Tenecteplase in acute ischemic stroke: Review of the literature and expert consensus from the French Neurovascular Society.

BACKGROUND: Intravenous alteplase is the only thrombolytic treatment approved for patients with acute ischemic stroke (AIS). Although no randomized controlled trial (RCT) has shown the superiority of tenecteplase over alteplase in AIS, tenecteplase is increasingly used off-label in Stroke Units. The purpose of the present work was to provide an up-to-date set of expert consensus statements on the use of tenecteplase in AIS. METHODS: Members of the working group were selected by the French Neurovascular Society. RCTs comparing tenecteplase and alteplase in the treatment of AIS were reviewed. Recent meta-analysis and real-life experience data on tenecteplase published until 30th October 2021 were also analyzed. After a description of the available data, we tried to answer the subsequent questions about the use of tenecteplase in AIS: What dosage of tenecteplase should be preferred? How effective is tenecteplase for cerebral artery recanalization? What is the clinical effectiveness of tenecteplase? What is the therapeutic safety of tenecteplase? What are the benefits associated with tenecteplase ease of use? Then expert consensus statements for tenecteplase use were submitted. In October 2021 the working group was asked to review and revise the manuscript. In November 2021, the current version of the manuscript was approved. EXPERT CONSENSUS: A set of three expert consensus statements for the use of tenecteplase within 4.5hours of symptom onset in AIS patients were issued: (1) It is reasonable to use tenecteplase 0.25mg/kg when mechanical thrombectomy (MT) is planned. (2) Tenecteplase 0.25mg/kg can be used as an alternative to alteplase 0.9mg/kg in patients with medium- or small-vessel occlusion not retrievable with MT. (3) Tenecteplase 0.25mg/kg could be considered as an alternative to alteplase 0.9mg/kg in patients without vessel occlusion. CONCLUSIONS: These expert consensus statements could provide a framework to guide the clinical decision-making process for the use of tenecteplase according to admission characteristics of AIS patients. However, existing data are limited, requiring inclusions in ongoing RCTs or real-life registries.

The impact of anti-mould prophylaxis on Aspergillus PCR blood testing for the diagnosis of invasive aspergillosis.

BACKGROUND: The performance of the galactomannan enzyme immunoassay (GM-EIA) is impaired in patients receiving mould-active antifungal therapy. The impact of mould-active antifungal therapy on Aspergillus PCR testing needs to be determined. OBJECTIVES: To determine the influence of anti-mould prophylaxis (AMP) on the performance of PCR blood testing to aid the diagnosis of proven/probable invasive aspergillosis (IA). METHODS: As part of the systematic review and meta-analysis of 22 cohort studies investigating Aspergillus PCR blood testing in 2912 patients at risk of IA, subgroup analysis was performed to determine the impact of AMP on the accuracy of Aspergillus PCR. The incidence of IA was calculated in patients receiving and not receiving AMP. The impact of two different positivity thresholds (requiring either a single PCR positive test result or ≥2 consecutive PCR positive test results) on accuracy was evaluated. Meta-analytical pooling of sensitivity and specificity was performed by logistic mixed-model regression. RESULTS: In total, 1661 (57%) patients received prophylaxis. The incidence of IA was 14.2%, significantly lower in the prophylaxis group (11%-12%) compared with the non-prophylaxis group (18%-19%) (P < 0.001). The use of AMP did not affect sensitivity, but significantly decreased specificity [single PCR positive result threshold: 26% reduction (P = 0.005); ≥2 consecutive PCR positive results threshold: 12% reduction (P = 0.019)]. CONCLUSIONS: Contrary to its influence on GM-EIA, AMP significantly decreases Aspergillus PCR specificity, without affecting sensitivity, possibly as a consequence of AMP limiting the clinical progression of IA and/or leading to false-negative GM-EIA results, preventing the classification of probable IA using the EORTC/MSGERC definitions.

Benefit of first-pass complete reperfusion in thrombectomy is mediated by limited infarct growth.

BACKGROUND AND PURPOSE: The number of clot retrieval attempts required to achieve complete reperfusion by mechanical thrombectomy impacts functional outcome in acute ischaemic stroke (AIS). Complete reperfusion [expanded Treatment In Cerebral Infarction (eTICI) score = 3] at first pass (FP), is associated with the highest rates of favorable outcome compared to complete reperfusion by multiple passes. The aim of the present study was to investigate the relationship between FP complete reperfusion and infarct growth (IG). METHODS: Anterior AIS patients with baseline and 24-h diffusion-weighted magnetic resonance imaging were included from two prospective registries. IG was measured by voxel-based segmentation of initial and 24-h diffusion-weighted imaging lesions. IG and favorable 3-month modified Rankin Scale (mRS) score (≤ 2) were compared between patients in whom complete reperfusion (eTICI 3) was achieved with a single pass (FP group) and those for whom multiple passes were required (MP group), after matching for confounding factors. Mediation analysis was performed to examine the association between FP and 3-month mRS score, with IG as mediating variable. RESULTS: A total of 200 patients were included, of whom 118 (28.9%) had FP complete reperfusion. In case-control analysis, the FP group had lower IG than the MP group [8.7 (5.4-12.9) ml vs. 15.2 (11-22.6) ml, respectively; P = 0.03). Favorable outcome was higher in the FP population compared to a matched MP population (70.9% vs. 53.2%, respectively; P = 0.04). FP compete reperfusion (eTICI 3) was independently associated with favorable outcome in multivariable regression analysis [odds ratio 1.86, 95% confidence interval (CI) 1.01-4.39; P = 0.04]. The effect of complete reperfusion at FP on functional outcome was explained by limited IG in mediation analysis [indirect effect: -0.32 (95% CI -0.47 to -0.09)]. CONCLUSION: Complete reperfusion at FP is independently associated with significant decrease in IG compared to complete reperfusion by multiple attempts, explaining better functional outcomes.

Career aspirations among specialty residents in France: a cross-sectional gender-based comparison.

BACKGROUND: Most studies evaluating career aspirations among gender are performed in Anglo-Saxon countries. Two recent French studies looked at the career choice of residents in obstetrics & gynecology. It seemed useful to us to broaden this questioning to other specialties, by proposing a study to all residents in the same Faculty. The objective of our study was to describe residents' career aspirations and possible barriers according to gender. METHODS: Declarative cross-sectional survey, using questionnaires sent by email to the specialty residents of the Faculty of Medicine of Lille (France). An analysis by specialty group (i.e., medicine, surgery, obstetrics & gynecology, and anesthesia & resuscitation) and a comparison of the results according to gender were performed. RESULTS: Of the 1384 specialty residents currently in training, 462 answered the questionnaire (33.38%), among whom 289 women and 173 men (average age = 27.08 ± 0.091 years). Seventeen women (5.9%) were currently considering a university hospital career versus 37 men (21.4%) (p = 0.001). Gender analysis made it possible to identify obstacles to engaging in a university career: lacking a female model, more frequent doubting the ability to undertake this type of career among women (61.6%) than men (35.3%) (p < 0.001), and gender discrimination felt in the workplace for 51.6% of women (versus 7.5% of men, p < 0.001). Subgroup analysis showed specificities related to each specialty. CONCLUSIONS: Few residents plan to embark upon a university hospital career, let alone female residents. There are considerations specific to each specialty and marked gender differences regarding career aspirations. Many features have been identified as obstacles to access to university hospital positions for women. It is important to develop strategies to remove these barriers and enable women to pursue such university careers. TRIAL REGISTRATION: Not applicable (no intervention).

Intracerebral haemorrhage, microbleeds and antithrombotic drugs.

Antithrombotic therapy is a cornerstone for secondary prevention of ischaemic events, cerebral and extra-cerebral. A number of clinical questions remain unanswered concerning the impact of antithrombotic drugs on the risk of first-ever and recurrent macro or micro cerebral haemorrhages, raising the clinical dilemma on the risk/benefit balance of giving antiplatelets and anticoagulants in patients with potential high risk of brain bleeds. High field magnetic resonance imaging (MRI) blood-weighted sequences, including susceptibility weighted imaging (SWI), have expanded the spectrum of these clinical questions, because of their increasing sensitivity in detecting radiological markers of small vessel disease. This review will summarise the literature, focusing on four main clinical questions: how do cerebral microbleeds impact the risk of cerebrovascular events in healthy patients, in patients with previous ischaemic stroke or transient ischaemic attack, and in patients with intracerebral haemorrhage? Is the risk/benefit balance of oral anticoagulants shifted by the presence of microbleeds in patients with atrial fibrillation after recent ischaemic stroke or transient ischaemic attack? Should we restart antiplatelet drugs after symptomatic intracerebral haemorrhage or not? Are oral anticoagulants allowed in patients with a history of atrial fibrillation and previous intracerebral haemorrhage?

Impact of recanalisation by mechanical thrombectomy in mild acute ischemic stroke with large anterior vessel occlusion.

BACKGROUND: The net clinical benefit of mechanical thrombectomy (MT) in patients presenting acute anterior circulation ischemic stroke with large-vessel occlusion (AIS-LVO) and mild neurological deficit is uncertain. AIMS: To investigate efficacy and safety of MT in patients with acute AIS-LVO and mild neurological deficit by evaluating i) the influence of recanalisation on three-month outcome and ii) mortality, symptomatic intracerebral hemorrhage (sICH) and procedural complications. METHODS: We included consecutive patients with acute AIS-LVO and National Institute of Stroke Scale (NIHSS) score<8, treated by MT at Lille University Hospital. Recanalisation was graded according to modified thrombolysis in cerebral infarction (mTICI) score, mTICI 2b/2c/3 being considered successful. We recorded procedural complications and classified intra-cerebral hemorrhages (ICH) and sICH according with European Cooperative Acute Stroke Study (ECASS) and ECASS2 criteria. Three-month outcome was evaluated by modified Rankin scale (mRS). Excellent and favourable outcomes were respectively defined as mRS 0-1 and 0-2 (or similar to pre-stroke). RESULTS: We included 95 patients. At three months, 56 patients (59. 0%) achieved an excellent outcome and 69 (72, 6%) a favourable outcome, both being more frequent in patients with successful recanalisation than in patients without (excellent outcome 71, 1% versus 10, 5%, P<0.001 and favourable outcome 82.9% versus 31.6%, P<0.001). The difference remained unchanged after adjustment for age and pre-MT infarct volume. Similar results were observed in patients with pre-MT NIHSS ≤5. Death occurred in five patients (5.3%), procedural complications in 12 (12.6%), any ICH in 38 (40.0%), including 3 (3.2%) sICH. CONCLUSIONS: Achieving successful recanalisation appears beneficial and safe in acute AIS-LVO patients with NIHSS<8 before MT.

Cerebral ischaemia with unknown onset: Outcome after recanalization procedure.

BACKGROUND: Stroke of unknown time of onset (UTOS) accounts for one-third of contra-indications for revascularization procedures. With modern neuroimaging techniques it is possible to differentiate the core infarcts and the presence of penumbra. OBJECTIVE: To evaluate outcomes in patients with UTOS, treated with intravenous (i.v.) recombinant tissue-plasminogen activator (rt-PA), mechanical thrombectomy (MT), or both. METHOD: We conducted this observational study in patients treated by i.v. rt-PA, MT, or both, selected by a diffusion-weighted image/fluid-attenuated inversion recovery mismatch. We evaluated outcomes with the modified Rankin scale (mRS) at 3 months. RESULTS: Of 992 consecutive patients (522 women, 52.6%; median age 76 years; median baseline national institutes of health stroke scale [NIHSS] 10), 153 (15.4%) had UTOS, including 101 with wake-up strokes. Compared to other patients, they were more likely to have pre-existing mRS scores >2 (P=0.022), multiple infarcts (P<0.001), middle cerebral artery occlusions (P=0.023), and to undergo MT (P=0.003), and less likely to receive i.v. rt-PA (P<0.001). They had higher NIHSS scores (P<0.001) and longer discovery to treatment initiation times (P<0.001). They were more likely to develop pulmonary (P=0.001) and urinary (P=0.006) infections, and pulmonary embolism (P=0.019), and tended to have a higher mortality rate (P=0.052) within 7 days. After adjustment, there was no association of UTOS with any of these outcome measures anymore. CONCLUSION: Patients with UTOS have more severe strokes and more comorbidities, but after adjustment, their outcomes did not differ from those of other patients.

Access to mechanical thrombectomy for cerebral ischaemia: A population-based study in the North-of-France.

BACKGROUND AND PURPOSE: Hospitals admitting acute strokes should offer access to mechanical thrombectomy (MT), but local organisations are still based on facilities available before MT was proven effective. MT rates and outcomes at population levels are needed to adapt organisations. We evaluated rates of MT and outcomes in inhabitants from the North-of-France (NoF) area. METHOD: We prospectively evaluated rates of MT and outcomes of patients at 3 months, good outcomes being defined as a modified Rankin scale (mRS) 0 to 2 or like the pre-stroke mRS. RESULTS: During the study period (2016-2017), 666 patients underwent MT (454, 68.1% associated with intravenous thrombolysis [IVT]). Besides, 1595 other patients received IVT alone. The rate of MT was 81 (95% confidence interval [CI] 72-90) per million inhabitants-year, ranging from 36 to 108 between districts. The rate of IVT was 249 (95% CI 234-264) per million inhabitants-year, ranging from 155 to 268. After 3 months, 279 (41.9%) patients who underwent MT had good outcomes, and 167 (25.1%) had died. Patients living outside the district of Lille where the only MT centre is, were less likely to have good outcomes at 3 months, after adjustment on age, sex, baseline severity, and delay. CONCLUSION: The rate of MT is one of the highest reported up to now, even in low-rate districts, but outcomes were significantly worse in patients living outside the district of Lille, and this is not only explained by the delay.

MRI for in vivo diagnosis of cerebral amyloid angiopathy: Tailoring artifacts to image hemorrhagic biomarkers.

Cerebral amyloid angiopathy (CAA) is a frequent age-related small vessel disease (SVD) with cardinal magnetic resonance imaging (MRI) signatures that are hemorrhagic in nature, and include the presence of strictly lobar (superficial) cerebral microbleeds and intracerebral hemorrhages as well as cortical superficial siderosis. When investigating a patient with suspected CAA in the context of intracranial hemorrhage (parenchymal or subarachnoid) or cognitive dysfunction, various MRI parameters influence the optimal detection and characterization (and prognostication) of this frequent SVD. The present report describes the influence of imaging techniques on the detection of the key hemorrhagic CAA imaging signatures in clinical practice, in research studies, and the imaging parameters that must be understood when encountering a CAA patient, as well as reviewing CAA literature.

Are the results of intravenous thrombolysis trials reproduced in clinical practice? Comparison of observed and expected outcomes with the stroke-thrombolytic predictive instrument (STPI).

AIM: In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice. METHOD: Data from a registry of consecutive patients treated by rt-PA at Lille University Hospital were retrospectively analyzed for outcomes, using modified Rankin Scale (mRS) scores, at 3 months. The observed outcomes were then compared with the probability of good (mRS 0-1) and of catastrophic (mRS 5-6) outcomes, as predicted by the stroke-thrombolytic predictive instrument (STPI). RESULTS: Of the 1000 consecutive patients (469 male, median age 74 years, median baseline National Institutes of Health Stroke Scale 11, median onset-to-needle time 143min), 438 (43.8%) had a good outcome, 565 (56.5%) had an mRS score 0-2 or similar to their pre-stroke mRS, 155 (15.5%) died within 3 months and 74 (7.4%) developed symptomatic intracerebral hemorrhage according to ECASS-II (Second European-Australasian Acute Stroke Study) criteria. Of the 613 patients (61.3%) eligible for evaluation by the s-TPI, the observed rate of good outcomes was 41.3% (95% CI: 37.5-45.3%), while expected rates with and without rt-PA were 48.8% (95% CI: 44.8-52.7%) and 32.5% (95% CI: 28.8-36.2%), respectively; the observed rate of catastrophic outcomes was 17.0% (95% CI: 14.0-19.9%), while the expected rate was 19.2% (95% CI: 16.1-22.4%) with or without rt-PA. CONCLUSION: In clinical practice, the rate of good outcomes is slightly lower than expected, according to the s-TPI, except for the most severe cases, whereas the rate of catastrophic outcomes is roughly similar. However, the rate of good outcomes is higher than predicted without treatment. This finding suggests that rt-PA is effective for improving outcomes in clinical practice.

[Long-term blood pressure outcome after unilateral adrenalectomy for primary hyperaldosteronism]. / Contrôle à long terme de la pression artérielle après surrénalectomie pour hyperaldostéronisme primaire.

OBJECTIVES: To evaluate long-term results of adrenalectomy for primary aldosteronism (PA) and to identify prognostic factors associated. METHODS: Exhaustive retrospective review of all consecutive patients undergoing adrenalectomy for PA between 2002 and 2013 in our department. All patients underwent preoperative: clinical evaluation (age, sex, height, weight, systolic and diastolic BP under treatment, identification of anti-hypertension treatment), biological evaluation (potassium, renin, aldosterone) and radiological evaluation (CT and/or MRI). Blood pressure was assessed postoperatively at 1 month, 1 year, then at the date of the latest news. The patients were classified into three categories: cured (no antihypertensive therapy in postoperative associated with strictly lower blood pressures of 140/90mmHg), improved (decreased number of drugs or number unchanged but with better blood pressure control), and refractory (no change in the number of drug and blood pressure, or deterioration of one or other of these two parameters). RESULTS: We evaluated 43 patients, 23 men and 20 women, with a median follow-up of 74.4 months [16.8 to 141]. Pathological analysis described 34 adenomas (79%), 7 hyperplasias (16%) (5 micro-nodular and 2 macro-nodular) and 2 adrenocortical carcinoma (5%). The postoperative long-term assessment found 20% of cured patients (n=8), 65% of improved (n=26) and 15% of refractory (n=6). Prognostic factors associated with favorable long-term blood pressure outcome were those typically associated with ARS score [preoperative number of anti-hypertension drugs (P=0.005), BMI<25kg/m2 (P=0.009), and duration of hypertension (P=0.007)]. CONCLUSION: Adrenalectomy for PA is a long-term effective treatment for blood pressure control. Prognostic factors associated with long-term success are those conventionally described in ARS score. LEVEL OF EVIDENCE: 4.

Blood biomarkers in the early stage of cerebral ischemia.

In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed.

EFNS-ENS/EAN Guideline on concomitant use of cholinesterase inhibitors and memantine in moderate to severe Alzheimer's disease.

BACKGROUND AND PURPOSE: Previous studies have indicated clinical benefits of a combination of cholinesterase inhibitors (ChEI) and memantine over ChEI monotherapy in Alzheimer's disease (AD). Our objective was the development of guidelines on the question of whether combined ChEI/memantine treatment rather than ChEI alone should be used in patients with moderate to severe AD to improve global clinical impression (GCI), cognition, behaviour and activities of daily living (ADL). METHODS: A systematic review and meta-analysis of randomized controlled trials based on a literature search in ALOIS, the register of the Cochrane Dementia and Cognitive Improvement Group, was carried out with subsequent guideline development according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Pooled data from four trials including 1549 AD patients in the moderate to severe disease stage demonstrated significant beneficial effects of combination therapy compared to ChEI monotherapy for GCI [standardized mean difference (SMD) -0.20; 95% confidence interval (CI) -0.31; -0.09], cognitive functioning (SMD -0.27, 95% CI -0.37; -0.17) and behaviour (SMD -0.19; 95% CI -0.31; -0.07). The quality of evidence was high for behaviour, moderate for cognitive function and GCI and low for ADL. Agreement of panellists was reached after the second round of the consensus finding procedure. The desirable effects of combined ChEI and memantine treatment were considered to outweigh undesirable effects. The evidence was weak for cognition, GCI and ADL so that the general recommendation for using combination therapy was weak. CONCLUSIONS: We suggest the use of a combination of ChEI plus memantine rather than ChEI alone in patients with moderate to severe AD. The strength of this recommendation is weak.

Enterohemorrhagic Escherichia coli infection has donor-dependent effect on human gut microbiota and may be antagonized by probiotic yeast during interaction with Peyer's patches.

Enterohemorrhagic Escherichia coli (EHEC) are major food-borne pathogens responsible for serious infections ranging from mild diarrhea to hemorrhagic colitis and life-threatening complications. Shiga toxins (Stxs) are the main virulence factor of EHEC. The antagonistic effect of a prophylactic treatment with the probiotic strain Saccharomyces cerevisiae against EHEC O157:H7 was investigated using complementary in vitro human colonic model and in vivo murine ileal loop assays. In vitro, the probiotic treatment had no effect on O157:H7 survival but favorably influenced gut microbiota activity through modulation of short-chain fatty acid production, increasing acetate production and decreasing that of butyrate. Both pathogen and probiotic strains had individual-dependent effects on human gut microbiota. For the first time, stx expression was followed in human colonic environment: at 9 and 12 h post EHEC infection, probiotic treatment significantly decreased stx mRNA levels. Besides, in murine ileal loops, the probiotic yeast specifically exerted a trophic effect on intestinal mucosa and inhibited O157:H7 interactions with Peyer's patches and subsequent hemorrhagic lesions. Taken together, the results suggest that S. cerevisiae may be useful in the fight against EHEC infection and that host associated factors such as microbiota could influence clinical evolution of EHEC infection and the effectiveness of probiotics.

Surgical management of Moyamoya disease and syndrome: Current concepts and personal experience.

In this focus, we review, in the light of the recent literature, the modalities and indications of surgical cerebral revascularization for Moyamoya (MM) disease or syndrome. We also report our experience in the surgical management of adult MM. In symptomatic forms, with presence of severe disturbances of perfusion or cerebrovascular reactivity on multimodal imaging work-up, the risks of recurrent ischemic or hemorrhagic stroke is high (respectively 10-13%/yr and 2-7%/yr). The objective of treatment is to augment cerebral perfusion (in ischemic forms) or to reduce lenticulo-striate neovessel overload (in hemorrhagic forms), by initiating the development of a cortical neovascularization and/or by directly increasing cerebral blood flow. The risk of immediate postoperative death or stroke is similar between indirect and direct or combined techniques and respectively 0-0.5% and 3-6%, provided a strict perioperative anesthetic management is applied (normocapnia, normoxia and controlled hypertension). Indirect techniques (i.e. encephalo-duro-arterio-myo-periosteo-synangiosis or multiple burr-holes) are technically easy, allow wide cortical revascularization and are very efficient in children: absence of clinical recurrence in more than 95% of cases and presence of a good neovascularization in 83%. However, their effect is delayed for several months, the impact on the hemorrhagic risk is moderate and the global response is uncertain in adults. Direct (superficial temporal artery to middle cerebral artery bypass) or combined techniques improve cerebral blood flow immediately and significantly. They are associated with a higher rate of stroke-free survival at 5 years (95% vs 85%). A recent randomized study has proven that they could reduce the hemorrhagic risk by 2- to 3-fold in comparison with conservative treatment alone. However, their feasibility in children is limited by the very small size of vessels. We present also our results in the surgical management of 12 adult MM patients (mean age 41.3, sex ratio=1) operated between 2009 and 2014 (14 revascularization procedures: EDAMS 2, multiple burr-holes 1, combined revascularization procedures 11). MM types according to clinical presentation were the following: ischemic 8, hemorrhagic 2, combined 2. All patients were recently symptomatic, with recurrent ischemic/hemorrhagic events (2/3) or crescendo neurological deficit (1/3) in association with severe alterations of cerebral blood flow. Mean clinical and radiological follow-up was 22 months. Postoperative mRS at 6 months was improved or stable in 92%. None of the patients suffered recurring stroke. In conclusion, surgical treatment should be discussed quickly in symptomatic forms of MM (progressive or recurring) because of their poor outcome. Indirect techniques are favored in pediatric patients due to their simplicity and good clinical results. Direct, or preferentially combined techniques would be more effective in adult patients to prevent the recurrence of ischemic or hemorrhagic stroke.

The impact of total body irradiation on the outcome of patients with follicular lymphoma treated with autologous stem-cell transplantation in the modern era: a retrospective study of the EBMT Lymphoma Working Party.

BACKGROUND: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period. PATIENTS: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission. RESULTS: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission. CONCLUSIONS: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.

Iron deposits in post-mortem brains of patients with neurodegenerative and cerebrovascular diseases: a semi-quantitative 7.0 T magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Accumulation of iron (Fe) is often detected in brains of people suffering from neurodegenerative diseases. However, no studies have compared the Fe load between these disease entities. The present study investigates by T2*-weighted gradient-echo 7.0 T magnetic resonance imaging (MRI) the Fe content in post-mortem brains with different neurodegenerative and cerebrovascular diseases. METHODS: One hundred and fifty-two post-mortem brains, composed of 46 with Alzheimer's disease (AD), 37 with frontotemporal lobar degeneration (FTLD), 11 with amyotrophic lateral sclerosis, 13 with Lewy body disease, 14 with progressive supranuclear palsy, 16 with vascular dementia (VaD) and 15 controls without a brain disease, were examined. The Fe load was determined semi-quantitatively on T2*-weighted MRI serial brain sections in the claustrum, caudate nucleus, putamen, globus pallidus, thalamus, subthalamic nucleus, hippocampus, mamillary body, lateral geniculate body, red nucleus, substantia nigra and dentate nucleus. The disease diagnosis was made on subsequent neuropathological examination. RESULTS: The Fe load was significantly increased in the claustrum, caudate nucleus and putamen of FTLD brains and to a lesser degree in the globus pallidus, thalamus and subthalamic nucleus. In the other neurodegenerative diseases no Fe accumulation was observed, except for a mild increase in the caudate nucleus of AD brains. In VaD brains no Fe increase was detected. CONCLUSIONS: Only FTLD displays a significant Fe load, suggesting that impaired Fe homeostasis plays an important role in the pathogenesis of this heterogeneous disease entity.

Influence of cognitive impairment on the management of ischaemic stroke.

BACKGROUND: Because of ageing of the population, it is more and more frequent to treat ischaemic stroke patients with pre-stroke cognitive impairment (PSCI). Currently, there is no specific recommendation on ischaemic stroke management in these patients, both at the acute stage and in secondary prevention. However, these patients are less likely to receive treatments proven effective in randomised controlled trials, even in the absence of contra-indication. OBJECTIVE: To review the literature to assess efficacy and safety of validated therapies for acute ischaemic stroke and secondary prevention in PSCI patients. RESULTS: Most randomised trials did not take into account the pre-stroke cognitive status. The few observational studies conducted at the acute stage or in secondary prevention, did not provide any information that the benefit could be either lost or replaced by harm in the presence of PSCI. CONCLUSIONS: There is no reason not to treat ischaemic stroke patients with PSCI according to the currently available recommendations for acute management and secondary prevention. Further observational studies are needed and pre-stroke cognition should be taken into account in future stroke trials.

Superficial siderosis of the central nervous system: a post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates.

BACKGROUND: Superficial siderosis (SS) is a rare finding on T2*-weighted magnetic resonance imaging (MRI), regarded as a radiological marker of cerebral amyloid angiopathy (CAA). The present study investigates with 7.0-tesla MRI the prevalence of SS and its underlying pathological substrate in a consecutive series of post-mortem brains of elderly patients with various neurodegenerative and cerebrovascular lesions. MATERIALS AND METHODS: The prevalence of SS and associated lesions was screened using 7.0-tesla MRI and their neuropathological correlates in 120 post-mortem brains of patients with various neurodegenerative and cerebrovascular diseases. RESULTS: Eighty-three separate zones of SS were detected in 45 brains (37.5%), including 25 areas of disseminated SS (dSS) and 58 areas of focal SS (fSS), restricted to less than 3 sulci. dSS was spatially related to sequels of 14 lobar haematomas and 11 cerebral infarcts, while fSS was connected to 19 microbleeds and 39 micro-infarcts (p < 0.001). Comparison of the 15 CAA to the 30 non-CAA brains showed that dSS was due to an old lobar haematoma in 53% of the former group compared to 3% of the latter group (p = 0.003). fSS was due to a microbleed in 7% of the CAA brains and to 40% of the non-CAA brains (p = 0.03). CONCLUSIONS: SS is associated with both haemorrhagic and ischaemic underlying lesions. It is frequently observed on T2*-weighted 7.0-tesla MRI, and two types of SS may be described. Clinicians should keep in mind that SS may be found in other settings than CAA.

European guidelines for prevention and management of influenza in hematopoietic stem cell transplantation and leukemia patients: summary of ECIL-4 (2011), on behalf of ECIL, a joint venture of EBMT, EORTC, ICHS, and ELN.

Influenza may cause severe disease and mortality in leukemia patients and in hematopoietic stem cell transplantation recipients. The 4th European Conference of Infections in Leukemia (ECIL-4) has developed evidence-based guidelines for prevention and management of influenza infections in these patients. Real-time reverse-transcription polymerase chain reaction is the diagnostic test of choice, as it is the most sensitive and specific test for influenza. The risks for severe influenza and fatal outcome include lymphopenia, older age, influenza soon after transplantation or chemotherapy, steroid treatment, and lack of early antiviral therapy. Neuraminidase inhibitors (oral oseltamivir or inhalation of zanamivir) are currently the most effective therapeutic agents for influenza. Main preventive measures include annual vaccination of patients, household contacts, and hospital staff. This review summarizes ECIL-4's main recommendations.