G. J. E. Rinkel

Subarachnoid haemorrhage in Sweden 1987-2002: regional incidence and case fatality rates

Background: Incidence estimates of subarachnoid haemorrhage (SAH) in Sweden vary, which may be caused by regional variations. Reliable estimates of age-specific case fatality rates are lacking. We analysed regional incidence rates and case fatality rates of SAH in Sweden. Methods: The Swedish Hospital Discharge and Cause of Death Registries from 1987 to 2002 yielded data on 18 443 patients with SAH. Incidence and case fatality rates by age, gender, region and time period were calculated by Poisson regression. Results: The incidence rate was 12.4 per 100 000 person-years (95% CI 12.2 to 12.6) and increased with age, from 6.4/100 000 person-years in patients who were 30–39 years old to 25.8/100 000 person-years in patients who were older than 80 years. Incidence was higher for women (14.4 (95% CI 14.2 to 14.7)) than for men (10.3 (95% CI 10.3 to 10.6)), and higher in the north than in the south (RR 1.31 (95% CI 1.25 to 1.37)). This geographical gradient was more evident in women (RR 1.41 (95% CI 1.33 to1.49)) than in men (RR 1.23 (95% CI 1.15 to 1.33)). The 28-day case fatality rate was 31.7% (95% CI 31.0 to 32.3). It increased with age from 18.1% (95% CI 16.0 to 20.3) in patients who were 30–39 years old to 57.6% (95% CI 55.2 to 59.9) in patients over 80 years, then levelling off. Over time (1995–2002 compared with 1987–1994), the incidence rate decreased (RR 0.93 (95% CI 0.90 to 0.96)) and case fatality rate decreased (RR 0.89 (95% CI 0.85 to 0.93)). Conclusions: SAH incidence rates in Sweden increase from south to north, more in women than in men. Octogenarians have a quadrupled incidence and a tripled case fatality compared with young adults. During 16 years, both incidence and case fatality have decreased.

Glucose levels and outcome after subarachnoid hemorrhage

Abstract– In a cohort of 337 patients with subarachnoid hemorrhage (SAH), we investigated the relationship between blood glucose levels, baseline characteristics, and outcome by means of Student’s t-test and multivariate logistic regression. The mean glucose levels on admission and from day 1 to 10 were significantly higher in patients with poor condition on admission and in patients with poor outcome. In a multivariate analysis, glucose level on admission was not an independent predictor of outcome. Hyperglycemia may be a link in the association between poor condition on admission and poor outcome.

Prevalence and Determinants of Cognitive Complaints after Aneurysmal Subarachnoid Hemorrhage

Background: To investigate the prevalence of cognitive complaints after subarachnoid hemorrhage (SAH) and the relationships between cognitive complaints and cognitive impairments, disability and emotional problems. Methods: Cognitive complaints were assessed with the Checklist for Cognitive and Emotional Consequences following stroke (CLCE-24) in 111 persons who visited our outpatient clinic 3 months after SAH. Associations between cognitive complaints and cognitive functioning, demographic characteristics, disability and emotional problems were examined using Spearman correlations and linear regression analysis. Results: In this study group, 105 patients (94.6%) reported at least one cognitive or emotional complaint that hampered everyday functioning. The most frequently reported cognitive complaints were mental slowness, short-term memory problems and attention deficits. All cognitive domains, disability, depressive symptoms and feelings of anxiety were significantly associated with the CLCE-24 cognition score. In the final regression model, memory functioning (β value –0.21), disability (–0.28) and depressive symptoms (0.40) were significant determinants of cognitive complaints, together explaining 35.4% of the variance. Conclusion: Cognitive complaints are common after SAH and associated with memory deficits, disability and depressive symptoms. Rehabilitation programs should focus on these symptoms and deficits.

Applicability and relevance of models that predict short term outcome after intracerebral haemorrhage

Objectives: Several models for prediction of short term outcome after intracerebral haemorrhage (ICH) have been published, however, these are rarely used in clinical practice for treatment decisions. This study was conducted to identify current models for prediction of short term outcome after ICH and to evaluate their clinical applicability and relevance in treatment decisions. Methods: MEDLINE was searched from 1966 to June 2003 and studies were included if they met predefined criteria. Regression coefficients of multivariate models were extracted. Two neurologists independently evaluated the models for applicability in clinical practice. To assess clinical relevance and accuracy of each model, in a validation series of 122 patients the proportion with a ⩾95% probability of death or poor outcome and the actual 30 day case fatality in these patients were calculated. Receiver operator characteristic (ROC) curves were computed for assessment of discriminatory power. Results: A total of 18 prognostic models were identified, of which 14 appeared easy to apply. In the validation series, the proportion of patients with a ⩾95% probability of death or poor outcome ranged from 0% to 43% (median 23%). The 30 day case fatality in these patients ranged from 75% to 100% (median 93%). The area under the ROC curves ranged from 0.81 to 0.90. Conclusions: Most models are easy to apply and can generate a high probability of death or poor outcome. However, only a small proportion of patients have such a high probability, and 30 day case fatality is not always correctly predicted. Therefore, current models have limited relevance in triage, but can be used to estimate the chances of survival of individual patients.

Familial occurrence of brain arteriovenous malformations: a systematic review

Background: Brain arteriovenous malformations (BAVMs) are thought to be sporadic developmental vascular lesions, but familial occurrence has been described. We compared the characteristics of patients with familial BAVMs with those of patients with sporadic BAVMs. Methods: We systematically reviewed the literature on patients with familial BAVMs. Three families that were found in our centre were added. Age, sex distribution and clinical presentation of the identified patients were compared with those in population based series of patients with sporadic BAVMs. Furthermore, we calculated the difference in mean age at diagnosis of parents and children to study possible anticipation. Results: We identified 53 patients in 25 families with BAVMs. Mean age at diagnosis of patients with familial BAVMs was 27 years (range 9 months to 58 years), which was younger than in the reference population (difference between means 8 years, 95% CI 3 to 13 years). Patients with familial BAVMs did not differ from the reference populations with respect to sex or mode of presentation. In families with BAVMs in successive generations, the age of the child at diagnosis was younger than the age of the parent (difference between means 22 years, 95% CI 13 to 30 years), which suggests clinical anticipation. Conclusions: Few patients with familial BAVMs have been described. These patients were diagnosed at a younger age than sporadic BAVMs whereas their mode of presentation was similar. Although there are indications of anticipation, it remains as yet unclear whether the described families represent accidental aggregation or indicate true familial occurrence of BAVMs.

Endothelial cell activation markers and delayed cerebral ischaemia in patients with subarachnoid haemorrhage

Background: Endothelial cell activation may be connected with the pathogenesis of delayed cerebral ischaemia (DCI) after subarachnoid haemorrhage (SAH). Aim: To assess the relationship between serial concentrations of circulating markers of endothelial cell activation (soluble intercellular adhesion molecule-1, soluble platelet selectin (sP-selectin), soluble endothelial selectin, ED1-fibronectin, Von Willebrand Factor (VWF) and VWF propeptide) and development of DCI. Methods: 687 blood samples were collected from 106 consecutive patients admitted within 72 h after onset of SAH. Changes in levels were analysed in the last sample before and in the first sample after the onset of DCI (n = 30), and in subgroups with DCI occurring within 24 h after treatment of the aneurysm (n = 12) or unrelated to treatment of the aneurysm (n = 18). Patients without DCI (n = 56) served as controls. Results: Concentrations of sP-selectin, but not of the other markers, were found to increase considerably after DCI unrelated to treatment of the aneurysm (increase 25 ng/ml, 95% CI 8 to 43), whereas they tended to decrease in the control patients without DCI (decrease 13 ng/ml, 95% CI −28 to 2.4). Surgery was found to profoundly influence the levels of the markers irrespective of the occurrence of DCI. Conclusion: The rise in sP-selectin level during DCI is suggested to be the result of platelet activation, as levels of the other markers of endothelial cell activation were not increased after DCI unrelated to treatment. Whether a causal role of platelet activation is implicated in the development of DCI should be determined in further studies in which the relationship between concentrations of markers and treatment is taken into account.

High mean fasting glucose levels independently predict poor outcome and delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage

Background: Hyperglycaemia has been related to poor outcome and delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH). Objective: This study aimed to assess whether in patients with aSAH, levels of mean fasting glucose within the first week predict poor outcome and DCI better than single admission glucose levels alone. Methods: Data on non-diabetic patients admitted within 48 h after aSAH with at least two fasting glucose assessments in the first week were retrieved from a prospective database (n = 265). The association of admission glucose or mean fasting glucose, dichotomised at the median levels, with outcome was assessed using logistic regression, and for DCI using Cox regression. To explore whether the association between glucose levels and outcome was mediated by DCI, we adjusted for DCI. Results: The crude and multivariable adjusted odds ratios and 95% confidence intervals for poor outcome were 1.9 (1.1 to 3.2) and 1.6 (0.9 to 2.7) for high admission glucose and 3.5 (2.0 to 6.1) and 2.5 (1.4 to 4.6) for high mean fasting glucose. The crude and adjusted hazard ratios for DCI were 1.7 (1.1 to 2.5) and 1.4 (0.9 to 2.1) for high admission glucose and 2.0 (1.3 to 3.0) and 1.7 (1.1 to 2.7) for high mean fasting glucose. After adjusting for DCI, the odds ratios on poor outcome for high mean fasting glucose decreased only marginally. Conclusions: Compared with high admission glucose, high mean fasting glucose, representing impaired glucose metabolism, is a better and independent predictor of poor outcome and DCI. DCI is not the key determinant in the relationship between high fasting glucose and poor outcome.

Dose evaluation for long-term magnesium treatment in aneurysmal subarachnoid haemorrhage.

Background:  Magnesium is a neuroprotective agent that might prevent or reverse delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). We are presently running a randomized, placebo‐controlled, double blind trial with magnesium sulphate (64 mmol/day intravenously). We studied whether this treatment regime resulted in our target serum magnesium levels of 1·0–2·0 mmol/L.

Spinal arteriovenous shunts presenting as intracranial subarachnoid haemorrhage.

BackgroundIn approximately 5% of patients with intracranial subarachnoid haemorrhage (SAH), the cause is another than a ruptured aneurysm or perimesencephalic haemorrhage. One of these causes is a spinal arteriovenous shunt (SAVS). The aim of this study was to investigate the characteristics of patients with SAVS who present with intracranial SAH without symptoms and signs suggesting a spinal cause.MethodsWe systematically reviewed the literature and searched the SAH database of the University Medical Center Utrecht, The Netherlands, for patients with SAVS presenting with intracranial SAH and studied the characteristics of patients with SAVS whose clinical presentation mimicked intracranial SAH caused by rupture of a saccular aneurysm.ResultsThirty-five patients were identified after a review of the literature. In our SAH database, comprising 2142 patients included in the period 1985–2004, we found one patient (0.05%, 95 % CI 0.006–0.3%). SAH due to SAVS occurred at any age (4–72 years). The SAVS was located at the craniocervical junction in 14 patients, at the cervical level in 11, and at the thoracolumbar level in the remaining 11 patients. The majority of patients (n = 26, 72%) had no disabling deficits at discharge or follow-up.ConclusionRupture of a SAVS presenting as intracranial SAH is rare and can occur at any age. The SAVS can be located not only at the craniocervical junction or cervical level but also in the thoracolumbar region. Most patients with SAVS presenting as intracranial SAH have a good recovery.

Post-Traumatic Stress Disorder in Patients 3 Years after Aneurysmal Subarachnoid Haemorrhage

Background: Subarachnoid haemorrhage (SAH) from a ruptured intracranial aneurysm accounts for approximately 5% of all strokes. Post-traumatic stress disorder (PTSD) is common in the early phase after recovery from aneurysmal SAH. The aim of our study was to examine the prevalence of PTSD 3 years after SAH, its predictors, and relationship with health-related quality of life (HRQoL) in patients living independently in the community. Methods: From a prospectively collected cohort of 143 patients with aneurysmal SAH who visited our outpatient clinic 3 months after SAH, 94 patients (65.7%) completed a mailed questionnaire 3 years after SAH. We assessed PTSD with the Impact of Event Scale and HRQoL with the Stroke-Specific Quality of Life Scale (SS-QoL). The χ2 and t tests were used to investigate if patients who returned the questionnaires were different from those who did not reply. Non-parametric tests (χ2 and Mann-Whitney tests) were used to test for differences between patients with and without PTSD. Relative risks and 95% confidence intervals were calculated. Results: No relevant differences in demographic (age, sex, education) or SAH characteristics (clinical condition on admission, complication, location of aneurysm, Glasgow Outcome Scale score at 3 months) were seen between participants and drop-outs. In 24 patients (26%), Impact of Event Scale scores indicated PTSD. Passive coping style (relative risk, 5.7; 95% confidence interval, 2.1-15.3), but none of the demographic or SAH-related factors, predicted PTSD. The mean SS-QoL total score was 4.2 (SD 1.1), indicative of a relatively satisfactory HRQoL. PTSD was associated with lower HRQoL (p < 0.001), a mean SS-QoL score of 4.4 (SD 1.0) without PTSD, and a mean SS-QoL score of 3.5 (SD 1.1) with PTSD. Conclusions: Even 3 years after SAH, 1 out of 4 patients had PTSD, which was associated with reduced HRQoL. Passive coping style was the most important predictor. There is a need to organize SAH care with more attention to and treatment of PTSD. Strategies shown to reduce PTSD in other conditions should be tested for effectiveness in SAH patients.