Publications by authors named "Eckhard Schlemm"

17 Publications

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Functional connectivity changes in cerebral small vessel disease - a systematic review of the resting-state MRI literature.

BMC Med 2021 May 5;19(1):103. Epub 2021 May 5.

Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.

Background: Cerebral small vessel disease (CSVD) is a common neurological disease present in the ageing population that is associated with an increased risk of dementia and stroke. Damage to white matter tracts compromises the substrate for interneuronal connectivity. Analysing resting-state functional magnetic resonance imaging (fMRI) can reveal dysfunctional patterns of brain connectivity and contribute to explaining the pathophysiology of clinical phenotypes in CSVD.

Materials And Methods: This systematic review provides an overview of methods and results of recent resting-state functional MRI studies in patients with CSVD. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, a systematic search of the literature was performed.

Results: Of 493 studies that were screened, 44 reports were identified that investigated resting-state fMRI connectivity in the context of cerebral small vessel disease. The risk of bias and heterogeneity of results were moderate to high. Patterns associated with CSVD included disturbed connectivity within and between intrinsic brain networks, in particular the default mode, dorsal attention, frontoparietal control, and salience networks; decoupling of neuronal activity along an anterior-posterior axis; and increases in functional connectivity in the early stage of the disease.

Conclusion: The recent literature provides further evidence for a functional disconnection model of cognitive impairment in CSVD. We suggest that the salience network might play a hitherto underappreciated role in this model. Low quality of evidence and the lack of preregistered multi-centre studies remain challenges to be overcome in the future.
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http://dx.doi.org/10.1186/s12916-021-01962-1DOI Listing
May 2021

Sex Differences in Outcome After Thrombectomy for Acute Ischemic Stroke are Explained by Confounding Factors.

Clin Neuroradiol 2020 Dec 21. Epub 2020 Dec 21.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Purpose: The aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry.

Methods: Data of consecutive stroke patients treated with thrombectomy (June 2015-April 2018) derived from an industry-independent registry (German Stroke Registry-Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale [mRS] 0-2) 90 days after stroke.

Results: In total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years; p < 0.001) and more frequently had a prestroke functional impairment defined by mRS >1 (24.8% vs. 14.1%; p < 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%; p < 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%; p = 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome.

Conclusion: Women showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status.
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http://dx.doi.org/10.1007/s00062-020-00983-2DOI Listing
December 2020

White matter integrity and structural brain network topology in cerebral small vessel disease: The Hamburg city health study.

Hum Brain Mapp 2021 Apr 8;42(5):1406-1415. Epub 2020 Dec 8.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cerebral small vessel disease is a common finding in the elderly and associated with various clinical sequelae. Previous studies suggest disturbances in the integration capabilities of structural brain networks as a mediating link between imaging and clinical presentations. To what extent cerebral small vessel disease might interfere with other measures of global network topology is not well understood. Connectomes were reconstructed via diffusion weighted imaging in a sample of 930 participants from a population based epidemiologic study. Linear models were fitted testing for an association of graph-theoretical measures reflecting integration and segregation with both the Peak width of Skeletonized Mean Diffusivity (PSMD) and the load of white matter hyperintensities of presumed vascular origin (WMH). The latter were subdivided in periventricular and deep for an analysis of localisation-dependent correlations of cerebral small vessel disease. The median WMH volume was 0.6 mL (1.4) and the median PSMD 2.18 mm /s x 10 (0.5). The connectomes showed a median density of 0.880 (0.030), the median values for normalised global efficiency, normalised clustering coefficient, modularity Q and small-world propensity were 0.780 (0.045), 1.182 (0.034), 0.593 (0.026) and 0.876 (0.040) respectively. An increasing burden of cerebral small vessel disease was significantly associated with a decreased integration and increased segregation and thus decreased small-worldness of structural brain networks. Even in rather healthy subjects increased cerebral small vessel disease burden is accompanied by topological brain network disturbances. Segregation parameters and small-worldness might as well contribute to the understanding of the known clinical sequelae of cerebral small vessel disease.
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http://dx.doi.org/10.1002/hbm.25301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927298PMC
April 2021

Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.

J Cereb Blood Flow Metab 2020 Dec 1:271678X20974170. Epub 2020 Dec 1.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

We examined the relationship between white matter hyperintensities (WMH) and cortical neurodegeneration in cerebral small vessel disease (CSVD) by investigating whether cortical thickness is a remote effect of WMH through structural fiber tract connectivity in a population at increased risk of CSVD. We measured cortical thickness on T1-weighted images and segmented WMH on FLAIR images in 930 participants of a population-based cohort study at baseline. DWI-derived whole-brain probabilistic tractography was used to define WMH connectivity to cortical regions. Linear mixed-effects models were applied to analyze the relationship between cortical thickness and connectivity to WMH. Factors associated with cortical thickness (age, sex, hemisphere, region, individual differences in cortical thickness) were added as covariates. Median age was 64 [IQR 46-76] years. Visual inspection of surface maps revealed distinct connectivity patterns of cortical regions to WMH. WMH connectivity to the cortex was associated with reduced cortical thickness ( = 0.009) after controlling for covariates. This association was found for periventricular WMH ( = 0.001) only. Our results indicate an association between WMH and cortical thickness via connecting fiber tracts. The results imply a mechanism of secondary neurodegeneration in cortical regions distant, yet connected to subcortical vascular lesions, which appears to be driven by periventricular WMH.
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http://dx.doi.org/10.1177/0271678X20974170DOI Listing
December 2020

Clinical Characteristics and Outcome of Patients With Hemorrhagic Transformation After Intravenous Thrombolysis in the WAKE-UP Trial.

Front Neurol 2020 28;11:957. Epub 2020 Aug 28.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hemorrhagic transformation (HT) is an important complication of intravenous thrombolysis with alteplase. HT can show a wide range from petechiae to parenchymal hematoma with mass effect with varying clinical impact. We studied clinical and imaging characteristics of patients with HT and evaluated whether different types of HT are associated with functional outcome. We performed a analysis of WAKE-UP, a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in unknown onset stroke. HT was assessed on follow-up MRI or CT and diagnosed as hemorrhagic infarction type 1 and type 2 (HI1 and HI2, combined as HI), and parenchymal hemorrhage type 1 and type 2 (PH1 and PH2, combined as PH). Severity of stroke symptoms was assessed using the National Institutes of Health Stroke Scale (NIHSS) at baseline. Stroke lesion volume was measured on baseline diffusion weighted imaging (DWI). Primary endpoint was a favorable outcome defined as a modified Rankin Scale score 0-1 at 90 days. Of 483 patients included in the analysis, 95 (19.7%) showed HI and 21 (4.4%) had PH. Multiple logistic regression analysis identified treatment with alteplase (OR, 2.08 [95% CI, 1.28-3.40]), baseline NIHSS score (OR, 1.11 [95% CI, 1.05-1.17]), DWI lesion volume (OR, 1.03 [95% CI, 1.01-1.05]), baseline glucose levels (OR, 1.01 [95% CI, 1.00-1.01]) and atrial fibrillation (OR, 3.02 [95% CI, 1.57-5.80]) as predictors of any HT. The same parameters predicted HI. Predictors of PH were baseline NIHSS score (OR, 1.11 [95% CI, 1.01-1.22]) and as a trend treatment with alteplase (OR, 2.40 [95% CI, 0.93-6.96]). PH was associated with lower odds of favorable outcome (OR 0.25, 95% [CI 0.05-0.86]), while HI was not. Our results indicate that HI is associated with stroke severity, cardiovascular risk factors and thrombolysis. PH is a rare complication, more frequent in severe stroke and with thrombolysis. In contrast to HI, PH is associated with worse functional outcome. The impact of HT after MRI-guided intravenous alteplase for unknown onset stroke on clinical outcome is similar as in the trials of stroke thrombolysis within a known early time-window.
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http://dx.doi.org/10.3389/fneur.2020.00957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483750PMC
August 2020

Structural brain networks and functional motor outcome after stroke-a prospective cohort study.

Brain Commun 2020 10;2(1):fcaa001. Epub 2020 Jan 10.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.

The time course of topological reorganization that occurs in the structural connectome after an ischaemic stroke is currently not well understood. We aimed to determine the evolution of structural brain networks in stroke patients with motor deficits and relate changes in their global topology to residual symptom burden and functional impairment. In this prospective cohort study, ischaemic stroke patients with supratentorial infarcts and motor symptoms were assessed longitudinally by advanced diffusion MRI and detailed clinical testing of upper extremity motor function at four time points from the acute to the chronic stage. For each time point, structural connectomes were reconstructed, and whole-hemisphere global network topology was quantified in terms of integration and segregation parameters. Using non-linear joint mixed-effects regression modelling, network evolution was related to lesion volume and clinical outcome. Thirty patients were included for analysis. Graph-theoretical analysis demonstrated that, over time, brain networks became less integrated and more segregated with decreasing global efficiency and increasing modularity. Changes occurred in both stroke and intact hemispheres and, in the latter, were positively associated with lesion volume. Greater change in topology was associated with larger residual symptom burden and greater motor impairment 1, 3 and 12 months after stroke. After ischaemic stroke, brain networks underwent characteristic changes in both ipsi- and contralesional hemispheres. Topological network changes reflect the severity of damage to the structural network and are associated with functional outcome beyond the impact of lesion volume.
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http://dx.doi.org/10.1093/braincomms/fcaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425342PMC
January 2020

Altered topology of large-scale structural brain networks in chronic stroke.

Brain Commun 2019 4;1(1):fcz020. Epub 2019 Oct 4.

Department of Neurology, University Medical Center Hamburg-Eppendorf, D20246 Hamburg, Germany.

Beyond disruption of neuronal pathways, focal stroke lesions induce structural disintegration of distant, yet connected brain regions via retrograde neuronal degeneration. Stroke lesions alter functional brain connectivity and topology in large-scale brain networks. These changes are associated with the degree of clinical impairment and recovery. In contrast, changes of large scale, structural brain networks after stroke are less well reported. We therefore aimed to analyse the impact of focal lesions on the structural connectome after stroke based on data from diffusion-weighted imaging and probabilistic fibre tracking. In total, 17 patients (mean age 64.5 ± 8.4 years) with upper limb motor deficits in the chronic stage after stroke and 21 healthy participants (mean age 64.9 ± 10.3 years) were included. Clinical deficits were evaluated by grip strength and the upper extremity Fugl-Meyer assessment. We calculated global and local graph theoretical measures to characterize topological changes in the structural connectome. Results from our analysis demonstrated significant alterations of network topology in both ipsi- and contralesional, primarily unaffected, hemispheres after stroke. Global efficiency was significantly lower in stroke connectomes as an indicator of overall reduced capacity for information transfer between distant brain areas. Furthermore, topology of structural connectomes was shifted toward a higher degree of segregation as indicated by significantly higher values of global clustering and modularity. On a level of local network parameters, these effects were most pronounced in a subnetwork of cortico-subcortical brain regions involved in motor control. Structural changes were not significantly associated with clinical measures. We propose that the observed network changes in our patients are best explained by the disruption of inter- and intrahemispheric, long white matter fibre tracts connecting distant brain regions. Our results add novel insights on topological changes of structural large-scale brain networks in the ipsi- and contralesional hemisphere after stroke.
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http://dx.doi.org/10.1093/braincomms/fcz020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425306PMC
October 2019

Modeling the Optimal Transportation for Acute Stroke Treatment : Impact of Diurnal Variations in Traffic Rate.

Clin Neuroradiol 2020 Jul 16. Epub 2020 Jul 16.

Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Haus Ost 22 (O 22), Martinistr. 52, 20246, Hamburg, Germany.

Purpose: Prolonged transfer times between the primary stroke center (PSC) and the comprehensive stroke center (CSC) are one of the major causes of treatment delay for endovascular stroke treatment. We aimed to analyze the effect of the diurnal variations in traffic rates at weekdays and weekends on the catchment area size of three transportation paradigms, i.e. mothership, drip-and-ship (DS) and drip-and-drive (DD).

Methods: A conditional probability model that predicts the probability of good outcome for patients with suspected large vessel occlusion was used to analyze the prehospital stroke triage in northwest Germany and produce catchment area maps. Transportation times were calculated during each hour of a weekday and a Sunday using Google Maps. For comparison, real DD transportation times from our CSC in Hamburg-Eppendorf (blinded for review) to a PSC in Lüneburg were prospectively recorded.

Result: On weekdays, the mothership catchment area was the largest (≥40,000 km, 63%) except for a decrease during morning rush hours, when the DD catchment area was highest (30,879 km, 48%). The DS catchment area was higher than the DD catchment area during the afternoon rush hours both during the week as well as on Sundays.

Conclusion: Our study showed a considerable impact of the diurnal variations in traffic rate and direction of travel on optimal stroke transportation. Stroke systems of care should take real time traffic information into account.
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http://dx.doi.org/10.1007/s00062-020-00933-yDOI Listing
July 2020

Network Localisation of White Matter Damage in Cerebral Small Vessel Disease.

Sci Rep 2020 06 8;10(1):9210. Epub 2020 Jun 8.

Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Cerebral small vessel disease (CSVD) is a widespread condition associated to stroke, dementia and depression. To shed light on its opaque pathophysiology, we conducted a neuroimaging study aiming to assess the location of CSVD-induced damage in the human brain network. Structural connectomes of 930 subjects of the Hamburg City Health Study were reconstructed from diffusion weighted imaging. The connectome edges were partitioned into groups according to specific schemes: (1) connection to grey matter regions, (2) course and length of underlying streamlines. Peak-width of skeletonised mean diffusivity (PSMD) - a surrogate marker for CSVD - was related to each edge group's connectivity in a linear regression analysis allowing localisation of CSVD-induced effects. PSMD was associated with statistically significant decreases in connectivity of most investigated edge groups except those involved in connecting limbic, insular, temporal or cerebellar regions. Connectivity of interhemispheric and long intrahemispheric edges as well as edges connecting subcortical and frontal brain regions decreased most severely with increasing PSMD. In conclusion, MRI findings of CSVD are associated with widespread impairment of structural brain network connectivity, which supports the understanding of CSVD as a global brain disease. The pattern of regional preference might provide a link to clinical phenotypes of CSVD.
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http://dx.doi.org/10.1038/s41598-020-66013-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280237PMC
June 2020

Letter by L. Schlemm and E. Schlemm Regarding Article, "Efficacy of Clopidogrel-Aspirin Therapy for Stroke Does Not Exist in CYP2C19 Loss-of-Function Allele Noncarriers With Overweight/Obesity".

Stroke 2020 03 3;51(3):e54. Epub 2020 Feb 3.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany.

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http://dx.doi.org/10.1161/STROKEAHA.119.028453DOI Listing
March 2020

Modeling the Optimal Transportation for Acute Stroke Treatment: The Impact of the Drip-and-Drive Paradigm.

Stroke 2020 01 18;51(1):275-281. Epub 2019 Nov 18.

From the Department of Diagnostic and Interventional Neuroradiology (M.E., J.F., C.B.), University Medical Center Hamburg-Eppendorf, Germany.

Background and Purpose- Health systems are faced with the challenge of ensuring fast access to appropriate therapy for patients with acute stroke. The paradigms primarily discussed are mothership and drip and ship. Less attention has been focused on the drip-and-drive (DD) paradigm. Our aim was to analyze whether and under what conditions DD would predict the greatest probability of good outcome for patients with suspected ischemic stroke in Northwestern Germany. Methods- Conditional probability models based on the decay curves for endovascular therapy and intravenous thrombolysis were created to determine the best transport paradigm, and results were displayed using map visualizations. Our study area consisted of the federal states of Lower Saxony, Hamburg, and Schleswig-Holstein in Northwestern Germany covering an area of 64 065 km with a population of 12 703 561 in 2017 (198 persons per km). In several scenarios, the catchment area, that is, the region that would result in the greatest probability of good outcomes, was calculated for each of the mothership, drip-and-ship, and the DD paradigms. Several different treatment time parameters were varied including onset-to-first-medical-response time, ambulance-on-scene time, door-to-needle time at primary stroke center, needle-to-door time, door-to-needle time at comprehensive stroke center, door-to-groin-puncture time, needle-to-interventionalist-leave time, and interventionalist-arrival-to-groin-puncture time. Results- The mothership paradigm had the largest catchment area; however, the DD catchment area was larger than the drip-and-ship catchment area so long as the needle-to-interventionalist-leave time and the interventionalist-arrival-to-groin-puncture time remain <40 minutes each. A slowed workflow in the DD paradigm resulted in a decrease of the DD catchment area to 1221 km (2%). Conclusions- Our study suggests the largest catchment area for the mothership paradigm and a larger catchment area of DD paradigm compared with the drip-and-ship paradigm in Northwestern Germany in most scenarios. The existence of different paradigms allows the spread of capacities, shares the cost and hospital income, and gives primary stroke centers the possibility to provide endovascular therapy services 24/7.
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http://dx.doi.org/10.1161/STROKEAHA.119.027493DOI Listing
January 2020

Comparative Evaluation of 10 Prehospital Triage Strategy Paradigms for Patients With Suspected Acute Ischemic Stroke.

J Am Heart Assoc 2019 06 13;8(12):e012665. Epub 2019 Jun 13.

6 Medizinische Fakultät Universität Hamburg Germany.

Background The best strategy to identify patients with suspected acute ischemic stroke and unknown vessel status (large vessel occlusion) for direct transport to a comprehensive stroke center instead of a nearer primary stroke center is unknown. Methods and Results We used mathematical modeling to estimate the impact of 10 increasingly complex prehospital triage strategy paradigms on the reduction of population-wide stroke-related disability. The model was applied to suspected acute ischemic stroke patients in (1) abstract geographies, and (2) 3 real-world urban and rural geographies in Germany. Transport times were estimated based on stroke center location and road infrastructure; spatial distribution of emergency medical services calls was derived from census data with high spatial granularity. Parameter uncertainty was quantified in sensitivity analyses. The mothership strategy was associated with a statistically significant population-wide gain of 8 to 18 disability-adjusted life years in the 3 real-world geographies and in most simulated abstract geographies (net gain -4 to 66 disability-adjusted life years). Of the more complex paradigms, transportation of patients with clinically suspected large vessel occlusion based on a dichotomous large vessel occlusion detection scale to the nearest comprehensive stroke center yielded an additional clinical benefit of up to 12 disability-adjusted life years in some rural but not in urban geographies. Triage strategy paradigms based on probabilistic conditional modeling added an additional benefit of 0 to 4 disability-adjusted life years over less complex strategies if based on variable cutoff scores. Conclusions Variable stroke severity cutoff scores were associated with the highest reduction in stroke-related disability. The mothership strategy yielded better clinical outcome than the drip-'n'-ship strategy in most geographies.
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http://dx.doi.org/10.1161/JAHA.119.012665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645624PMC
June 2019

Pre-hospital Triage of Acute Ischemic Stroke Patients-Importance of Considering More Than Two Transport Options.

Front Neurol 2019 26;10:437. Epub 2019 Apr 26.

Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.

Patients with acute ischemic stroke (AIS) and large vessel occlusion benefit from rapid access to mechanical thrombectomy in addition to intravenous thrombolysis. Prehospital triage algorithms to determine the optimal transport destination for AIS patients with unknown vessel status have so far only considered two alternatives: the nearest comprehensive (CSC) and the nearest primary stroke center (PSC). This study explores the importance of considering a larger number of PSCs during pre-hospital triage of AIS patients. Analysis was performed in random two-dimensional abstract geographic stroke care infrastructure environments and two models based on real-world geographic scenarios. Transport times to CSCs and PSCs were calculated to define sub-regions with specific triage properties. Possible transport destinations included the nearest CSC, the nearest PSC, and any of the remaining PSCs that are not closest to the scene, but transport to which would imply a shorter total time-to-CSC-via-PSC. In abstract geographic environments, the median relative size of the sub-region where a triage decision is required ranged from 34 to 92%. The median relative size of the sub-region where more than two triage options need to be considered ranged from 0 to 56%. The achievable reduction in time-to-thrombectomy ("benefit") exceeded the increase in time-to-thrombolysis ("harm") by a factor of 2 in 30.5-37.0% of the sub-region where more than two triage options need to be considered. Results were confirmed in geographic environments based on real-world urban and rural stroke care infrastructures. Pre-hospital triage algorithms for AIS patients that only take into account the nearest CSC and the nearest PSC as transport destinations may be unable to identify the optimal transport destination for a significant proportion of patients.
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http://dx.doi.org/10.3389/fneur.2019.00437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503645PMC
April 2019

Somatosensory Deficits After Ischemic Stroke.

Stroke 2019 05;50(5):1116-1123

From the Department of Neurology (S.S.K., E.S., B.C., C.G., G.T.), University Medical Center Hamburg-Eppendorf, Germany.

Background and Purpose- About 50% to 80% of stroke survivors present with somatosensory deficits. Somatosensory deficits because of an ischemic stroke are determined by the infarct location. However, a detailed understanding of the long-term effect of lesions on somatosensory performance is lacking. Methods- This prospective observational study enrolled 101 ischemic stroke patients. For voxel-based lesion-symptom mapping, magnetic resonance imaging fluid-attenuated inversion recovery imaging infarct lesions were segmented within 5 days after stroke. Standardized tests such as the National Institutes of Health Stroke Scale and the Rivermead Assessment of Somatosensory Performance were performed during acute stage, after 3 and 12 months. This included bilateral testing for multiple tactile and proprioceptive somatosensory modalities (pressure, light touch, sharp-dull discrimination, temperature discrimination, sensory extinction, 2-point discrimination, and joint position and movement sense). We further study the association of acute somatosensory deficit with functional outcome 12 months after stroke assessed by the modified Rankin Scale using univariate and multiple linear regression analysis also including acute motor deficit assessed by the arm research action test. Results- Sixty patients (59.4%) showed impairment in at least one somatosensory modality. Light touch was most frequently affected (38.7%), whereas temperature was least frequently affected (21.8%). After 3 months, significant recovery was observed in all somatosensory modalities, with only minor additional improvements after 12 months. Voxel-based lesion-symptom mapping revealed significant associations of lesions in the primary and secondary somatosensory and insular cortex with somatosensory deficits. Acute somatosensory deficit was associated with functional outcome at 12 months. However, including the acute motor deficit, somatosensory deficit was no longer an independent predictor of functional outcome. Conclusions- Our study confirms that somatosensory deficits are frequent in acute ischemic stroke but largely recover over time. Infarct lesions in the primary and secondary somatosensory cortex and insula show a robust association with somatosensory impairment. Long-term disability is influenced by somatosensory deficits but driven by motor symptoms.
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http://dx.doi.org/10.1161/STROKEAHA.118.023750DOI Listing
May 2019

Clinical benefit of improved Prehospital stroke scales to detect stroke patients with large vessel occlusions: results from a conditional probabilistic model.

BMC Neurol 2018 Feb 10;18(1):16. Epub 2018 Feb 10.

Universität Hamburg, Medizinische Fakultät, Hamburg, Germany.

Background: Clinical scales to detect large vessel occlusion (LVO) may help to determine the optimal transport destination for patients with suspected acute ischemic stroke (AIS). The clinical benefit associated with improved diagnostic accuracy of these scales has not been quantified.

Methods: We used a previously reported conditional model to estimate the probability of good outcome (modified Rankin scale sore ≤2) for patients with AIS and unknown vessel status occurring in regions with greater proximity to a primary than to a comprehensive stroke center. Optimal rapid arterial occlusion evaluation (RACE) scale cutoff scores were calculated based on time-dependent effect-size estimates from recent randomized controlled trials. Probabilities of good outcome were compared between a triage strategy based on these cutoffs and a strategy based on a hypothetical perfect LVO detection tool with 100% diagnostic accuracy.

Results: In our model, the additional benefit of a perfect LVO detection tool as compared to optimal transport-time dependent RACE cutoff scores ranges from 0 to 5%. It is largest for patients with medium stroke symptom severity (RACE score 5) and in geographic environments with longer transfer time between the primary and comprehensive stroke center.

Conclusion: Based on a probabilistic conditional model, the results of our simulation indicate that more accurate prehospital clinical LVO detections scales may be associated with only modest improvements in the expected probability of good outcome for patients with suspected acute ischemic stroke and unknown vessel status.
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http://dx.doi.org/10.1186/s12883-018-1021-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5807751PMC
February 2018

Optimal Transport Destination for Ischemic Stroke Patients With Unknown Vessel Status: Use of Prehospital Triage Scores.

Stroke 2017 08 27;48(8):2184-2191. Epub 2017 Jun 27.

From the University of Glasgow, School of Life Sciences, United Kingdom (E.S.); Queen Elizabeth University Hospital Glasgow, NHS Greater Glasgow and Clyde, United Kingdom (E.S.); Universität Hamburg, Medizinische Fakultät, Germany (E.S.); Department of Neurology (M. Ebinger, C.H.N., M. Endres, L.S.) and Center for Stroke Research Berlin (CSB) (M. Ebinger, C.H.N., M. Endres, L.S.), Charité-Universitätsmedizin, Germany; Department of Neurology, MEDICAL PARK Berlin Humboldtmühle, Germany (M. Ebinger); Berlin Institute of Health (BIH), Germany (C.H.N., M. Endres, L.S.); DZHK (German Center for Cardiovascular Research) (M. Endres) and DZNE (German Center for Neurodegenerative Diseases) (M. Endres), Partner Site, Berlin, Germany; and London School of Economics and Political Science, United Kingdom (L.S.).

Background And Purpose: Patients with acute ischemic stroke (AIS) and large vessel occlusion may benefit from direct transportation to an endovascular capable comprehensive stroke center (mothership approach) as opposed to direct transportation to the nearest stroke unit without endovascular therapy (drip and ship approach). The optimal transport strategy for patients with AIS and unknown vessel status is uncertain. The rapid arterial occlusion evaluation scale (RACE, scores ranging from 0 to 9, with higher scores indicating higher stroke severity) correlates with the National Institutes of Health Stroke Scale and was developed to identify patients with large vessel occlusion in a prehospital setting. We evaluate how the RACE scale can help to inform prehospital triage decisions for AIS patients.

Methods: In a model-based approach, we estimate probabilities of good outcome (modified Rankin Scale score of ≤2 at 3 months) as a function of severity of stroke symptoms and transport times for the mothership approach and the drip and ship approach. We use these probabilities to obtain optimal RACE cutoff scores for different transfer time settings and combinations of treatment options (time-based eligibility for secondary transfer under the drip and ship approach, time-based eligibility for thrombolysis at the comprehensive stroke center under the mothership approach).

Results: In our model, patients with AIS are more likely to benefit from direct transportation to the comprehensive stroke center if they have more severe strokes. Values of the optimal RACE cutoff scores range from 0 (mothership for all patients) to >9 (drip and ship for all patients). Shorter transfer times and longer door-to-needle and needle-to-transfer (door out) times are associated with lower optimal RACE cutoff scores.

Conclusions: Use of RACE cutoff scores that take into account transport times to triage AIS patients to the nearest appropriate hospital may lead to improved outcomes. Further studies should examine the feasibility of translation into clinical practice.
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http://dx.doi.org/10.1161/STROKEAHA.117.017281DOI Listing
August 2017

A differential equation for the asymptotic fitness distribution in the Bak-Sneppen model with five species.

Authors:
Eckhard Schlemm

Math Biosci 2015 Sep 3;267:53-60. Epub 2015 Jul 3.

University College London Medical School, Gower Street, London WC1E 6BT, United Kingdom. Electronic address:

The Bak-Sneppen model is an abstract representation of a biological system that evolves according to the Darwinian principles of random mutation and selection. The species in the system are characterized by a numerical fitness value between zero and one. We show that in the case of five species the steady-state fitness distribution can be obtained as a solution to a linear differential equation of order five with hypergeometric coefficients. Similar representations for the asymptotic fitness distribution in larger systems may help pave the way towards a resolution of the question of whether or not, in the limit of infinitely many species, the fitness is asymptotically uniformly distributed on the interval [fc, 1] with fc ≳ 2/3.
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http://dx.doi.org/10.1016/j.mbs.2015.06.011DOI Listing
September 2015