Mild fever as a catalyst for consumption of the ischaemic penumbra despite endovascular reperfusion.

Cerebrovascular ischaemia is potentiated by hyperthermia, and even mild temperature elevation has proved detrimental to ischaemic brain. Infarction progression following endovascular reperfusion relates to multiple patient-specific and procedural variables; however, the potential influence of mild systemic temperature fluctuations is not fully understood. This study aims to assess the relationship between systemic temperatures in the early aftermath of acute ischaemic stroke and the loss of at-risk penumbral tissues, hypothesizing consumption of the ischaemic penumbra as a function of systemic temperatures, irrespective of reperfusion status. A cross-sectional, retrospective evaluation of a single-institution, prospectively collected endovascular therapy registry was conducted. Patients with anterior circulation, large vessel occlusion acute ischaemic stroke who underwent initial CT perfusion, and in whom at least four-hourly systemic temperatures were recorded beginning from presentation and until the time of final imaging outcome were included. Initial CT perfusion core and penumbra volumes and final MRI infarction volumes were computed. Systemic temperature indices including temperature maxima were recorded, and pre-defined temperature thresholds varying between 37°C and 38°C were examined in unadjusted and adjusted regression models which included glucose, collateral status, reperfusion status, CT perfusion-to-reperfusion delay, general anaesthesia and antipyretic exposure. The primary outcome was the relative consumption of the penumbra, reflecting normalized growth of the at-risk tissue volume ≥10%. The final study population comprised 126 acute ischaemic stroke subjects (mean 63 ± 14.5 years, 63% women). The primary outcome of penumbra consumption ≥10% occurred in 51 (40.1%) subjects. No significant differences in baseline characteristics were present between groups, with the exception of presentation glucose (118 ± 26.6 without versus 143.1 ± 61.6 with penumbra consumption, P = 0.009). Significant differences in the likelihood of penumbra consumption relating to systemic temperature maxima were observed [37°C (interquartile range 36.5 - 37.5°C) without versus 37.5°C (interquartile range 36.8 - 38.2°C) with penumbra consumption, P = 0.001]. An increased likelihood of penumbra consumption was observed for temperature maxima in unadjusted (odds ratio 3.57, 95% confidence interval 1.65 - 7.75; P = 0.001) and adjusted (odds ratio 3.06, 95% confidence interval 1.33 - 7.06; P = 0.009) regression models. Significant differences in median penumbra consumption were present at a pre-defined temperature maxima threshold of 37.5°C [4.8 ml (interquartile range 0 - 11.5 ml) versus 21.1 ml (0 - 44.7 ml) for subjects not reaching or reaching the threshold, respectively, P = 0.007]. Mild fever may promote loss of the ischaemic penumbra irrespective of reperfusion, potentially influencing successful salvage of at-risk tissue volumes following acute ischaemic stroke.

Automated CT Perfusion Prediction of Large Vessel Acute Stroke from Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: We have observed that large vessel occlusion acute strokes (LVOS) due to intracranial atherosclerotic disease (ICAD) present with more benign CT perfusion (CTP) profiles, which we presume to potentially represent enhanced collateralization compared to embolic LVOS. We aim to determine if CTP profiles can predict ICAD in LVOS. METHODS: Retrospective review of a prospectively collected interventional stroke database from September 2010 to March 2015. Patients with intracranial ICA/MCA-M1/M2 occlusions and CTP were dichotomized into ICAD versus non-ICAD etiologies. Ischemic core (relative cerebral blood flow < 30%) and hypoperfusion volumes were estimated by automated CTP. RESULTS: A total of 250 patients met the inclusion criteria, comprised of 21 (8%) ICAD and 229 non-ICAD etiologies. Baseline characteristics were similar between groups, except for higher HbA1c levels (p < 0.01), LDL cholesterol (p < 0.01), systolic blood pressure (p < 0.01), and lower rate of atrial fibrillation (p < 0.01) in ICAD patients. There were no significant differences in volumes of baseline ischemic core (p = 0.54) among groups. ICAD patients had smaller Tmax > 4 s, Tmax > 6 s, and Tmax > 10 s absolute lesions, and a higher ratio of Tmax > 4 s/Tmax > 6 s volumes (median 2 [1.6-2.3] vs. 1.6 [1.4-2.0]; p = 0.02). A Tmax > 4 s/Tmax > 6 s ratio ≥2 showed specificity = 73%/sensitivity = 52% for ICAD and was observed in 47.6% of ICAD versus 26.1% of non-ICAD patients (p = 0.07). Clinical outcomes were comparable amongst groups. Multivariate logistic regression revealed that Tmax > 4 s/Tmax > 6 s ratio ≥2 (OR 3.75, 95% CI 1.05-13.14, p = 0.04), higher LDL cholesterol (OR 1.1, 95% CI 1.01-1.03, p = 0.01), and higher systolic pressure (OR 1.03, 95% CI 1.01-1.04, p = 0.01) were independently associated with ICAD. CONCLUSION: An automated CTP Tmax > 4 s/Tmax > 6 s ratio ≥2 profile was found independently associated with underlying ICAD LVOS.

Beyond Large Vessel Occlusion Strokes: Distal Occlusion Thrombectomy.

BACKGROUND AND PURPOSE: Endovascular therapy is the standard of care for the treatment of proximal large vessel occlusion strokes. Its safety and efficacy in the treatment of distal intracranial occlusions has not been well studied. METHODS: The data that support the findings of this study are available from the corresponding author on reasonable request. Retrospective review of a prospectively collected endovascular database (2010-2015, n=949) for all patients with distal intracranial occlusions treated endovascularly. Distal occlusions were defined as any segment of the anterior cerebral artery (ACA), posterior cerebral artery, or occlusion at or distal to the middle cerebral artery (MCA)-M3 opercular segment. RESULTS: Distal occlusions were treated in 69 patients. The mean age was 66.7±15.8 and 57% were male. Patients (29 [42%]) received intravenous tPA (tissue-type plasminogen activator). The median preprocedure National Institutes of Health Stroke Scale score was 18 (interquartile range, 13-23). The distal occlusion was the primary treatment location in 45 patients, in 23 patients the distal occlusion was treated as a rescue strategy after successful treatment of a proximal large vessel occlusion strokes, and 1 patient had both primary and rescue treatment. The locations of the primary cases were MCA-M3 (n=21), ACA alone (n=8), ACA with a concomitant MCA-M1 or MCA-M2 (n=10), ACA with a concomitant MCA-M3 (n=3), and posterior cerebral artery (n=3). The locations of the rescue cases were MCA-M3 (n=11), ACA (n=7), posterior cerebral artery (n=4), and both MCA-M3 and ACA (n=1). There was a single patient with primary ACA and MCA-M2 occlusions treated, who then had a rescue MCA-M3 thrombectomy addressed after initial reperfusion. The most common treatment modalities used were stent-retrievers (n=37, 54%), intra-arterial tPA (n=36, 52%), and thromboaspiration (n=31, 45%). Near complete or complete reperfusion of the distal territory (modified Treatment In Cerebral Ischemia [mTICI] 2b-3) was achieved in 57 cases (83%). Three parenchymal hematomas (4%) occurred in the territory of the treated distal occlusion with 2 of these patients also receiving intravenous tPA. At 90 days, 21 patients (30%) had a modified Rankin Scale score of 0 to 2 and 14 (20%) had died. CONCLUSIONS: Distal intracranial occlusions can be treated safely and successfully with endovascular therapy. These results need to be corroborated by larger prospective controlled studies.

Clinical and Imaging Outcomes of Endovascular Therapy in Patients with Acute Large Vessel Occlusion Stroke and Mild Clinical Symptoms.

BACKGROUND: The minimal stroke severity justifying endovascular intervention remains elusive. However, a significant proportion of patients presenting with large vessel occlusion stroke (LVOS) and mild symptoms go untreated and face poor outcomes. We aimed to evaluate the clinical outcomes of patients presenting with LVOS and low symptom scores (National Institutes of Health Stroke Scale [NIHSS] score ≤8) undergoing endovascular therapy (ET). METHODS: We performed a retrospective analysis of a prospectively collected ET database between September 2010 and March 2016. Endovascularly treated patients with LVOS and a baseline NIHSS score ≤8 were included. Baseline patient characteristics, procedural details, and outcome parameters were collected. Efficacy outcomes were the rate of good outcome (90-day modified Rankin Scale score 0-2) and of successful reperfusion (modified Treatment in Cerebral Infarction [mTICI] score 2b-3). Safety was assessed by the rate of parenchymal hematoma (parenchymal hematoma type 1 [PH-1] and parenchymal hematoma type 2 [PH-2]) and 90-day mortality. Logistic regression was used to identify predictors of good clinical outcomes. RESULTS: A total of 935 patients were considered; 72 patients with an NIHSS score ≤8 were included. Median [IQR] age was 61.5 years [56.2-73.0]; 39 patients (54%) were men. Mean (SD) baseline NIHSS score, computed tomography perfusion core volume, and ASPECTS were 6.3 (1.5), 7.5 mL (16.1), and 8.5 (1.3), respectively. Twenty-eight patients (39%) received intravenous tissue plasminogen activator. Occlusions locations were as follows: 29 (40%) proximal MCA-M1, 20 (28%) MCA-M2, 6 (8%) ICA terminus, and 9 (13%) vertebrobasilar. Tandem occlusion was documented in 7 patients (10%). Sixty-seven patients (93%) achieved successful reperfusion (mTICI score 2b-3); 52 (72%) had good 90-day outcomes. Mean final infarct volume was 32.2 ± 59.9 mL. Parenchymal hematoma occurred in 4 patients (6%). Ninety-day mortality was 10% (n = 7). Logistic regression showed that only successful reperfusion (OR 27.7, 95% CI 1.1-655.5, p = 0.04) was an independent predictor of good outcomes. CONCLUSION: Our findings demonstrate that ET is safe and feasible for LVOS patients presenting with mild clinical syndromes. Future controlled studies are warranted.

Selection Paradigms for Large Vessel Occlusion Acute Ischemic Stroke Endovascular Therapy.

BACKGROUND: Optimal patient selection methods for thrombectomy in large vessel occlusion stroke (LVOS) are yet to be established. We sought to evaluate the ability of different selection paradigms to predict favorable outcomes. METHODS: Review of a prospectively collected database of endovascular patients with anterior circulation LVOS, adequate CT perfusion (CTP), National Institutes of Health Stroke Scale (NIHSS) ≥10 from September 2010 to March 2016. Patients were retrospectively assessed for thrombectomy eligibility by 4 mismatch criteria: Perfusion-Imaging Mismatch (PIM): between CTP-derived perfusion defect and ischemic core volumes; Clinical-Core Mismatch (CCM): between age-adjusted NIHSS and CTP core; Clinical-ASPECTS Mismatch (CAM-1): between age-adjusted NIHSS and ASPECTS; Clinical-ASPECTS Mismatch (CAM-2): between NIHSS and ASPECTS. Outcome measures were inclusion rates for each paradigm and their ability to predict good outcomes (90-day modified Rankin Scale 0-2). RESULTS: Three hundred eighty-four patients qualified. CAM-2 and CCM had higher inclusion (89.3 and 82.3%) vs. CAM-1 (67.7%) and PIM (63.3%). Proportions of selected patients were statistically different except for PIM and CAM-1 (p = 0.19), with PIM having the highest disagreement. There were no differences in good outcome rates between PIM(+)/PIM(-) (52.2 vs. 48.5%; p = 0.51) and CAM-2(+)/CAM-2(-) (52.4 vs. 38.5%; p = 0.12). CCM(+) and CAM-1(+) had higher rates compared to nonselected counterparts (53.4 vs. 38.7%, p = 0.03; 56.6 vs. 38.6%; p = 0.002). The abilities of PIM, CCM, CAM-1, and CAM-2 to predict outcomes were similar according to the c-statistic, Akaike and Bayesian information criterion. CONCLUSIONS: For patients with NIHSS ≥10, PIM appears to disqualify more patients without improving outcomes. CCM may improve selection, combining a high inclusion rate with optimal outcome discrimination across (+) and (-) patients. Future studies are warranted.

ACCIDENTAL DUPLICATION: MR Imaging Findings in Children with Spasmus Nutans.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jaapos.2017.03.001. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Computed Tomographic Perfusion Selection and Clinical Outcomes After Endovascular Therapy in Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Different imaging paradigms have been used to select patients for endovascular therapy in stroke. We sought to determine whether computed tomographic perfusion (CTP) selection improves endovascular therapy outcomes compared with noncontrast computed tomography alone. METHODS: Review of a prospectively collected registry of anterior circulation stroke patients undergoing stent-retriever thrombectomy at a tertiary care center between September 2010 and March 2016. Patients undergoing CTP were compared with those with noncontrast computed tomography alone. The primary outcome was the shift in the 90-day modified Rankin scale (mRS). RESULTS: A total of 602 patients were included. CTP-selected patients (n=365, 61%) were younger (P=0.02) and had fewer comorbidities. CTP selection (n=365, 61%) was associated with a favorable 90-day mRS shift (adjusted odds ratio [aOR]=1.49; 95% confidence interval [CI], 1.06-2.09; P=0.02), higher rates of good outcomes (90-day mRS score 0-2: 52.9% versus 40.4%; P=0.005), modified Thrombolysis in Cerebral Infarction-3 reperfusion (54.8% versus 40.1%; P<0.001), smaller final infarct volumes (24.7 mL [9.8-63.1 mL] versus 34.6 mL [13.1-88 mL]; P=0.017), and lower mortality (16.6% versus 26.8%; P=0.005). When matched on age, National Institutes of Health Stroke Scale (NIHSS) score, and glucose (n=424), CTP remained associated with a favorable 90-day mRS shift (P=0.016), lower mortality (P=0.02), and higher rates of reperfusion (P<0.001). CTP better predicted functional outcomes in patients presenting after 6 hours (as assessed by comparison of logistic regression models: Akaike information criterion: 199.35 versus 287.49 and Bayesian information criterion: 196.71 versus 283.27) and those with an Alberta Stroke Program Early Computed Tomography Score ≤7 (Akaike information criterion: 216.69 versus 334.96 and Bayesian information criterion: 213.6 versus 329.94). CONCLUSIONS: CTP selection is associated with a favorable mRS shift in patients undergoing stent-retriever thrombectomy. Future prospective studies are warranted.

Magnetic resonance imaging findings in children with spasmus nutans.

BACKGROUND: Spasmus nutans (SN) is a rare pediatric ophthalmologic syndrome characterized by nystagmus, head bobbing, and abnormal head positioning. Historically, SN has been associated with underlying optic pathway gliomas (OPG); however, evidence of this association is based primarily on a small number of isolated case reports. Prior retrospective analyses have found the rate of OPG to be <2%, but these studies only intermittently used neuroimaging with computed tomography, which has limited sensitivity for detection of small lesions in the optic pathway. The purpose of this study was to investigate the association of SN with intracranial abnormalities, particularly OPG, using magnetic resonance imaging of the brain and orbits. METHODS: Neuroradiology databases at three institutions spanning January 2010 to May 2016 were queried for examinations ordered for evaluation of SN; MRI examinations of the brain and/or orbits were included and evaluated for OPG and other structural abnormalities. Medical records were reviewed to confirm a diagnosis of SN, presence of other underlying neurological disease, or preexisting diagnoses. RESULTS: A total of 40 patients with eligible MRI examinations were identified. None had optic nerve pathway gliomas. Two children had optic nerve hypoplasia; no other patients had optic pathway abnormalities. None had intracranial or orbital masses. MRI examinations were normal in 25 patients. CONCLUSIONS: This series represents the largest collection of MRI examinations for SN in the literature to date and shows no association between OPG and SN. In children presenting with SN but no other findings suggesting OPG or neurological abnormalities, neuroimaging may not be required.

Automated CT Perfusion for Ischemic Core Volume Prediction in Tandem Anterior Circulation Occlusions.

BACKGROUND/AIM: CT perfusion (CTP) predicts ischemic core volumes in acute ischemic stroke (AIS); however, assumptions made within the pharmacokinetic model may engender errors by the presence of tracer delay or dispersion. We aimed to evaluate the impact of hemodynamic disturbance due to extracranial anterior circulation occlusions upon the accuracy of ischemic core volume estimation with an automated perfusion analysis tool (RAPID) among AIS patients with large-vessel occlusions. METHODS: A prospectively collected, interventional database was retrospectively reviewed for all cases of endovascular treatment of AIS between September 2010 and March 2015 for patients with anterior circulation occlusions with baseline CTP and full reperfusion (mTICI3). RESULTS: Out of 685 treated patients, 114 fit the inclusion criteria. Comparison between tandem (n = 21) and nontandem groups (n = 93) revealed similar baseline ischemic core (20 ± 19 vs. 19 ± 25 cm(3); p = 0.8), Tmax >6 s (175 ± 109 vs. 162 ± 118 cm(3); p = 0.6), Tmax >10 s (90 ± 84 vs. 90 ± 91 cm(3); p = 0.9), and final infarct volumes (45 ± 47 vs. 37 ± 45 cm(3); p = 0.5). Baseline core volumes were found to correlate with final infarct volumes for the tandem (r = 0.49; p = 0.02) and nontandem (r = 0.44; p < 0.01) groups. The mean absolute difference between estimated core and final infarct volume was similar between patients with and those without (24 ± 41 vs. 17 ± 41 cm(3); p = 0.5) tandem lesions. CONCLUSIONS: The prediction of baseline ischemic core volumes through an optimized CTP analysis employing rigorous normalization, thresholding, and voxel-wise analysis is not significantly influenced by the presence of underlying extracranial carotid steno-occlusive disease in large-vessel AIS.

Large Volumes of Critically Hypoperfused Penumbral Tissue Do Not Preclude Good Outcomes After Complete Endovascular Reperfusion: Redefining Malignant Profile.

BACKGROUND AND PURPOSE: Acute ischemic stroke patients with large volumes of severe hypoperfusion (Tmax>10 s>100 mL) on magnetic resonance imaging have a higher likelihood of intracranial hemorrhage and poor outcomes after reperfusion. We aim to evaluate the impact of the extent of Tmax>10 s CTP lesions in patients undergoing successful treatment. METHODS: Retrospective database review of endovascular acute ischemic stroke treatment between September 2010 and March 2015 for patients with anterior circulation occlusions with baseline RAPID CTP and full reperfusion (mTICI 3). The primary outcome was the impact of the Tmax>10 s lesion spectrum on infarct growth. Secondary safety and efficacy outcomes included parenchymal hematomas and good clinical outcomes (90-day modified Rankin Scale score, 0-2). RESULTS: Of 684 treated patients, 113 patients fit the inclusion criteria. Tmax>10 s>100 mL patients (n=37) had significantly higher baseline National Institutes of Health Stroke Scale (20.7±3.8 versus 17.0±5.9; P<0.01), more internal carotid artery terminus occlusions (29% versus 9%; P=0.02), and larger baseline (38.6±29.6 versus 11.7±15.8 mL; P<0.01) and final (60.7±60.0 versus 29.4±33.9 mL; P<0.01) infarct volumes when compared with patients without Tmax>10 s>100 mL (n=76); however, the 2 groups were otherwise well balanced. There were no significant differences in infarct growth (22.1±51.6 versus 17.8±32.4 mL; P=0.78), severe intracranial hemorrhage (PH2: 2% versus 4%; P=0.73), good outcomes (90-day mRS score, 0-2: 56% versus 59%; P=0.83), or 90-day mortality (16% versus 7%; P=0.28). On multivariate analysis, only baseline National Institutes of Health Stroke Scale (odds ratio, 1.19; 95% confidence interval, 1.06-1.34; P<0.01) and baseline infarct core volume (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P<0.01) were independently associated with Tmax>10 s>100 mL. There was no association between Tmax>10 s>100 mL with any PH, good outcome, or infarct growth. CONCLUSIONS: In the setting of limited baseline ischemic cores, large Tmax>10 s lesions on computed tomographic perfusion do not seem to be associated with a higher risk of parenchymal hematomas and do not preclude good outcomes in patients undergoing endovascular reperfusion with contemporary technology.

Utilization of Workflow Process Maps to Analyze Gaps in Critical Event Notification at a Large, Urban Hospital.

Stroke care is a time-sensitive workflow involving multiple specialties acting in unison, often relying on one-way paging systems to alert care providers. The goal of this study was to map and quantitatively evaluate such a system and address communication gaps with system improvements. A workflow process map of the stroke notification system at a large, urban hospital was created via observation and interviews with hospital staff. We recorded pager communication regarding 45 patients in the emergency department (ED), neuroradiology reading room (NRR), and a clinician residence (CR), categorizing transmissions as successful or unsuccessful (dropped or unintelligible). Data analysis and consultation with information technology staff and the vendor informed a quality intervention-replacing one paging antenna and adding another. Data from a 1-month post-intervention period was collected. Error rates before and after were compared using a chi-squared test. Seventy-five pages regarding 45 patients were recorded pre-intervention; 88 pages regarding 86 patients were recorded post-intervention. Initial transmission error rates in the ED, NRR, and CR were 40.0, 22.7, and 12.0 %. Post-intervention, error rates were 5.1, 18.8, and 1.1 %, a statistically significant improvement in the ED (p < 0.0001) and CR (p = 0.004) but not NRR (p = 0.208). This intervention resulted in measureable improvement in pager communication to the ED and CR. While results in the NRR were not significant, this intervention bolsters the utility of workflow process maps. The workflow process map effectively defined communication failure parameters, allowing for systematic testing and intervention to improve communication in essential clinical locations.