Robert J. Brown

Aβ-related angiitis: Comparison with CAA without inflammation and primary CNS vasculitis

Objective:To analyze the clinical findings, response to therapy, and outcomes of patients with cerebral vascular amyloid-&bgr; (A&bgr;) deposition with and without inflammatory vascular infiltration. Methods:We report 78 consecutive patients with cerebral vascular A&bgr; deposition examined at Mayo Clinic Rochester over 25 years (1987 through 2011). Specimens reviewed by a neuropathologist showed 40 with vascular A&bgr; peptide without inflammation (cerebral amyloid angiopathy [CAA]), 28 with granulomatous vasculitis (A&bgr;-related angiitis or ABRA), and 10 with perivascular CAA-related inflammation. We also matched findings in 118 consecutive patients with primary CNS vasculitis (PCNSV) without A&bgr; seen over 25 years (1983 through 2007). Results:Compared to the 40 with CAA, the 28 with ABRA were younger at diagnosis (p = 0.05), had less altered cognition (p = 0.02), fewer neurologic deficits (p = 0.02), and fewer intracranial hemorrhages (<0.001), but increased gadolinium leptomeningeal enhancement (p = 0.01) at presentation, and less mortality and disability at last follow-up (p < 0.001). Compared with PCNSV, the 28 patients with ABRA were older at diagnosis (p < 0.001), had a higher frequency of altered cognition (p = 0.05), seizures/spells (p = 0.006), gadolinium leptomeningeal enhancement (p < 0.001), and intracerebral hemorrhage (p = 0.02), lower frequency of hemiparesis (p = 0.01), visual symptoms (p = 0.04), and MRI evidence of cerebral infarction (p = 0.003), but higher CSF protein levels (p = 0.03). Results of treatment and outcomes in ABRA and PCNSV were similar. Conclusions:ABRA appears to represent a distinct subset of PCNSV.Objective: To analyze the clinical findings, response to therapy, and outcomes of patients with cerebral vascular amyloid-β (Aβ) deposition with and without inflammatory vascular infiltration. Methods: We report 78 consecutive patients with cerebral vascular Aβ deposition examined at Mayo Clinic Rochester over 25 years (1987 through 2011). Specimens reviewed by a neuropathologist showed 40 with vascular Aβ peptide without inflammation (cerebral amyloid angiopathy [CAA]), 28 with granulomatous vasculitis (Aβ-related angiitis or ABRA), and 10 with perivascular CAA-related inflammation. We also matched findings in 118 consecutive patients with primary CNS vasculitis (PCNSV) without Aβ seen over 25 years (1983 through 2007). Results: Compared to the 40 with CAA, the 28 with ABRA were younger at diagnosis (p = 0.05), had less altered cognition (p = 0.02), fewer neurologic deficits (p = 0.02), and fewer intracranial hemorrhages (<0.001), but increased gadolinium leptomeningeal enhancement (p = 0.01) at presentation, and less mortality and disability at last follow-up (p < 0.001). Compared with PCNSV, the 28 patients with ABRA were older at diagnosis (p < 0.001), had a higher frequency of altered cognition (p = 0.05), seizures/spells (p = 0.006), gadolinium leptomeningeal enhancement (p < 0.001), and intracerebral hemorrhage (p = 0.02), lower frequency of hemiparesis (p = 0.01), visual symptoms (p = 0.04), and MRI evidence of cerebral infarction (p = 0.003), but higher CSF protein levels (p = 0.03). Results of treatment and outcomes in ABRA and PCNSV were similar. Conclusions: ABRA appears to represent a distinct subset of PCNSV.

The relationship between delayed infarcts and angiographic vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUNDnDelayed cerebral ischemia is common after aneurysmal subarachnoid hemorrhage (aSAH) and is a major contributor to poor outcome. Yet, although generally attributed to arterial vasospasm, neurological deterioration may also occur in the absence of vasospasm.nnnOBJECTIVEnTo determine the relationship between delayed infarction and angiographic vasospasm and compare the characteristics of infarcts related to vasospasm vs those unrelated.nnnMETHODSnA retrospective review of patients with aSAH admitted from July 2007 through June 2011. Patients were included if they were admitted within 48 hours of SAH, had a computed tomography scan both 24 to 48 hours following aneurysm treatment and ≥7 days after SAH, and had a catheter angiogram to evaluate for vasospasm. Delayed infarcts seen on late computed tomography but not postprocedurally were attributed to vasospasm if there was moderate or severe vasospasm in the corresponding vascular territory on angiography. Infarct volume was measured by perimeter tracing.nnnRESULTSnOf 276 aSAH survivors, 134 had all imaging requisite for inclusion. Fifty-four (34%) had moderate or severe vasospasm, of whom 17 (31%) had delayed infarcts, compared with only 3 (4%) of 80 patients without vasospasm (P < .001). There were a total of 29 delayed infarcts in these 20 patients; 21 were in a territory with angiographic vasospasm, but 8 (28%) were not. Infarct volume did not differ between vasospasm-related (18 ± 25 mL) and vasospasm-unrelated (11 ± 12 mL) infarcts (P = .54), but infarcts in the absence of vasospasm were more likely watershed (50% vs. 10%, P = .03).nnnCONCLUSIONnDelayed infarcts following aSAH can occur in territories without angiographic vasospasm and are more likely watershed in distribution.

Early vs Delayed Cerebral Infarction After Aneurysm Repair After Subarachnoid Hemorrhage

BACKGROUNDnCerebral infarction is a major contributor to poor outcome after subarachnoid hemorrhage (SAH). Although usually considered a complication of delayed cerebral ischemia, infarcts may also occur early, in relation to initial brain injury or aneurysm-securing procedures.nnnOBJECTIVEnWe analyzed the relative frequency and volume of early vs delayed infarcts after SAH and their relationship to hospital outcome.nnnMETHODSnRetrospective review of consecutive patients admitted with aneurysmal SAH over 4 years who had follow-up brain imaging 7 days or later after admission. Imaging 24 to 48-hours after aneurysm-securing procedures was reviewed to classify infarcts seen on final imaging as early or delayed. Infarct volumes were measured by perimeter tracing and infarct burden calculated for each patient.nnnRESULTSnOf 250 eligible patients, 205 had follow-up imaging; infarcts were present in 61 patients. Of these, 29 had early infarcts, 16 had delayed infarcts, and 5 had both early and delayed infarcts. Eleven patients with infarcts did not undergo postprocedure computed tomography; these were presumptively classified as having late infarcts. Early and delayed infarcts contributed equally to infarct burden. Early infarcts were associated with aneurysm clipping (odds ratio: 4.2, 95% confidence interval: 1.8-9.5 compared with coiling), whereas delayed infarcts were almost always seen in association with angiographic vasospasm (odds ratio: 3.3, 95% confidence interval: 1.5-7.3). Patients with early as well as late infarcts, especially those with infarct burden more than 30 cm had worse hospital discharge disposition.nnnCONCLUSIONnEarly infarction occurs frequently after SAH and contributes as much as delayed cerebral ischemia to infarct burden and hospital outcome. Efforts to better understand and modify contributors to early infarction appear warranted.

Clinical outcomes after neurogenic stress induced cardiomyopathy in aneurysmal sub-arachnoid hemorrhage: A prospective cohort study

INTRODUCTIONnNeurogenic stress cardiomyopathy (NCM) has been associated with poor outcomes in the setting of aneurysmal subarachnoid hemorrhage (aSAH). Much less is known regarding recovery of cardiac function. The aim of this prospective cohort study was to study the rate of early cardiac recovery after NCM and the potential effect of NCM on short term functional recovery. A secondary aim sought to determine whether certain biomarkers may be associated with the development of NCM.nnnMETHODSnPatients with confirmed aSAH between November 2012 and October 2013 were prospectively enrolled and received echocardiograms within 48 h of admission. Ejection fraction (%) and regional wall motion abnormality score index (RWMI) were noted. All patients with confirmed aSAH had a troponin and BNP level drawn on admission. Patients with confirmed NCM received a follow up echocardiogram 7-21 days after the initial echocardiogram. Clinical follow up at 3 months evaluated mortality, mRS and mBI scores.nnnRESULTSn63 patients with confirmed aSAH were enrolled. In this cohort 11 (17%) patients were confirmed to have NCM. The NCM group had higher in-hospital mortality [n = 4(36.4%)] compared to the non-NCM group [n = 5(9.6%)] (p = .021). At 3 months the development of NCM was associated with an unfavorable mRS (p = 0.042) and mBI (p = 0.005). Both an elevated BNP (> 100 pg/mL) and elevated troponin (>0.3 mg/dL) were associated with the development of NCM. Follow-up echocardiograms were performed within 21 days of admission on 8 patients with NCM. An abnormal RWMI of 1.5 or higher was present in 5(71%) patients.nnnCONCLUSIONnNCM is a frequent complication associated with aSAH. The onset of the disease occurs early in the course of aSAH and an elevated BNP and troponin may be associated with the onset of NCM. Cardiac function often remains impaired during the acute recovery phase potentially impeding resuscitation during this period. The routine use of short term follow-up echocardiography may be recommended.

Neuroimaging Findings in Cardiac Myxoma Patients: A Single-Center Case Series of 47 Patients

Background and Purpose: Cardiac myxomas can present with a myriad of neurological complications including stroke, cerebral aneurysm formation and metastatic disease. Our study had two objectives: (1) to describe the neuroimaging findings of patients with cardiac myxomas and (2) to examine the relationship between a history of embolic complications secondary to myxoma and intracranial aneurysm formation, hemorrhage and metastatic disease. We hypothesized that patients who present with embolic complications related to myxoma would be more likely to have such complications. Materials and Methods: We searched our institutional database for all patients with pathologically proven cardiac myxomas from 1995 to 2014 who received neuroimaging. Neuroimaging findings were categorized as acute ischemic stroke, intracerebral hemorrhage, oncotic aneurysm, and cerebral metastasis. Cardiac myxoma patients were divided into those presenting with embolic complications (i.e. lower extremity emboli or cerebral emboli) and those presenting with non-embolic complications prior to surgical resection of the myxoma. The prevalence of intracranial hemorrhage, myxomatous aneurysm formation, and cerebral metastases was compared in myxoma patients presenting with and without embolic complications using a Chi-squared test. Results: Forty-seven consecutive patients were included in this study. Sixteen patients (34.0%) had imaging evidence of acute ischemic stroke. Of these, 13 had acute ischemic strokes directly attributed to the cardiac myxoma (27.7%) and 3 had acute ischemic strokes secondary to causes other than myxoma (6.4%). Seven patients (14.9%) had aneurysms. Two patients (4.3%) had parenchymal metastatic disease on long-term imaging. Fourteen patients (29.8%) presented with ischemic symptoms that were attributed to cardiac myxoma (1 with lower extremity ischemia, 1 with lower extremity ischemia and ischemic stroke, and 12 with ischemic stroke). Patients presenting with embolic complications related to the myxoma (ischemic stroke or lower extremity ischemia) were more likely to have imaging evidence of intracranial hemorrhage (21.4 vs. 3.0%, p = 0.09), oncotic aneurysm (35.7 vs. 6.1%, p = 0.03), and cerebral metastasis (14.3 vs. 0.0%, p = 0.07) on follow-up imaging. Conclusions: Ischemic stroke and intracranial oncotic aneurysm were found in a substantial proportion of cardiac myxoma patients undergoing neuroimaging. Patients presenting with embolic complications of cardiac myxoma are more likely to have intracranial hemorrhage, intracranial oncotic aneurysms, and cerebral metastatic disease.

Polyuria and cerebral vasospasm after aneurysmal subarachnoid hemorrhage

BackgroundNatriuresis with polyuria is common after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have shown an increased risk of symptomatic cerebral vasospasm or delayed cerebral ischemia (DCI) in patients with hyponatremia and/or the cerebral salt wasting syndrome (CSW). However, natriuresis may occur in the absence of hyponatremia or hypovolemia and it is not known whether the increase in DCI in patients with CSW is secondary to a concomitant hypovolemia or because the physiology that predisposes to natriuretic peptide release also predisposes to cerebral vasospasm. Therefore, we investigated whether polyuria per se was associated with vasospasm and whether a temporal relationship existed.MethodsA retrospective review of patients with aSAH was performed. Exclusion criteria were admission more than 48xa0h after aneurysmal rupture, death within 5xa0days, and the development of diabetes insipidus or acute renal failure. Polyuria was defined asu2009>6 liters of urine in a 24xa0h period. Vasospasm was defined as a mean velocityu2009>u2009120xa0m/s on Transcranial Doppler Ultrasonography (TCDs) or by evidence of vasospasm on computerized tomography (CT) or catheter angiography. Multivariable logistic regression was performed to assess the relationship between polyuria and vasospasm.Results95 patients were included in the study. 51 had cerebral vasospasm and 63 met the definition of polyuria. Patients with polyuria were significantly more likely to have vasospasm (OR 4.301, 95xa0% CI 1.378–13.419) in multivariate analysis. Polyuria was more common in younger patients (52 vs 68, pu2009<.001) but did not impact mortality after controlling for age and disease severity. The timing of the development of polyuria was clustered around the diagnosis of vasospasm and patients with polyuria developed vasospasm faster than those without polyuria.ConclusionsPolyuria is common after aSAH and is significantly associated with cerebral vasospasm. The development of polyuria may be temporally related to the development of vasospasm. An increase in urine volume may be a useful clinical predictor of patients at risk for vasospasm.

Comparison of Initial Vasopressors Used for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Background: The main reason for morbidity after aneurysmal subarachnoid hemorrhage (aSAH) is delayed cerebral ischemia (DCI). The mainstay of medical therapy for treating DCI is induced hypertension with vasopressors to restore cerebral perfusion. Both phenylephrine (PE) and norepinephrine (NE) are commonly used for induced hypertension, but the impact of the initial choice of vasopressor on the efficacy, adverse effects, or outcome after hemodynamic therapy for DCI is unknown. Methods: Sixty-three patients with aSAH between January 2012 and October 2014, who developed DCI (defined as new focal deficit or decline in Glasgow Coma Score) and in which PE (n = 45) or NE (n = 18) treatment was initiated were evaluated in this retrospective study. Baseline characteristics, adverse effects, the need to change or add vasopressors, the response to therapy, the need for endovascular therapy, new infarct development, discharge disposition, and 3 months modified Rankin score were all compared between pressor groups. Results: Baseline characteristics (e.g., Hunt Hess and Fisher grades) were similar. There were no differences in the overall rate of complications including arrhythmia, pulmonary edema, or kidney injury. However, those initiated on PE were more likely to be changed to an alternate vasopressor (64 vs. 33%, p = 0.016), mostly for bradycardia or failure to reach therapeutic targets. Patients initially treated with PE were less likely to respond neurologically (71 vs. 94%, p = 0.01) or to be discharged to home or acute rehabilitation facilities (73 vs. 94%, p = 0.02) and were more likely to have a delayed infarct on imaging (62 vs. 33%, p = 0.04). Conclusions: Our study suggests that patients with DCI after aSAH initiated on PE are more likely to require treatment change to another vasopressor and are at greater risk for poor clinical outcomes compared to patients started on NE. Larger comparative studies are warranted.

A survey of blood pressure parameters after aneurysmal subarachnoid hemorrhage

Purpose/aim: Blood pressure (BP) regulation is recommended following aneurysmal subarachnoid hemorrhage (aSAH) to prevent re-bleeding and to treat delayed cerebral ischemia. However, optimal BP thresholds are not well established. There is also variation with regard to the BP component (e.g. systolic vs. mean) that is targeted or manipulated. Materials and methods: An 18-question survey was distributed to physicians and advanced practitioner members of the Neurocritical Care Society. Respondents were asked which BP parameter they manipulated and what their thresholds were in different clinical scenarios. They were also asked whether they were influenced by the presence of incidental aneurysms. Answers were analyzed for differences in training background and treatment setting. Results: There were 128 responses. The majority were neurointensivists (47 neurology and 37 non-neurology) and treated patients in dedicated neurointensive care units (n = 98). Systolic BP (SBP) was preferred over mean arterial pressure (MAP). Prior to aneurysm treatment, SBP limits ranged from 140 to 180 mm Hg. After aneurysm treatment, SBP limits ranged from 160 to 240 mm Hg. The maximum and minimum MAPs varied by as much as 50%. Nearly two-thirds of the respondents were influenced by the presence of incidental aneurysms. Training background influenced tolerance to BP limits with neurology-trained neurointensivists accepting higher BP limits when treating delayed ischemia (u2009p = .018). They were also more likely to follow SBP (u2009p = .018) and have a limit of 140 mm Hg prior to aneurysm treatment (u2009p = .001). Conclusions: There is large practice variability in BP management following aSAH. There is also uncertainty over the importance of incidental aneurysms. Further research could evaluate whether this variability has clinical significance.

Oral Presentations of the 2016 Annual Meeting of the Congress of Neurological Surgeons: San Diego, California: September 24-28, 2016: 100 Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice.

INTRODUCTIONnWe previously found that aspirin decreases the risk of cerebral aneurysm (CA) rupture in humans. We aim to assess whether a sex differential exists in the response of human CAs to aspirin and confirm these observations in a mouse model of CA.nnnMETHODSnA nested case-control analysis from the International Study of Unruptured Intracranial Aneurysms (ISUIA) was performed to assess whether a sex differential exists in the response of human CAs to aspirin. A series of experiments were subsequently performed in a mouse model of CAs. Aneurysms were induced with hypertension and elastase injection into mice basal cisterns.nnnRESULTSnAspirin decreased the risk of aneurysm rupture in men significantly more than women in ISUIA. There was a significantly decreasing odds ratio (OR) for hemorrhage with the increasing use of aspirin in men (OR, 0.05; P = .0024) but not in women (OR, 0.46; P = .23). In mice, aspirin and cyclooxygenase-2 (COX-2) inhibitor did not affect CA formation but significantly decreased the incidence of rupture. The incidence of CA rupture was significantly lower in male vs female mice on aspirin. Gene expression analysis from cerebral arteries showed higher 15-PGDH levels in male mice. The rate of CA rupture was similar in male mice receiving aspirin and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitor compared with females receiving aspirin and 15-PGDH agonist signaling a reversal of the sex-differential response to aspirin. Compared with superficial temporal arteries, female human CAs showed higher COX-2 levels and lower 15-PGDH levels.nnnCONCLUSIONnAspirin decreases aneurysm rupture in humans and mice, in part, through COX-2 pathways. Evidence from animal and human studies suggests a consistent differential effect by sex. 15-PGDH activation in females reduces the incidence of rupture and eliminates the sex-differential response to aspirin.