Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study

International audienceBACKGROUND:Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH.METHODS:In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation.RESULTS:We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23–100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15–80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2–2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6–3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4–1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1–0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7–50 months), with a cumulative hazard of 47% at 10 years.CONCLUSIONS:The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted

Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced p

ANOSMIA AFTER ANEURYSMAL SUBARACHNOID HEMORRHAGE

Abstract OBJECTIVE Anosmia has an important impact on well-being but is often neglected by physicians. In patients with subarachnoid hemorrhage (SAH), anosmia has mainly been reported after surgery for aneurysms of the anterior communicating artery. We studied the prevalence, predisposing factors (aneurysm site and type of treatment), impact, and prognosis of anosmia in patients with SAH. METHODS Of the patients with SAH who resumed independent living, we included all patients treated by coiling between 1997 and 2003 and a sample of patients treated by clipping between 1985 and 2001. Patients underwent structured interviews regarding the presence and duration of anosmia. The impact of anosmia was scored using a visual analog scale ranging from 0 (no influence) to 100 (the worst thing that ever happened to them). Risk factors for anosmia were assessed by logistic regression analysis. RESULTS Overall, 89 of the 315 interviewed patients (28%; 95% confidence interval [CI], 23–34%) reported anosmia after SAH (mean follow-up period, 7.4 yr), including 10 (15%) of the 67 coiled patients and 79 (32%) of the 248 clipped patients. The median visual analog scale impact score was 53 (range, 0–100). In 20 of the 89 patients (23%; 95% CI, 15–33), the symptoms had improved over time. Risk factors for anosmia were treatment by clipping (odds ratio [OR], 2.7; 95% CI, 1.3–5.7) and anterior communicating artery aneurysms (OR, 2.0; 95% CI, 1.2–3.3). CONCLUSION Anosmia after SAH has a high prevalence, considerable impact, and poor prognosis. Its occurrence after coiling suggests not only damage to the olfactory nerve by clipping but also that the SAH itself plays a role in its pathogenesis

Assessment of the Most Optimal Control Tissue for Intracranial Aneurysm Gene Expression Studies

Background and Purpose- Finding adequate control tissue for intracranial aneurysm (IA) pathophysiological studies, including gene expression studies, can be challenging. We compared gene expression profiles of superficial temporal, cortical, and circle of Willis (CoW) arteries and IA in search of the most optimal control tissue for future experiments. Methods- We compared RNA-sequencing data of IA samples and of superficial temporal, cortical, and CoW artery samples using Pearson correlation, Euclidean distance, and principal component analysis. We used the Mann-Whitney U test for comparison of Pearson correlation coefficients and Euclidean distances, to assess which control tissue is most similar to IA in terms of gene expression. Other unrelated tissues were used as negative controls. Results- The cortical and the CoW arteries were more similar to IA in terms of gene expression than the superficial temporal artery. This was based on Pearson correlation (+0.023 [90% CI, 0.017/0.029; P=1.9E-09] for the cortical artery and +0.034 [90% CI, 0.028/0.040; P=6.0E-15] for the CoW artery compared with the superficial temporal artery), Euclidean distance (-25.71 [90% CI, -31.54/-20.02; P=1.9E-11] for the cortical artery and -38.09 [90% CI, -44.08/-32.19; P<2.2E-16] for the CoW artery compared with the superficial temporal artery) and principal component analysis. In all analyses, the unrelated tissues formed separate groups compared with IA and the 3 control arteries. Conclusions- The cortical arteries and the CoW arteries are better controls for gene expression studies on IA than the superficial temporal artery. This probably relates to differences in anatomy of these tissues, such as the presence of an external elastic lamina in the extracranial vasculature and absence in the intracranial vasculature, because IAs, cortical arteries, and CoW arteries are all intracranial while the superficial temporal artery is extracranial. Since CoW arteries can only be obtained postmortem, cortical arteries are preferred over CoW arteries

Hypomagnesemia after aneurysmal subarachnoid hemorrhage

OBJECTIVE: Hypomagnesemia frequently occurs in hospitalized patients, and it is associated with poor outcome. We assessed the frequency and time distribution of hypomagnesemia after aneurysmal subarachnoid hemorrhage (SAH) and its relationship to the severity of SAH, delayed cerebral ischemia (DCI), and outcome after 3 months. METHODS: Serum magnesium was measured in 107 consecutive patients admitted within 48 hours after SAH. Hypomagnesemia (serum magnesium <0.70 mmol/L) at admission was related to clinical and initial computed tomographic characteristics by means of the Mann-Whitney U test. Hypomagnesemia at admission and during the DCI onset period (Days 2-12) was related to the occurrence of DCI and hypomagnesemia at admission, and hypomagnesemia that occurred any time during the first 3 weeks after SAH was related to outcome. RESULTS: Hypomagnesemia at admission was found in 41 patients (38%) and was associated with more cisternal (P = 0.006) and ventricular (P = 0.005) blood, a longer duration of unconsciousness (P = 0.007), and a worse World Federation of Neurosurgical Societies scale score at admission (P = 0.001). The crude hazard ratio for DCI with hypomagnesemia at admission was 2.4 (95% confidence interval, 1.0-5.6), and after multivariate adjustment it was 1.9 (95% confidence interval, 0.7-4.7). The hazard ratio of hypomagnesemia from Days 2 to 12 for patients with DCI was 3.2 (range, 1.1-8.9) after multivariate adjustment. The crude odds ratio for poor outcome (Glasgow Outcome Scale score, 1-3) with hypomagnesemia at admission was 2.5 (range, 1.1-5.5). Hypomagnesemia at admission did not contribute to the prediction of outcome in the multivariate model. CONCLUSION: Hypomagnesemia is frequently present after SAH and is associated with severity of SAH. Hypomagnesemia occurring between Days 2 and 12 after SAH predicts DCI

Histological differences of the Vascular wall between sites with high and low prevalence of intracranial aneurysm

Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle ofWillis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA]) using histological sections of 10 CoWs without IAs. Medial defect density in the AcomA was 0.24 medial defects/mm compared with 0.02 for the A1 part and 0.03 for the A2 part of the ACA. In the basilar tip we found 0.15 medial defects/mm compared with 0.14 in the BA. Vascular smooth muscle cells (VSMCs) were more often disorganized in both high-prevalence sites (AcomA: 10/ 10, basilar tip: 5/10) compared with low-prevalence sites (both ACA and BA: 1/10). Intima thickening was more severe in the highprevalence sites. Vascular wall thickness was not significantly different between high- and low-prevalence sites, but had a larger variance in high- compared with low-prevalence sites (AcomA vs ACA: p=6.8E-12, basilar tip vs BA: p=0.02). Disorganized VSMCs at high-prevalence sites likely result in a higher susceptibility to hemodynamic stress, leading to more vascular remodeling (such as intima thickening), which could increase the likelihood of IA formation

Histological differences of the Vascular wall between sites with high and low prevalence of intracranial aneurysm

Intracranial aneurysms (IAs) develop more often on bifurcations compared with the rest of the circle ofWillis (CoW). We investigated histological differences between 2 high IA prevalence sites (anterior communicating artery [AcomA] and basilar tip) and 2 corresponding low IA prevalence sites (anterior cerebral artery [ACA] and basilar artery [BA]) using histological sections of 10 CoWs without IAs. Medial defect density in the AcomA was 0.24 medial defects/mm compared with 0.02 for the A1 part and 0.03 for the A2 part of the ACA. In the basilar tip we found 0.15 medial defects/mm compared with 0.14 in the BA. Vascular smooth muscle cells (VSMCs) were more often disorganized in both high-prevalence sites (AcomA: 10/ 10, basilar tip: 5/10) compared with low-prevalence sites (both ACA and BA: 1/10). Intima thickening was more severe in the highprevalence sites. Vascular wall thickness was not significantly different between high- and low-prevalence sites, but had a larger variance in high- compared with low-prevalence sites (AcomA vs ACA: p=6.8E-12, basilar tip vs BA: p=0.02). Disorganized VSMCs at high-prevalence sites likely result in a higher susceptibility to hemodynamic stress, leading to more vascular remodeling (such as intima thickening), which could increase the likelihood of IA formation

Interobserver agreement and predictive value for outcome of two rating scales for the amount of extravasated blood after aneurysmal subarachnoid haemorrhage.

Item does not contain fulltextBACKGROUND: In patients with SAH the amount of extravasated blood on the initial CT scan is related with delayed cerebral ischemia and clinical outcome. We investigated the interobserver variation of the Hijdra and Fisher scales for the amount of extravasated blood and the predictive values of these scales for delayed cerebral ischemia and outcome. METHODS: For 132 patients admitted within 48 hours after SAH three observers assessed the amount of blood on the initial CT scan by means of the Hijdra and Fisher scale. We analyzed interobserver agreement with kappa statistics and used multivariate logistic regression for the association with delayed cerebral ischemia and clinical outcome. RESULTS: The interobserver agreement of all three pairs of observers was good for the Hijdra scale (kappas for total sum scores ranging from 0.67 to 0.75) and mild to moderate for the Fisher scale (kappas ranging from 0.37 to 0.55). For the Hijdra scale the risk of DCI was higher for intermediate (OR 4.2; 95% CI 1.1-16.3) and large (OR 3.6; 95% CI 0.8-16.4) amounts of blood with small amount as reference. Fisher grade III (OR 1.0; 95% CI 0.2-5.2) and IV (OR 0.3; 95% CI 0.02-4.0) were not related with DCI. For the Hijdra scale and clinical outcome we found an increasing risk for poor outcome with intermediate (OR 3.9; 95% CI 1.0-15.9) and large (OR 10.7; 95% CI 2.3-50.1) amounts of blood. Such a relation was not found for Fisher grade III (OR 1.2; 95% CI 0.2-7.0) and IV (OR 0.2; 95% CI 0.01-3.4). CONCLUSIONS: For the Hijdra scale we found a distinct better interobserver agreement than for the Fisher score. Moreover, the Hijdra scale was an independent prognosticator for DCI and clinical outcome, which was not the case for the Fisher score