Salvatore Rudilosso

Uric Acid Therapy Prevents Early Ischemic Stroke Progression: A Tertiary Analysis of the URICO-ICTUS Trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke).

Background and Purpose— Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation. Methods— URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography. Results— EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (&khgr;2; P=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (&khgr;2; P=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (P=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively; P=0.048). Conclusions— UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00860366.

Complete reperfusion is required for maximal benefits of mechanical thrombectomy in stroke patients

A mTICI 2b or a mTICI 3 score are currently considered success following mechanical thrombectomy (MT) in acute stroke but is undetermined whether the two scores translate equivalent outcomes. We present a single-center, retrospective cohort of patients with anterior circulation stroke treated with MT and achieving a final mTICI score 2b or 3. A multimodal CT at baseline and a multimodal MRI at 24 hours assessed the growth of the infarct, and the modified Rankin Scale (mRS) assessed functional outcome at 90 days. The primary outcome was the shift analysis of the mRS at day 90 in ordinal regression adjusted for covariates (age, sex, pretreatment NIHSS score, target occlusion, infarct core, pretreatment alteplase), and the collateral score. Infarct growth was explored in a similarly adjusted multiple linear regression model. MT was started within a median of 285 minutes of symptom onset; 51 (41%) patients achieved a mTICI 2b, and 74 (59%), a mTICI 3. mTICI 3 resulted in better mRS score transitions than mTICI 2b (odds ratio 2.018 [95% CI 1.033–3.945], p = 0. 040), and reduced infarct growth (p = 0.002). We conclude that in patients with acute stroke receiving MT, success should be redefined as achieving a mTICI 3 score.

Perfusion Deficits and Mismatch in Patients with Acute Lacunar Infarcts Studied with Whole-Brain CT Perfusion

BACKGROUND AND PURPOSE: The incidence and significance of perfusion abnormalities on brain imaging in patients with lacunar infarct are controversial. We studied the diagnostic yield of CTP and the type of perfusion abnormalities in patients presenting with a lacunar syndrome and in those with MR imaging–confirmed lacunar infarcts. MATERIALS AND METHODS: A cohort of 33 patients with lacunar syndrome underwent whole-brain CTP on admission. Twenty-eight patients had an acute ischemic lesion at follow-up MR imaging; 16 were classified as lacunar infarcts. Two independent readers evaluated NCCT and CTP to compare their diagnostic yield. In patients with DWI-confirmed lacunar infarcts and visible deficits on CTP, the presence of mismatch tissue was measured by using different perfusion thresholds. RESULTS: The symptomatic acute lesion was seen on CTP in 50% of patients presenting with a lacunar syndrome compared with only 17% on NCCT, and in 62% on CTP compared with 19% on NCCT, respectively, in patients with DWI-confirmed lacunar infarcts. CTP was more sensitive in supratentorial than in infratentorial lesions. In the nonblinded analysis, a perfusion deficit was observed in 12/16 patients with DWI-confirmed lacunar infarcts. The proportion of mismatch tissue was similar in patients with lacunar infarcts or nonlacunar strokes (32% versus 36%, P = .734). CONCLUSIONS: Whole-brain CTP is superior to NCCT in identifying small ischemic lesions, including lacunar infarcts, in patients presenting with a lacunar syndrome. Perfusion deficits and mismatch are frequent in lacunar infarcts, but larger studies are warranted to elucidate the clinical significance of these CTP findings.

Neuroanatomical correlates of stroke-associated infection and stroke-induced immunodepression

BACKGROUND Infections represent the most frequent medical complications in stroke patients. Their main determinants are dysphagia and a transient state of immunodepression. We analyzed whether distinct anatomical brain regions were associated with the occurrence of stroke-associated infections or immunodepression. MATERIALS AND METHODS In 106 patients with acute ischemic stroke, we evaluated the incidence of pneumonia, urinary tract infection, or other infections together with the characterization of biomarkers of immunodepression. Twenty control subjects served to provide reference values. Using voxel-based lesion-symptom mapping, the involvement of gray and white matter structures was correlated with clinical and laboratory findings in crude analyses and in volume adjusted models to rule out associations reflecting differences in the size of the infarction. RESULTS Stroke-associated infection occurred in 22 (21%) patients and prevailed in patients with larger infarcts. Volume adjusted voxel-based lesion-symptom mapping revealed the involvement of the superior and middle temporal gyri, the orbitofrontal cortex, the superior longitudinal fasciculus and the inferior fronto-occipital fasciculus amongst infected patients. These associations were similar for pneumonia but not for urinary tract infections. Lymphopenia was associated with lesions of the superior and middle temporal gyri. Laterality did not influence stroke-associated infections or the presence of immunodepressive traits after volume control. The greatest overlap in the neuroanatomical correlates occurred between pneumonia and dysphagia. CONCLUSION Infarct volume plays a relevant role in the occurrence of stroke-associated infections, but lesions in specific brain locations such as the superior and lateral temporal lobe and the orbitofrontal cortex are also associated with increased infectious risk, especially pneumonia.

Altered Brain Computed Tomography Perfusion in Patients With Fluctuating Lacunar Syndrome and Normal Magnetic Resonance Imaging

We present the cases of an 83-year-old woman and a 53-year-old man who presented to the emergency service with acute right hemiparesis and right ataxic-hemiparesis within 3 hours from symptom onset. The nonenhanced computed tomography (CT) scan was normal while the CT perfusion (CTP) scan showed a delay in time maps in the left pons and in the left thalamus, respectively (Figure). The first patient was treated with intravenous thrombolysis and partially recovered whereas the second patient recovered spontaneously. In both cases, magnetic resonance imaging within 24 hours of admission did not show any acute ischemic lesion on diffusion-weighted imaging (DWI) (Figure). Both patients had progression of the initial focal deficit (3 days and 1 day after admission, respectively), and a repeated magnetic resonance image (Figure) demonstrated hyperintensities on DWI in the left paramedian and thalamoperforator territories, matching with the previous CTP abnormalities and consistent with mature infarctions. Despite the high magnetic resonance accuracy in detecting acute ischemic lesions, even the most sensitive DWI can be normal in the hyperacute phase, especially in infratentorial strokes, probably because subtle cellular apoptotic changes could not be detected in the very initial phases of stroke. 1 Recent studies have shown a high sensitivity of CTP in the acute assessment of lacunar infarcts. 2,3 These 2 representative cases reflect the value of CTP in the workup of acute stroke by highlighting small perfusion deficits in the territory of perforating arteries before an ischemic lesion is established and visible in DWI. The delayed progression to infarction could be related to inflammatory mechanisms that have been associated with early deterioration and poor functional outcome in lacunar infarcts. 4 The CTP findings and the clinical fluctuations may also reflect critically hypoperfused tissue due to limited collateral microcirculation after the occlusion of small perforating arteries 3 that could theoretically benefit from revascularization even in delayed time windows in the scenario of altered perfusion in a small vessel with no established infarct.

Adrenal hormones and circulating leukocyte subtypes in stroke patients treated with reperfusion therapy

Ischemic stroke sets in motion a dialogue between the central nervous and the immune systems that includes the sympathetic/adrenal system. We investigated the course of immune cells and adrenocortical and adrenomedullary effectors in a cohort of 51 patients with acute stroke receiving reperfusion therapy (intravenous alteplase or mechanical thrombectomy) and its correlation with stroke outcomes and infarct growth. Cortisol increased rapidly and fleetingly after stroke, but 39% of patients who had larger infarctions on admission showed a positive delta cortisol at day 1. It was associated with enhanced infarct growth (p = 0.002) and poor outcome [OR (95% CI) 5.30 (1.30-21.69)], and correlated with less lymphocytes and T cells at follow up. Likewise, fewer circulating lymphocytes, T cells, and Tregs were associated with infarct growth. By contrast, metanephrines did not increase at clinical onset, and decreased over time. Higher levels of NMN correlated with more Treg and B cells. Eventually, complete reperfusion at the end of therapy headed the identification of more circulating Tregs at day 1. Then activation of cortical or medullar compartments of the adrenal gland result in specific signatures on leukocyte subpopulations. Manipulation of the adrenal gland hormone levels warrants further investigation.

Different Perfusion Patterns in a Patient with Acute Ischemic Stroke

A 29-year-old male patient with aphasia and mild weakness of the right arm arrived at the emergency room 4 hours after symptom onset. The computed tomography perfusion showed a typical delay in the time-based maps in the left occipital lobe and another hyperperfused area in the left frontal lobe. The follow-up magnetic resonance imaging confirmed cortical ischemic lesions in both areas. This case shows that besides hypoperfusion, hyperperfusion can also be found in the first stages of acute stroke, and it is highly suggestive of established ischemic lesions.

Prognostic Significance of Infarct Size and Location: The Case of Insular Stroke

The prognostic relevance of strokes in different locations is debated. For example, insular strokes have been associated with increased mortality, but this association could reflect their greater severity. In two independent cohorts of patients with supratentorial ischemic stroke (n = 90 and 105), we studied the prognostic consequences of lesion size and location using voxel-based lesion-symptom mapping before and after volume control, which better accounts for total lesion volume. Strokes affecting the insula were larger than non-insular strokes (28 vs 2cc and 25 vs 3cc, p < 0.001 in both cohorts). A number of supratentorial areas (mainly in the left hemisphere), including the insula, were associated with poor functional outcome in both cohorts before (4014 voxels) and after volume control (1378 voxels), while the associations with death were greatly reduced after volume control (from 8716 to 325 voxels). Exploratory analyses suggested that the method of lesion volume quantification, the National Institutes of Health Stroke Scale hemispheric bias and patient selection can result in false associations between specific brain lesions and outcomes. In conclusion, death in the first months after stroke is mainly explained by large infarct volumes, whereas lesions of specific supratentorial structures, mostly in the left hemisphere, also contribute to poor functional outcomes.

Evaluation of white matter hypodensities on computed tomography in stroke patients using the Fazekas score

PURPOSE To assess the reliability of the Fazekas score on brain CT in acute stroke patients. METHODS Two raters evaluated the Fazekas score in 157 CT scans from consecutive patients with acute stroke. RESULTS The Fazekas scores on brain CT scans showed consistent (weighted κ, 0.73) and moderate (weighted κ, 0.56) interobserver agreement for periventricular and deep white matter areas, respectively. Intraobserver reliability was substantial for both areas (weighted κ, 0.85 and 0.8). CONCLUSION The Fazekas score on CT can be used to reliably grade white matter changes, and can be a useful tool when MRI is not available.