Irregular Shape Identifies Ruptured Intracranial Aneurysm in Subarachnoid Hemorrhage Patients With Multiple Aneurysms.

BACKGROUND AND PURPOSE: We investigated which aneurysm-related risk factors for rupture best discriminate ruptured versus unruptured saccular intracranial aneurysms (sIAs) in subarachnoid hemorrhage patients with multiple sIAs. METHODS: We included 264 subarachnoid hemorrhage patients with a ruptured sIA and at least one additional unruptured sIA, from the Kuopio Intracranial Aneurysm database from 2003 to 2015. These patients had 268 ruptured and 445 unruptured sIAs. Angiograms of the 713 sIAs were reevaluated for multiple variables describing aneurysm shape. Multivariate generalized linear mixed models were used to calculate odds ratios with corresponding 95% confidence intervals for the independent risk factors for aneurysm rupture. RESULTS: In the multivariate analysis, only sIA size (P<0.004) and irregular shape (P<0.000) independently associated with sIA rupture. As an independent risk factor, irregular shape showed the strongest association with rupture (odds ratio 90.3; 95% confidence interval, 47.0-173.5). The sIA location, flow angles, bottleneck factor, or aspect ratio were not significantly associated with rupture. CONCLUSIONS: Irregular shape may identify the ruptured sIA better than size in patients presenting with aSAH and multiple sIAs.

Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Follow-up imaging is often performed in intracranial aneurysms that are not treated. We performed a systematic review and meta-analysis on patient- and aneurysm-specific risk factors for aneurysm growth. METHODS: We searched EMBASE and MEDLINE for cohort studies describing risk factors for aneurysm growth. Two authors independently assessed study eligibility and rated quality with the Newcastle Ottawa Scale. With univariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals (95% CI) of risk factors for aneurysm growth. Heterogeneity was assessed with I(2). RESULTS: Eighteen studies on 15 patient-populations described 3990 patients with 4972 unruptured aneurysms. A total of 437 aneurysms (9%) enlarged during 13 987 aneurysm-years of follow-up. Compared with aneurysms ≤4 mm, RRs were 2.56 (95% CI, 1.93-3.39; I(2)=98%) for ≥5 mm, 2.80 (95% CI, 2.01-3.90; I(2)=96%) for ≥7 mm, and 5.38 (95% CI, 3.76-7.70; I(2)=97%) for ≥10 mm. Compared with aneurysms on the middle cerebral artery, the RR for basilar artery was 1.94 (95% CI, 1.32-2.83; I(2)=57%). RRs were 2.03 (95% CI, 1.52-2.71; I(2)=59%) for smoking at baseline, 2.04 (95% CI, 1.56-2.66; I(2)=90%) for multiple unruptured aneurysms, 1.26 (95% CI, 0.97-1.62; I(2)=59%) for women, 1.24 (95% CI, 0.98-1.58; I(2)=40%) for hypertension, and 2.32 (95% CI, 1.46-3.68; I(2)=91%) for irregular aneurysm shape. Compared with other regions, RR was 0.75 (95% CI, 0.58-0.96) for Japan and 0.64 (95% CI, 0.45-0.90) for Finland. CONCLUSIONS: Most risk factors for aneurysm growth are consistent with risk factors for rupture. In contrast with rupture, the risk of growth was smaller in Japanese and Finnish cohorts compared with other regions. Pooling of individual patient data from low- and high-risk geographical regions is needed to assess independent predictors of aneurysm growth.

Recovery to Preinterventional Functioning, Return-to-Work, and Life Satisfaction After Treatment of Unruptured Aneurysms.

BACKGROUND AND PURPOSE: The eventual goal of preventive treatment of unruptured intracranial aneurysms is to increase the number of life years with high life satisfaction. Insight in the time with reduced functioning, working capacity, and life satisfaction after aneurysm treatment is pivotal to balance the pros and cons of preventive aneurysm occlusion. METHODS: We sent a questionnaire on time-to-recovery to preintervention functioning and return-to-work and life satisfaction to patients treated for an unruptured aneurysm between 2000 and 2013. Changes in life satisfaction before treatment, during recovery, and at follow-up were assessed with Wilcoxon signed-rank tests. RESULTS: The questionnaire was sent to 159 patients of whom 110 (69%) responded. The mean follow-up time after aneurysm treatment was 6 years (SD 4). Fifty-four patients had endovascular and 56 had microsurgical occlusion. Complete recovery to preintervention functioning was reported by 81% (95% confidence interval [CI], 74-88) of patients, with a median time-to-recovery of 3 months (range 0-48). Complete work recovery was reported by 78% (95% CI, 66-87) of patients. The proportion of patients with high life satisfaction reduced from 76% (95% CI, 67-84) before treatment to 52% (95% CI, 43-61) during the period of recovery (P<0.01) and restored largely at long-term follow-up (67% [95% CI, 59-76], P=0.08). CONCLUSION: Life satisfaction is significantly reduced during the period of recovery after treatment of unruptured aneurysms. In the long-term, ≈1 out of 5 patients reports incomplete recovery. These treatment effects should be kept in mind when considering preventive aneurysm treatment. Prospective studies are needed to better compare these losses in patients treated for unruptured aneurysms with those who had subarachnoid hemorrhage.

PHASES Score for Prediction of Intracranial Aneurysm Growth.

BACKGROUND AND PURPOSE: Growth of an intracranial aneurysm occurs in around 10% of patients at 2-year follow-up imaging and may be associated with aneurysm rupture. We investigated whether PHASES, a score providing absolute risks of aneurysm rupture based on 6 easily retrievable risk factors, also predicts aneurysm growth. METHODS: In a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography, we performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. We calculated hazard ratios and corresponding 95% confidence intervals (CI), with the PHASES score as continuous variable and after division into quartiles. RESULTS: We included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5-10.8). Per point increase in PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22-1.43). With the lowest quartile of the PHASES score (0-1) as reference, hazard ratios were for the second (PHASES 2-3) 1.07 (95% CI, 0.49-2.32), the third (PHASES 4) 2.29 (95% CI, 1.05-4.95), and the fourth quartile (PHASES 5-14) 2.85 (95% CI, 1.43-5.67). CONCLUSIONS: Higher PHASES scores were associated with an increased risk of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture, our findings suggest that aneurysm growth can be used as surrogate outcome measure of aneurysm rupture in follow-up studies on risk prediction or interventions aimed to reduce the risk of rupture.

Difference in aneurysm characteristics between ruptured and unruptured aneurysms in patients with multiple intracranial aneurysms.

BACKGROUND AND PURPOSE: Prediction of the risk of rupture of unruptured intracranial aneurysms is mainly based on aneurysm size and location. Previous studies identified features of aneurysm shape and flow angles as additional risk factors for aneurysm rupture, but these studies were at risk for confounding by patient-specific risk factors such as hypertension and age. In this study, we avoided this risk by comparing characteristics of ruptured and unruptured aneurysms in patients with both aneurysmal subarachnoid hemorrhage and multiple intracranial aneurysms. METHODS: We included patients with aneurysmal subarachnoid hemorrhage and multiple aneurysms who presented to our hospital between 2003 and 2013. We identified the ruptured aneurysm based on bleeding pattern on head computed tomography or surgical findings. Aneurysm characteristics (size, location, shape, aspect ratio [neck-to-dome length/neck-width], flow angles, sidewall or bifurcation type, and contact with bone) were evaluated on computed tomographic angiograms. We calculated odds ratios with 95% confidence intervals with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size and location. RESULTS: The largest aneurysm had not ruptured in 36 (29%) of the 124 included patients with 302 aneurysms. Odds ratios for aspect ratio≥1.3 was 3.3 (95% confidence intervals [1.3-8.4]) and odds ratios for irregular shape was 3.0 (95% confidence intervals [1.0-8.8]), both after adjustment for aneurysm size and location. CONCLUSIONS: Aspect ratio≥1.3 and irregular shape are associated with aneurysm rupture independent of aneurysm size and location, and independent of patient characteristics. Additional studies need to assess to what extent these factors increase the risks of rupture of small aneurysms in absolute terms.

Aneurysm treatment <24 versus 24-72 h after subarachnoid hemorrhage.

INTRODUCTION: In patients with aneurysmal subarachnoid hemorrhage (aSAH), it is unclear whether aneurysm treatment <24 h after ictus results in better outcomes than treatment 24-72 h after aSAH. We studied whether aneurysm occlusion <24 h is associated with better outcomes than occlusion 24-72 h after aSAH. METHODS: We used two cohorts of patients with aSAH: (1) the UMC Utrecht cohort with patients admitted between 2008 and 2012 and (2) the International Subarachnoid Aneurysm Trial cohort. Aneurysm treatment was categorized into <24 h and 24-72 h after ictus. We calculated adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) using Poisson regression analyses for poor functional outcome (death or dependency) for both cohorts separately, and performed a pooled analysis based on individual patient data. We also performed a worst-case scenario analysis wherein all patients with rebleeding >3 h after admission were re-categorized into the group with aneurysm treatment 24-72 h after aSAH. RESULTS: We included 1,238 patients (UMC Utrecht cohort: n = 330; ISAT: n = 908). The aRR for poor outcome after treatment <24 h was in the UMC Utrecht cohort 1.84 (95% CI: 1.25-2.70), in ISAT 1.14 (95% CI 0.84-1.55), in the pooled analysis 1.37 (95% CI 1.11-1.68), and in the worst-case scenario pooled analysis 1.24 (95% CI 1.01-1.52). CONCLUSION: Our results suggest that aneurysm occlusion can be performed in day time within 72 h after ictus, instead of on an emergency basis. However, due to the retrospective, non-randomized design of our study, our results cannot be considered as definitive evidence.

Computed tomography angiography spot sign does not predict case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension.

BACKGROUND AND PURPOSE: Many patients with aneurysmal subarachnoid hemorrhage (SAH) with intraparenchymal extension develop early hematoma expansion, which is not explained by aneurysmal rerupture in half of cases. In patients with primary intracerebral hemorrhage, the computed tomography angiography (CTA) spot sign predicts hematoma expansion and poor outcome. We conducted a 2-center prospective cohort study to evaluate whether CTA spot sign predicts case fatality in aneurysmal subarachnoid hemorrhage with intraparenchymal extension. METHODS: We studied consecutive patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension. Two experienced readers, blinded to clinical data, analyzed CTAs for spot sign presence. We assessed the proportion of patients with the CTA spot sign and tested its association with in-hospital and 90-day case fatality, using univariable and multivariable logistic regression. RESULTS: In 32 of 236 patients (14%), we found at least 1 spot sign. Acute surgical hematoma evacuation with aneurysm occlusion occurred in 120 patients (51%). The overall in-hospital case fatality rate was 37%. The CTA spot sign was not associated with in-hospital (multivariable odds ratio, 0.51 [95% confidence interval, 0.06-3.26]) or 90-day (multivariable odds ratio, 0.59 [0.21-1.65]) case fatality. CONCLUSIONS: The found frequency of CTA spot signs is lower after aneurysmal than primary intracerebral hemorrhage and is not associated with in-hospital or 90-day case fatality in patients with aneurysmal subarachnoid hemorrhage with intraparenchymal extension.

Time-dependent test characteristics of head computed tomography in patients suspected of nontraumatic subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: A recent study suggested that in patients with acute headache suspicious of nontraumatic subarachnoid hemorrhage (SAH), cerebrospinal fluid (CSF) analysis is not needed to rule out SAH if head CT performed ≤6 hours after ictus is negative. Before implementation in daily practice, these results need replication. Therefore, we investigated test characteristics of head CT in patients with a clinical suspicion of SAH. METHODS: Patients suspicious of SAH and a normal level of consciousness presenting to our tertiary care hospital between 2005 and 2012 were included. All patients had a head CT interpreted by experienced neuroradiologists and CSF spectrophotometry if head CT was negative or inconclusive. We determined test characteristics with 95% confidence intervals (CI) for nontraumatic SAH of head CT performed ≤6 or >6 hours after onset of headache. RESULTS: Sensitivity of head CT ≤6 hours after ictus (n=137) was 98.5% (95% CI, 92.1%-100%), diagnosing all patients with aneurysmal and perimesencephalic SAH, but not with a cervical arteriovenous malformation. Sensitivity of head CT performed >6 hours after ictus (n=113) was 90.0% (95% CI, 76.3-97.2). After exclusion of patients with an atypical presentation without headache, sensitivity, specificity, negative predictive value, and positive predictive value of head CT ≤6 hours were all 100%. CONCLUSIONS: In patients presenting with acute headache and a normal head CT ≤6 hours after ictus, as interpreted by experienced neuroradiologists, there is no added value of CSF analysis. In patients with an atypical presentation without headache and in patients presenting >6 hours after ictus, CSF analysis is still indicated.

Pharmacotherapy for chronic non-specific low back pain: current and future options.

INTRODUCTION: Low back pain is associated with a large burden-of-illness. It is responsible for the most years lived with disability as compared with any other medical condition. A comprehensive overview of the evidence on pharmacological treatment options for chronic low back pain is lacking. This review evaluates the evidence for the benefits and risks of currently available pharmacological treatments for chronic low back pain. AREAS COVERED: The authors focus on the recent (Cochrane) systematic reviews and meta-analyses of randomized clinical trials covering paracetamol (acetaminophen), NSAIDs, muscle relaxants, antidepressants, anticonvulsants, opioids, and other (new) drugs. EXPERT OPINION: The overall impression of the efficacy of pharmacological treatments for patients with chronic low back pain is rather sobering. The effects on pain reduction and improvement of function are commonly small to moderate and short lasting when compared to placebo. At the same time, the various types of drugs are not without side-effects. This holds especially true for serious side-effects associated with (prolonged) use of strong opioids. Future studies on patients with chronic back pain should aim to identify subgroups of patients with good response to specific pharmacological treatment to facilitate personalized care.

Determinants of Gadolinium-Enhancement of the Aneurysm Wall in Unruptured Intracranial Aneurysms.

BACKGROUND: Recent studies suggest that gadolinium-enhancement of the aneurysm wall may reflect aneurysm wall inflammation, which might increase the risk of aneurysm growth or rupture. OBJECTIVE: To determine the prevalence of gadolinium-enhancement and its determinants in patients with predominantly small (<7 mm) unruptured intracranial aneurysms. METHODS: We performed 3 T MRI aneurysm wall imaging in patients with ≥1 unruptured aneurysm. With Poisson regression analysis, we calculated crude and adjusted risk ratios (RRs) with 95% confidence intervals (CI) to assess determinants of gadolinium-enhancement. RESULTS: Gadolinium-enhancement was observed in 25/79 patients (32%; 95% CI: 21%-42%) and 26/89 aneurysms (29%; 95% CI: 20%-39%). With aneurysms 1.0-2.9 mm as reference, RRs were 4.6 (95% CI: 0.6-36.5) for 3.0 to 4.9 mm, 9.4 (95% CI: 1.3-67.2) for 5.0 to 6.9 mm, and 14.8 (95% CI: 2.1-104.6) for ≥7.0 mm. With internal carotid artery as reference, RRs adjusted for aneurysm size were 3.6 (95% CI: 1.1-11.4) for posterior communicating artery and 3.0 (95% CI: 1.0-8.6) for middle cerebral artery. RRs were 0.8 (95% CI: 0.4-1.8) for acetylsalicylic acid use, 0.9 (95% CI: 0.5-1.8) for statin use, 1.4 (95% CI: 0.7-2.8) for hypertension, 0.9 (95% CI: 0.4-1.8) for previous smoking, 0.9 (95% CI: 0.3-2.6) for never smoking, and 1.4 (95% CI: 0.7-2.7) for irregular aneurysm shape. CONCLUSION: Approximately one-third of patients had gadolinium-enhancement. Because aneurysm size is the strongest determinant of gadolinium-enhancement and also an established predictor for aneurysm growth and rupture, prospective studies with serial imaging need to investigate if gadolinium-enhancement predicts aneurysm growth and rupture.

ELAPSS score for prediction of risk of growth of unruptured intracranial aneurysms.

OBJECTIVE: To develop a risk score that estimates 3-year and 5-year absolute risks for aneurysm growth. METHODS: From 10 cohorts of patients with unruptured intracranial aneurysms and follow-up imaging, we pooled individual data on sex, population, age, hypertension, history of subarachnoid hemorrhage, and aneurysm location, size, aspect ratio, and shape but not on smoking during follow-up and family history of intracranial aneurysms in 1,507 patients with 1,909 unruptured intracranial aneurysms and used aneurysm growth as outcome. With aneurysm-based multivariable Cox regression analysis, we determined predictors for aneurysm growth, which were presented as a risk score to calculate 3-year and 5-year risks for aneurysm growth by risk factor status. RESULTS: Aneurysm growth occurred in 257 patients (17%) and 267 aneurysms (14%) during 5,782 patient-years of follow-up. Predictors for aneurysm growth were earlier subarachnoid hemorrhage, location of the aneurysm, age >60 years, population, size of the aneurysm, and shape of the aneurysm (ELAPSS). The 3-year growth risk ranged from <5% to >42% and the 5-year growth risk from <9% to >60%, depending on the risk factor status. CONCLUSIONS: The ELAPSS score consists of 6 easily retrievable predictors and can help physicians in decision making on the need for and timing of follow-up imaging in patients with unruptured intracranial aneurysms.

Increased incidence of subarachnoid hemorrhage during cold temperatures and influenza epidemics.

OBJECTIVE This study investigated whether the increased incidence of aneurysmal subarachnoid hemorrhage (SAH) in winter is related to temperature or increased incidence of influenza. Such relationships may elucidate the pathogenesis of intracranial aneurysm rupture. METHODS A nationwide sample of 18,714 patients with SAH was linked with weekly temperature and influenza-like illness consultation data. Poisson regression analyses were used to calculate incidence density ratios (IDRs) with corresponding 95% CIs for the association of SAH incidence with temperature and influenza epidemics; IDRs were adjusted for study year (aIDR). In addition, SAH incidence data from 30 European population-based studies were linked with daily temperature data from the European Climate Assessment. RESULTS The aIDR for SAH during influenza epidemics was 1.061 (95% CI 1.022-1.101) in the univariable and 1.030 (95% CI 0.989-1.074) in the multivariable analysis. This association declined gradually during the weeks after epidemics. Per 1°C temperature drop, the aIDR was 1.005 (95% CI 1.003-1.008) in the univariable and 1.004 (95% CI 1.002-1.007) in the multivariable analysis. In the European population-based studies, the IDR was 1.143 (95% CI 1.129-1.157) per 1°C temperature drop. CONCLUSIONS The incidence of SAH is increased during cold temperatures and epidemic influenza. Future studies with individual patient data are needed to investigate causality between temperature or influenza and SAH.

Time-dependent test characteristics of neck stiffness in patients suspected of nontraumatic subarachnoid haemorrhage.

BACKGROUND: Neck stiffness can be the only diagnostic clue for subarachnoid haemorrhage (SAH) at neurological examination in patients with a clinical suspicion of nontraumatic SAH who present with a normal level of consciousness and no focal neurologic deficits. Since the clinical impression is that neck stiffness may take several hours to develop, we determined time-dependent test characteristics of neck stiffness. METHODS: We retrieved the presence of neck stiffness from the medical records of consecutive patients presenting between 2005 and 2013 with a clinical suspicion of SAH, a normal level of consciousness and no focal neurologic deficits. Test characteristics with corresponding 95% confidence intervals (CIs) were calculated for the evaluation of neck stiffness ≤6 h and 6-72 h after symptom onset for the diagnosis of nontraumatic SAH. In a secondary analysis, multiple imputation was used to account for missing values. RESULTS: 114 of 247 included patients were diagnosed with nontraumatic SAH. Neck stiffness at neurological examination performed ≤6 h after symptom onset had a positive predictive value (PPV) of 90% (95% CI: 78%-97%) and negative predictive value (NPV) of 69% (95% CI: 59%-78%). Between 6 and 72 h after symptom onset the PPV was 76% (95% CI: 58%-89%) and NPV 91% (95% CI: 78%-98%). Multiple imputation to account for missing values yielded similar results. CONCLUSION: In patients with a normal level of consciousness without focal neurologic deficits the presence of neck stiffness is helpful but not pathognomic for the diagnosis of SAH. Moreover, the absence of neck stiffness does not rule out SAH, especially when evaluated ≤6 h after symptom onset.

Cerebrovascular complications of left ventricular assist devices.

Left ventricular assist devices (LVADs) are increasingly being used as a bridge to heart transplantation or destination therapy. It is unclear which antithrombotic regimen should be used to reduce the risk of stroke. We systematically reviewed the literature on all types of antithrombotic regimens and stroke in patients with any type of LVADs. Our primary outcome measure was the mean incidence of any type of stroke. Twenty-six articles were selected as relevant, comprehending 1989 patients with a mean LVAD support of 200 days (range 30-621). The mean proportion of patients affected with stroke was 20% (range 0-55%), with a mean incidence of 0.74 (range 0-6.91) events/patient-year. Support with HeartMate II and a regimen of postoperative heparin converted to coumarins, acetylsalicylic acid (ASA) and dipyridamole resulted in 0.17 (mean; range 0.06-0.29) strokes/patient-year. HeartMate II support and the same regime without heparin was associated with 0.07 (mean; range 0.03-0.11) strokes/patient-year. A Novacor device with heparin, converted to coumarins, was associated with 3.82 (mean; range 1.03-6.91) strokes/patient-year, while ASA added to this regime resulted in 0.97 ischaemic strokes/patient-year (mean; range 0.53-1.48). Other combinations of assist devices and antithrombotic regimes were investigated in one or two studies only. This systematic review provides risk estimates for stroke for various LVADs and antithrombotic regimes. Our findings indicate that the postoperative use of heparin in HeartMate II patients is doubtful, and suggest an important role for antiplatelet drugs to prevent stroke in patients supported with a Novacor device.

[Langerhans cell histiocytosis of the dens axis]. / Langerhanscelhistiocytose van de dens axis.

BACKGROUND: Langerhans cell histiocytosis, formerly known as histiocytosis X, is characterised by clonal proliferation of pathologic cells resembling Langerhans cells. Langerhans cell histiocytosis is commonly localised in the bones of the skull or in the skin; however, a great variety of foci has been described. CASE: A general practitioner referred a 25-year-old man to the neurologist because of progressive pain in the neck that had arisen spontaneously. The pain had become so severe over a period of 3 weeks that he had had to support his head with both hands to ease it. Chiropractic treatment had resulted in a worsening of the symptoms. On physical examination, two pathologically enlarged lymph nodes were palpable on the left side of the neck. CT, MRI and PET scans revealed an osteolytic lesion at the site of the dens axis (C2). Immunohistochemistry of the lymph node demonstrated positive staining for CD1a and S100, characteristic of Langerhans cell histiocytosis. The patient was treated with chemotherapy and osteosynthesis of the C1-C2-C3 vertebrae; he was able to return to work after 9 months. CONCLUSION: Langerhans cell histiocytosis is an extremely rare condition; its diagnosis is often missed or made at a later time. The golden diagnostic standard is histopathological analysis of the abnormality. The condition's prognosis is related to its extent. Its localisation in the dens axis has not been previously described.