Association of carotid atherosclerosis and recurrent cerebral infarction in the Chinese population: a meta-analysis

Jianping Liu, Yun Zhu, Yuhuai Wu, Yan Liu, Zhaowei Teng, Yinglu Hao
Dovepress. Published 20 February 2017 Volume 2017:13 Pages 527—533
DOI https://doi.org/10.2147/NDT.S124386

Stroke, when poor blood flow to the brain results in cell death, is the third leading cause of disability and mortality worldwide, and appears as an unequal distribution in the global population. The cumulative risk of recurrence varies greatly up to 10 years after the first stroke. Carotid atherosclerosis is a major risk factor for stroke. The aim of this study was to investigate and estimate the relationship between carotid atherosclerosis and risk of stroke recurrence in the Chinese population. We performed a systematic review and meta-analysis of randomized controlled trials published from 2000 to 2013, using the following databases: PubMed, Embase, Medline, Wanfang, and the China National Knowledge Infrastructure. The odds ratios with 95% confidence intervals were calculated to examine this strength. A total of 22 studies, including 3,912 patients, 2,506 first-ever cases, and 1,406 recurrent cases, were pooled in this meta-analysis. Our results showed that the frequency of carotid atherosclerosis is higher in recurrent cases than that in the first-ever controls (78.88% vs 59.38%), and the statistical analysis demonstrated significant positive association between carotid atherosclerosis and recurrent cerebral infarction (odds ratio: 2.87; 95% confidence interval: 2.42–3.37; P<0.00001) in a fixed-effect model. No significant heterogeneity was observed across all studies. In conclusion, our results showed that carotid atherosclerosis was associated with increased risk of recurrent stroke. However, further well-designed research with large sample sizes is still needed to identify the clear mechanism.

Perfusion computed tomography in patients with stroke thrombolysis.

Kawano HBivard ALin LMa HCheng XAviv RO'Brien BButcher KLou MZhang JJannes JDong QLevi CRParsons MW
Brain. 2016 Dec 31. pii: aww338. doi: 10.1093/brain/aww338. 


Stroke shortens an individual's disability-free life. We aimed to assess the relative prognostic influence of pre- and post-treatment perfusion computed tomography imaging variables (e.g. ischaemic core and penumbral volumes) compared to standard clinical predictors (such as onset-to-treatment time) on long-term stroke disability in patients undergoing thrombolysis. We used data from a prospectively collected international, multicentre, observational registry of acute ischaemic stroke patients who had perfusion computed tomography and computed tomography angiography before treatment with intravenous alteplase. Baseline perfusion computed tomography and follow-up magnetic resonance imaging were analysed to derive the baseline penumbra volume, baseline ischaemic core volume, and penumbra salvaged from infarction. The primary outcome measure was the effect of imaging and clinical variables on Disability-Adjusted Life Year. Clinical variables were age, sex, National Institutes of Health Stroke Scale score, and onset-to-treatment time. Age, sex, country, and 3-month modified Rankin Scale were extracted from the registry to calculate disability-adjusted life-year due to stroke, such that 1 year of disability-adjusted life-year equates to 1 year of healthy life lost due to stroke. There were 772 patients receiving alteplase therapy. The number of disability-adjusted life-year days lost per 1 ml of baseline ischaemic core volume was 17.5 (95% confidence interval, 13.2-21.9 days, P < 0.001). For every millilitre of penumbra salvaged, 7.2 days of disability-adjusted life-year days were saved (β = -7.2, 95% confidence interval, -10.4 to -4.1 days, P < 0.001). Each minute of earlier onset-to-treatment time resulted in a saving of 4.4 disability-free days after stroke (1.3-7.5 days, P = 0.006). However, after adjustment for imaging variables, onset-to-treatment time was not significantly associated with savings in disability-adjusted life-year days. Pretreatment perfusion computed tomography can (independently of clinical variables) predict significant gains, or loss, of disability-free life in patients undergoing reperfusion therapy for stroke. The effect of earlier treatment on disability-free life appears explained by salvage of penumbra, particularly when the ischaemic core is not too large.

Complex neurological symptoms in bilateral thalamic stroke due to Percheron artery occlusion.

Caruso PManganotti PMoretti RVasc Health Risk Manag. 2016 Dec 22;13:11-14. doi: 10.2147/VHRM.S119395. eCollection 2017.


The artery of Percheron is a rare anatomical variant where a single thalamic perforating artery arises from the proximal posterior cerebral artery (P1 segment) between the basilar artery and the posterior communicating artery and supplies the rostral mesencephalon and both paramedian territories of the thalami. Almost one-third of human brains present this variant. Occlusion of the artery of Percheron mostly results in a bilateral medial thalamic infarction, which usually manifests with altered consciousness (including coma), vertical gaze paresis, and cognitive disturbance. The presentation is similar to the "top of the basilar syndrome", and early recognition should be prompted. We describe the case of a young female with this vessel variant who experienced a bilateral thalamic stroke. Magnetic resonance angiography demonstrated bilateral thalamic infarcts and a truncated artery of Percheron. Occlusion of the vessel was presumably due to embolism from a patent foramen ovale. Thrombolysis was performed, with incomplete symptom remission, cognitive impairment, and persistence of speech disorders. Early recognition and treatment of posterior circulation strokes is mandatory, and further investigation for underlying stroke etiologies is needed.

Carotid intima media thickness and blood biomarkers of atherosclerosis in patients after stroke or myocardial infarction.

Blausen.com staff. "Blausen gallery 2014".
 https://commons.wikimedia.org/w/index.php?curid=30634275
Kurkowska-Jastrzebska I, Karlinski MA, Błazejewska-Hyzorek B, Sarzynska-Dlugosz I, Filipiak KJ, Czlonkowska A

Croat Med J. 2016 Dec 31;57(6):548-557


The aim of the study was to test if circulating levels of markers of inflammation, endothelial function, and chronic infections, as well as association between these markers and carotid intima media thickness (CIMT), depend on the stage of atherosclerosis expressed as a history of a major vascular event.
The associations were analyzed separately in 75 healthy controls, 79 patients 3-6 months after the first-ever non-cardioembolic ischemic stroke (IS), and 37 patients 3-6 months after the first-ever myocardial infarction (MI). Data were collected prospectively in 2005. We measured high sensitivity C-reactive protein (hs-CRP), procalcitonin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), serum level of immune complexes (IC), and identified antibodies against Herpes simplex virus type 1 (HSV), Cytomegalovirus, Chlamydia pneumonia, and Helicobacter pylori. Correlations with CIMT were determined using Pearson R and verified after adjustment for age, sex, hypertension, diabetes, and statin therapy.
Median ICAM-1 concentration was significantly lower in controls than in post-IS patients (188 μg/L vs 215 μg/L), and significantly lower in post-IS patients than in post-MI patients (215 μg/L vs 260 μg/L). Control patients also had significantly lower IC level (0.03 U/L) and HSV antibody index (6.0) compared to both post-IS (0.6 U/L, 9.6) and post-MI (0.4 U/L, 9.2) patients. CIMT was correlated with age (Pearson R=0.38, P=0.001) in the control group, immune complexes (R=0.26, P=0.023) in the post-IS group, and with hs-CRP (R=0.40, P=0.017) in the post-MI group. These correlations were confirmed using multiple regression analysis.
This study supports linear correlations between CIMT and IC and hs-CRP levels. However, these associations seem to depend on the type of vascular burden.

MicroRNA-181c Exacerbates Brain Injury in Acute Ischemic Stroke.

Ma Q, Zhao H, Tao Z, Wang R, Liu P, Han Z, Ma S, Luo Y, Jia J

Aging Dis. 2016 Dec;7(6):705-714


MicroRNA-181 (miR-181) is highly expressed in the brain, and downregulated in miRNA expression profiles of acute ischemic stroke patients. However, the roles of miR-181c in stroke are not known. The clinical relevance of miR-181c in acute stroke patients was evaluated by real-time PCR and correlation analyses. Proliferation and apoptosis of BV2 microglial cells and Neuro-2a cells cultured separately or together under oxidative stress or inflammation were assessed with the Cell Counting Kit-8 and by flow cytometry, respectively. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in C57/BL6 mice, and cerebral infarct volume, microglia activation, and expression of pro-apoptotic factors were evaluated by 2,3,5-triphenyl-2H-tetrazolium chloride staining, immunocytochemistry, and western blotting, respectively. Plasma levels of miR-181c were decreased in stroke patients relative to healthy individuals, and were positively correlated with neutrophil number and blood platelet count and negatively correlated with lymphocyte number. Lipopolysaccharide (LPS)/hydrogen peroxide (H2O2) treatment inhibited BV2 microglia proliferation without inducing apoptosis, while miR-181c reduced proliferation but increased the apoptosis of these cells with or without LPS/H2O2 treatment. LPS/H2O2 induced apoptosis in Neuro-2a cells co-cultured with BV2 cells, an effect that was potentiated by miR-181c. In the MCAO model, miR-181c agomir modestly increased infarct volume, markedly decreased microglia activation and B cell lymphoma-2 expression, and increased the levels of pro-apoptotic proteins in the ischemic brain. Our data indicate that miR-181c contributes to brain injury in acute ischemic stroke by promoting apoptosis of microglia and neurons via modulation of pro- and anti-apoptotic proteins.

Network-Based Approach to Identify Potential Targets and Drugs that Promote Neuroprotection and Neurorepair in Acute Ischemic Stroke.

Wang Y, Liu H, Lin Y, Liu G, Chu H, Zhao P, Yang X, Zheng T, Fan M, Zhou X, Meng J, Sun C

Sci Rep. 2017 Jan 05;7:40137


Acute ischemic stroke (AIS) accounts for more than 80% of the approximately 610,000 new stroke cases worldwide every year. Both ischemia and reperfusion can cause death, damage, and functional changes of affected nerve cells, and these alterations can result in high rates of disability and mortality. Therefore, therapies aimed at increasing neuroprotection and neurorepair would make significant contributions to AIS management. However, with regard to AIS therapies, there is currently a large gap between experimental achievements and practical clinical solutions (EC-GAP-AIS). Here, by integrating curated disease-gene associations and interactome network known to be related to AIS, we investigated the molecular network mechanisms of multi-module structures underlying AIS, which might be relevant to the time frame subtypes of AIS. In addition, the EC-GAP-AIS phenomenon was confirmed and elucidated by the shortest path lengths and the inconsistencies in the molecular functionalities and overlapping pathways between AIS-related genes and drug targets. Furthermore, we identified 23 potential targets (e.g. ADORA3, which is involved in the regulation of cellular reprogramming and the extracellular matrix) and 46 candidate drugs (e.g. felbamate, methylphenobarbital and memantine) that may have value for the treatment of AIS.

Bleeding outcomes associated with rivaroxaban and dabigatran in patients treated for atrial fibrillation: a systematic review and meta-analysis.

Bundhun PK, Soogund MZ, Teeluck AR, Pursun M, Bhurtu A, Huang WQ

BMC Cardiovasc Disord. 2017 Jan 06;17(1):15


Warfarin is commonly used as a secondary prevention of stroke in patients with atrial fibrillation (AF). However, limitations have been observed even with the use of this medication. Recently, several newer direct oral anticoagulants (DOACs) have been approved for use by the food and drug administrations. Unfortunately, these newer drugs have seldom been compared directly with each other. Therefore, this study aimed to compare the bleeding events associated with rivaroxaban and dabigatran in patients treated for non-valvular AF.
EMBASE, Medline (National Library of Medicine) and the Cochrane Central Registry of Controlled Trials were searched for studies comparing rivaroxaban with dabigatran using the terms 'rivaroxaban, dabigatran and atrial fibrillation'. Primary endpoints were: any bleeding outcomes, intracranial bleeding and gastro-intestinal (GI) bleeding. Secondary outcomes included stroke/systemic embolism (SE)/transient ischemic attack (TIA), venous thromboembolism and mortality. Odds ratios (OR) with 95% confidence intervals (CIs) were calculated. The pooled analyses were carried out with RevMan 5.3 software. All the authors had full access to the data and approved the manuscript as written.
A total number of 4895 patients were included. This analysis showed that rivaroxaban was not associated with a significantly higher bleeding event when compared to dabigatran (OR: 1.28, 95% CI: 0.95-1.72; P = 0.11). GI bleeding was similarly manifested between these two DOACs (OR: 0.98, 95% CI: 0.43-2.25; P = 0.97). Even if intracranial bleeding was higher with the use of rivaroxaban, (OR: 2.18, 95% CI: 0.51-9.25; P = 0.29), the result was not statistically significant. Moreover, stroke/SE/TIA and venous thromboembolism were also not significantly different (OR: 0.81, 95% CI: 0.53-1.23; P = 0.32) and (OR: 2.06, 95% CI: 0.73-5.82; P = 0.17) respectively. However, even if mortality favored dabigatran (OR: 1.42, 95% CI: 0.99-2.06; P = 0.06), this result only approached statistical significance.
Head to head comparison showed that rivaroxaban was not associated with significantly higher bleeding events compared to dabigatran. Intracranial bleeding, GI bleeding, stroke/SE/TIA, venous thromboembolism and mortality were also not significantly different between these two DOACs. However, due to the limited number of patients analyzed, and which were mainly obtained from observational studies, this hypothesis might only be confirmed in future randomized trials. Furthermore, the CHADS2-VASC and HAS-BLED score which might play an important role in predicting bleeding risks should also not be ignored.

Hemodynamic effects of intraoperative anesthetics administration in photothrombotic stroke model: a study using laser speckle imaging.

Lu H, Li Y, Bo B, Yuan L, Lu X, Li H, Tong S
BMC Neurosci. 2017 Jan 05;18(1):10


Previous neuroimaging studies have shown the hemodynamic effect of either preconditioning or postconditioning anesthesia in ischemic stroke model. However, the anesthetic effect in hemodynamics during and immediately after the stroke modeling surgery remains unknown due to the lack of appropriate anesthesia-free stroke model and intraoperative imaging technology. In the present study, we utilized our recently developed photothrombotic model of focal cerebral ischemia in conscious and freely moving rats, and investigated transient hemodynamic changes with or without isoflurane administration. Laser speckle imaging was applied to acquire real-time two-dimensional full-field cerebral blood flow (CBF) information throughout the surgical operations and early after.
Significantly larger CBF reduction area was observed in conscious rats from 8 min immediately after the onset of stroke modeling, compared with anesthetized rats. Stroke rats without isoflurane administration also showed larger lesion volume identified by magnetic resonance imaging 3 h post occlusion (58.9%), higher neurological severity score 24 h post occlusion (28.3%), and larger infarct volume from 2,3,5-triphenyltetrazolium chloride staining 24 h post occlusion (46.9%).
Our results demonstrated that the hemodynamic features were affected by anesthetics at as early as during the stroke induction. Also, our findings about the neuroprotection of intraoperative anesthetics administration bring additional insights into understanding the translational difficulty in stroke research.

Polymorphisms in Telomere Length Associated TERC and TERT predispose for Ischemic Stroke in a Chinese Han population.

CC BY-SA 3.0,
https://commons.wikimedia.org/w/index.php?curid=75190
Zhang S, Ji G, Liang Y, Zhang R, Shi P, Guo D, Li C, Feng J, Liu F, Peng R, Chen M
Sci Rep. 2017 Jan 06;7:40151

The role of telomere in genomic stability is an established fact. Variation in leukocyte telomere length (LTL) has been considered a crucial factor that associated with age-associated diseases. To elucidate the association between LTL variation and ischemic stroke (IS) risk, we selected ten single nucleotide polymorphisms (SNPs) in three genes (TERC, TERT and RTEL1) that previously reported link to LTL, and genotyped SNPs of these genes in a case-control study. The association between polymorphisms and IS risk were tested by Chi squared test and haplotype analysis. In allele association analysis, allele "C" in rs10936599 of TERC gene and allele "G" in rs2853677 of TERT gene were found to have an increased risk of IS when compared with allele "T" and "A", respectively. Model association analysis showed that genotype "G/A" in the overdominant model and genotypes "G/A" and "A/A" in the dominant model of rs2242652 presented a more likelihood to have IS. Another TERT locus (rs2853677) with genotype "G" was also found IS-related risky in the log-additive model. Taken together, our results suggest a potential association between LTL related TERC, TERT gene variants and ischemic stroke risk.

Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

Pace M, Adamantidis A, Facchin L, Bassetti C
PLoS One. 2017;12(1):e0168430


Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke.
Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.
A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.
Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

CX3C chemokine receptor 1 deficiency modulates microglia morphology but does not affect lesion size and short-term deficits after experimental stroke.

van der Maten G, Henck V, Wieloch T, Ruscher K

BMC Neurosci. 2017 Jan 06;18(1):11


The fractalkine/CX3C chemokine receptor 1 (CX3CR1) pathway has been identified to play an essential role in the chemotaxis of microglia, leukocyte trafficking and microglia/macrophage recruitment. It has also been shown to be important in the regulation of the inflammatory response in the early phase after experimental stroke. The present study was performed to investigate if CX3CR1 deficiency affects microglia during the first 14 days with consequences for tissue damage after experimental stroke.
CX3CR1 deficiency significantly increased the number of intersections of GFP positive microglia in the proximal peri-infarct area at 2, 7 and 14 days following tMCAO compared to heterozygous and wildtype littermates. In addition, the length of microglial branches increased until day 7 in CX3CR1 knockout mice while the presence of a functional CX3CR1 allele resulted in a gradual reduction of their length following tMCAO. After stroke, wildtype, heterozygous and CX3CR1 deficient mice did not show differences in the composite neuroscore and assessment of infarct volumes from CX3CR1 wildtype, heterozygous and deficient mice revealed no differences between the genotypes 7 and 14 days after stroke.
Results demonstrate that CX3CR1 deficiency affects the morphology of GFP positive microglia located in the proximal peri-infarct region during the first 14 days after tMCAO. Our data also indicate that CX3CR1 deficiency does not affect definite infarct volumes. Modulation of the CX3CR1 pathway may have implication for microglia function contributing to mechanisms of tissue reorganization in the post-ischemic brain.

Ischemic stroke: experimental models and reality.

By Blausen Medical Communications, Inc.
 Donated via OTRS, see ticket for details, CC BY 3.0,
https://commons.wikimedia.org/w/index.php?curid=26986798
Sommer CJ

Acta Neuropathol. 2017 Jan 07;:


The vast majority of cerebral stroke cases are caused by transient or permanent occlusion of a cerebral blood vessel ("ischemic stroke") eventually leading to brain infarction. The final infarct size and the neurological outcome depend on a multitude of factors such as the duration and severity of ischemia, the existence of collateral systems and an adequate systemic blood pressure, etiology and localization of the infarct, but also on age, sex, comorbidities with the respective multimedication and genetic background. Thus, ischemic stroke is a highly complex and heterogeneous disorder. It is immediately obvious that experimental models of stroke can cover only individual specific aspects of this multifaceted disease. A basic understanding of the principal molecular pathways induced by ischemia-like conditions comes already from in vitro studies. One of the most frequently used in vivo models in stroke research is the endovascular suture or filament model in rodents with occlusion of the middle cerebral artery (MCA), which causes reproducible infarcts in the MCA territory. It does not require craniectomy and allows reperfusion by withdrawal of the occluding filament. Although promptly restored blood flow is far from the pathophysiology of spontaneous human stroke, it more closely mimics the therapeutic situation of mechanical thrombectomy which is expected to be increasingly applied to stroke patients. Direct transient or permanent occlusion of cerebral arteries represents an alternative approach but requires craniectomy. Application of endothelin-1, a potent vasoconstrictor, allows induction of transient focal ischemia in nearly any brain region and is frequently used to model lacunar stroke. Circumscribed and highly reproducible cortical lesions are characteristic of photothrombotic stroke where infarcts are induced by photoactivation of a systemically given dye through the intact skull. The major shortcoming of this model is near complete lack of a penumbra. The two models mimicking human stroke most closely are various embolic stroke models and spontaneous stroke models. Closeness to reality has its price and goes along with higher variability of infarct size and location as well as unpredictable stroke onset in spontaneous models versus unpredictable reperfusion in embolic clot models.

Multiple Cerebrovascular Complications due to Sphenoid Sinusitis.

Sadineni RT, Velicheti S, Kondragunta CS, Bellap NC

J Clin Diagn Res. 2016 Nov;10(11):TD03-TD05

Sphenoiditis is of particular interest because the sphenoid sinus has thin wall and its special anatomical location facilitate dissemination of infection to many intracranial structures including vascular structures. The main objective of this report is to gain insight into patterns of presentation and imaging findings in cerebrovascular complications of sphenoid sinusitis and to emphasize the need of reviewing Brain Computed Tomography Scan in all windows. This is a report of 32-year-old young female presented with fever and headache who was diagnosed to have sphenoid sinusitis after radiological examination. Sphenoid sinusitis may involve several intracranial structures, with potentially severe or even fatal complications. Prompt diagnosis and antibiotic/antifungal therapy is essential to minimize mortality and morbidity.

Neurovascular 4D Parametric Imaging Using Co-Registration of Biplane DSA Sequences with 3D Vascular Geometry Obtained From Cone Beam CT.

Balasubramoniam A, Bednarek D, Rudin S, Ionita C
Med Phys. 2016 Jun;43(6):3784-3785

PURPOSE: To create 4D parametric images using biplane Digital Subtraction Angiography (DSA) sequences co-registered with the 3D vascular geometry obtained from Cone Beam-CT (CBCT).
METHODS: We investigated a method to derive multiple 4D Parametric Imaging (PI) maps using only one CBCT acquisition. During this procedure a 3D-DSA geometry is stored and used subsequently for all 4D images. Each time a biplane DSA is acquired, we calculate 2D parametric maps of Bolus Arrival Time (BAT), Mean Transit Time (MTT) and Time to Peak (TTP). Arterial segments which are nearly parallel with one of the biplane imaging planes in the 2D parametric maps are co-registered with the 3D geometry. The values in the remaining vascular network are found using spline interpolation since the points chosen for co-registration on the vasculature are discrete and remaining regions need to be interpolated. To evaluate the method we used a patient CT volume data set for 3D printing a neurovascular phantom containing a complete Circle of Willis. We connected the phantom to a flow loop with a peristaltic pump, simulating physiological flow conditions. Contrast media was injected with an automatic injector at 10 ml/sec. Images were acquired with a Toshiba Infinix C-arm and 4D parametric image maps of the vasculature were calculated.
RESULTS: 4D BAT, MTT, and TTP parametric image maps of the Circle of Willis were derived. We generated color-coded 3D geometries which avoided artifacts due to vessel overlap or foreshortening in the projection direction.
CONCLUSION: The software was tested successfully and multiple 4D parametric images were obtained from biplane DSA sequences without the need to acquire additional 3D-DSA runs. This can benefit the patient by reducing the contrast media and the radiation dose normally associated with these procedures. Partial support from NIH Grant R01-EB002873 and Toshiba Medical Systems Corp.

Functional Long-Term Outcome after Left- versus Right-Sided Intracerebral Hemorrhage.

Beuscher VD, Kuramatsu JB, Gerner ST, Köhn J, Lücking H, Kloska SP, Huttner HB
Cerebrovasc Dis. 2017 Jan 04;43(3-4):117-123


Hemispheric location might influence outcome after intracerebral hemorrhage (ICH). INTERACT suggested higher short-term mortality in right hemispheric ICH, yet statistical imbalances were not addressed. This study aimed at determining the differences in long-term functional outcome in patients with right- vs. left-sided ICH with a priori-defined sub-analysis of lobar vs. deep bleedings.
METHODS: Data from a prospective hospital registry were analyzed including patients with ICH admitted between January 2006 and August 2014. Data were retrieved from institutional databases. Outcome was assessed using the modified Rankin Scale (mRS) score. Outcome measures (long-term mortality and functional outcome at 12 months) were correlated with ICH location and hemisphere, and the imbalances of baseline characteristics were addressed by propensity score matching.
RESULTS: A total of 831 patients with supratentorial ICH (429 left and 402 right) were analyzed. Regarding clinical baseline characteristics in the unadjusted overall cohort, there were differences in disfavor of right-sided ICH (antiplatelets: 25.2% in left ICH vs. 34.3% in right ICH; p < 0.01; previous ischemic stroke: 14.7% in left ICH vs. 19.7% in right ICH; p = 0.057; and presence/extent of intraventricular hemorrhage: 45.0% in left ICH vs. 53.0% in right ICH; p = 0.021; Graeb-score: 0 [0-4] in left ICH vs. 1 [0-5] in right ICH; p = 0.017). While there were no differences in mortality and in the proportion of patients with favorable vs. unfavorable outcome (mRS 0-3: 142/375 [37.9%] in left ICH vs. 117/362 [32.3%] in right ICH; p = 0.115), patients with left-sided ICH showed excellent outcome more frequently (mRS 0-1: 64/375 [17.1%] in left ICH vs. 43/362 [11.9%] in right ICH; p = 0.046) in the unadjusted analysis. After adjusting for confounding variables, a well-balanced group of patients (n = 360/hemisphere) was compared showing no differences in long-term functional outcome (mRS 0-3: 36.4% in left ICH vs. 33.9% in right ICH; p = 0.51). Sub-analyses of patients with deep vs. lobar ICH revealed also no differences in outcome measures (mRS 0-3: 53/151 [35.1%] in left deep ICH vs. 53/165 [32.1%] in right deep ICH; p = 0.58).
CONCLUSION: Previously described differences in clinical end points among patients with left- vs. right-hemispheric ICH may be driven by different baseline characteristics rather than by functional deficits emerging from different hemispheric functions affected. After statistical corrections for confounding variables, there was no impact of hemispheric location on functional outcome after ICH.

Systemic Atherosclerosis Relate to Brain Arterial Diameters: The Northern Manhattan Study.

Gutierrez J, Rundek T, Cheung K, Bagci A, Alperin N, Sacco RL, Wright CB, Elkind MS, Di Tullio MR
Cerebrovasc Dis. 2017 Jan 04;43(3-4):124-131

Phenotypic expressions of arterial disease vary throughout the body and it is not clear to what extent systemic atherosclerosis influences brain arterial remodeling. We aim to test the hypothesis that systemic atherosclerosis is associated with brain arterial diameters.
METHODS: Stroke-free participants in the Northern Manhattan Study MRI subcohort in whom carotid ultrasound, transthoracic echocardiogram, and brain MRA (n = 482) were performed were included in this analysis. Brain arterial diameters were measured with semi-automated software as continuous and categorical variables. Ultrasound and echocardiography provided the sum of maximum carotid plaque thickness (sMCPT) and aortic plaque thickness. Associations between brain arterial diameters and aortic and carotid plaque thickness were assessed with semi-parametric generalized additive models.
RESULTS: Aortic plaque thickness was inversely and linearly associated with brain arterial diameters (B per mm = -0.073 ± 0.034, p = 0.03), while sMCPT was associated nonlinearly in a u-shaped curve with anterior brain arterial diameters (spline regression χ2 = 9.19, p = 0.02). Coexisting carotid and aortic atherosclerosis were more prevalent in participants with small luminal diameters (40%) compared with participants with average (30%) or with large (13%) luminal diameters, while carotid atherosclerosis without aortic atherosclerosis was more prevalent among participants with large luminal diameters (31%) compared with those with average (12%) or small luminal diameters (2%, p < 0.001 for both trends).
CONCLUSIONS: We confirmed the hypothesis that systemic arterial disease is associated with brain arterial diameters. Gaining knowledge about the origin of these phenotypic expressions of atherosclerosis in the human body may lead to a better understanding of the cerebrovascular consequences of the systemic arterial disease.

Aortic Atherosclerosis Determines Increased Retrograde Blood Flow as a Potential Mechanism of Retrograde Embolic Stroke

Wehrum T, Guenther F, Vach W, Gladstone BP, Wendel S, Fuchs A, Wu K, Maurer CJ, Harloff A
Cerebrovasc Dis. 2017 Jan 04;43(3-4):132-138

Retrograde brain embolization from complex plaques of the proximal descending aorta (DAo) has been identified as a new potential mechanism of stroke. Our purpose was to identify predictors of increased retrograde aortic blood flow indicating an elevated risk of brain embolization from the DAo.
METHODS: A total of 485 patients with acute ischemic stroke were prospectively included and underwent transesophageal echocardiography. Blood flow velocities in the proximal DAo were studied using 2D pulse-wave Doppler ultrasound. Velocity-time integrals (VTI) were calculated for antegrade and retrograde velocity directions. The ratio (VTIretrograde/VTIantegrade) was used to estimate retrograde flow extent. Associations between patient demographics, cardiovascular risk factors, echocardiographic parameters, and VTIratio were analyzed using multivariate linear regression.
RESULTS: Retrograde blood flow in the DAo occurred in all patients. Velocity profiles in the proximal DAo were as follows (mean ± SD): VTIantegrade = 21.1 ± 6.5, VTIretrograde = 11.0 ± 3.6, and VTIratio = 0.54 ± 0.16. Diameter (r = 0.25, p < 0.001), presence of complex plaques (r = 0.12, p = 0.007), and reduced strain of the DAo (r = -0.23, p < 0.001) had significant partial effects in a predictor model based on predefined variables, which predicted 26% (adjusted R2 = 0.26) of the variance in VTIratio. A unit increase in the DAo diameter was associated with a 2% increase in VTIratio (95% CI 1-2.8%, p < 0.001). Presence of complex plaques increased VTIratio by 7% (95% CI 2-13%, p = 0.007) and an increase in strain by 0.1 indicated a decrease in VTIratio by about 11% (95% CI 6.2-15.5%, p < 0.001). Complex atheroma was found in the proximal DAo of 79 subjects, of which 40 (50.6%) had a VTIratio above average (VTIratio ≥0.54) compared to 87 of 261 (33.3%) patients without any complex plaques (p < 0.001). Twenty-five of 79 (31.7%) patients with complex DAo plaques had a VTIratio ≥0.60, which indicates a high likelihood of retrograde pathline length of ≥3 cm and thus increased risk of retrograde cerebral embolization. Stroke etiology of those 25 patients was determined in 13 and cryptogenic in 12 cases.
CONCLUSIONS: Retrograde blood flow in the DAo was found in all stroke patients. However, it increased further in patients with concomitant complex plaques, low strain, and/or large aortic diameter, that is, in those with atherosclerosis of the DAo. Accordingly, such patients may be predisposed to retrograde embolization in case of occurrence of a complex plaque in proximity to a brain-supplying artery.
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Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke.

Champaloux SW, Tepper NK, Monsour M, Curtis KM, Whiteman MK, Marchbanks PA, Jamieson DJ
Am J Obstet Gynecol. 2016 Dec 26;:

    Migraine with aura and combined hormonal contraceptives are independently associated with an increased risk of ischemic stroke. However, little is known about whether there are any joint effects of migraine and hormonal contraceptives on risk of stroke.
To estimate the incidence of stroke in women of reproductive age and examine the association between combined hormonal contraceptive use, migraine type (with or without aura), and ischemic stroke.
This study used a nationwide health care claims database and employed a nested case control study design. Women ages 15-49 years with first-ever stroke during 2006-2012 were identified using the International Classification of Diseases-9th Revision-Clinical Modifications inpatient services diagnosis codes. Four controls were matched to each case based on age. Migraine headache with and without aura was identified using inpatient or outpatient diagnosis codes. Current combined hormonal contraceptive use was identified using the National Drug Code from the pharmacy database. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals of ischemic stroke by migraine type and combined hormonal contraceptive use.
Between 2006-2012, there were 25,887 ischemic strokes among women ages 15-49, for a cumulative incidence of 11 strokes per 100,000 women. Compared to women with neither migraine nor combined hormonal contraceptive use, the odds ratio of ischemic stroke was highest among women with migraine with aura using combined hormonal contraceptives (odds ratio 6.1, 95% confidence interval 3.1-12.1); odds ratios were also elevated for migraine with aura without combined hormonal contraceptive use (odds ratio 2.7, 95% confidence interval 1.9-3.7), migraine without aura and combined hormonal contraceptive use (odds ratio 1.8, 95% confidence interval 1.1-2.9), and migraine without aura without combined hormonal contraceptive use (odds ratio 2.2, 95% confidence interval 1.9-2.7).
The joint effect of combined hormonal contraceptives and migraine with aura was associated with a 6-fold increased risk of ischemic stroke compared with neither risk factor. Use of combined hormonal contraceptives did not substantially further increase risk of ischemic stroke among women with migraine without aura. Determining migraine type is critical in assessing safety of combined hormonal contraceptives among women with migraine.

Stroke Rehabilitation Long Term Rehabilitation After Stroke

NICE Clinical Guidelines, No. 162

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London: Royal College of Physicians (UK).
The aim of this guideline development group was to review the structure, processes and interventions currently used in rehabilitation care, and to evaluate whether they improve outcomes for people with stroke. Such studies are complex and research methodologies need to be robust. Evaluation of clinical effectiveness needs studies that have robust theoretical underpinnings, capture changes that are relevant to the treatment evaluated and reflect what is important to patients, and be large enough to allow reliable data interpretation. This guideline reviews some of the available interventions that can be used in stroke rehabilitation, and highlights where there are gaps in the evidence. It is not intended to be comprehensive.

Rehabilitation robotics for the upper extremity: review with new directions for orthopaedic disorders.

Hakim RM, Tunis BG, Ross MD
Disabil Rehabil Assist Technol. 2016 Dec 30;:1-7  
The focus of research using technological innovations such as robotic devices has been on interventions to improve upper extremity function in neurologic populations, particularly patients with stroke. There is a growing body of evidence describing rehabilitation programs using various types of supportive/assistive and/or resistive robotic and virtual reality-enhanced devices to improve outcomes for patients with neurologic disorders. The most promising approaches are task-oriented, based on current concepts of motor control/learning and practice-induced neuroplasticity. Based on this evidence, we describe application and feasibility of virtual reality-enhanced robotics integrated with current concepts in orthopaedic rehabilitation shifting from an impairment-based focus to inclusion of more intense, task-specific training for patients with upper extremity disorders, specifically emphasizing the wrist and hand. The purpose of this paper is to describe virtual reality-enhanced rehabilitation robotic devices, review evidence of application in patients with upper extremity deficits related to neurologic disorders, and suggest how this technology and task-oriented rehabilitation approach can also benefit patients with orthopaedic disorders of the wrist and hand. We will also discuss areas for further research and development using a task-oriented approach and a commercially available haptic robotic device to focus on training of grasp and manipulation tasks. Implications for Rehabilitation There is a growing body of evidence describing rehabilitation programs using various types of supportive/assistive and/or resistive robotic and virtual reality-enhanced devices to improve outcomes for patients with neurologic disorders. The most promising approaches using rehabilitation robotics are task-oriented, based on current concepts of motor control/learning and practice-induced neuroplasticity. Based on the evidence in neurologic populations, virtual reality-enhanced robotics may be integrated with current concepts in orthopaedic rehabilitation shifting from an impairment-based focus to inclusion of more intense, task-specific training for patients with UE disorders, specifically emphasizing the wrist and hand. Clinical application of a task-oriented approach may be accomplished using commercially available haptic robotic device to focus on training of grasp and manipulation tasks.