Stroke Factors Associated with Thrombolysis Use in Hospitals in Singapore and US: A Cross-Registry Comparative Study.

BACKGROUND AND OBJECTIVES: This paper aims to describe and compare the characteristics of 2 stroke populations in Singapore and in St. Louis, USA, and to document thrombolysis rates and contrast factors associated with its uptake in both populations. METHODS: The stroke populations described were from the Singapore Stroke Registry (SSR) in -Singapore and the Cognitive Rehabilitation Research Group Stroke Registry (CRRGSR) in St. Louis, MO, USA. The registries were compared in terms of demographics and stroke risk factor history. Logistic regression was used to determine factors associated with thrombolysis uptake. RESULTS: A total of 39,323 and 8,106 episodes were recorded in SSR and CRRGSR, respectively, from 2005 to 2012. Compared to CRRGSR, patients in SSR were older, male, and from the ethnic majority. Thrombolysis rates in SSR and CRRGSR were 2.5 and 8.2%, respectively, for the study period. History of ischemic heart disease or atrial fibrillation was associated with increased uptake in both populations, while history of stroke was associated with lower uptake. For SSR, younger age and males were associated with increased uptake, while having a history of smoking or diabetes was associated with decreased uptake. For CRRGSR, ethnic minority status was associated with decreased uptake. CONCLUSIONS: The comparison of stroke populations in Singapore and St Louis revealed distinct differences in clinicodemographics of the 2 groups. Thrombolysis uptake was driven by nonethnicity demographics in Singapore. Ethnicity was the only demographic driver of uptake in the CRRGSR population, highlighting the need to target ethnic minorities in increasing access to thrombolysis.

Early Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Infarction in Asian Patients: A Single-Center Study.

INTRODUCTION: Early decompression craniectomy (within 48 hours of stroke onset) in acute and malignant middle cerebral artery (MCA) ischemic stroke (IS) reduces mortality and increases the proportion of patients with favorable functional outcome. Various cultural and social issues among Asians lead to some differences in clinical practice, especially when surgical interventions are involved. Accordingly, decompressive craniectomy in Asian patients with stroke is often delayed. MATERIALS AND METHODS: Data for all patients with acute IS hospitalized in our center were entered into a prospectively maintained registry. In this retrospective analysis, data for all patients with malignant MCA IS who underwent decompressive craniectomy were extracted. Various demographic, clinical, and neuroimaging factors were analyzed for identifying independent predictors of favorable functional outcome at 6 months, which was defined as modified Rankin Scale score of 0-3 points. RESULTS: From January 2005 to December 2014, a total of 75 patients with acute MCA IS underwent decompressive craniectomy. Median age was 55 years (interquartile range 44-64) with male preponderance (66%) and median National Institute of Health Stroke Scale score 21 points (interquartile range 18-24). A considerable proportion of these patients (38.7%) received intravenous thrombolysis. The majority (70%) of patients suffered right MCA IS, and decompressive surgery was performed within 48 hours of symptom onset in 50 (67%) of the patients. Favorable functional outcome was achieved in 25 (33.3%) patients at 6 months. Right MCA stroke (odds ratio 9.158; 95% confidence interval 1.881-44.596, P = 0.006) and early decompression surgery (odds ratio 4.011; 95% confidence interval 1.058-15.208, P = 0.041) were independent predictors of favorable functional outcome at 6 months. CONCLUSIONS: Early decompression craniectomy, especially in right MCA ischemic stroke, is associated with better favorable functional outcome.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

Improvement in cerebral hemodynamic parameters and outcomes after superficial temporal artery-middle cerebral artery bypass in patients with severe stenoocclusive disease of the intracranial internal carotid or middle cerebral arteries.

OBJECT: Both the older and the recent extracranial-intracranial (EC-IC) bypass trials for symptomatic carotid occlusion failed to demonstrate a reduction in stroke recurrence. However, the role of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass in patients with symptomatic intracranial stenoocclusive disease has been rarely evaluated. The authors evaluated serial changes in various cerebral hemodynamic parameters in patients with severe stenoocclusive disease of the intracranial internal carotid artery (ICA) or middle cerebral artery (MCA) and impaired cerebral vasodilatory reserve (CVR), treated by STA-MCA bypass surgery or medical treatment. METHODS: Patients with severe stenoocclusive disease of the intracranial ICA or MCA underwent transcranial Doppler (TCD) ultrasonography and CVR assessment using the breath-holding index (BHI). Patients with impaired BHI (< 0.69) were further evaluated with acetazolamide-challenge technitium-99m hexamethylpropyleneamine oxime ((99m)Tc HMPAO) SPECT. STA-MCA bypass surgery was offered to patients with impaired CVR on SPECT. All patients underwent TCD and SPECT at 4 ± 1 months and were followed up for cerebral ischemic events. RESULTS: A total of 112 patients were included. This total included 73 men, and the mean age of the entire study population was 56 years (range 23-78 years). (99m)Tc HMPAO SPECT demonstrated impaired CVR in 77 patients (69%). Of these 77 patients, 46 underwent STA-MCA bypass while 31 received best medical treatment. TCD and acetazolamide-challenge (99m)Tc HMPAO SPECT repeated at 4 ± 1 months showed significant improvement in the STA-MCA bypass group. During a mean follow-up of 34 months (range 18-39 months), only 6 (13%) of 46 patients in the bypass group developed cerebral ischemic events, as compared with 14 (45%) of 31 patients receiving medical therapy (absolute risk reduction 32%, p = 0.008). CONCLUSIONS: STA-MCA bypass surgery in carefully selected patients with symptomatic severe intracranial stenoocclusive disease of the intracranial ICA or MCA results in significant improvement in hemodynamic parameters and reduction in stroke recurrence.

CHInese Medicine NeuroAiD Efficacy on Stroke Recovery - Extension Study (CHIMES-E): A Multicenter Study of Long-Term Efficacy.

BACKGROUND: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. METHODS: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. RESULTS: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. CONCLUSIONS: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke.

The synergy in cytokine production through MyD88-TRIF pathways is co-ordinated with ERK phosphorylation in macrophages.

Although specific single Toll-like receptor (TLR) ligands are known to drive the development of Th1 or Th2 immunity, the outcome of different combinations of TLR ligands on innate immunity is not well defined. Spatiotemporal dynamics are critical in determining the specificity of the immune response, but the mechanisms underlying combinatorial TLR stimulation remain unclear. Here, we tested pairwise combinations of TLR ligands separated by different time intervals for their effect on cytokine production in macrophages. We observed that stimulation via a combination of MyD88- and TRIF-utilizing adaptors leads to a highly synergistic cytokine response. On a timescale of 4-24 h, macrophages pretreated with poly(I:C) (TLR3 ligand) are cross-primed to a second stimulation with R848 (TLR7 ligand) and vice versa, and each condition exhibits different optimal time windows of synergistic response for each cytokine. We show that the synergy resulting from combinatorial stimuli (poly(I:C) and R848 is also regulated by the order and dosage of the TLR agonists. Secondary response genes, which depend on new protein synthesis for transcription, show greater synergy than primary response genes, and such enhancement is abolished when new protein synthesis is inhibited. Synergistic cytokine production appears concordant with sustained ERK phosphorylation, suggesting that the de novo factors act via inhibition of ERK dephosphorylation, for example, by the downregulation of dual specificity phosphatase 6. Taken together, our findings illustrate a checkpoint in the innate immune system, where the synchronization of timing of both MyD88 and TRIF pathways is required for a maximal cytokine response and potential memory effect in macrophages.

Cerebral hyperperfusion syndrome after superficial temporal artery-middle cerebral artery bypass for severe intracranial steno-occlusive disease: a case control study.

BACKGROUND: Intracranial stenoses carry increased risk for cerebral ischemia. We perform external carotid-internal carotid (EC-IC) artery bypass in our patients with severe stenosis of the intracranial internal carotid (ICA) or middle cerebral artery (MCA) with impaired cerebral vasodilatory reserve (CVR). OBJECTIVE: To evaluate cerebral hemodynamics and cerebral hyperperfusion syndrome (HPS) in patients who develop focal neurological deficits after EC-IC bypass surgery. METHODS: Patients with severe intracranial ICA or MCA stenosis and impaired CVR on transcranial Doppler (TCD) derived breath-holding index (BHI) were evaluated with acetazolamide-challenged technetium-99m hexamethylpropyleneamineoxime-single-photon emission computed tomography (SPECT). EC-IC bypass surgery was offered to patients with impaired CVR on SPECT. Close monitoring was performed in patients developing focal neurological deficits within 7 days of surgery. RESULTS: Of 112 patients with severe intracranial ICA/MCA stenosis, 77 (69%) showed impaired CVR and 46 (41%) underwent EC-IC bypass. Transient neurological deficits within 7 days of surgery developed in 8 (17%). HPS was confirmed by CT perfusion and/or SPECT in 7 cases. A strong correlation was observed between HPS and preoperative TCD-BHI values (0%, 6.3%, and 41% in patients with BHI 0.3-0.69, 0-0.3 and <0, respectively; P = .012). HPS patients showed more than a 50% increase in MCA flow velocity on TCD (compared with preoperative values) on the operated side (63.3% vs 3.3% on control side, P < .001). Meticulous control of blood pressure and hydration led to rapid and complete resolution of neurological deficits in all cases. CONCLUSION: Symptomatic cerebral HPS is common in the early postoperative period after EC-IC bypass surgery. Early diagnosis and appropriate management might prevent the complications of this syndrome.

Changes in cerebral hemodynamic and cognitive parameters after external carotid-internal carotid bypass surgery in patients with severe steno-occlusive disease: a pilot study.

BACKGROUND: The direct impact of external carotid-internal carotid (EC-IC) bypass surgery on cognition of patients with severe steno-occlusive disease of internal carotid (ICA) or middle cerebral artery (MCA) is unknown. In this pilot study, we evaluated changes in cerebral hemodynamic and cognition in these patients. METHODS: Patients with severe steno-occlusive disease and impaired cerebral vasodilatory reserve (CVR) with transcranial Doppler (TCD) breath holding index (BHI) and acetazolamide-challenged HMPAO-Single Photon Emission Tomographic (SPECT) imaging were offered EC-IC bypass surgery. CVR and cognitive performance using a formal neuropsychological battery were evaluated before and 3-6 months after surgery. RESULTS: Nine patients and 9 matched controls were recruited. Significant CVR improvement from TCD-BHI [median 0 (Inter-quartile range IQR 0.45) to 1.10 (IQR 0.73), p<0.001] and SPECT (p<0.001) was observed in surgery patients. EC-IC bypass patients had significant improvement in verbal memory (p=0.037) and executive function (p=0.043) and a trend of improvement in visual memory (p=0.052) compared to controls. CONCLUSION: EC-IC bypass surgery in carefully selected patients could improve cerebral hemodynamics and verbal memory and executive function.

Safety of transcranial Doppler 'bubble study' for identification of right to left shunts: an international multicentre study.

BACKGROUND AND PURPOSE: A recent retrospective study using an online list service established by the American Academy of Neurology has suggested that ischaemic cerebrovascular events may occur in patients who undergo 'bubble studies' (BS) with either transcranial Doppler (TCD) or transoesophageal echocardiography (TOE). The safety of TCD-BS for right to left shunt (RLS) identification was evaluated prospectively in an international multicentre study. METHODS: Consecutive patients with cerebral ischaemia (ischaemic stroke or transient ischaemic attack (TIA)) were screened for potential ischaemic cerebrovascular events following injection of microbubbles during TCD-BS for identification of RLS at three tertiary care stroke centres. TCD-BS was performed according to the standardised International Consensus Protocol. TOE-BS was performed in selected cases for confirmation of TCD-BS. RESULTS: 508 patients hospitalised with acute cerebral ischaemia (mean age 46±12 years, 59% men; 63% ischaemic stroke, 37% TIA) were investigated with TCD-BS within 1 week of ictus. RLS was identified in 151 cases (30%). TOE-BS was performed in 101 out of 151 patients with RLS identified on TCD-BS (67%). It was positive in 99 patients (98%). The rate of ischaemic cerebrovascular complications during or after TCD-BS was 0% (95% CI by the adjusted Wald METHOD: 0-0.6%). Structural cardiac abnormalities were identified in 38 patients, including atrial septal aneurysm (n=23), tetralogy of Fallot (n=1), intracardiac thrombus (n=2), ventricular septal defect (n=3) and atrial myxoma (n=1). CONCLUSION: TCD-BS is a safe screening test for identification of RLS, independent of the presence of cardiac structural abnormalities.

Chronic brainstem ischemia in subclavian steal syndrome.

Subclavian steal syndrome is usually an incidental finding and rarely causes vertebrobasilar ischemia. We present a 58-year-old man who, over six months, experienced progressive slowing in both talking and walking. Cervical duplex sonography revealed severe stenosis of the right subclavian artery; fixed retrograde flow was noted in the right vertebral artery on transcranial Doppler. The hyperemia-ischemia cuff test resulted in considerable reduction in flow velocities in both posterior cerebral arteries. We attributed his slowness to chronic vertebrobasilar ischemia and surgical revascularization was performed. His symptoms subsided immediately after surgery. The improved perfusion in the posterior circulation was demonstrated on technetium-99 hexamethylpropyleneamine oxime single photon-emission CT. Early diagnosis and prompt treatment resulted in an improved quality of life.

[Isokinetic strength measurement and training of the shoulder: methodology and results]. / Evaluation et rééducation des muscles de l'épaule en isocinétisme: méthodologie, résultats et applications.

OBJECTIVE: To evaluate the contribution of isokinetic methods of shoulder strength measurement and training. METHOD: A Medline search of English and French publications, including referenced articles, allowed us to analyse non-indexed publications. Eighty-seven articles were retained for analysis. RESULTS: The isokinetic evaluation of the shoulder is valid. Although reproducibility of shoulder evaluation is inferior to that of the knee, it is nevertheless satisfactory when a rigorous test method is used. Normal values for the rotators, abductors-adductors, and extensors-flexors depend on diverse parameters such as age, gender, fat mass, and the type and intensity of physical activity. The agonist to antagonist ratio is particularly informative in pathological conditions. The ratio is modified in cases of impingement syndrome and shoulder instability, and this modification appears to be a cause rather than a consequence of pathologic features. The ratio generally remains modified post-surgery, and normalization must be a major focus of post-surgery rehabilitation. CONCLUSION: Isokinetic measurement, particularly disturbances in the agonist-antagonist balance, is a reference method for evaluating shoulder muscle strength and detecting deficits in specific muscle groups seen in certain shoulder abnormalities. Such measurement is a valuable tool for orienting rehabilitation towards the deficient muscle groups, complements classical techniques of muscle strengthening, and is an accurate means for following the rehabilitation progress.