Diagnostic Value of Perfusion Parameters for Differentiation of Underlying Etiology in Internal Carotid Artery Occlusions.

PURPOSE: Occlusions of the internal carotid artery (ICA) may be caused by dissection, embolic or macroangiopathic pathogenesis, which partially influences the treatment; however, inferring the underlying etiology in computed tomography angiography can be challenging. In this study, we investigated whether computed tomography perfusion (CT-P) parameters could be used to distinguish between etiologies. METHODS: Patients who received CT­P in acute ischemic stroke due to ICA occlusion between 2012 and 2019 were retrospectively analyzed. Group comparisons between etiologies regarding the ratios of CT­P parameters between both hemispheres for relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), time to maximum (Tmax), and mean transit time (MTT) were calculated by one-factorial analysis of variance (ANOVA) and compared by pairwise Bonferroni post hoc tests. An receiver operating characteristics (ROC) analysis was performed if differences in group comparisons were found. Multinomial logistic regression (MLR) including pretherapeutic parameters was calculated for etiologies. RESULTS: In this study 69 patients (age = 70 ± 14 years, dissection = 10, 14.5%, embolic = 19, 27.5% and macroangiopathic = 40, 58.0%) were included. Group differences in ANOVA were only found for MTT ratio (p = 0.003, η2 = 0.164). In the post hoc test, MTT ratio showed a differentiability between embolic and macroangiopathic occlusions (p = 0.002). ROC analysis for differentiating embolic and macroangiopathic ICA occlusions based on MTT ratio showed an AUC of 0.77 (p < 0.001, CI = 0.65-0.89) and a cut-off was yielded at a value of 1.15 for the MTT ratio (sensitivity 73%, specificity 68%). The MLR showed an overall good model performance. CONCLUSION: It was possible to differentiate between patients with embolic and macroangiopathic ICA occlusions based on MTT ratios and to define a corresponding cut-off. Differentiation from patients with dissection versus the other etiologies was not possible by CT­P parameters in our sample.

A Novel Ex Vivo Model to Study Therapeutic Treatments for Myelin Repair following Ischemic Damage.

Stroke is a major reason for persistent disability due to insufficient treatment strategies beyond reperfusion, leading to oligodendrocyte death and axon demyelination, persistent inflammation and astrogliosis in peri-infarct areas. After injury, oligodendroglial precursor cells (OPCs) have been shown to compensate for myelin loss and prevent axonal loss through the replacement of lost oligodendrocytes, an inefficient process leaving axons chronically demyelinated. Phenotypic screening approaches in demyelinating paradigms revealed substances that promote myelin repair. We established an ex vivo adult organotypic coronal slice culture (OCSC) system to study repair after stroke in a resource-efficient way. Post-photothrombotic OCSCs can be manipulated for 8 d by exposure to pharmacologically active substances testing remyelination activity. OCSCs were isolated from a NG2-CreERT2-td-Tomato knock-in transgenic mouse line to analyze oligodendroglial fate/differentiation and kinetics. Parbendazole boosted differentiation of NG2+ cells and stabilized oligodendroglial fate reflected by altered expression of associated markers PDGFR-α, CC1, BCAS1 and Sox10 and GFAP. In vitro scratch assay and chemical ischemia confirmed the observed effects upon parbendazole treatment. Adult OCSCs represent a fast, reproducible, and quantifiable model to study OPC differentiation competence after stroke. Pharmacological stimulation by means of parbendazole promoted OPC differentiation.

Mothership vs. drip-and-ship: evaluation of initial treatment strategies for acute ischemic stroke in a well-developed network of specialized hospitals.

PURPOSE: Two strategies of initial patient care exist in endovascular thrombectomy (ET) depending on the site of initial admission: the mothership (MS) and drip-and-ship (DnS) principles. This study compares both strategies in regard to patient outcome in a local network of specialized hospitals. METHODS: Two-hundred-and-two patients undergoing ET in anterior circulation ischemic stroke between June 2016 and May 2018 were enrolled. Ninety two patients were directly admitted to our local facility (MS), One-hundred-and-ten were secondarily referred to our facility. Group comparisons between admission strategies in three-months modified Rankin Scale (mRS), Maas Score and Alberta-Stroke-Program-Early-computed-tomography-score (ASPECTS), National-Institutes-of-Health-Stroke-Scale (NIHSS), age and onset-to-recanalization-time were performed. Correlation between admission strategy and mRS was calculated. A binary logistic regression model was computed including mRS as dependent variable. RESULTS: There were neither significant group differences in three-months mRS between MS and DnS nor significant correlations. Patients tended to achieve a better outcome with DnS. Collateralization status differed between MS and DnS (p = 0.003) with better collateralization in DnS. There were no significant group differences in NIHSS or ASPECTS but in onset-to-recanalization-time (p < 0.001) between MS and DnS. Binary logistic regression showed a high explanation of variance of mRS but no significant results for admission strategy. CONCLUSIONS: Functional outcome in patients treated with ET is comparable between the MS and DnS principles. Tendentially better outcome in the DnS subgroup may be explained by selection bias due to a higher willingness to apply ET in patients with worse baseline conditions (e.g. worse collateralization), if patients undergoing MS are already on site.

Case report: First case of neuromelioidosis in Europe: CNS infection caused by Burkholderia pseudomallei.

Neuromelioidosis is a rare CNS infection caused by Burkholderia pseudomallei and is characterized by high morbidity and mortality. Our report presents the diagnostic and therapeutic approach of the first case of neuromelioidosis confirmed in Europe. A 47-year-old man with a medical history of recurrent otitis with otorrhea and fever after tympanoplasty and radical cavity revision operation on the left ear was admitted with headache, decreased level of consciousness, dysarthria, left-sided hemiparesis, and urinary incontinence. After extensive investigations including MRI, microbiological, serological, and CSF analyses, and, ultimately, brain biopsy, a diagnosis of neuromelioidosis was established. Despite antibiotic treatment, the patient showed no clinical improvement and remained in a severely compromised neurological state under mandatory mechanical ventilation. Neuromelioidosis can pose a diagnostic challenge requiring an extensive diagnostic evaluation because of its uncommon clinical and radiological presentations.

Myelitis with flaccid paralysis due to Japanese encephalitis: case report and review of the literature.

BACKGROUND: Japanese encephalitis is an arthropod-borne zoonotic flavivirus infection endemic to tropical and subtropical Asia. A minority of infections leads to a symptomatic course, but affected patients often develop life-threatening encephalitis with severe sequelae. LITERATURE REVIEW: Myelitis with flaccid paralysis is a rare complication of Japanese Encephalitis, which-according to our literature search-was reported in 27 cases, some of which were published as case reports and others as case series. Overall, there is a broad clinical spectrum with typically asymmetric manifestation and partly severe motor sequelae and partly mild courses. Lower limb paralysis appears to be more frequent than upper limb paralysis. An encephalitic component is not apparent in all cases CASE PRESENTATION: We herein add the case of a 29 year-old female who developed encephalitis and myelitis with flaccid paralysis during a long-time stay in Indonesia. Diagnostic workup in Indonesia did not clearly reveal an underlying cause. Upon clinical stabilization, the patient was evacuated to her home country Germany, where further diagnostics confirmed Japanese encephalitis virus as the causative agent. The patient has partly recovered, but still suffers from residual paralysis of the upper limb. CONCLUSION: Flaccid paralysis is a rare, and likely underdiagnosed complication of Japanese encephalitis, which, to the best of our knowledge, has never been diagnosed outside endemic areas before.

Increased Remyelination and Proregenerative Microglia Under Siponimod Therapy in Mechanistic Models.

BACKGROUND AND OBJECTIVES: Siponimod is an oral, selective sphingosine-1-phosphate receptor-1/5 modulator approved for treatment of multiple sclerosis. METHODS: Mouse MRI was used to investigate remyelination in the cuprizone model. We then used a conditional demyelination Xenopus laevis model to assess the dose-response of siponimod on remyelination. In experimental autoimmune encephalomyelitis-optic neuritis (EAEON) in C57Bl/6J mice, we monitored the retinal thickness and the visual acuity using optical coherence tomography and optomotor response. Optic nerve inflammatory infiltrates, demyelination, and microglial and oligodendroglial differentiation were assessed by immunohistochemistry, quantitative real-time PCR, and bulk RNA sequencing. RESULTS: An increased remyelination was observed in the cuprizone model. Siponimod treatment of demyelinated tadpoles improved remyelination in comparison to control in a bell-shaped dose-response curve. Siponimod in the EAEON model attenuated the clinical score, reduced the retinal degeneration, and improved the visual function after prophylactic and therapeutic treatment, also in a bell-shaped manner. Inflammatory infiltrates and demyelination of the optic nerve were reduced, the latter even after therapeutic treatment, which also shifted microglial differentiation to a promyelinating phenotype. DISCUSSION: These results confirm the immunomodulatory effects of siponimod and suggest additional regenerative and promyelinating effects, which follow the dynamics of a bell-shaped curve with high being less efficient than low concentrations.

Mechanical thrombectomy in stroke patients with acute occlusion of the M1- compared to the M2-segment: Safety, efficacy, and clinical outcome.

PURPOSE: Endovascular treatment (ET) in occlusions of the M1- and proximal M2-segment of the middle cerebral artery (MCA) is an established procedure. In contrast, ET in distal M2-occlusions has not been sufficiently evaluated yet. The purpose of this study was to assess relevant parameters for clinical outcome, efficacy, and safety of patients undergoing ET in M1-, proximal M2-, and distal M2-occlusions. METHODS: One hundred seventy-four patients undergoing ET in acute ischemic stroke with an occlusion of the M1- or M2-segment of the MCA were enrolled prospectively. Non-parametric analysis of variance in 3-month mRS, TICI scale, and complication rates were performed with Kruskal-Wallis test between M1- and proximal and distal M2-occlusions. Subsequent pairwise group comparisons were calculated using Mann-Whitney U-tests. Binary logistic regression models were calculated for each occlusion site. RESULTS: There were no significant group differences in 3-month mRS, mTICI scale, or complication rates between M1- and M2-occlusions nor between proximal and distal M2-occlusions. Binary logistic regression in patients with M1-occlusions showed a substantial explanation of variance (NR2=0.35). NIHSS (p=0.009) and Maas Score as parameter for collateralization (p=0.01) appeared as significant contributing parameters. Binary logistic regression in M2-occlusions showed a high explanation of variance (NR2=0.50) of mRS but no significant factors. CONCLUSIONS: Clinical outcome and procedural safety of patients with M2-occlusions undergoing ET are comparable to those of patients with M1-occlusions. Clinical outcome of patients with M1-occlusions undergoing ET is primarily influenced by the initial neurological deficit and the collateralization of the occlusions. By contrast, clinical outcome in patients with M2-occlusions undergoing ET is more multifactorial.

Natural Killer Cells Are Present in Rag1-/- Mice and Promote Tissue Damage During the Acute Phase of Ischemic Stroke.

Rag1-/- mice, lacking functional B and T cells, have been extensively used as an adoptive transfer model to evaluate neuroinflammation in stroke research. However, it remains unknown whether natural killer (NK) cell development and functions are altered in Rag1-/- mice as well. This connection has been rarely discussed in previous studies but might have important implications for data interpretation. In contrast, the NOD-Rag1nullIL2rgnull (NRG) mouse model is devoid of NK cells and might therefore eliminate this potential shortcoming. Here, we compare immune-cell frequencies as well as phenotype and effector functions of NK cells in Rag1-/- and wildtype (WT) mice using flow cytometry and functional in vitro assays. Further, we investigate the effect of Rag1-/- NK cells in the transient middle cerebral artery occlusion (tMCAO) model using antibody-mediated depletion of NK cells and adoptive transfer to NRG mice in vivo. NK cells in Rag1-/- were comparable in number and function to those in WT mice. Rag1-/- mice treated with an anti-NK1.1 antibody developed significantly smaller infarctions and improved behavioral scores. Correspondingly, NRG mice supplemented with NK cells were more susceptible to tMCAO, developing infarctions and neurological deficits similar to Rag1-/- controls. Our results indicate that NK cells from Rag1-/- mice are fully functional and should therefore be considered in the interpretation of immune-cell transfer models in experimental stroke. Fortunately, we identified the NRG mice, as a potentially better-suited transfer model to characterize individual cell subset-mediated neuroinflammation in stroke.

Microglia contributes to remyelination in cerebral but not spinal cord ischemia.

Inflammation after injury of the central nervous system (CNS) is increasingly viewed as a therapeutic target. However, comparative studies in different CNS compartments are sparse. To date only few studies based on immunohistochemical data and all referring to mechanical injury have directly compared inflammation in different CNS compartments. These studies revealed that inflammation is more pronounced in spinal cord than in brain. Therefore, it is unclear whether concepts and treatments established in the cerebral cortex can be transferred to spinal cord lesions and vice versa or whether immunological treatments must be adapted to different CNS compartments. By use of transcriptomic and flow cytometry analysis of equally sized photothrombotically induced lesions in the cerebral cortex and the spinal cord, we could document an overall comparable inflammatory reaction and repair activity in brain and spinal cord between day 1 and day 7 after ischemia. However, remyelination was increased after cerebral versus spinal cord ischemia which is in line with increased remyelination in gray matter in previous analyses and was accompanied by microglia dominated inflammation opposed to monocytes/macrophages dominated inflammation after spinal cord ischemia. Interestingly remyelination could be reduced by microglia and not hematogenous macrophage depletion. Our results show that despite different cellular composition of the postischemic infiltrate the inflammatory response in cerebral cortex and spinal cord are comparable between day 1 and day 7. A striking difference was higher remyelination capacity in the cerebral cortex, which seems to be supported by microglia dominance.

Consequences of COVID-19 pandemic lockdown on emergency and stroke care in a German tertiary stroke center.

BACKGROUND: COVID-19 pandemic caused a decline in stroke care in several countries. The objective was to describe lockdown stroke care in a tertiary stroke center in Düsseldorf, Germany near Heinsberg, a German hot spot for COVID-19 in spring 2020. METHODS: In a retrospective, observational, single-center study, we compared all patients treated in our emergency department (ED), patients seen by a neurologist in the ED, ED patients suffering from ischemic and hemorrhagic strokes and transient ischemic attacks (TIAs) as well as stroke patients admitted to our stroke unit during lockdown in spring 2020 (16 March 2020-12 April 2020) to those cared for during the same period in 2019 and lockdown light in fall 2020 (2 November - 29 November 2020). RESULTS: In spring 2020 lockdown the mean number of patients admitted to our ED dropped by 37.4%, seen by a neurologist by 35.6%, ED stroke patients by 19.2% and number of patients admitted to our stroke unit by 10% compared to the same period in 2019. In fall lockdown light 2020 effects were comparable but less pronounced. Thrombolysis rate was stable during spring and fall lockdown, however, endovascular treatment (EVT) rate declined by 58% in spring lockdown and by 51% in fall lockdown compared to the period in 2019. CONCLUSIONS: Our study indicates a profound reduction of overall ED patients, neurological ED patients and EVT during COVID-19 pandemic caused lockdowns. Planning for pandemic scenarios should include access to effective emergency therapies.

Acute Heart Failure After Reperfused Ischemic Stroke: Association With Systemic and Cardiac Inflammatory Responses.

Patients with acute ischemic stroke (AIS) present an increased incidence of systemic inflammatory response syndrome and release of Troponin T coinciding with cardiac dysfunction. The nature of the cardiocirculatory alterations remains obscure as models to investigate systemic interferences of the brain-heart-axis following AIS are sparse. Thus, this study aims to investigate acute cardiocirculatory dysfunction and myocardial injury in mice after reperfused AIS. Ischemic stroke was induced in mice by transient right-sided middle cerebral artery occlusion (tMCAO). Cardiac effects were investigated by electrocardiograms, 3D-echocardiography, magnetic resonance imaging (MRI), invasive conductance catheter measurements, histology, flow-cytometry, and determination of high-sensitive Troponin T (hsTnT). Systemic hemodynamics were recorded and catecholamines and inflammatory markers in circulating blood and myocardial tissue were determined by immuno-assay and flow-cytometry. Twenty-four hours following tMCAO hsTnT was elevated 4-fold compared to controls and predicted long-term survival. In parallel, systolic left ventricular dysfunction occurred with impaired global longitudinal strain, lower blood pressure, reduced stroke volume, and severe bradycardia leading to reduced cardiac output. This was accompanied by a systemic inflammatory response characterized by granulocytosis, lymphopenia, and increased levels of serum-amyloid P and interleukin-6. Within myocardial tissue, MRI relaxometry indicated expansion of extracellular space, most likely due to inflammatory edema and a reduced fluid volume. Accordingly, we found an increased abundance of granulocytes, apoptotic cells, and upregulation of pro-inflammatory cytokines within myocardial tissue following tMCAO. Therefore, reperfused ischemic stroke leads to specific cardiocirculatory alterations that are characterized by acute heart failure with reduced stroke volume, bradycardia, and changes in cardiac tissue and accompanied by systemic and local inflammatory responses.

Long-term adherence and response to botulinum toxin in different indications.

OBJECTIVE: The objective of the study was the analysis of adherence and self-perceived treatment response to long-term botulinum neurotoxin type A (BoNT-A) treatment in different neurological indications. METHODS: In this retrospective, monocentric, observational study, cross-sectional and longitudinal data of 1351 patients documenting 20705 injection appointments at the BoNT outpatient clinic of Heinrich Heine University Duesseldorf between 1989 and 2014 were retrospectively analyzed. Patients had been treated with BoNT for neurological conditions, including cervical dystonia (CD), blepharospasm (BSP), other dystonia (ODT), hemifacial spasm (HFS), and spasticity (SPAS). The parameters longitudinally analyzed for the entire cohort were therapy duration as well as the mean and cumulative BoNT-A dose. Cross-sectionally, for subgroups of at least 721, patients' global self-perceived quality of health and life, global self-perceived reduction of symptoms by BoNT-A treatment as well as the clinical global impression were evaluated. Furthermore, mouse hemidiaphragm assay antibodies (MHDA-ABs) were analyzed in a subgroup. RESULTS: The mean treatment duration was 4.58 years (95% CI 4.32-4.84), and 678 (50.2%) therapy dropouts of 1351 patients occurred within the first 8 years. Therapy adherence and self-perceived symptom reduction in long-term BoNT-A treatment over the years were significantly longer in BSP, HFS, and CD patients than in ODT and SPAS patients. INTERPRETATION: The treatment indication determines long-term adherence and self-perceived symptom reduction in BoNT-A therapy, which are better in BSP, HFS, and CD patients than in ODT and SPAS patients. MHDA-ABs had a significant impact on global self-perceived symptom reduction, but with only a limited degree.

Retinal layers and visual conductivity changes in a case series of microangiopathic ischemic stroke patients.

BACKGROUND: It is unknown whether microangiopathic ischemic strokes outside the visual pathway go along with subclinical changes of the retinal structure or the visual system. The objectives of this prospective non-interventional case series were to investigate if spectral-domain optical coherence tomography (SD-OCT) or multifocal visual evoked potentials (mfVEPs) can detect structural retinal changes or functional impairment of the visual system in patients with microangiopathic ischemic stroke. METHODS: We used SD-OCT to cross-sectionally analyze the retinal morphology of 15 patients with microangiopathic ischemic stroke according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification not affecting the visual pathway. We employed semi-automated segmentation of macular volume scans to analyze the thickness of the macular retinal layers and peripapillary ring scans to investigate the retinal morphology in comparison to a control group without stroke. Visual function was assessed by the mfVEP technique in 13 microangiopathic ischemic stroke patients. RESULTS: First peak latency of mfVEPs was significantly delayed in the microangiopathic ischemic stroke group compared to the control patients. Neither the retinal layers nor the mfVEPs' amplitude differed between the microangiopathic ischemic stroke patients and the control group. CONCLUSIONS: In conclusion, microangiopathic ischemic stroke patients presented a delayed first peak latency in mfVEPs as a sign of subclinical functional impairment of the visual pathway. However, our case series suggests no influence on retinal structure resulting from microangiopathic ischemic stroke outside the visual system. Larger and longitudinal studies are needed to confirm these mfVEP findings.

Retinal Changes After Posterior Cerebral Artery Infarctions Display Different Patterns of the Nasal und Temporal Sector in a Case Series.

Background: Visual field defects are a common and disabling consequence of stroke and a negative prognostic factor of patient's quality of life. They result from lesions in different parts of the visual system, most commonly the visual cortex and optic radiation. An important pathophysiological mechanism is transsynaptic retrograde degeneration (TRD). Methods: In a case series 21 patients with posterior cerebral artery (PCA) territory infarctions were analyzed by spectral-domain optical coherence tomography (SD-OCT) and multifocal visual evoked potentials (mfVEPs) cross-sectionally and longitudinally for up to 6 months. In OCT, symptomatic affected nasal and temporal sectors and corresponding visual fields in mfVEPs were compared to the contralateral side. Results: SD-OCT revealed a significant reduction (-2.92 ±2.53 µm, mean ± SD) of the symptomatic nasal macular retinal nerve fiber layer (RNFL) thickness and of the symptomatic temporal peripapillary RNFL after 6 months compared to baseline whereas the symptomatic temporal macular quadrant already showed a significantly thinner RNFL at baseline. The mfVEP first peak latency at baseline was significantly different (nasal visual field +11.69 ±11.17 ms, mean ± SD; temporal visual field +16.63 ±7.97 ms, mean ± SD) on the symptomatic compared to the asymptomatic field. The nasal visual fields partly recovered in amplitude and first peak latency of mfVEPs over the following 6 months compared to baseline. Conclusion: The dynamics of OCT and mfVEP outcomes for degeneration and recovery after PCA infarction differ between the nasal and temporal retinal sector. We postulate that retinal sectors may differ in their temporal pattern of TRD over time after retrogeniculate cerebral infarction.

Mechanical thrombectomy in acute middle cerebral artery M2 segment occlusion with regard to vessel involvement.

BACKGROUND: Endovascular treatment (EVT) is an established procedure in patients with acute ischemic stroke due to occlusion of the proximal M1-segment of middle cerebral artery. The assessment of distal thrombectomy in daily clinical routine has not yet been sufficiently evaluated. METHODS: Patients with M2-segment-occlusions treated by EVT in the local department (January 2012-December 2017) were included (n = 57, mean National-Institutes-of-Health-Stroke-Scale of 11, range 0-20). Patients were grouped according to localization of M2-occlusion (Cohort A (n = 14): central region only, B (n = 24): central region and involvement of frontal vessels, C (n = 19): parietal, occipital, and/or temporal vessels). Differences in proximal (M2-trunk, n = 34) and distal (M2-branches, n = 23) occlusions were also examined. Reperfusion (Thrombolysis-In-Cerebral-Infarction (TICI)), early clinical outcome at discharge (modified Rankin Scale (mRS)), and complications (hemorrhage, new emboli) were noted. RESULT: Successful reperfusion (TICI2b-3) was found in 49 patients (86.0%). Favorable early clinical outcome (mRS0-2) was achieved in n = 19 (37.7%). Compared to admission, mRS at discharge improved significantly (median (admission) 5 vs. median (discharge) 4, p < 0.001). Early clinical outcome was more favorable in patients with better reperfusion (TICI2b-3: mean mRS 3 ± 1.7 vs. TICI0-2a: mean mRS 4.4 ± 1.4, p = 0.037). Six (10.5%) patients suffered from symptomatic intracranial hemorrhage during treatment or hospitalization. Four patients died (7.0%). No significant differences in favorable clinical outcome (mRS ≤ 2: Cohort A 42.9%, B 50.0%, C 16.7%, p = 0.4; χ2-test) or periinterventional complications were found with regard to vessel involvement. CONCLUSION: EVT in patients with acute M2-occlusion is safe and leads to a significant clinical improvement at discharge. No significant differences in clinical outcome or complications were found with regard to the localization of the M2-occlusion.

No Alteration of Optical Coherence Tomography and Multifocal Visual Evoked Potentials in Eyes With Symptomatic Carotid Artery Disease.

Background: Symptomatic carotid artery disease (CAD) may cause modified blood supply to the retina possibly leading to retinal structure changes. Results of previous studies in asymptomatic CAD were heterogeneous in retinal layer changes measured by OCT. The objectives of this prospective, non-interventional study were to investigate if structural retinal changes occur in symptomatic CAD patients with macroangiopathic ischemic stroke or transient ischemic attack (TIA). Methods: We used spectral-domain optical coherence tomography (SD-OCT) to cross-sectionally and longitudinally analyze the retinal morphology of CAD patients with macroangiopathic ischemic stroke or TIA not permanently affecting the visual pathway. We employed semi-automated segmentation of macular volume scans to assess the macular retinal layers' thickness and peripapillary ring scans to determine the peripapillary retinal nerve fiber layer thickness using the contralateral eye and eyes of microangiopathic ischemic stroke patients with matched age, gender, and vascular risk factors as control. Visual function and visual field deficits were assessed by multifocal visual evoked potentials (mfVEP). Results: Neither the thickness of retinal layers measured by SD-OCT in 17 patients nor the mfVEP latency or amplitude in 10 patients differed between the symptomatic stenotic, the contralateral internal carotid artery (ICA) side and the control group of 17 microangiopathic stroke patients at baseline. Furthermore, longitudinal investigations of 10 patients revealed no significant changes of any retinal layer 4 months after ischemic stroke or TIA. Conclusion: In conclusion, our study revealed no evidence for an impact of symptomatic carotid artery disease on retinal structure or functional impairment of the visual pathway.

Systematic evaluation of computed tomography angiography collateral scores for estimation of long-term outcome after mechanical thrombectomy in acute ischaemic stroke.

PURPOSE: This study compares computed tomography angiography-based collateral scoring systems in regard to their inter-rater reliability and potential to predict functional outcome after endovascular thrombectomy, and relates them to parenchymal perfusion as measured by computed tomography perfusion. METHODS: Eighty-four patients undergoing endovascular thrombectomy in anterior circulation ischaemic stroke were enrolled. Modified Tan Score, Miteff Score, Maas Score and Opercular Index Score ratio were assessed in pre-interventional computed tomography angiographies independently by two readers. Collateral scores were tested for inter-rater reliability by weighted-kappa, for correlations with three-months modified Rankin Scale, and their potential to differentiate between patients with favourable (modified Rankin Scale ≤2) and poor outcome (modified Rankin Scale ≥3). Correlations with relative cerebral blood volume and relative cerebral blood flow were tested in patients with available computed tomography perfusion. RESULTS: Very good inter-rater reliability was found for Modified Tan, Miteff and Opercular Index Score ratio, and substantial reliability for Maas. There were no significant correlations between collateral scores and three-months modified Rankin Scale, but significant group differences between patients with favourable and poor outcome for Maas, Miteff and Opercular Index Score ratio. Miteff and Maas were significant predictors of favourable outcome in binary logistic regression analysis. Miteff best differentiated between both outcome groups in receiver-operating characteristics, and Maas reached highest sensitivity for favourable outcome prediction of 96%. All collateral scores significantly correlated with mean relative cerebral blood volume and relative cerebral blood flow. CONCLUSIONS: Computed tomography angiography scores are valuable in estimating functional outcome after mechanical thrombectomy and reliable across readers. The more complex scores, Maas and Miteff, show the best performances in predicting favourable outcome.

Predictors for basal ganglia viability after mechanical thrombectomy in proximal middle cerebral artery occlusion.

BACKGROUND/PURPOSE: In acute proximal middle cerebral artery (MCA) occlusion covering the lenticulostriate arteries (LSA), ischemic tolerance of basal ganglia is limited due to supposed lack of collateral supply. However, in several patients, basal ganglia (BG) infarction was absent after successful mechanical thrombectomy (MTE). Purpose of our study was to evaluate predictors for BG viability in stroke patients despite prolonged MCA mainstem occlusion. MATERIAL/METHODS: We retrospectively reviewed all stroke patients from our local registry with MCA mainstem occlusion after mechanical thrombectomy between November 2009 and October 2016. All patients underwent non-enhanced post-interventional cranial CT imaging (NCCT) and were classified according to 6 patterns of BG viability: complete: putamen (P) and globus pallidus (GP); partial: P or GP, and combination of complete or partial BG and/or adjacent white matter/cortical (WMC) viability. We compared viability patterns with respect to pre-interventional stroke imaging including NCCT, CT-angiography (CTA), CT perfusion (CTP); demographics, pre- and intra-procedural data and occurrence of post-procedural intracerebral hematoma (ICH). CTP imaging of the affected and contralateral BG-territories were obtained separately and CTA-collateral score (CS) was assessed. RESULTS: A significant correlation between higher collateral score and viability of GP (OR = 1.949; p = .011), P (OR = 2.039, p = .011), and the combination of GP, P and WMC (OR = 2.767, p = .007) was revealed. Higher relative CBV ratio (rCBVR) was significantly associated with viability of the pattern GP + WMC (univariate: OR = 3.160, p = .014; multivariate: OR = 6.058; p = .021). CONCLUSION: CTA collateral score and rCBVR were predictive for BG viability in stroke patients after successful MTE in prolonged complete MCA-mainstem and LSA occlusion.

One-year single-center experience with the Aperio thrombectomy device in large vessel occlusion in the anterior circulation: safety, efficacy, and clinical outcome.

BACKGROUND AND PURPOSE: The Aperio thrombectomy device (Aperio) is a stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke due to large-vessel occlusions (LVOs). We evaluated the safety and efficacy of the Aperio device and compared it with published data of established stent retrievers. METHODS: We retrospectively analyzed institutional data of consecutive stroke procedures in patients with LVO in the anterior circulation that were treated between January 2017 and December 2017 with the Aperio. Reperfusion rate regarding to the extended thrombolysis in cerebral infarction scale (eTICI), procedural times, early clinical outcome, and complications were documented. RESULTS: Eighty-two patients were treated by using the Aperio in LVO in the anterior circulation. Median age was 77 (± 12) years (w = 59.8%). Median Baseline National Institutes of Health Stroke Scale (NIHSS) score was 14. Fifty-three (64.6%) patients received intravenous thrombolysis. Successful recanalization (eTICI≥2b) was achieved in 85.3%. Mean time from groin puncture to final recanalization was 52.3 ± 34.8 min. Embolization to new territories occurred in one case. Symptomatic intracranial hemorrhage within 24 h was observed in six patients (7.3%). Twenty-eight (41.2%) out of 68 patients available for assessment of functional outcome at 3 months achieved favorable outcome (mRS 0-2). CONCLUSION: The Aperio stent retriever mechanical thrombectomy device demonstrated high rates of successful reperfusion and a good safety profile in patients with acute ischemic stroke due to LVO in the anterior circulation.

Endovascular Thrombectomy as a Means to Improve Survival in Acute Ischemic Stroke: A Meta-analysis.

Importance: Although endovascular thrombectomy (EVT) in acute ischemic stroke is recommended by guidelines to improve functional recovery, thus far there are insufficient data on its association with mortality. Objective: To identify guideline-relevant trials of EVT vs medical therapy reporting 90-day mortality and perform a meta-analysis. Data Sources: All randomized clinical trials cited for recommendations on EVT vs medical therapy in the latest 2018 American Stroke Association/American Heart Association guidelines. Study Selection: Ten American Stroke Association/American Heart Association guideline-relevant randomized clinical trials of EVT vs medical therapy were selected for inclusion. Two EVT trials were excluded owing to infrequent use of EVT. Data Extraction and Synthesis: Data were abstracted by 2 independent investigators and double-checked by 4 others. Singular study data were integrated using the Cochran-Mantel-Haenszel method and a random-effects model to compute summary statistics of risk ratios (RR) with 95% CIs. Main Outcomes and Measures: Risk of 90-day mortality and 90-day intracranial hemorrhage was analyzed; sensitivity analyses were performed in early-window EVT trials (which included patients from the onset of symptoms onward) vs late-window EVT trials (which included patients from 6 hours after onset of symptoms onward). Results: In 10 trials with 2313 patients, EVT significantly reduced the risk for 90-day mortality by 3.7% compared with medical therapy (15.0% vs 18.7%; RR, 0.81; 95% CI, 0.68-0.98; P = .03). Trends were similar in early-window (RR, 0.83; 95% CI, 0.67-1.01; P = .06) and late-window trials only (RR, 0.76; 95% CI, 0.41-1.40; P = .38). There was no difference in the risk for intracranial hemorrhage in EVT vs medical therapy (4.2% vs 4.0%; RR, 1.11; 95% CI, 0.71-1.72; P = .65). Limitations of the studies include trial protocol heterogeneity and bias originating from prematurely terminated trials. Conclusions and Relevance: This meta-analysis of all evidence on EVT cited in the 2018 American Stroke Association/American Heart Association guidelines shows significant benefits for survival during the first 90 days after acute ischemic stroke compared with medical therapy alone.