70 e-Letters

  • Reply

    Dear Editor,
    We would like the thank Drs. Berndt, Zimmer, Kaesmacher, and Boeckh-Behrens for their interest in our study titled “Clot permeability and histopathology: Is a clot’s perviousness on CT imaging correlated with its histologic composition?” We read their letter with interest. The authors have been pioneers in stroke clot analysis and we greatly respect their academic rigor and expertise.

    While we agree that there are certainly some methodological differences between our two studies, we do not believe that these are to blame for the differences in results. Rather, we feel that the observed differences in results between our studies could be due to differences in our patient populations.

    Our group has previously shown that there is indeed a correlation between clot composition and etiology. In a recently published article in Stroke we found that large artery atherosclerosis clots were more likely to be platelet rich than those of a cardioembolic origin.1 To date, however, we have yet to find any definite correlation between etiology and RBC density or fibrin density, and we think it is too early to make any definite conclusions on the association between clot composition and etiology.

    We agree that the association between perviousness, clot composition, etiology and clinical outcome is not conclusively clarified yet, and hence warrants further research, especially in a larger patient group in a multi-centric setting. Currently, our gr...

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  • Letter by Berndt et al. Regarding Article “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?”

    Recently, we have read with great interest the article by Benson et al. “Clot permeability and histopathology: is a clot’s perviousness on CT imaging correlated with its histologic composition?” [1].
    It is pleasing, that research in the field of thrombus characterization by perviousness and its association to thrombus composition is emerging. Benson et al. report a higher clot perviousness for RBC rich clots in comparison to fibrin dominant thrombi [1]. These results stand in contrast to our previously published study [2], that shows an association between perviousness and fibrin rich clots. We furthermore validated those findings in a large collective by showing a relationship between perviousness and cardioembolic origin. Further research to this special topic is scarce. However, there is another experimental and therefore well controllable study on artificial clots, that showed a strong association of fibrin content and contrast agent uptake [3], similar as it has been shown for in vivo thrombi in our study [2].
    Consequently, these contradictory results demand further explanations. In our opinion, the differing results might be caused by methodological differences, which we want to discuss.
    First, thrombus localizations should be taken into account. Benson et al. used a collective of 57 thrombi with different thrombus locations (38 MCA, 6 ICA, 5 ICA/MCA, 3 basilar artery, 2 posterior cerebral artery, 2 ICA/MCA/ACA, 1 ICC/MCA). It is at least questiona...

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  • Contraindicated micro catheters

    The authors describe two endovascular techniques for delivering IA chemotherapy to retinoblastoma patients. Technique A where a 1.2 Fr or 1.5 Fr micro catheter with continuous verapamil flush is advanced without a guide and technique B where a1.5 Fr or 1.7 Fr micro catheter is advanced within a 4 Fr catheter, through a 4 Fr sheath. We usually use a no sheath technique, using a 4Fr diagnostic catheter as a guide catheter for neonatal and pediatric cases. Most importantly, we do not use Echelon or Marathon micro catheters in neonatal and pediatric patients because their use is contraindicated per "instructions for use".

  • Early neurological improvement following mechanical thrombectomy with general anesthesia

    We read with interest the article by Soize et al. “Can early neurological improvement after mechanical thrombectomy be used as a surrogate for final stroke outcome?”[1] Based on their results, the authors concluded that early neurological improvement (ENI) 24 hours after thrombectomy is a straightforward surrogate of long-term outcome. However, all patients in this study were treated with conscious sedation (CS), and not general anesthesia (GA). The residual effects of GA may mask ENI and limit its utility as a surrogate for long-term outcome.[2]

    We performed a similar analysis of patients enrolled in a prospective single-center registry. The ability of ENI to predict 3-month functional independence was assessed by the area under the receiver operating characteristic curve (AUC) and compared using the independent-samples Hanley test. Multivariable linear regression assessing the relationship between anesthetic technique and ENI was also performed. The analysis received ethics approval.

    291 patients were treated with thrombectomy, with 261 (89.7%) procedures performed with GA, and 30 (10.3%) with CS. All patients were de-sedated and extubated more than 12 hours before 24-hour National Institutes of Health Stroke Scale assessment. 174 (59.8%) patients achieved 3-month functional independence. Baseline and procedural characteristics did not differ between GA and CS patients (all P>0.05). ENI demonstrated better prognostic ability in CS (AUC 0.91, 95% confiden...

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  • SPOT as a clinical decision aid

    We read with interest the response to our manuscript on using machine learning to optimize elderly patient selection for endovascular thrombectomy (1). We acknowledge here, as the author reports, the limitation of SPOT being based on single center data, and the need for multicenter prospective validation of SPOT as next step in development. The author raises additional technical concerns that we do not necessarily view as applicable to this study.

    First, we would like to stress the general limitations of artificial intelligence based techniques such as the overfitting and the data specific local optima problems. However, the specific comments brought by the author are not applicable in our case. First, studies on the number of events per predictor are applicable for logistic regressions (LRs) which is not used in the SPOT algorithm. In fact, our results show poor LR performance which is consistent with the rule of thumb of 1 to 10 referred to by the author. Hence, while serving as a good guidance for LR, the rule is not binding and more importantly it does not guarantee the generalization of the learned model. To further illustrate, classification models using convolutional neural networks have millions of parameters and are trained with datasets that, in most cases, do not have millions of samples in each group. However, these models have acceptable generalization capabilities and are tested using the data-split method. In SPOT, the model at its core is a regressi...

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  • Multiple Factors Related to Vessel Perforations in Endovascular Thrombectomy

    Congratulations to Annika Keuler et al¹ on their experience with the wireless microcatheter technique preventing vessel perforations in endovascular thrombectomy. Based on their results, the authors conclude that in most cases of mechanical recanalization, the clot can be passed more safely with a wireless microcatheter. In our daily work, we also find the wireless microcatheter technique seems to reduce subarachnoid hyperdensity resulting from vessel perforations. However it seems difficult to confirm this correlation; the details of which will be discussed as follows. After reading and analyzing the article carefully, we have some opinions about the study which we would like to communicate with the authors because the conclusions of the paper directly relate to our clinical experience.
    In the article, two radiological manifestations are defined as vessel perforations——contrast extravasation during angiography and angiographically occult ipsilateral circumscribed subarachnoid contrast extravasation which is identified by post-interventional CT scans. As confirmed by previous studies2-3, we agree with the authors on using immediate post-interventional CT examination to identify the subarachnoid hyperdensity due to intraoperative contrast extravasation. Based on their results, post-thrombectomy subarachnoid hyperdensity was observed on CT scans in 22 patients, in 18 of whom, the clot was passed using a microwire, and in the other four, using a wireless microcathete...

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  • Response to: "Using machine learning to optimize selection of elderly patients for endovascular thrombectomy"

    It is with great interest that we read the study of Alawieh et al(1), in which they developed a machine learning algorithm, called ‘SPOT’, to select stroke patients older than 80 years for endovascular therapy (EVT). Prediction modeling to optimize patient selection for EVT is an emerging topic of interest and we agree that predicting individual patient outcomes is increasingly important for decision making in medicine. However, we were surprised by the strong conclusions that were drawn by the authors, considering some serious limitations of the study.

    First, the size of the training set is insufficient to develop a complex model with twelve predictor variables and many correlations. Only 22 patients had a good functional outcome, which means that the number of events per tested predictor variable is less than two. For the development of a reliable model, a sample size of at least ten events per variable is needed to minimize the risk of overfitting(2, 3). It has been suggested that even far more events per variable are needed to achieve stable predictions with machine learning techniques(4). Especially complex models developed on small sample sizes have a high risk of overfitting, resulting in unstable predictions and too optimistic model performance measures. The reported AUC of 0.92 is therefore very likely to be an overestimation.

    Second, the SPOT algorithm provides a treatment advice based on the predicted outcome after treatment, without providing the...

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  • The AIS Denominator

    We had an opportunity to read the article by Lakomkin et al regarding systematic literature review of LVO prevalence. Since one of our studies is part of this review we feel compelled to comment on the paper. We do appreciate the authors’ efforts in conducting this analysis which is important in understanding the burden of disease – but, with respect offer some criticisms. The major limitation of the paper which the authors recognize is the heterogeneity of the included studies. Unfortunately, this limitation is so critical that it yields unreliable information at best and misleading at worst.

    The paper intends to study the prevalence of large vessel strokes. However, apart from a couple of population based studies in their review, the rest are a heterogenous mix describing an LVO rate from very selective cohorts of patients from single centers. Several are centered around validation of clinical scales for detecting LVOs. The key features of a population based study include a defined catchment population, access to a large part of that population and a reliable marker of disease. Without these a “prevalence” constitutes a report of a center’s experience of disease rate as it pertains to their patient intake. While still valuable it is not an estimation of the disease burden in the population that the center serves unless an overwhelming majority of that population comes to that center.

    The authors determine an average rate of about 30% LVO amongst acute isch...

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  • Reply to: Decreasing incidence of subarachnoid hemorrhage

    We would like to congratulate Nicholson et al. on their highly interesting work on the declining rate of SAH in the Irish population. This will certainly provide some very interesting points. Also in Germany there is - at least subjectively - the phenomenon of the declining rate of SAH. The authors can establish a clear correlation to the decline in the smoking rate. Now the question arises whether this is the only relevant correlation. In particular, it would certainly be necessary to investigate whether there has been an increased rate of detection of unruptered Aneurysma and an increasing rate of treatment of those during the study period and whether this may also have a relevant influence on the decrease in SAH.

  • Using an intermediate catheter triaxial system for Direct Aspiration first Pass Technique: the easiest way for thrombectomy?

    Dear Editor,
    we read with great interest the paper from Sallustio et al 1 regarding the use of new thromboaspiration catheter, AXS Catalyst 6 (Stryker Neurovascular, Mountain View, CA, USA), for endovascular treatment (EVT) of large vessel stroke (LVS) with A Direct Aspiration first Pass Technique (ADAPT)2.
    In our center, a team composed by 4 vascular interventional radiologists, two physicians with certified experience in stroke treatment and two physicians with large carotid stent experience, and 4 stroke neurologist with large experience in intravenous thrombolysis, started to perform EVT in patients with LVS of anterior or posterior circulation from September 2017.
    Given the wide availability of different systems of neurothrombectomy we decided to use AXS Catalyst 6 both for its technical features, as reported by Sallustio et al, both for its lower costs than the others available (6F SOFIA plus catheter, MicroVention, Tustin, CA, USA; the X Penumbra ACE catheters, Penumbra Inc., Alameda, CA, USA).
    Between September 2017 and May 2018, 24 patients (72.1 ± 13.2 years old) affected by acute ischemic stroke with LVS underwent to EVT in our center. Median baseline NIHSS was 18 (range: 7-24). Intravenous thrombolysis was used in 5 patients.
    The most frequent site of occlusion was the middle cerebral artery (MCA) (70.8%), while in 16.7% of cases was basilar artery. Tandem occlusions occurred in 12.5% of patients and the most frequent stroke etiolo...

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