Bridging Therapy or IV Thrombolysis in Minor Stroke with Large Vessel Occlusion.

OBJECTIVE: Whether bridging therapy (intravenous thrombolysis [IVT] followed by endovascular treatment) is superior to IVT alone in minor stroke with large vessel occlusion (LVO) is unknown. METHODS: Multicentric retrospective observational study including, in intention-to-treat, consecutive IVT-treated minor strokes (National Institutes of Health Stroke Scale [NIHSS] ≤ 5) with LVO, with or without additional mechanical thrombectomy. Propensity-score (inverse probability of treatment weighting) was used to reduce baseline between-groups differences. The primary outcome was excellent outcome, that is, modified Rankin score 0 to 1 at 3 months follow-up. RESULTS: Overall, 598 patients were included (214 and 384 in the bridging therapy and IVT groups, respectively). Following propensity-score weighting, the distribution of baseline clinical and radiological variables was similar across the two patient groups. Compared with IVT alone, bridging therapy was not associated with excellent outcome (odds ratio [OR] = 0.96; 95% confidence interval [CI] = 0.75-1.24; p = 0.76), but was associated with symptomatic intracranial hemorrhage (OR = 3.01; 95% CI = 1.77-5.11; p < 0.0001). Occlusion site was a strong modifier of the effect of bridging therapy on outcome (pinteraction < 0.0001), with bridging therapy associated with higher odds of excellent outcome in proximal M1 (OR = 3.26; 95% CI = 1.67-6.35; p = 0.0006) and distal M1 (OR = 1.69; 95% CI = 1.01-2.82; p = 0.04) occlusions, but with lower odds of excellent outcome for M2 (OR = 0.53; 95% CI = 0.38-0.75; p = 0.0003) occlusions. Bridging therapy was associated with higher rates of symptomatic intracranial hemorrhage in M2 occlusions only (OR = 4.40; 95% CI = 2.20-8.83; p < 0.0001). INTERPRETATION: Although overall outcomes were similar in intended bridging therapy as compared to intended IVT alone in minor strokes with LVO, our results suggest that intended bridging therapy may be beneficial in M1 occlusions, whereas the benefit-risk profile may favor IVT alone in M2 occlusions. ANN NEUROL 2020 ANN NEUROL 2020;88:160-169.

Relationships between brain perfusion and early recanalization after intravenous thrombolysis for acute stroke with large vessel occlusion.

In large vessel occlusion (LVO) stroke, it is unclear whether severity of ischemia is involved in early post-thrombolysis recanalization over and above thrombus site and length. Here we assessed the relationships between perfusion parameters and early recanalization following intravenous thrombolysis administration in LVO patients. From a multicenter registry, we identified 218 thrombolysed LVO patients referred for thrombectomy with both (i) pre-thrombolysis MRI, including diffusion-weighted imaging (DWI), T2*-imaging, MR-angiography and dynamic susceptibility-contrast perfusion-weighted imaging (PWI); and (ii) evaluation of recanalization on first angiographic run or non-invasive imaging ≤ 3 h from thrombolysis start. Infarct core volume on DWI, PWI-DWI mismatch volume and hypoperfusion intensity ratio (HIR; defined as Tmax ≥ 10 s volume/ Tmax ≥ 6 s volume, low HIR indicating milder hypoperfusion) were determined using a commercially available software. Early recanalization occurred in 34 (16%) patients, and multivariable analysis was associated with lower HIR (P = 0.006), shorter thrombus on T2*-imaging (P < 0.001) and more distal occlusion (P = 0.006). However, the relationship between HIR and early recanalization was robust only for thrombus length <14 mm. In summary, the present study disclosed an association between lower HIR and early post-thrombolysis recanalization. Early post-thrombolysis recanalization is therefore determined not only by thrombus site and length but also by severity of ischemia.

Better Collaterals Are Independently Associated With Post-Thrombolysis Recanalization Before Thrombectomy.

Background and Purpose- In acute stroke patients with large vessel occlusion, the goal of intravenous thrombolysis (IVT) is to achieve early recanalization (ER). Apart from occlusion site and thrombus length, predictors of early post-IVT recanalization are poorly known. Better collaterals might also facilitate ER, for instance, by improving delivery of the thrombolytic agent to both ends of the thrombus. In this proof-of-concept study, we tested the hypothesis that good collaterals independently predict post-IVT recanalization before thrombectomy. Methods- Patients from the registries of 6 French stroke centers with the following criteria were included: (1) acute stroke with large vessel occlusion treated with IVT and referred for thrombectomy between May 2015 and March 2017; (2) pre-IVT brain magnetic resonance imaging, including diffusion-weighted imaging, T2*, MR angiography, and dynamic susceptibility contrast perfusion-weighted imaging; and (3) ER evaluated ≤3 hours from IVT start on either first angiographic run or noninvasive imaging. A collateral flow map derived from perfusion-weighted imaging source data was automatically generated, replicating a previously validated method. Thrombus length was measured on T2*-based susceptibility vessel sign. Results- Of 224 eligible patients, 37 (16%) experienced ER. ER occurred in 10 of 83 (12%), 17 of 116 (15%), and 10 of 25 (40%) patients with poor/moderate, good, and excellent collaterals, respectively. In multivariable analysis, better collaterals were independently associated with ER ( P=0.029), together with shorter thrombus ( P<0.001) and more distal occlusion site ( P=0.010). Conclusions- In our sample of patients with stroke imaged with perfusion-weighted imaging before IVT and intended for thrombectomy, better collaterals were independently associated with post-IVT recanalization, supporting our hypothesis. These findings strengthen the idea that advanced imaging may play a key role for personalized medicine in identifying patients with large vessel occlusion most likely to benefit from IVT in the thrombectomy era.

Thrombus Length Predicts Lack of Post-Thrombolysis Early Recanalization in Minor Stroke With Large Vessel Occlusion.

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy: Incidence, Predictors, and Prediction Scores.

Background and Purpose­Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods­Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance­ or computed tomography­based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results­In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography­based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions­The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

Susceptibility-Diffusion Mismatch in Hyperacute Stroke: Correlation with Perfusion-Diffusion Mismatch and Clinical Outcome.

BACKGROUND: A prominent vein (PV) on susceptibility-weighted imaging (SWI) was recently proposed to be a marker of the penumbra. We aimed to compare the utility of SWI and perfusion-weighted imaging (PWI) sequences for the evaluation of the penumbra in hyperacute middle cerebral artery (MCA) stroke, and to determine whether SWI-DWI mismatch is a neuroimaging marker of clinical outcome. METHODS: A total of 149 consecutive patients with MCA stroke were prospectively enrolled. Magnetic resonance imaging (MRI) was performed within 6 hours of the onset of stroke. The ASPECTS values on diffusion-weighted imaging (DWI), PWI (delayed mean transit time), and SWI (visualization of PVs) were calculated by 2 independent raters. Correlation between PWI-ASPECTS and SWI-ASPECTS was calculated with the Pearson coefficient. Reliability of the PV rating system was calculated by an intraclass correlation coefficient (ICC). Favorable outcome was defined as a modified Rankin Scale score of 0-2 at 3 months for the 88 patients who received thrombolytic therapy. RESULTS: The ASPECTS-SWI and ASPECTS-PWI scores showed a good correlation (Pearson coefficient of .69, P <.001). The reproducibility between the findings of the junior and the senior radiologists was excellent with an ICC of .89 (confidence interval of 95% (IC95): .85-.92, P <.001). However, neither SWI-DWI mismatch nor PWI-SWI mismatch was associated with clinical outcome. CONCLUSION: SWI and PWI were complementary but not commutable for the assessment of the penumbra. Susceptibility-diffusion mismatch was not found in this study to have predictive value for stroke outcome.

Functional Outcome of Hemorrhagic Transformation after Thrombolysis for Ischemic Stroke: A Prospective Study.

BACKGROUND/AIMS: Hemorrhagic transformation (HT) is usually taken into account when symptomatic, but the role of asymptomatic HT is not well known. The aim of our study was to evaluate the link between HT after thrombolysis for ischemic stroke and functional outcome at 3 months, with particular emphasis on asymptomatic HT. METHODS: Our study was performed prospectively between June 2012 and June 2013 in the Stroke Unit of the University Hospital Center of Tours (France). All patients treated with intravenous thrombolysis were consecutively included. HT was classified on susceptibility-weighted imaging (SWI) with 3-tesla MRI at 7 ± 3 days after treatment. We evaluated functional outcome at 3 months using the modified Rankin Scale (mRS). Dependency was defined as an mRS score of ≥ 3. RESULTS: After 1 year, 128 patients had received thrombolytic therapy for ischemic stroke, of whom 90 patients underwent both 3-tesla MRI and SWI at day 7. Fifty-two had HT, including 8 symptomatic cases. At 3 months, 68% of those patients were dependent compared to 31% of patients without HT [OR 4.6 (1.9-11.4), p = 0.001]. In asymptomatic HT, the rate was 62% [OR 3.5 (1.4-8.9), p = 0.007], but did not reach significance after adjustment for stroke severity. DISCUSSION: Our study found no statistically significant effect of HT on outcome after adjustment for initial stroke severity. However, the innocuousness of HT is not certain, and only few studies have already highlighted the increased risk of dependency. Using 3-tesla MRI with SWI allows us to increase the detection rate of small hemorrhage. CONCLUSION: HT after thrombolysis is very frequent on SWI, but the initial stroke severity is an important predictor to assess the role of HT for patient outcome.

Quality of Life After Off-Label Thrombolysis for Ischemic Stroke in Elderly Patients.

INTRODUCTION: The use of intravenous thrombolysis with alteplase for ischemic stroke in Europe is restricted to subjects aged <80 years. Recent studies have reported the efficacy and safety of alteplase in older patients. However, data concerning the quality of life (QOL) of these elderly subjects are sparse. OBJECTIVES: The aim of this study was to compare the QOL of patients aged ≥80 years with that of patients aged <80 years at 3 months after thrombolysis. METHOD: This was a prospective study comprising French-speaking patients aged >18 years treated using thrombolytic therapy for ischemic stroke at the Hospital of Tours (Tours, France) between June 2012 and January 2013. QOL was assessed using the Stroke Impact Scale (SIS). The presence of mood disorders or cognitive impairments was also assessed. RESULTS: QOL was evaluated for 62 subjects among the 83 enrolled patients who received thrombolytic treatment; 21 patients were aged >80 years. Concerning scores on the SIS, using a multivariate analysis, only the memory and thinking score was significantly and negatively associated with the elderly population [odds ratio (OR) 0.036, 95% confidence interval (CI) 0.004-0.339; p = 0.004]. No significant difference was observed among all the other QOL scores. Neurological recovery and functional status did not differ between the two groups. CONCLUSION: QOL after intravenous thrombolysis in the elderly population was comparable to that of younger subjects. Despite its small sample size, this study showed promising results in favor of intravenous thrombolysis in the elderly population and highlighted the importance of systematic screening for post-stroke cognitive impairment, particularly in this population.

Diagnostic and therapeutic value of echocardiography during the acute phase of ischemic stroke.

BACKGROUND: Echocardiography is routinely used to identify potential cardiac sources of embolism (CSE) in the acute phase of ischemic stroke (IS). We know that transoesophageal echography (TEE) is superior to detect CSE than transthoracic echography (TTE). However, the indications of each technique remain controversial. We aimed to evaluate the diagnostic yield (DY) and the therapeutic impact (TI) of echocardiography (both techniques combined) in IS and to analyze impact of clinical factors on these values. METHODS: We included consecutive IS patients over a period of 22 months. All patients underwent TTE, and selected patients (young or with a high suspicion of cardioembolic origin) then underwent TEE. DY (detection of CSE) and TI (introduction of oral anticoagulant, closure of patent foramen ovale and targeted cardiologic consultation) were systematically evaluated. RESULTS: We analyzed 300 patients (mean age 61 years). All patients underwent TTE and 127 patients underwent TTE and TEE. Echocardiography overall detected CSE in 22% of patients with a TI in 11% of all cases. The TI was higher in patients less than or equal to 55 years of age. In contrast to other studies, the DY and TI of echocardiography were not associated with vascular risk factors. CONCLUSIONS: Echocardiography, as currently practiced in our stroke unit, allows detection of CSE in one patient in five, and leads to change in therapy in half of these cases. Our results suggest that TTE should be used for all patients admitted for IS, and to limit the use of TEE to younger patients.

Could (18) F-DPA-714 PET imaging be interesting to use in the early post-stroke period?

BACKGROUND: Cerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis. If administered shortly after the first symptoms manifest themselves, IV thrombolysis has been shown to increase the functional prognosis by restoring brain reperfusion. However, a better understanding of the pathophysiology of stroke should help to identify potential new therapeutic targets. Stroke is known to induce an inflammatory brain reaction that involves overexpression of the 18-kDa translocator protein (TSPO) in glial cells and infiltrated leukocytes, which can be visualised by positron emission tomography (PET). We aimed to evaluate post-stroke neuroinflammation using the PET TSPO radioligand (18) F-DPA-714. METHODS: Nine patients underwent (18) F-DPA-714 PET and magnetic resonance imaging (MRI) between 8 and 18 days after the ictus. Co-registration of MRI and PET images was used to define three volumes of interest (VOIs): core infarction, contralateral region, and cerebellum ipsilateral to the stroke lesion. Time activity curves were obtained from each VOI, and ratios of mean and maximum activities between the VOIs were calculated. RESULTS: We observed an increased uptake of (18) F-DPA-714 co-localised with the infarct tissue and extension beyond the region corresponding to the damage in the blood brain barrier. No correlation was identified between (18) F-DPA-714 uptake and infarct volume. (18) F-DPA-714 uptake in ischemic lesion (mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood) slowly decreased from 10 min pi to the end of the PET acquisition, remaining higher than that in both contralateral region and ipsilateral cerebellum. CONCLUSION: Our results show that (18) F-DPA-714 uptake after acute ischemia is mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood. We also demonstrated that the kinetics of (18) F-DPA-714 differs in injured tissue compared to normal tissue. Therefore, (18) F-DPA-714 may be useful in assessing the extent of neuroinflammation associated with acute stroke and could also help to predict clinical outcomes and functional recovery, as well as to assess therapeutic strategies, such as the use of neuroprotective/anti-inflammatory drugs.

Is early surgical revascularization of symptomatic carotid stenoses safe?

BACKGROUND: The objective of this exploratory study was to determine the rate of the complications of early surgery for symptomatic carotid stenosis, in 2 centers of Western France. METHODS: Between January 2011 and January 2013, we prospectively enrolled all the patients admitted for transient ischemic accident (TIA) or minor stroke (Rankin ≤ 3) associated with an ipsilateral carotid stenosis >50% (North American Symptomatic Carotid Endarterectomy Trial) and operated before the 14th day following the neurologic event at the University hospitals of Angers and Tours. The demographic data (gender, age, and medical history) and the characteristics of the procedures were recorded. The rates of stroke, TIA, and postoperative deaths defined the cumulative morbidity and mortality rate (CMMR) of the study. RESULTS: Ninety-one patients were included in the study. They presented 27 TIAs and 64 strokes. The average elapsed time between the neurologic event and surgery was 9.8 days. During this time, 10 patients, that is, 11% of the operated cohort, presented a new ischemic neurologic event while waiting for surgery. Surgical operations consisted of 56 eversions (61.5%), 32 endarterectomies with patch (35.1%), 2 bypasses, and 1 direct closure. The CMMR reached 3.3%. Two patients presented with a stroke and 1 patient died of a cardiologic cause during the postoperative period. CONCLUSIONS: This study confirms the interest of an early surgery for symptomatic carotid stenoses with a Rankin score of ≤3. The risk of recurrence of a cerebral ischemic accident during the preoperative period remains high.

CADASIL and ALS: a link?

We report the case of a 66-year-old female who presented with dysarthria and dysphonia. Brain MRI abnormalities showed confluent white matter lesions and subcortical lacunar infarcts, suggesting cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), confirmed by the presence of a heterozygous mutation in the Notch3 gene. Clinical signs and course were consistent with amyotrophic lateral sclerosis (ALS) as was the electromyographic pattern. The possible pathogenic role for a mutation in the Notch3 gene is discussed considering recent data on hypoxia in the pathophysiology of ALS.

Abrupt onset of disturbed vigilance, bilateral third nerve palsy and masturbating behaviour: a rare presentation of stroke.

The clinical presentation of stroke usually includes sensory-motor impairment, cranial nerve palsies, or cognitive dysfunction. Disorders in behaviour are less frequently seen. The case of a patient with a very disturbing presentation, which included a disturbance in vigilance, bilateral third nerve palsy and masturbating behaviour, is presented. The topography of the lesions and its implications on the deficits observed are discussed.

Epilepsy and language development: the continuous spike-waves during slow sleep syndrome.

BACKGROUND: Continuous spike-waves during slow sleep syndrome (CSWSS) is a rare epileptic syndrome occurring in children, which is characterized by the association of epilepsy, neuropsychological disorders, and abnormal paroxysmal electroencephalographic (EEG) discharges activated by sleep. Language can be affected but, to date, language disorders and their long-term outcome have been documented only rarely. PURPOSES: Description of language impairment in patients with the CSWSS. METHODS: We performed a detailed language testing in 10 right-handed children and adolescents with the CSWSS. Their pragmatic performance was compared to that of a control population of 36 children aged 6-10 years. RESULTS: Patients with CSWSS had lower scores in tests measuring their lexical, morphosyntactic, and pragmatic skills compared to controls. Comprehension remains unaffected. In addition, language impairment was found to be just as severe in patients in remission as those still in an active phase. CONCLUSIONS: We found severe language impairments in lexical and syntactic skills. The language profile is different from that observed in the Landau-Kleffner syndrome. Moreover patients in remission and those in an active phase of the CSWSS have the same language impairment profiles. This confirms the poor long-term neuropsychological prognosis. Our results raise points about the relationship between epileptic activity and language development. This pilot study underscores the need to assess language, and especially pragmatic skills, and to study long-term outcome in such childhood epileptic syndromes.