Long-term reintegration and quality of life in patients with subarachnoid hemorrhage and a good neurological outcome: findings after more than 20 years.

OBJECTIVE The goal of this study was to examine long-term quality of life (QOL) and reintegration in patients with good neurological recovery after aneurysmal subarachnoid hemorrhage (aSAH) and SAH of unknown cause (SAH NUD). METHODS A long-term follow-up was performed in an original cohort of 113 individuals who had suffered SAH (93 with aSAH and 20 with SAH NUD) between 1977 and 1984. Self-reporting assessments, performed > 20 years after the bleeding episode, included the Quality of Life Scale (QOLS), Psychological General Well-Being (PGWB) index, and Reintegration to Normal Living (RNL) index, along with information on sleep disturbances and work status. RESULTS Seventy-one survivors were identified. Questionnaires were returned by 67 individuals who had suffered SAH 20-28 years previously. The QOL was rated in the normal range for both the QOLS score (aSAH 90.3 vs SAH NUD 88.6) and the PGWB index (aSAH 105.9 vs SAH NUD 102.8). Ninety percent of patients had returned to their previous employment. Complete RNL was reported by 40% of patients with aSAH and by 46% of patients with SAH NUD; mild to moderate readjustment difficulties by 55% and 38%, respectively; and severe difficulties by 5% of patients with aSAH and 15% of patients with SAH NUD. Self-rated aspects of cognition, mood, and energy resources in addition resulted in a substantial drop in overall reintegration. Sleep disturbances were reported by 26%. CONCLUSIONS More than half of patients with SAH who had early good neurological recovery experienced reintegration difficulties after > 20 years. However, the general QOL was not adversely affected by this impairment. Inability to return to work after SAH was associated with lower QOLS scores. Sleep disturbances were associated with lower PGWB scores.

Reduced Quality of Life in Patients with Pituitary Dysfunction After Aneurysmal Subarachnoid Hemorrhage: A Prospective Longitudinal Study.

OBJECTIVE: Pituitary dysfunction (PD) after aneurysmal subarachnoid hemorrhage (SAH) has been demonstrated in several studies. Given the similarities between psychological symptoms and reduced quality of life (QoL) in patients with PD and fatigue commonly seen in patients after SAH, we investigated the relationship between QoL and PD after SAH. METHODS: There were 51 patients with aneurysmal SAH prospectively recruited and evaluated for health-related QoL using the Psychological General Well-Being Index. Evaluations were conducted 3-6 months (n = 45), 6-12 months (n = 44), and 12-24 months (n = 44) after SAH, with concomitant assessment of endocrine function. The study protocol also included a magnetic resonance imaging examination 3 months after SAH. RESULTS: Mean general well-being scores showed a positive trend from 97.3 at 3-6 months to 104.3 at 12-24 months for all patients. Multiple regression analysis identified age, sex, Hunt and Hess grade, and PD as independent predictors for general well-being. Patients with PD had significantly lower scores compared with patients with normal pituitary function at 3-6 months (85.4 vs. 101.7) and 6-12 months (90.4 vs. 105.3). This result was due to central hypoadrenalism (score 81.6 at 3-6 months and score 82.2 at 6-12 months) but not other types of PD. The extent of magnetic resonance imaging lesions had a significant negative correlation to Glasgow Outcome Scale score at all follow-up evaluations. All patients with hypothalamic magnetic resonance imaging lesions had evidence of PD at some point during the follow-up period. CONCLUSIONS: The results support PD, and central hypoadrenalism in particular, as a contributing factor for impaired health-related QoL in patients after SAH.

High prevalence of pituitary dysfunction after aneurysmal subarachnoid hemorrhage: a long-term prospective study using dynamic endocrine testing.

OBJECTIVE: Impaired systemic hormonal activity caused by hypothalamic and pituitary injury may contribute to neuropsychologic disturbances and poor quality of life after aneurysmal subarachnoid hemorrhage (SAH). This prospective study was designed to longitudinally evaluate long-term clinical outcome and pituitary function after SAH using dynamic tests for adrencorticotropic and somatotropic secretory capacity. METHODS: Endocrine function was assessed by basal hormonal concentrations at 6-12 months and 12-24 months after SAH. At the 12-24 months follow-up, dynamic provocative evaluation of adrenocorticotropic hormone (ACTH) and growth hormone (GH) was performed using the insulin tolerance test (ITT). In patients where ITT was contraindicated, an ACTH stimulation test was used to assess ACTH capacity, and a growth hormone releasing hormone (GHRH)-arginine stimulation test was used to assess GH capacity. RESULTS: Of 60 patients with SAH screened, 51 were included in the study, and 44 remained to be tested at the two follow-up visits. As assessed by basal hormone concentrations alone, the prevalence of pituitary dysfunction was 34% at 6-12 months and 41% at 12-24 months. When using dynamic tests (12-24 months), impaired pituitary function was detected in 43%. The ITT detected more cases of central hypoadrenalism and GH deficiency compared with the ACTH- and GHRH-arginine-stimulation tests, respectively. CONCLUSIONS: Application of dynamic endocrine tests revealed a high frequency of long-term hypothalamic-pituitary dysfunction after aneurysmal SAH. The role of pituitary dysfunction in the recovery after SAH merits further evaluation.

Pituitary dysfunction after aneurysmal subarachnoid hemorrhage is associated with impaired early outcome.

OBJECTIVE: Poor outcome and neuropsychological sequelae after aneurysmal subarachnoid hemorrhage (SAH) is a persistent problem. Pituitary dysfunction has been proposed as a contributing factor. Clinical studies have given variable and conflicting results on its importance and incidence after SAH. The aim of this study was to prospectively examine SAH patients with assessment of endocrine function in the acute stage and at early follow-up and to compare clinical SAH features to endocrine abnormalities indicating pituitary dysfunction. METHODS: Endocrine function was assessed by basal hormonal concentrations at 5 to 10 days and 3 to 6 months after SAH. Growth hormone deficiency also was evaluated by the growth hormone releasing hormone-arginine stimulation test at follow-up. Clinical outcome was assessed and scored according to the Glasgow Outcome Scale. RESULTS: Fifty-one SAH patients were included and assessed in the acute stage after the bleed. Six were lost to follow-up. The overall prevalence of pituitary dysfunction was 37% and 27% in the acute stage and at follow-up, respectively. Patients with evidence of pituitary dysfunction had significantly worse outcome according to Glasgow Outcome Scale at both occasions. The ruptured aneurysm was more commonly located in the circle of Willis among patients with pituitary dysfunction in the acute stage. CONCLUSIONS: The present results support earlier findings that hormonal abnormalities are not infrequent after SAH. Furthermore, our data suggest that pituitary dysfunction is associated with worse clinical outcome and is more common among patients with bleeding sites close to the hypothalamus.

Male-female differences in upregulation of vasoconstrictor responses in human cerebral arteries.

BACKGROUND AND PURPOSE: Male-female differences may significantly impact stroke prevention and treatment in men and women, however underlying mechanisms for sexual dimorphism in stroke are not understood. We previously found in males that cerebral ischemia upregulates contractile receptors in cerebral arteries, which is associated with lower blood flow. The present study investigates if cerebral arteries from men and women differ in cerebrovascular receptor upregulation. EXPERIMENTAL APPROACH: Freshly obtained human cerebral arteries were placed in organ culture, an established model for studying receptor upregulation. 5-hydroxtryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1) and endothelin-1 type A and B (ETA and ETB) receptors were evaluated using wire myograph for contractile responses, real-time PCR for mRNA and immunohistochemistry for receptor expression. KEY RESULTS: Vascular sensitivity to angiotensin II and endothelin-1 was markedly lower in cultured cerebral arteries from women as compared to men. ETB receptor-mediated contraction occurred in male but not female arteries. Interestingly, there were similar upregulation in mRNA and expression of 5-HT1B, AT1, and ETB receptors and in local expression of Ang II after organ culture. CONCLUSIONS AND IMPLICATIONS: In spite of receptor upregulation after organ culture in both sexes, cerebral arteries from women were significantly less responsive to vasoconstrictors angiotensin II and endothelin-1 as compared to arteries from men. This suggests receptor coupling and/or signal transduction mechanisms involved in cerebrovascular contractility may be suppressed in females. This is the first study to demonstrate sex differences in the vascular function of human brain arteries.

Long term (13 years) prognosis after primary intracerebral haemorrhage: a prospective population based study of long term mortality, prognostic factors and causes of death.

INTRODUCTION: Many studies have focused on short term mortality after primary intracerebral haemorrhage (ICH) whereas long term prognosis and causes of death have been less studied. We therefore examined these issues in a population based cohort of 1 year ICH survivors. METHODS: ICH patients in a defined Swedish population (1.14 million inhabitants) were prospectively registered during 1996. Patients surviving 1 year after ICH onset were followed-up regarding survival status and cause of death until December 2009 using data from the National Census Office and the National Cause of Death Register. Patient prognosis was also compared with the general population using official Swedish mortality data. Clinical and radiological prognostic factors were evaluated. RESULTS: Of 323 patients with ICH, 172 (53%) survived after 1 year, 127 (39%) after 5 years and 57 (18%) after 13 years. Mortality of the 172, 1 year survivors (mean age 67.7 years at ICH) persistently exceeded expected mortality; 13 years post ictus survival was only 34% compared with 61% in the general population. Of 115 deaths among the 172, 1 year survivors, 36% were from cerebrovascular disease and 19% from ischaemic heart disease. Independent risk factors for death among 1 year survivors were age (HR 1.08 per year; 95% CI 1.06 to 1.10; p<0.001), diabetes mellitus at baseline (HR 2.10; 95% CI 1.18 to 3.74; p=0.012) and anticoagulant therapy (HR 1.99; 95% CI 1.12 to 3.53; p=0.018) at ICH onset. CONCLUSIONS: One year survivors after ICH had a substantial and persisting excess mortality compared with the general population. Major causes of death were stroke and ischaemic heart disease.

MAPK signaling pathway regulates cerebrovascular receptor expression in human cerebral arteries.

BACKGROUND: Cerebral ischemia results in enhanced expression of contractile cerebrovascular receptors, such as endothelin type B (ET(B)), 5-hydroxytryptamine type 1B (5-HT(1B)), angiotensin II type 1 (AT(1)) and thromboxane (TP) receptors in the cerebral arteries within the ischemic area. The receptor upregulation occurs via activation of the mitogen-activated protein kinases (MAPK) pathway. Previous studies have shown that inhibitors of the MAPK pathway diminished the ischemic area and contractile cerebrovascular receptors after experimental cerebral ischemia. The aim of this study was to examine if the upregulation of contractile cerebrovascular receptors after 48 h of organ culture of human cerebral arteries involves MAPK pathways and if it can be prevented by a MEK1/2 inhibitor. Human cerebral arteries were obtained from patients undergoing intracranial tumor surgery. The vessels were divided into ring segments and incubated for 48 h in the presence or absence of the specific MEK1/2 inhibitor U0126. The vessels were then examined by using in vitro pharmacological methods and protein immunohistochemistry. RESULTS: After organ culture of the cerebral arteries the contractile responses to endothelin (ET)-1, angiotensin (Ang) II and thromboxane (TP) were enhanced in comparison with fresh human arteries. However, 5-carboxamidotryptamine (5-CT) induced decreased contractile responses after organ culture as compared to fresh arteries. Incubation with U0126 diminished the maximum contraction elicited by application of ET-1, Ang II and U46619 in human cerebral arteries. In addition, the MEK1/2 inhibitor decreased the contractile response to 5-CT. Immunohistochemistry revealed that organ culture resulted in increased expression of endothelin ET(A), endothelin ET(B) angiotensin AT(2), 5-hydroxytryptamine 5-HT(1B) and thromboxane A2 receptors, and elevated levels of activated pERK1/2, all localized to the smooth muscle cells of the cerebral arteries. Co-incubation with U0126 normalized these proteins. CONCLUSION: The study demonstrated that there is a clear association between human cerebrovascular receptor upregulation via transcription involving activation of the MAPK pathway after organ culture. Inhibition of the MAPK pathways attenuated the vasoconstriction mediated by ET, AT and TP receptors in human cerebral arteries and the enhanced expression of their receptors. The results indicate that MAPK inhibition might be a novel target for treatment of cerebrovascular disorders.

Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway.

BACKGROUND: Cerebral ischemia results in a rapid increase in contractile cerebrovascular receptors, such as the 5-hydroxytryptamine type 1B (5-HT1(B)), angiotensin II type 1 (AT1), and endothelin type B (ET(B)) receptors, in the vessel walls within the ischemic region, which further impairs local blood flow and aggravates tissue damage. This receptor upregulation occurs via activation of the mitogen-activated protein kinase pathway. We therefore hypothesized an important role for B-Raf, the first signaling molecule in the pathway. To test our hypothesis, human cerebral arteries were incubated at 37°C for 48 h in the absence or presence of a B-Raf inhibitor: SB-386023 or SB-590885. Contractile properties were evaluated in a myograph and protein expression of the individual receptors and activated phosphorylated B-Raf (p-B-Raf) was evaluated immunohistochemically. RESULTS: 5-HT1(B), AT1, and ET(B) receptor-mediated contractions were significantly reduced by application of SB-590885, and to a smaller extent by SB-386023. A marked reduction in AT1 receptor immunoreactivity was observed after treatment with SB-590885. Treatment with SB-590885 and SB-386023 diminished the culture-induced increase of p-B-Raf immunoreactivity. CONCLUSIONS: B-Raf signaling has a key function in the altered expression of vascular contractile receptors observed after organ culture. Therefore, specific targeting of B-Raf might be a novel approach to reduce tissue damage after cerebral ischemia by preventing the previously observed upregulation of contractile receptors in smooth muscle cells.

Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.

INTRODUCTION: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. We also studied the expression of the CGRP receptor components in cranial arteries with immunocytochemistry. Concentration response curves to αCGRP were performed in human isolated cerebral and middle meningeal arteries in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the αCGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.

Nimodipine in aneurysmal subarachnoid hemorrhage: a randomized study of intravenous or peroral administration.

OBJECT: The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH). Although most randomized studies have been focused on the effect of the peroral administration of nimodipine, intravenous infusion is an alternative and the preferred mode of treatment in many centers. It is unknown whether the route of administration is of any importance for the clinical efficacy of the drug. METHODS: One hundred six patients with acute aneurysmal SAH were randomized to receive either peroral or intravenous nimodipine treatment. The patients were monitored for at least 10 days after bleeding in terms of delayed ischemic neurological deficits (DINDs) and with daily measurements of blood flow velocities in the middle cerebral arteries by using transcranial Doppler ultrasonography. Three months after SAH, clinical outcome and new cerebral infarctions according to MR imaging studies were recorded. RESULTS: Baseline characteristics (age, sex distribution, clinical status on admission, radiological findings, and aneurysm treatment) did not differ between the treatment groups. There was no significant difference in the incidence of DINDs (28 vs 30% in the peroral and intravenous groups, respectively) or middle cerebral artery blood flow velocities (> 120 cm/second, 50 vs 45%, respectively). Clinical outcome according to the Glasgow Outcome Scale was the same in both groups, and there was no difference in the number of patients with new infarctions on MR imaging. CONCLUSIONS: The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH.

Transforaminal steroid injections for the treatment of cervical radiculopathy: a prospective and randomised study.

Steroid injections are often employed as an alternative treatment for radicular pain in patients with degenerative spinal disorders. Prospective randomised studies of the lumbar spine reveal contradictory results and non-randomised and most often retrospective studies of the cervical spine indicate pain reduction from steroid injections. No prospective randomised study on transforaminal steroid injections for the treatment of radicular pain in the cervical spine focusing on short-term results has been performed. Forty consecutive patients were employed for the study. The inclusion criteria were one-sided cervical radiculopathy with radicular distribution of arm pain distal to the elbow and corresponding significant degenerative pathology of the cervical spine at one or two levels on the same side as the radicular pain and visualised by MRI. A transforaminal technique was used for all injections. A positive response to a diagnostic selective nerve root block at one or two nerve roots was mandatory for all patients. The patients were randomised for treatment with steroids/local anaesthetics or saline/local anaesthetic. Only the neuroradiologist performing the blocks was aware of the content of the injection; all other persons involved in the study were blinded. Follow up was made 3 weeks after the randomised treatment by a clinical investigation and with a questionnaire focusing on the subjective effects from the injections. At follow up, there were no differences in treatment results in the two patient groups. Statistical analysis of the results confirmed the lack of difference in treatment effect. Further studies have to be performed before excluding steroids in such treatment and for evaluating the influence of local anaesthetics on radiculopathy in transforaminal injections.

Are primary supratentorial intracerebral hemorrhages surrounded by a biochemical penumbra? A microdialysis study.

OBJECTIVE: Opinions vary regarding the indications for surgical evacuation of spontaneous intracerebral hemorrhages (ICH) and whether or not penumbra zones surround them. METHODS: We performed intracerebral microdialysis (mean duration, 3.5 d) after surgical evacuation of ICH in 22 patients. Probes were placed in the parenchyma within 1 to 2 cm of the evacuated hematoma; a postoperative computed tomographic scanning verified their positions. The catheters were perfused with an artificial cerebrospinal fluid solution at 0.3 microl/min. Biochemical variables (glucose, pyruvate, lactate, glutamate, and glycerol) were analyzed and displayed at the bedside. The levels obtained were compared with previous data from normal human brains and the pericontusional penumbra zones of patients with severe traumatic brain lesions. RESULTS: During 1 to 12 hours after surgery, interstitial levels of glucose (median level, 1.3 mmol/L; interquartile range, 0.6-2.2 mmol/L) were within normal variations, whereas the levels of lactate (median level, 6.4 mmol/L; interquartile range, 3.9-9.0 mmol/L), glutamate (median level, 14 micromol/L; interquartile range, 5-370 micromol/L), and glycerol (median level, 190 micromol/L; interquartile range, 74-380 micromol/L), as well as the lactate/pyruvate ratio (median ratio, 35; interquartile range, 23-50) were increased. A gradual normalization of the lactate/pyruvate ratio and glycerol level was observed within 48 hours. CONCLUSION: The area close to an evacuated ICH exhibits a biochemical pattern similar to that of the biochemical penumbra zone surrounding focal traumatic brain contusions. The presence of a penumbra zone around large ICH may be of importance for making surgical decisions.

Selective diagnostic nerve root block for the evaluation of radicular pain in the multilevel degenerated cervical spine.

In patients with radiculopathy due to degenerative disease in the cervical spine, surgical outcome is still presenting with moderate results. The preoperative investigations consist of clinical investigation, careful history and most often magnetic resonance imaging (MRI) of the cervical spine. When MRI shows multilevel degeneration, different strategies are used for indicating which nerve root/roots are affected. Some authors use selective diagnostic nerve root blocks (SNRB) for segregating pain mediating nerve roots from non-pain mediators in such patients. The aim of the present study is to assess the ability of transforaminal SNRB to correlate clinical symptoms with MRI findings in patients with cervical radiculopathy and a two-level MRI degeneration, on the same side as the radicular pain. Thirty consecutive patients with cervical radiculopathy and two levels MRI pathology on the same side as the radicular pain were studied with SNRBs at both levels. All patients underwent clinical investigation and neck and arm pain assessment with visual analogue scales (VAS) before and after the blocks. The results from the SNRBs were compared to the clinical findings from neurological investigation as well as the MRI pathology and treatment results. Correlation between SNRB results and the level with most severe degree of MRI degeneration were 60% and correlation between SNRB results and levels decided by neurological deficits/dermatome radicular pain distribution were 28%. Twenty-two of the 30 patients underwent treatment guided by the SNRB results and 18 reported good/excellent outcome results. We conclude that the degree of MRI pathology, neurological investigation and the pain distribution in the arm are not reliable parameters enough when deciding the affected nerve root/roots in patients with cervical radiculopathy and a two-level degenerative disease in the cervical spine. SNRB might be a helpful tool together with clinical findings/history and MRI of the cervical spine when performing preoperative investigations in patients with two or more level of degeneration presenting with radicular pain that can be attributed to the degenerative findings.

Distribution patterns of transforaminal injections in the cervical spine evaluated by multi-slice computed tomography.

Transforaminal injections are sometimes used for the diagnosis and treatment of painful conditions in the lumbar and to a lesser degree in the cervical spine. The technique is most often used when investigating/treating radiculopathy caused by degenerative disease. But how selective are the nerve root blocks? What possible structures other than the intended nerve root are affected from such injections? This study was undertaken in order to try to answer these questions, as no study focusing on the possible spread from the transforaminal selective nerve root blocks in the cervical spine has been performed earlier. In three groups of patients, each group including three patients, we injected three different volumes (0.6, 1.1 and 1.7 ml) with a transforaminal technique in the cervical spine. In all the injections, a small amount of contrast media was added. The spread of the injections were then investigated using multi-slice computed tomography with reconstructions. The imaging revealed a possible effect on other nerve roots than the intended ones when a larger volume was used for the root blocks. The spread was related to the injected volume as well as to local anatomy (size of foraminal area). In this study, only 0.6-ml injections could be accepted for being selective enough for diagnostic investigations.

Impact of coil embolization on overall management and outcome of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: We report on the consequences of introducing coil embolization for the total management of and outcome in patients with subarachnoid hemorrhage (SAH). METHODS: In southern Sweden, a prospective analysis of all patients with SAH of verified aneurysmal origin was conducted during the 3 years when coiling was gradually being introduced. The incidence of acute or chronic hydrocephalus, vasospasm, delayed ischemic deterioration, and outcome at 3 to 6 months after bleeding was analyzed. RESULTS: Coiling of aneurysms was used progressively more compared with clipping during the study period. The number of patients subjected to coiling was 26 (36%) of 73 patients during calendar year 1997, 43 (53%) of 81 patients in 1999, and 55 (74%) of 74 patients in 2001 (P < 0.0001). Gradually, more elderly patients were admitted during the study period. Virtually all aneurysms located in the posterior circulation were treated by coil embolization, even at the start of the study, whereas aneurysms at all other locations were progressively more likely to be treated similarly. The incidence of hydrocephalus in the acute (average for all 3 yr, 39%) or chronic (16%) phase, vasospasm as measured by Doppler sonography (33%), and delayed ischemic deterioration (29%), as well as outcome at 3 to 6 months (61% good recovery, 13% deceased), did not change significantly during the study. The main cause of unfavorable outcome was the severity of the SAH. CONCLUSION: The increasing use of coil embolization for ruptured aneurysms in the anterior circulation did not have any significant impact on the overall incidence of SAH-related complications or outcome. The main determinant for outcome after SAH is still the severity of the SAH.

Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study.

OBJECT: By pursuing a policy of very early aneurysm treatment in neurosurgical centers, in-hospital rebleeds can be virtually eliminated. Nonetheless, as many as 15% of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates, and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral. Only drugs given immediately after the diagnosis of subarachnoid hemorrhage (SAH) has been established at the local hospital level can, in theory, contribute to the minimization of such ultraearly rebleeding. The object of this randomized, prospective, multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding. METHODS: Only patients suffering SAH verified on computerized tomography (CT) scans within 48 hours prior to the first hospital admission were included. A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals (before the patients were transported), followed by doses of 1 g every 6 hours until the aneurysm was occluded; this treatment did not exceed 72 hours. In this study, 254 patients received tranexamic acid and 251 patients were randomized as controls. Age, sex, Hunt and Hess and Fisher grade distributions, as well as aneurysm locations, were congruent between the groups. Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale (GOS). Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler (TCD) studies. All events classified as rebleeding were verified on CT scans or during surgery. CONCLUSIONS: More than 90% of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH; 70% of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission. Given the protocol, only one rebleed occurred later than 24 hours after the first hospital admission. Despite this strong emphasis on early intervention, however, a cluster of 27 very early rebleeds still occurred in the control group within hours of randomization into the study, and 13 of these patients died. In the tranexamic acid group, six patients rebled and two died. A reduction in the rebleeding rate from 10.8 to 2.4% and an 80% reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred. Favorable outcome according to the GOS increased from 70.5 to 74.8%. According to TCD measurements and clinical findings, there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment. Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds. Currently available antifibrinolytic drugs can provide such protection, and at low cost. The number of potentially saved lives exceeds those lost to vasospasm.

Prediction of death in patients with primary intracerebral hemorrhage: a prospective study of a defined population.

OBJECT: Predictors of early (30-day) and long-term (1-year) mortality rates after primary intracerebral hemorrhage (ICH) were studied in a large population in southern Sweden. METHODS: All cases of primary ICH, verified using computerized tomography (CT) scanning or autopsy study, were prospectively registered at the 12 hospitals covering a defined population of 1.14 million during the calendar year 1996. Mortality was analyzed in relation to CT findings (hematoma location and volume and ventricular extension) and clinical parameters (patient age and sex, level of consciousness on admission, and history of preictal risk factors) by using univariate and multivariate statistical methods. Three hundred forty-one cases of primary ICH were detected. The overall mortality rate was 36% at the 30-day and 47% at the 1-year follow up. Multivariate analysis revealed that initial level of consciousness, hematoma volume, and a history of heart disease were independent predictors of death at 30 days postictus. One year after bleeding, independent predictors of mortality were the initial level of consciousness, patient age, and hematoma location. CONCLUSIONS: Primary ICH remains a stroke subtype associated with a high mortality rate and for which the level of consciousness on admission is the strongest predictor of fatal outcome both at 30 days and during the 1st year after bleeding. A preictal history of heart disease increased the 30-day mortality rate.

Intraoperative complications in aneurysm surgery: a prospective national study.

OBJECT: With increasing use of endovascular procedures, the number of aneurysms treated surgically will decline. In this study the authors review complications related to the surgical treatment of aneurysms and address the issue of maintaining quality standards on a national level. METHODS: A prospective, nonselected amalgamation of every aneurysm case treated in five of six neurosurgical centers in Sweden during 1 calendar year was undertaken (422 patients; 7.4 persons/100,000 population/year). The treatment protocols at these institutions were very similar. Outcome was assessed using clinical end points. In this series, 84.1% of the patients underwent surgery, and intraoperative complications occurred in 30% of these procedures. Poor outcome from technical complications was seen in 7.9% of the surgically treated patients. Intraoperative aneurysm rupture accounted for 60% and branch sacrifice for 12% of all technical difficulties. Although these complications were significantly related to aneurysm base geometry and the competence of the surgeon, problems still occurred apparently at random and also in the best of hands (17%). The temporary mean occlusion time in the patients who suffered intraoperative aneurysm rupture was twice as long as the temporary arrest of blood flow performed to aid dissection. CONCLUSIONS: The results obtained in this series closely reflect the overall management results of this disease and support the conclusion that surgical complications causing a poor outcome can be estimated on a large population-based scale. Intraoperative aneurysm rupture was the most common and most devastating technical complication that occurred. Support was found for a more liberal use of temporary clips early during dissection, regardless of the experience of the surgeon. Temporary regional interruption of arterial blood flow should be a routine method for aneurysm surgery on an everyday basis. A random occurrence of difficult intraoperative problems was clearly shown, and this factor of unpredictability, which is present in any preoperative assessment of risk, strengthens the case for recommending neuroprotection as a routine adjunct to virtually every aneurysm operation, regardless of the surgeon's experience.

Aneurismas: una experiencia escandinava; manejo de la ruptura de aneurismas intracraneanos; un analisis / Aneurisms: scandinavian experience; management of the intracranial aneurisms rupture; analysis

Se revisa la desalentadora historia asociada al manejo de la hemorragia subaracnoidea de los aneurismas (HSA), junto a los posibles perfeccionamientos atribuibles al progreso de la última década . Entre los nuevos avances se encuentra la introducción de técnicas micro-quirúrgicas que permiten la cirugía electiva en la etapa aguda, previniendo de este modo la repetición de las hemorragias. La operación temprana también ofrece la posibilidad de un tratamiento farmacológico anti-isquémico más agresivo. No obstante, los mejores resultados de la cirugía electiva aguda y el hecho de que el deterioro isquémico retardado (vasoespasmo cerebral sintomático) pueden estar practicamente eliminados en la actualidad, el resultado global es pesimista. A pesar de los recientes adelantos no se espera que más de una de tres personas que sufran la ruptura de un aneurisma intracraneano puedan tener una buena recuperación funcional y neurológica. La esperanza de nuevos progresos puede depender de desarrollo de técnicas que identifiquen los aneurisamas intracraneanos antes de su rompimiento y del aumento de conocimientos sobre la etiología de dichas lesiones de la pared arterial