Long-Term Brain Atrophy after Focal Ischemic Stroke: A Longitudinal Study Applying Deformation-Based Morphometry

2004 ◽  
Vol 35 (03) ◽  
Author(s):  
S Schnaudigel ◽  
T Ugur ◽  
F Kruggel ◽  
HJ Mentzel ◽  
C Fitzek ◽  
...  
Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ping Sun ◽  
Feifei Ma ◽  
Chao Zhou ◽  
R. Anne Stetler ◽  
Jun Chen ◽  
...  

Introduction: Cerebral angiogenesis is tightly controlled by certain microRNAs (miRs), such as the miR-15a/16-1 cluster, among others. Recently, we demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery by increasing protein levels of VEGFA, FGF2, and their receptors VEGFR2 and FGFR1. Here, we further investigated the downstream signaling pathways of these pro-angiogenic factors by using a potent Src family inhibitor, saracatinib (AZD0530), in endothelial cell-selective miR-15a/16-1 conditional knockout (EC-miR-15a/16-1 cKO) mice after ischemic stroke. Hypothesis: Pharmacological inhibition of Src signaling cascade using AZD0530 diminishes enhanced post-stroke angiogenesis and long-term neurological recovery induced by the genetic deletion of miR-15a/16-1 in the endothelium. Methods: EC-miR-15a/16-1 cKO and WT littermate controls were subjected to 1h MCAO and 28d reperfusion. AZD0530 (20 mg/kg) was administered daily to both genotypes at 3-21d after MCAO by oral gavage. Cognitive outcomes were determined by Morris water maze tests. Brain atrophy was measured by MAP2 immunostaining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Brain capillary density and functional vessels were examined by CD31/BrdU and tomato lectin/BrdU double-immunostaining, respectively. Src signaling pathway-related molecules were analyzed by western blotting. Results: Treatment with AZD0530 exacerbates cognitive impairments and brain atrophy in EC-miR-15a/16-1 cKO mice following MCAO. AZD0530 also attenuates the long-term CBF recovery, correlated with inhibiting the generation of newly formed microvessels and functional vessels in the peri-infarct brain regions in EC-miR-15a/16-1 cKO mice after cerebral ischemia. Moreover, EC-targeted deletion of miR-15a/16-1 upregulates the Src signaling pathway, while AZD0530 blocks the Src signaling pathway by downregulating p-Src and its downstream mediators (p-Stat3, p-Akt, p-FAK, p-p38 MAPK) in ischemic brains. Conclusions: Endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery via Src signaling pathway.


2019 ◽  
Vol 121 (2) ◽  
pp. 620-633
Author(s):  
Roman Rosipal ◽  
Natália Porubcová ◽  
Peter Barančok ◽  
Barbora Cimrová ◽  
Igor Farkaš ◽  
...  

We provide direct electrophysiological evidence that mirror therapy (MT) can change brain activity and aid in the recovery of motor function after stroke. In this longitudinal single-case study, the subject was a 58-yr-old man with right-hand hemiplegia due to ischemic stroke. Over a 9-mo period we treated him with MT twice a week and measured electroencephalograms (EEG) before, during, and after each therapy session. Using advanced signal processing methods, we identified five distinct movement-related oscillatory EEG components: one slow component designated as mu rhythm and four faster components designated as sensorimotor rhythms. Results show that MT produced long-term changes of two oscillatory EEG components including the mu rhythm, which is a well-documented correlate of voluntary movement in the frequency range of 7.5–12 Hz. Specifically, MT was significantly associated with an increase in the power of mu rhythm recorded over both hemispheres and a decrease in the power of one sensorimotor component recorded over the affected hemisphere. To obtain robust, repeatable individual measures of EEG components suitable for longitudinal study, we used irregular-resampling autospectral analysis to separate fractal and oscillatory components in the EEG power spectrum and three-way parallel factor analysis to isolate oscillatory EEG components and track their activations over time. The rhythms were identified over individual days of MT training and were clearly related to the periods of event-related desynchronization and synchronization (rest, observe, and move) during MT. Our results are consistent with a model in which MT promotes recovery of motor function by altering neural activity associated with voluntary movement. NEW & NOTEWORTHY We provide novel evidence that mirror therapy (MT), which helps in the recovery of motor function after a stroke, is also associated with long-lasting changes in brain electrical activity. Using precise measurements of oscillatory EEG components over a 9-mo period in a victim of ischemic stroke, we showed that MT produced long-term increases in the mu rhythm recorded over both hemispheres and a decrease in a sensorimotor EEG component recorded over the affected hemisphere.


2019 ◽  
Vol 24 (5) ◽  
pp. 558-571 ◽  
Author(s):  
Kartik Bhatia ◽  
Hans Kortman ◽  
Christopher Blair ◽  
Geoffrey Parker ◽  
David Brunacci ◽  
...  

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.


BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e024980 ◽  
Author(s):  
Tiia T M Reho ◽  
Salla A Atkins ◽  
Nina Talola ◽  
Markku P T Sumanen ◽  
Mervi Viljamaa ◽  
...  

ObjectivesFrequent attenders (FAs) create a substantial portion of primary care workload but little is known about FAs’ sickness absences. The aim of the study is to investigate how occasional and persistent frequent attendance is associated with sickness absences among the working population in occupational health (OH) primary care.Setting and participantsThis is a longitudinal study using medical record data (2014–2016) from an OH care provider in Finland. In total, 59 676 patients were included and categorised into occasional and persistent FAs or non-FAs. Sick-leave episodes and their lengths were collected along with associated diagnostic codes. Logistic regression was used to analyse associations between FA status and sick leaves of different lengths (1–3, 4–14 and ≥15 days).ResultsBoth occasional and persistent FA had more and longer duration of sick leave than non-FA through the study years. Persistent FAs had consistently high absence rates. Occasional FAs had elevated absence rates even 2 years after their frequent attendance period. Persistent FAs (OR=11 95% CI 7.54 to 16.06 in 2016) and occasional FAs (OR=2.95 95% CI 2.50 to 3.49 in 2016) were associated with long (≥15 days) sickness absence when compared with non-FAs. Both groups of FAs had an increased risk of long-term sick leaves indicating a risk of disability pension.ConclusionBoth occasional and persistent FAs should be identified in primary care units caring for working-age patients. As frequent attendance is associated with long sickness absences and possibly disability pensions, rehabilitation should be directed at this group to prevent work disability.


BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zheng Wang ◽  
Jiangyong Miao ◽  
Lina Wang ◽  
Ying Liu ◽  
Hui Ji ◽  
...  

Abstract Background Presentation with massive systemic embolization as the initial manifestation of occult malignancy is infrequent. The standard management of cancer-related arterial thromboembolism has not yet been established. Case presentation We described a case of Trousseau’s syndrome resulting in acute ischemic stroke concomitant with multiple embolizations in the spleen and kidney during oral administration of dabigatran for pulmonary embolism preceding the diagnosis of a malignant tumor. A cancer-related hypercoagulable state was suspected because the patient was admitted to the neurology department due to acute ischemic stroke with three territory infarcts on diffusion-weighted imaging (DWI) in the absence of identifiable conventional risk factors and brain vessel narrowing. The patient was subsequently diagnosed with epidermal growth factor receptor (EGFR) mutation–positive non-small-cell lung cancer (NSCLC) (stage IV) with pleural metastasis. Administration of low-molecular-weight heparin followed by long-term dabigatran under effective cancer therapy comprising gefitinib and subsequent chemotherapy did not cause stroke relapse during the 1-year follow-up. Conclusions This case suggests that cancer-related hypercoagulability should be considered an important etiology for stroke patients who develop unexplained disseminated acute cerebral infarction without conventional stroke risk factors, especially concomitant with multiple organ embolization. Novel oral anticoagulants may be an alternative therapy for the long-term management of cancer-related arterial thromboembolism under effective cancer therapy.


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