in 29% an intracerebral haemorrhage and in 19% a recent infarct was found. A hydrocephalus was seen in 13% of the patients. Of 12 patients with recent infarcts 8 showed vasospasm which correlated in time and location with the infarct.