Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke.

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P<0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P<0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.

Perfusion computed tomography-guided intravenous thrombolysis for acute ischemic stroke beyond 4.5 hours: a case-control study.

BACKGROUND: Extending the therapeutic window of intravenous thrombolysis for acute ischemic stroke beyond the established 4.5-hour limit is of critical importance in order to increase the proportion of thrombolysed stroke patients. In this setting, the capacity of MRI to select acute stroke patients for reperfusion therapies in delayed time windows has been and is being tested in clinical trials. However, whether the more available and cost-effective perfusion computed tomography (PCT) may be useful to select candidates for delayed intravenous thrombolysis remains largely unexplored. We aimed to evaluate the safety and efficacy of PCT-guided intravenous thrombolysis beyond 4.5 h after stroke onset. METHODS: We prospectively studied all consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA) in our stroke unit between January 2008 and December 2010. Patients treated within 0- 4.5 h were treated according to non-contrast CT (NCCT) criteria. Beyond 4.5 h, patients received intravenous tPA according to PCT criteria, i.e. an infarct core on cerebral blood volume (CBV) maps not exceeding one third of the middle cerebral artery (MCA) territory and tissue at risk as defined by mean transit time-CBV mismatch greater than 20%. Predetermined primary endpoints were symptomatic hemorrhagic transformation and favorable long-term outcome, while early neurological improvement and MCA recanalization were considered secondary endpoints. Statistical analysis included bivariate comparisons between the two groups for each endpoint and logistic regression models when significance was found in bivariate analyses. This study was approved by our local ethics committee. RESULTS: A total of 245 patients received intravenous thrombolysis. After the groups were matched by baseline National Institutes of Health Stroke Scale score, 172 patients treated at <4.5 h and 43 patients treated at >4.5 h were finally included. Early and late groups were comparable regarding baseline variables; only cardioembolic etiology was more frequent in the >4.5 h group. Rates of symptomatic hemorrhagic transformation (2.9% in the <4.5 h group vs. 2.3% in the >4.5 h group; p = 1.0) and good long-term outcome (64.5 vs. 60.5%, respectively; p = 0.620) were similar between the groups. However, delayed intravenous thrombolysis was independently associated with a worse early clinical course [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.04-4.1; p = 0.038] and lower 2-hour MCA recanalization rates (OR 0.4, 95% CI 0.17-0.92; p = 0.03). CONCLUSION: Primary safety and efficacy endpoints were comparable between the early and delayed thrombolysis groups. The results of our exploratory study may justify a randomized clinical trial to test the safety and efficacy of PCT-guided intravenous thrombolysis in acute ischemic stroke patients presenting beyond 4.5 h from symptom onset.

Quantified ischemic core's radiological hypodensity and risk of parenchymal hematoma in > 4.5 h-window stroke thrombectomy.

We aimed to study the relationship between the ischemic core's (IC) radiological hypodensity and the risk of parenchymal haematoma after endovascular therapy (EVT) in acute ischemic stroke (AIS) presenting > 4.5 h from onset. We studied AIS patients with a proximal anterior circulation occlusion > 4.5 h from symptoms onset treated with primary EVT. The IC regions of interest (ROI) were manually delineated on pretreatment CT within the affected hemisphere and their specular ROIs on the unaffected side. IC hypodensity ratio was calculated by dividing mean Hounsfield Unit (HU) value from all ROIs in affected/unaffected hemisphere. Primary endpoint: parenchymal hematoma (PH) type hemorrhagic transformation. Secondary: poor long-term clinical outcome. From May 2015 to November 2018, 648 consecutive AIS patients received reperfusion therapies and 107 met all inclusion criteria. PH after EVT was diagnosed in 33 (31%) patients. In bivariate analyses, IC hypodensity ratio (p < 0.001) and minimum HU value (p = 0.008) were associated with PH. A lower IC hypodensity ratio [OR < 0.001 (< 0.001-0.116) p 0.016] predicted PH but not poor clinical outcome in multivariable logistic regression models. A lower IC radiological density predicted a higher risk of PH in > 4.5 h-window AIS patients treated with primary EVT, although it was not independently associated with a worse clinical outcome.

Yield of atrial fibrillation detection with Textile Wearable Holter from the acute phase of stroke: Pilot study of Crypto-AF registry.

BACKGROUND: We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry. METHODS: We monitored cryptogenic stroke patients from stroke onset (<3days) continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0-3, 4-15 and 16-28days). RESULTS: The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3-5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR [521-639]) vs. Lead 566 (IQR [397-620]) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR [419-557]) vs. Lead (336h (IQR [140-520]) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0-3days); 21.7% (4-15days) and 19% (16-28days). CONCLUSIONS: 28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF.

Insulin resistance is associated with a poor response to intravenous thrombolysis in acute ischemic stroke.

OBJECTIVE: Insulin resistance (IR) may not only increase stroke risk, but could also contribute to aggravate stroke prognosis. Mainly through a derangement in endogenous fibrinolysis, IR could affect the response to intravenous thrombolysis, currently the only therapy proved to be efficacious for acute ischemic stroke. We hypothesized that high IR is associated with more persistent arterial occlusions and poorer long-term outcome after stroke thrombolysis. RESEARCH DESIGN AND METHODS: We performed a prospective, observational, longitudinal study in consecutive acute ischemic stroke patients presenting with middle cerebral artery (MCA) occlusion who received intravenous thrombolysis. Patients with acute hyperglycemia (≥155 mg/dL) receiving insulin were excluded. IR was determined during admission by the homeostatic model assessment index (HOMA-IR). Poor long-term outcome, as defined by a day 90 modified Rankin scale score ≥ 3, was considered the primary outcome variable. Transcranial Duplex-assessed resistance to MCA recanalization and symptomatic hemorrhagic transformation were considered secondary end points. RESULTS: A total of 109 thrombolysed MCA ischemic stroke patients were included (43.1% women, mean age 71 years). The HOMA-IR was higher in the group of patients with poor outcome (P = 0.02). The probability of good outcome decreased gradually with increasing HOMA-IR tertiles (80.6%, 1st tertile; 71.4%, 2nd tertile; and 55.3%, upper tertile). A HOMA-IR in the upper tertile was independently associated with poor outcome when compared with the lower tertile (odds ratio [OR] 8.54 [95% CI 1.67-43.55]; P = 0.01) and was associated with more persistent MCA occlusions (OR 8.2 [1.23-54.44]; P = 0.029). CONCLUSIONS: High IR may be associated with more persistent arterial occlusions and worse long-term outcome after acute ischemic stroke thrombolysis.

La tomografía computarizada de perfusión permite superar importantes criterios de exclusión SITS-MOST para la trombólisis endovenosa del infarto cerebral / Perfusion computed tomography makes it possible to overcome important SITS-MOST exclusion criteria for the endovenous thrombolysis of cerebral infarction

Objetivo. Estudiar la frecuencia, seguridad y eficacia de la trombólisis intravenosa guiada por tomografía computarizadade perfusión (TCP) mediante la identificación de tejido cerebral rescatable en ictus isquémicos a priori excluidos por criteriostradicionales (SITS-MOST y ECASS-3). Pacientes y métodos. Incluimos ictus isquémicos no lacunares consecutivos. Tras tomografía convencional, se realizó TCP en los siguientes supuestos: inicio 4,5-6 h, desconocido o al despertar, signos precoces de infarto extenso, ictus menoro grave, e inicio con crisis epiléptica o pérdida de conciencia. Se indicó alteplasa intravenosa 0,9 mg/kg si: ausencia de infarto establecido en tomografía simple, core en mapa de volumen sanguíneo cerebral menor de un tercio del territorio de la arteria cerebral media, mismatch > 20% entre mapas de tiempo de tránsito medio y volumen sanguíneo cerebral, y consentimiento informado. Las variables pronósticas fueron parámetros de seguridad-eficacia del SIST-MOST.Resultados. De mayo de 2009 a abril de 2010, 66 pacientes con ictus isquémico a priori no candidatos para trombólisis intravenosa fueron estudiados con TCP. Las indicaciones fueron: > 4,5 h en 18 pacientes, ictus del despertar o inicio desconocido en 25, signos precoces extensos en 6, inicio con crisis epilépticas en 11, e ictus menor (escala del ictus del NationalInstitute of Health < 4) en seis. Veintinueve (44%) recibieron trombólisis intravenosa de acuerdo con los hallazgos de la TCP. De ellos, 2 (6,9%) sufrieron transformación hemorrágica sintomática y 18 (62,1%) alcanzaron un Rankin igual o menor a 2 al tercer mes. Conclusión. Una alta proporción de pacientes con ictus isquémico, excluibles a priori según criterios tradicionales, podríarecibir trombólisis intravenosa de manera eficaz-segura utilizando protocolo de TCP. No obstante, estos hallazgos necesitaríanconfirmación en ensayos clínicos aleatorizados (AU)

Aim. To study the frequency, safety and efficacy of perfusion computed tomography (PCT), through identification of brain tissue-at-risk, to guide intravenous thrombolysis in stroke patients with regulatory exclusion criteria (SITS-MOST andECASS-3). Patients and methods. We studied consecutive acute non-lacunar ischemic stroke patients. After conventional CT wasconsidered eligible, PCT was performed in the following circumstances: 4.5 to 6 h window, wake-up stroke or unknowntime of onset; extent early infarct signs on CT; minor or severe stroke; seizures or loss of consciousness. Intravenous 0.9 mg/kg alteplase was indicated if: cerebral blood volume lesion covered < 1/3 of middle cerebral artery territory;mismatch > 20% between mean transit time and cerebral blood volume maps existed; and informed consent. SITS-MOST safety-efficacy parameters were used as endpoint variables. Results. Between May 2009-April 2010, 66 hyperacute ischemic stroke patients a priori not eligible for intravenous thrombolysis underwent PCT. Indications were: > 4.5 h in 18 patients, wake up stroke or unknown onset in 25, extentinfarct signs in 6, seizures at onset in 11, and minor stroke (NIHSS < 4) in 6. Twenty-nine (44%) of them finally received intravenous thrombolysis. Symptomatic hemorrhagic transformation occurred in 2 (6.9%) patient and 18 (62.1%) achieved a modified Rankin scale score equal or less than 2 on day 90. Conclusion. A high proportion of acute stroke patients with SITS-MOST and ECASS-3 exclusion criteria can be safely andefficaciously treated with intravenous thrombolysis using a PCT selection protocol. However randomized control trials willbe needed to confirm our results (AU)