David Orion

Chronic Kidney Disease and Clinical Outcome in Patients With Acute Stroke

Background and Purpose— Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for cardiovascular disease and stroke. Our aim was to examine the association between estimated glomerular filtration rate (GFR) and stroke outcome and to assess whether CKD and its severity affect stroke outcome in a large cohort of unselected patients with acute stroke. Methods— We examined the association between baseline estimated GFR and CKD and 1-year outcomes in 821 consecutive patients with acute stroke (ischemic or hemorrhagic). GFR was estimated by 2 methods: the Modification of Diet in Renal Disease and the Mayo Clinic quadratic equation. An estimated GFR rate ≤60 mL/min/1.73 m2 defined CKD. Results— Odds ratios (95% CI) for death across levels of estimated GFR based on both equations were estimated. CKD was present in 36% (n=291) of patients based on the Modification of Diet in Renal Disease equation and 18% (n=147) based on the Mayo Clinic equation. The adjusted ORs for mortality after 1-year based on the Modification of Diet in Renal Disease equation were 0.7 (95% CI, 0.4 to 1.2) associated with GFR 45 to 60 and 3.2 (1.7 to 6.4) associated with GFR 15 to 44 as compared with GFR >60 mL/min/1.73 m2, whereas those based on the Mayo Clinic equation were 2.3 (1.1 to 4.7) and 3.3 (1.6 to 7.1), respectively. The adjusted ORs for Barthel Index ≤75 or death after 1 year were 0.8 (0.5 to 1.5) and 2.1 (0.9 to 4.8) by the Modification of Diet in Renal Disease equation and 1.9 (0.8 to 4.4) and 3.9 (1.5 to 11.0) by the Mayo Clinic equation, respectively. Conclusions— CKD is a strong independent predictor of mortality and poor outcome in patients with acute stroke. The estimation of the prevalence of CKD and of the GFR cutoffs associated with poor outcome depend on the equation used to estimate GFR.

Chronic Kidney Disease in Patients with Acute Intracerebral Hemorrhage: Association with Large Hematoma Volume and Poor Outcome

Background: Chronic kidney disease (CKD) is associated with both a risk of adverse vascular outcome and a risk of bleeding. We have tested the hypothesis that in the setting of an acute intracerebral hemorrhage (ICH), CKD is associated with poor outcome and with larger hematoma volume. Methods: We examined the association between CKD and ICH characteristics and outcome within a prospective cohort study of consecutive patients hospitalized with an acute stroke and followed for 1 year. CKD was categorized by the estimated baseline glomerular filtration rate into moderate/severe impairment (<45), mild impairment (45–60) and no impairment (>60 ml/min/1.73 m2). Results: Among 128 patients with an ICH (mean age = 71.7 ± 12.3 years, 41.4% women) 46.1% had CKD (23.4% mild and 22.7% moderate/severe). Patients with moderate/severe impairment had >4-fold adjusted hazard ratio for mortality over 1 year (4.29; 95% CI = 1.69–10.90) compared to patients with no impairment. The hematoma volumes [median (25–75%)] were 15.3 ml (5.4–37.5) in patients with no impairment, 16.6 (6.8–36.9) in mild impairment and 50.2 (10.4–109.1) in moderate/severe impairment (p = 0.009). The location of the hematoma was lobar in 12% with no impairment, 17% with mild impairment and 39% with moderate/severe impairment (p = 0.02). Patients with moderate/severe impairment exhibited a 2.3-fold higher hematoma volume (p = 0.04) and a >6-fold higher odds of lobar location (95% CI = 1.59–24.02) as compared to no impairment. Further adjustment for antiplatelet use and for presence of leukoaraiosis attenuated the association with hematoma volume (p = 0.15), while moderate/severe impairment was associated with an adjusted OR of 5.35 (95% CI = 1.18–24.14) for lobar location. Conclusions: Presence of moderate/severe CKD among patients with ICH is associated with larger, lobar hematomas and with poor outcome.

Cerebral leukoaraiosis in patients with stroke or TIA: clinical correlates and 1-year outcome.

Background and purpose:  Cerebral leukoaraiosis is frequently observed in patients with acute stroke, but its clinical consequences on functional recovery remain incompletely defined. We evaluated the clinical correlates of leukoaraiosis, and its association with stroke‐outcome in a cohort of consecutively hospitalized patients.

Aspirin Responsiveness in Acute Brain Ischaemia: Association with Stroke Severity and Clinical Outcome

Purpose: Platelets play a critical role in the pathogenesis of acute brain ischaemia. We studied the association between the degree of inhibition of platelet function by aspirin (ASA) and the severity and outcome of acute brain ischaemia. Methods: Platelet responsiveness to ASA was assessed in patients with acute brain ischaemia, treated with ASA since hospital admission. The degree of ASA responsiveness was assessed by optical aggregometry and categorized into patients with good response, partial response and complete unresponsiveness to ASA (good responders, partial responders and non-responders, respectively). An additional evaluation of responsiveness to ASA was performed by Impact-R (cone and platelet analyzer). Patients underwent serial clinical assessment during hospitalization, at discharge and during follow-up. Results: Among 105 patients (mean age 63 ± 12 years; 66% men), impaired ASA responsiveness at baseline as assessed by aggregometry was associated with increased stroke severity at baseline, unfavourable clinical course, and poor functional outcome during follow-up (p < 0.05 for all). Age-adjusted odds ratios in non-responders compared to good responders were 9.8 for severe stroke on admission (95% CI 2.8–34.9), 3.1 for lack of early clinical improvement (95% CI 1.1–8.8) and 8.6 for poor functional outcome during follow-up (95% CI 2.4–30.4). Less robust trends were observed with the Impact-R. Conclusions: Impaired responsiveness to ASA in acute brain ischaemia is common and is associated with worse neurological deficits at stroke onset, early clinical deterioration and poorer functional outcome. The clinical significance of these findings requires further evaluation in larger longitudinal studies.

Antibodies from ALS patients inhibit dopamine release mediated by L-type calcium channels

Objective: To examine the presence of anti-L-type calcium channel antibodies in the serum of ALS patients. Background: Autoimmunity has been hypothesized as one of the mechanisms underlying the pathogenesis of sporadic ALS. Previous studies reported that sera from patients with sporadic ALS contain antibodies against voltagegated calcium channels (L-type and P-type), but others do not support these findings. Methods: Regulated secretion of tritiated dopamine ([3H]DA) in PC12 cells in mediated exclusively by calcium entry through L-type calcium channels. To examine whether purified ALS immunoglobulin G (IgG) inhibits [3H]DA release by interfering with calcium entry through L-type calcium channels, evoked release in PC12 cells was determined in the presence of ALS IgG. This functional assay provides a sensitive way to examine L-type calcium channel interaction with IgG from ALS patients. Results: A significant inhibition of depolarization-evoked [3H]DA release (32 ± 4%) was observed by purified IgG from ALS patients compared with control subjects (11 ± 2%; p < 0.01). Significant inhibition by IgG occurred in 79% (15/19) of the ALS patients compared with only 29% (5/17) in the control group (p < 0.01). The level of calcium channel inhibition by ALS IgG correlated positively with disease duration (r = 0.68; p < 0.01) and correlated negatively with age (r = -0.48; p < 0.05). Conclusions: These results confirm the presence of antibodies against the L-type calcium channel in the majority of sera from ALS patients, supporting their role in the pathogenesis of ALS.

Acute stroke intervention.

This review summarizes the current state-of-the-art regarding the endovascular management of acute ischemic stroke. Beginning with intravenous tissue plasminogen activator, this paper traces the gradual shift of systemic thrombolysis from a competing to complementary treatment modality. Intra-arterial thrombolysis, mechanical thrombectomy with the Merci (Concentric Medical, Mountain View, California) and Penumbra (Penumbra, Inc., Alameda, California) systems, angioplasty, primary intracranial stenting, and emerging stentriever devices are sequentially reviewed. Ultimately, this paper lays the foundation for current endovascular stroke management and considers future areas of progress and research.

Is Bridging with Intravenous Thrombolysis of Any Benefit in Endovascular Therapy for Acute Ischemic Stroke

OBJECTIVE Large vessel occlusions with heavy clot burden are less likely to improve with intravenous (IV) thrombolysis alone. The purpose of this study was to show whether a combination of IV thrombolysis and endovascular therapy was superior to endovascular treatment alone. METHODS Data for 104 patients with acute large artery occlusion treated between 2005 and 2010 were reviewed. Forty-two received endovascular therapy in combination with IV thrombolysis (bridging group), and 62 received endovascular therapy only. Clinical outcome, mortality rate, and symptomatic intracranial hemorrhage (sICH) rate were compared between the two groups. RESULTS The two groups had similar demographic and vascular risk factor distribution, as well as National Institutes of Health Stroke Scale score on admission (mean±SD: 14.8±4.7 and 16.0±5.3; P=0.23). No difference was found in Thrombolysis in Myocardial Infarction recanalization rates (score of 2 or 3) after combined or endovascular therapy alone (83.33% and 79.03%; P=0.585). Favorable outcome, defined as a modified Rankin Scale score of <2 at 90 days, also did not differ between the bridging group and the endovascular-only group (37.5% and 32.76%; P=0.643). There was no difference in mortality rate (19.04% and 29.03%; P=0.5618) and sICH rate (11.9% and 9.68%; P=0.734). A significant difference was found in mean time from symptom onset to treatment in the bridging group and the endovascular-only group (227±88 min vs. 125±40 min; P<0.0001). CONCLUSION Combining IV thrombolysis with endovascular therapy resulted in similar outcome, revascularization, sICH, and mortality rates compared with endovascular therapy alone. Prospective clinical studies comparing both treatment strategies in acute ischemic stroke are warranted.

Interleukin-6 and soluble intercellular adhesion molecule-1 in acute brain ischaemia

Inflammation plays a critical role in the pathogenesis of atherothrombosis. Our aim was to examine the association between plasma concentrations of inflammatory biomarkers and severity and outcome of acute brain ischaemia. Plasma samples were collected within 36 h of symptom onset in patients with acute brain ischaemia, and assessed by conventional ELISA kits for concentration of interleukin‐6 (IL‐6) and soluble intercellular adhesion molecule‐1 (sICAM‐1). Patients were assessed serially for stroke severity (National Institute of Health stroke scale) and outcome during follow‐up (modified Rankin Scale, mRS; and Stroke Impact Scale‐16, SIS). Patients (n = 113, 65% men, mean age 64 ± 12 years) had a mean IL‐6 concentrations of 5.1 ± 5.0 pg/ml and sICAM‐1 of 377 ± 145 ng/ml. IL‐6, but not sICAM‐1, concentrations were strongly associated with stroke severity (P < 0.01 at all serial assessments). Ln‐transformed IL‐6 levels (per 1 SD) were associated with disability (mRS ≥2, OR = 1.7; 95% CI 1.1–3.0) and poor physical function (SIS ≤85, OR = 1.7; 95% CI 1.0–2.8). Further adjustment for baseline stroke severity, however, eliminated these associations. Our results suggest that high plasma concentrations of the inflammatory biomarker IL‐6 but not sICAM‐1 are associated with stroke severity and poorer functional outcome. IL‐6 does not add, however, additional prognostic information for stroke outcome beyond that conveyed by the stroke severity.

Use of the Microangiographic Fluoroscope for Coiling of Intracranial Aneurysms

BACKGROUND Neurointervention is an ever-evolving specialty with tools including microcatheters, microwires, and coils that allow treatment of pathological conditions in increasingly smaller intracranial arteries, requiring increasing accuracy. As endovascular tools evolve, so too should the imaging. OBJECTIVE To detail the use of microangiography performed with a novel fluoroscope during coiling of intracranial aneurysms in 2 separate patients and discuss the benefits and potential limitations of the technology. METHODS The microangiographic fluoroscope (MAF) is an ultra high-resolution x-ray detector with superior resolution over a small field of view. The MAF can be incorporated into a standard angiographic C-arm system for use during endovascular procedures. RESULTS The MAF was useful for improved visualization during endovascular coiling of 2 unruptured intracranial aneurysms, without adding significant time to the procedure. No significant residual aneurysm filling was identified post-coiling, and no complications occurred. CONCLUSION The MAF is a high-resolution detector developed for use in neurointerventional cases in which superior image quality over a small field of view is required. It has been used with success for coiling of 2 unruptured aneurysms at our institution. It shows promise as an important tool in improving the accuracy with which neurointerventionists can perform certain intracranial procedures. ABBREVIATIONS AP: anteroposterior CT: computed tomography CTA: CT angiography DSA: digital subtraction angiography FOV: field of view ICA: internal carotid artery MAF: microangiographic fluoroscope

Occlusive concomitant dissections of the carotid and coronary arteries treated with stent placement

Spontaneous coronary artery dissection is rare and previously was associated with a high mortality rate. Spontaneous dissection of the internal carotid artery is a cause of ischemic stroke, especially in young patients. Medical therapy allows healing of the carotid dissection in most patients, although endovascular stent placement has been reported for the treatment of selected cases. A case is reported of a patient in their late 30s who presented with a symptomatic occlusive cervical carotid artery dissection and, 7 days later, developed an acute coronary syndrome due to an occlusive dissection of the intermediate artery. Both lesions were treated with stent placement.