CO2 reactivity in patients after subarachnoid haemorrhage

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

Management for subarachnoid hemorrhage with negative initial angiography

The diversity of neuronal glutamate receptors continues to increase with the discovery of multiple subunits and subunit families. The significance of this potential receptor heterogeneity is unknown because pharmacological tools that could clearly distinguish between different structural isoforms have not yet been identified. A novel glutamate receptor antagonist, 5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime (NS-102), has been shown previously to selectively block the low affinity [3H]kainate binding site in rat brain. We have examined the effect of NS-102 on receptors expressed in fibroblasts from either glur6 subunits or a combination of glurB and glurD (glurB/D receptors). NS-102 (3 microM) reduced currents mediated by glur6 receptors and had very little effect on currents mediated by glurB/D receptors. The binding of [3H]kainate to glur6 receptors showed properties similar to those of the brain low affinity [3H]kainate binding site, and NS-102 inhibited specific binding to glur6 receptors with a potency nearly identical to those sites in brain membranes. Our findings suggest that NS-102 will be useful in identifying the functional role of native receptors containing a glur6 subunit.     

Headache characteristics in subarachnoid haemorrhage and benign thunderclap headache

One third of patients with aneurysmal subarachnoid haemorrhage (ASAH) present with headache only. A prompt diagnosis is crucial, but these patients must be distinguished from patients with non-haemorrhagic benign thunderclap headache (BTH). The headache characteristics and associated features at onset in subarachnoid haemorrhage and benign thunderclap headache were studied to delineate the range of early features in these conditions. In this prospective study, one of two observers interviewed 102 patients with acute severe headache by means of a standard questionnaire. The patients were alert on admission and had no focal deficits. ASAH was subsequently diagnosed in 42 patients, non-aneurysmal perimesencephalic haemorrhage (PMH) in 23 patients, and BTH in 37 patients. Headache developed almost instantaneously in 50% of patients with ASAH, 35% of patients with PMH, and 68% of patients with BTH and within 1 to 5 minutes in 19%, 35%, and 19%, respectively. Loss of consciousness was reported in 26% of patients with ASAH, 4% of patients with PMH and 16% of patients with BTH, and transient focal symptoms in 33%, 9%, and 22% respectively. Seizures and double vision had occurred only in ASAH. Vomiting and physical exertion preceding the onset of headache were more frequent in patients with ASAH (69% and 50%) and those with PMH (83% and 39%) than in those with BTH (43% and 22%). Headache developed almost instantaneously in only half the patients with aneurysmal rupture and in two thirds of patients with benign thunderclap headache. In patients with acute severe headache, female sex, the presence of seizures, a history of loss of consciousness or focal symptoms, vomiting, or exertion increases the probability of ASAH, but these characteristics are of limited value in distinguishing ASAH from BTH. Aneurysmal rupture should be considered even if focal signs are absent and the headache starts within minutes.     

False-negative angiograms in subarachnoid haemorrhage due to intracranial aneurysms

In occupational epidemiology, the need to consider the age factor properly influences the choice of study design and analytical techniques. In most studies, age is viewed as a potential confounder. Age is strongly associated with end points of interest in occupational epidemiology (diseases, physiological characteristics, doses of xenobiotics, etc), but to measure age as a confounder it must be associated with the exposure under study. When the exposure of interest is time related-for example, duration of employment, time since first exposure, cumulative exposure-a strong intrinsic association with age can be anticipated, and age will behave as a (usually strong) confounder. When occupational exposures without a direct relation with age-for example, job, department, type of exposure-are evaluated, the degree and direction of confounding bias cannot be anticipated. Control of the confounding effect of age can be accomplished in the design phase of a study by way of randomisation, restriction, and matching. Randomisation is seldom viable in occupational settings. Restriction is rarely used in the case of age. Matching is often used in a case-control study as a method to increase the study efficiency, but it must be followed by proper matched or stratified analysis. Options for age adjustment in the analysis phase involve stratification and regression methods. In longitudinal studies the modified life table analysis is used to take into account the fact that subjects cross categories of age as the study proceeds. Stability of relative measures of effect over age strata favoured the greater use of relative risks than risk differences. In the presence of effect modification the influence of age should not be eliminated; its interaction with exposure should be explicitly considered.     

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid

A single poroid neoplasm composed of three histologically distinct lesions (hidroacanthomas simplex, eccrine poroma, and dermal duct tumor) is reported. Comparative histologic, histochemical, and electron-microscopic studies revealed that each tumor subtype contained varying proportions of poroid cells, clear cells, and cuticular cells. The major component of all three neoplasms was poroid cells, which, under the electron microscope, were characterized by a few, small, poorly developed desmosomes, and were histochemically characterized by a positive succinic dehydrogenase reaction. The dermal duct tumor was cultured, and showed similar histochemical findings to the in vivo poroid cells. These results suggest that poroid cells play the most important role in the histogenesis of these three neoplasms.     

Indications for cisternal irrigation with urokinase in postoperative patients with aneurysmal subarachnoid haemorrhage

The melatonin binding sites in membrane preparations of the young mouse thymus were studies using [125I] iodomelatonin as the radioligand. Effect of epinephrine (E) on melatonin receptor (MR) of young mouse thymus were investigated. Results: (1) E had inhibitory effect on MR of mouse thymus; (2) Propranolol could reverse the inhibitory effect of E but phentolamin could not; (3) cAMP had inhibitory effect on MR. These results indicate that E has the inhibitory effect on MR of the mouse thymus and the effect was mediated by beta-adrenergic receptor.     

Detection of aneurysm in subarachnoid hemorrhage--CT angiography vs. digital subtraction angiography

The purpose of this study was to investigate the feasibility and the efficacy of administering tirapazamine by a slow-releasing polymer disc that was implanted interstitially into a U251 (human glioblastoma multiforme) tumor grown in nude mice. Tumor-bearing animals, with a tumor nodule 0.8 cm3 in size, were distributed to groups receiving combinations of empty or drug-containing polymer implants in the tumor or contralateral leg, intraperitoneal (i.p.) drug, and/or irradiation. The drug (i.p.) alone (14 mg/kg x6) or in combination with tumor drug implant (2 mg) did not significantly increase the tumor volume doubling time compared to that of control animals. Given with 12 Gy of irradiation in twice a day 2-Gy fractions, combined i.p. drug and tumor drug implant significantly delayed tumor growth compared to irradiation alone, which was not achieved with either drug treatment alone added to irradiation. Toxicity, as manifested by transient weight loss, was primarily seen in animals receiving radiation and i.p. tirapazamine. These results indicated that a slow-releasing tirapazamine disc can be produced and the addition of an interstitially implanted tirapazamine disc further increased the effectiveness of i.p. tirapazamine.     

Effect of ultra-early referral on management outcome in subarachnoid haemorrhage

A study was conducted to clarify whether ultra-early referral of patients with subarachnoid haemorrhage (SAH) is effective for improving the management outcome. The subjects were 455 patients who were admitted within 6 h after initial SAH. Of these patients, 289 were treated surgically, 159 of them within 24 h. At 6 months, 228 patients (50%) had a favourable outcome including good recovery or moderate disability, 37 (8%) had severe disability, and 190 (42%) had an unfavourable outcome including vegetative state or death. Of 214 patients with an admission grade IV or V, 47 (22%) had a favourable outcome. In 10 patients, emergency procedures such as haematoma removal or ventriculostomy were definitely effective, and in 13, early surgery may have been the reason for the improved outcome. However, in 24 patients, the reasons for a favourable outcome were not related directly to ultra-early referral; in 19 of them, there was spontaneous improvement of clinical grade and/or no SAH on computed tomography. Of 218 patients with admission grade I or II, 30 (14%) had an unfavourable outcome, and in 12 of them, this was ascribed to rebleeding. The rebleeding rate and severity of vasospasm were not significantly reduced by surgery carried out within 24 h after SAH, in comparison with surgery carried out between 24 and 48 h, and there was no significant difference in surgical outcome between them. It is concluded that although ultra-early referral of patients with SAH was expected to improve the outcome in emergency cases, no substantial improvement in overall management outcome seems to have been achieved by this policy.     

S-100 protein plasma levels after aneurysmal subarachnoid haemorrhage

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-100b 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 microgram/l), 3 days (0.192 +/- 0.288 microgram/l) and 7 days (0.256 +/- 0.442 microgram/l) after onset of SAH symptoms compared to controls (0.050 +/- 0.081 microgram/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.     

Interleukin-6 and development of vasospasm after subarachnoid haemorrhage

The authors characterized the role of interleukins in the cerebrospinal fluid (CSF) in the development of vasospasm after subarachnoid haemorrhage (SAH), particularly interleukin-6 (IL-6). Concentrations of interleukin-1 beta (IL-1 beta), IL-6, and interleukin-8 (IL-8) were measured serially in CSF of 24 patients and in serum of 9 patients with SAH and correlated clinically. Additionally, the effects of the same cytokines on the cerebral arteries of dogs were analyzed on angiograms after intracisternal injection. Changes in levels of eicosanoids, angiogenic factors, and soluble cell adhesion molecules were investigated in the CSF of injected dogs. CSF concentrations of IL-6 and IL-8 were elevated significantly above control levels from the acute stage of SAH until the chronic stage. Patients with symptomatic vasospasm had significantly higher levels of IL-6 as well as IL-8 in CSF on days 5 and 7. Intracisternal injection of IL-6 induced long-lasting vasoconstriction in five out of eight dogs, while IL-8 did not. The diameter of canine basilar artery after IL-6 was reduced 29 +/- 5% from pretreatment diameter at 8 hours. Prostaglandins E2 and I2 were elevated in CSF for the first 4.5 hour of this IL-6-induced vasospasm. Neither angiogenic factors such as platelet-derived growth factor-AB and vascular endothelial growth factor nor soluble cell adhesion molecules were significantly elevated in CSF. IL-6, which increases to very high concentrations in CSF after SAH, may be important in inducing vasospasm, as IL-6 produced long-lasting vasoconstriction in the canine cerebral artery, which may be partly related to activation of the prostaglandin cascade.     

Role of the pneumo-encephalogram in the diagnosis of spontaneous subarachnoid haemorrhage

The authors have collected eighteen cases of primary intraventricular lesions revealed by a subarachnoid haemorrhage. Among these cases, the most important are the choroid plexus papillomas followed by ependymomas; some cases have no precise histological interpretation. Generally speaking, cerebral arteriography gives only indirect evidence of ventricular dilation and thus does not confirm the presence of a lesion. On the contrary, the pneumoencephalogram is consistantly positive, but does not give the differential diagnosis between intraventricular tumours and primary intraventricular haemorrhages. This test should therefore be given the same importance as spinal cord arteriography in the exploration of subarachnoid haemorrhages with negative cerebral angiograms.     

Vasopressin receptor antagonist OPC-31260 prevents cerebral oedema after subarachnoid haemorrhage

The effects of the non-peptide vasopressin V2 receptor antagonist, 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrah ydro-1 H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced significant water retention after water loading, increased the brain content of water and Na+ and increased plasma vasopressin levels. The water retention and brain water and Na+ accumulation were prevented by OPC-31260 administration, but the plasma vasopressin levels were further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of antidiuresis and disturbances in brain water and electrolyte balance in response to subarachnoid haemorrhage. The subarachnoid haemorrhage-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on renal tubular function: it blocks the renal vasopressin V2 receptors. These observations might suggest a new, effective approach to the treatment of subarachnoid haemorrhage-induced cerebral oedema in humans.     

Effect of subarachnoid haemorrhage on micro-circulation in hypothalamus and brain stem of dogs

In order to investigate the relationship between cerebral vasospasm and microvasculature in the hypothalamus and brain stem, colloidal carbon was infused into the vertebral artery at various time intervals after experimental subarachnoid haemorrhage in dogs. Experiments which demonstrated vasospasm on angiogram were always accompanied by ischaemic changes in serial sections taken from the anterior hypothalamus to the brain stem. However, when it was demonstrated by angiography that the vasospasm had disappeared, the micro-circulation was restored to normal. Electron microscopy of the hypothalamus 48 hours and one week after subarachnoid haemorrhage, demonstrated swelling of the endothelial cells, enlargement of the perivascular glia and increase in number of the pinocytic vesicles in the cytoplasm, thus showing vasogenic oedema in this area. It is assumed that in addition to the vasogenic substance in extravasated blood, changes in irritability of cerebral vessels through the vasomotor pathways in the hypothalamus and brain stem might play an important role in the production of cerebral vasospasm.     

Value of repeat angiography in patients with spontaneous subcortical hemorrhage

BACKGROUND and PURPOSE: Neuroradiological investigations do not disclose a source of bleeding in some patients with spontaneous subcortical hemorrhage. These patients may harbor undetected vascular malformations and may be at risk of rebleeding in the future. We investigated patients with subcortical hemorrhage with use of repeat angiography and MRI to determine the incidence of occult vascular malformations and the risk of bleeding during follow-up. METHODS: We reviewed a consecutive series of 137 patients with subcortical hemorrhage during a 10-year period (June 1987 through June 1997). If the patient was <65 years old and the first angiogram and/or MRI did not show a source of bleeding, repeat angiography was recommended. All angiographic and MRI studies were reviewed. The relationship between the identified bleeding source and clinical variables such as patient age, sex, and history of hypertension and the size and location of the hematoma were examined. RESULTS: One hundred seven patients (78%) underwent angiography on admission, 10 (7%) had immediate surgery for hematoma without angiography, and 20 (15%) had neither angiography nor surgery. Overall, an etiology for the hemorrhage was found in 55 cases (40%). Vascular malformations were common in young patients without preexisting hypertension. A second angiogram was obtained in 22 patients, and 4 arteriovenous malformations were demonstrated. Rebleeding at the site of the initial hemorrhage was not observed after a mean follow-up of 68 months. CONCLUSIONS: Angiography performed acutely after hemorrhage may not demonstrate vascular malformations. Consideration should be given to repeat angiography in patients who do not have a specific cause for hemorrhage.     

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

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 predictive 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.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term monitoring of CSF lactate levels and lactate/pyruvate ratios following subarachnoid haemorrhage

Ventricular cerebrospinal fluid (CSF) lactate concentrations and lactate/pyruvate (L/P) ratios were measured daily in 20 patients from day 1 to day 12 after subarachnoid haemorrhage due to ruptured aneurysms. Patients without symptomatic vasospasm were classified in Group 1, patients with symptomatic vasospasm were classified in Group 2, and patients who were Hunt and Kosnik grade 4 on admission clinically were classified in Group 3. Patients in all three groups had high CSF lactate concentrations on day 1, and, especially in Group 3, the high lactate was accompanied by an increased L/P ratio and a decreased CSF bicarbonate. Lactate concentrations in Group 1 decreased throughout the observation period. Lactate concentrations in Group 2 also decreased but then began to increase again on days 5 to 7, correlating well with the onset of cerebral vasospasm. The delayed increase of CSF lactate in Group 2 was also accompanied by increases in the CSF pyruvate level and the CSF L/P ratio. Daily monitoring of CSF lactate may thus serve as a chemical marker for cerebral vasospasm.     

Remote subarachnoid haemorrhage in the posterior fossa following supratentorial surgery. Clinical observation of 6 cases

Haemorrhage in regions remote from the site of following intracranial operations is rare, but they do occur. We performed supratentorial craniotomy on 639 patients between the time of introduction of computed tomography (CT) for clinical use in 1983 and June 1992; subarachnoid haemorrhage (SAH) in the posterior fossa occurred postoperatively in six of these cases. These included four patients with tumours in the sellar region, one with an arteriovenous malformation (AVM) and one who underwent superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis. The ages of the six patients ranged from 17-72 years. Haemorrhage occurred on the day of operation in one case and was detected on CT examination on the day following surgery in the remaining five cases. Of three patients with disturbance of consciousness, two underwent suboccipital craniectomy for reduction of intracranial pressure, while one received barbiturate therapy and later underwent cerebrospinal fluid (CSF) shunt surgery. No special treatment was necessary for the remaining three patients with less serious lesions. Five of the six patients ultimately recovered their pre-operative neurological status apart from the primary diseases. Factors inducing such haemorrhages seem likely to include displacement of the cerebellum by reduced CSF pressure during and after operations, and stretching and tearing of the veins and venules in the sulci of the tentorial surface of the cerebellum. Consideration should therefore be given to the maintenance of an appropriate CSF pressure during operation; this is particularly important in elderly patients and those with an atrophied cerebral cortex.