Acute stroke care in France: Survey in the 138 stroke units.

BACKGROUND: According to the French regulation, stroke units (SU) include both an intensive (I-SU) and a non-intensive (NI-SU) component. Their standard operating procedures have been detailed in governmental directives in 2003 and 2007. OBJECTIVES: To evaluate (i) resources available in French SU, (ii) differences between regions, and between France and the 2 close European countries of similar size, and (iii) to identify avenues for improvement. METHODS: We performed a survey of all French SU, with an online questionnaire, to evaluate available resources and activity. We compared the 17 French regions, and France, with Germany and Italy. We used 2019 as year of reference. RESULTS: The 138 French SU, shared 911 I-SU beds; 123 SU (89.1%) answered the questionnaire. The number of I-SU beds per million inhabitants was 13.6 for the whole country, with important differences between regions, ranging from 7.0 (Reunion Island) to 20.9 (Occitanie region). Per million inhabitants, France had fewer I-SU beds than Germany and Italy (13.5 vs. 29.9 and 23.2 respectively), and fewer thrombectomy centres (0.6 vs. 1.8 and 1.0). Per million inhabitants, France had also lower thrombolysis (203 vs. 402) and thrombectomy (104 vs. 194) rates than Germany, but, compared with Italy, similar thrombolysis rates (203 vs. 202) and higher thrombectomy rates (104 vs. 81). CONCLUSION: There are still avenues for improvement in acute stroke care in France, especially concerning the number and regional repartition of I-SU beds, and access to reperfusion therapies.

Spinal infarcts.

Compared to cerebral ischaemia, the frequency of spinal cord ischaemia is rare. Spinal infarcts lead to various types of neurological deficits, usually consisting of an abrupt and complete tetra- or paraplegia. Magnetic resonance imaging is the most valuable tool to show the infarct and to rule out other causes of acute spinal cord syndromes., such as myelitis or acute compressions. Nowadays, in western countries, most spinal cord infarcts are due to aortic diseases (atherosclerosis, aneurysm, dissection) or are of iatrogenic origin (mainly aortic surgery and interventional radiology), while other causes are rare. There is no specific treatment, besides prevention of complications, treatment of the underlying cause and rehabilitation.

The first case of traumatic internal carotid arterial dissection? Verneuil's case report from 1872.

Dissecting aneurysms of the internal carotid artery were considered as very rare disorders before the seventies. Undiagnosed carotid-artery dissections, however, may have gone hidden behind earlier reports of delayed "apoplexy" due to "traumatic carotid thrombosis". Here, we present a case report of delayed stroke after trauma, published by Aristide Verneuil in 1872 in the Bulletin de l'Académie de Médecine and cited under the heading of vascular rupture and dissecting aneurysm by Heinrich Quincke in 1876. Verneuil's case report represents, to our knowledge, the first detailed clinical description of a patient with a traumatic carotid dissection confirmed at autopsy. The author highlighted the diagnostic challenges of this case, head injury followed by delayed hemiplegia suggesting an intracranial bleeding.

EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke.

BACKGROUND: Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. AIM: Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy. MATERIALS AND METHODS: Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice. RESULTS: Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce. DISCUSSION/CONCLUSION: Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.

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.

Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient.

Stroke patients have an elevated risk of developing long-term cognitive disorders or dementia. The latter is often associated with atrophy of the medial temporal lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy is the sole predictor of long-term post-stroke dementia. We hypothesized that hippocampal deformation (rather than atrophy) is a predictive marker of long-term post-stroke dementia on a rat model and tested this hypothesis in a prospective cohort of stroke patients.Male Wistar rats were subjected to transient middle cerebral artery occlusion and assessed 6 months later. Ninety initially dementia-free patients having suffered a first-ever ischemic stroke were prospectively included in a clinical study. In the rat model, significant impairments in hippocampus-dependent memories were observed. MRI studies did not reveal significant atrophy of the hippocampus volume, but significant deformations were indeed observed-particularly on the ipsilateral side. There, the neuronal surface area was significantly lower in ischemic rats and was associated with a lower tissue density and a markedly thinner entorhinal cortex. At 6 months post-stroke, 49 of the 90 patients displayed cognitive impairment (males 55.10%). Shape analysis revealed marked deformations of their left hippocampus, a significantly lower entorhinal cortex surface area, and a wider rhinal sulcus but no hippocampal atrophy. Hence, hippocampal deformations and entorhinal cortex atrophy were associated with long-term impaired cognitive abilities in a stroke rat model and in stroke patients. When combined with existing biomarkers, these markers might constitute sensitive new tools for the early prediction of post-stroke dementia.

Structural insights into the ene-reductase synthesis of profens.

Reduction of double bonds of α,ß-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.

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.

The topography of cortical microbleeds in frontotemporal lobar degeneration: a post-mortem 7.0-tesla magnetic resonance study.

INTRODUCTION: Cerebrovascular lesions are rare in frontotemporal lobar degeneration (FTLD), in contrast to other neurodegenerative diseases. Cortical microbleeds (CoMBs) are frequent in Alzheimer's disease, in particular in cases associated with cerebral amyloid angiopathy. The present study investigates the gyral topographic distribution of CoMBs in post-mortem FTLD brains with 7.0-tesla magnetic resonance imaging. MATERIAL AND METHODS: The distribution of CoMBs in 11 post-mortem FTLD brains and in 12 control brains was compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean values of CoMBs were determined in twenty-two different gyri. The findings were correlated to those separately observed on neuropathological examination. RESULTS: As a whole there was a trend of more CoMBs in the prefrontal section of FTLD as well as of the control brains. CoMBs were significantly increased in the superior frontal gyrus and the insular cortex (p ≤ 0.001) and also in the inferior frontal gyrus and the superior temporal gyrus (p ≤ 0.01). CONCLUSIONS: CoMBs in FTLD are only increased in the regions mainly affected by the neurodegenerative lesions. They probably do not reflect additional cerebrovascular disease.

Prognostic significance of pulsatile tinnitus in cervical artery dissection.

BACKGROUND AND PURPOSE: Our aim was to investigate whether pulsatile tinnitus (PT) in cervical artery dissection (CeAD) has prognostic significance. METHODS: All CeAD patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) study with documentation of PT were analysed. The presence of PT was systematically assessed using a standardized questionnaire. Stroke severity at admission was defined according to the National Institutes of Health Stroke Scale (NIHSS). Excellent outcome after 3 months was defined as a modified Rankin Scale of 0-1. RESULTS: Sixty-three of 778 patients (8.1%) reported PT. PT+ patients presented less often with ischaemic stroke (41.3% vs. 63.9%, P < 0.001), more often with dissection in the internal carotid artery (85.7% vs. 64.2%, P = 0.001), less often with vessel occlusion (19.0% vs. 34.1%, P = 0.017) and more often with excellent outcome at 3 months (92.1% vs. 75.4%, P = 0.002). Logistic regression analysis identified PT as an independent predictor of excellent outcome after 3 months [odds ratio (OR) 3.96, 95% confidence interval (CI) 1.22-12.87] adjusted to significant outcome predictors NIHSS on admission (OR 0.82, 95% CI 0.79-0.86), Horner syndrome (OR 1.95, 95% CI 1.16-3.29) and vessel occlusion (OR 0.62, 95% CI 0.40-0.94) and to non-significant predictors age, sex, pain and location of CeAD. CONCLUSION: The presence of PT in CeAD is associated with a benign clinical course and predicts a favourable outcome.

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.

Topography of Cortical Microbleeds in Alzheimer's Disease with and without Cerebral Amyloid Angiopathy: A Post-Mortem 7.0-Tesla MRI Study.

Cortical microbleeds (CMBs) detected on T2*-weighted gradient-echo (GRE) magnetic resonance imaging (MRI) are considered as a possible hallmark of cerebral amyloid angiopathy (CAA). The present post-mortem 7.0-tesla MRI study investigates whether topographic differences exist in Alzheimer's brains without (AD) and with CAA (AD-CAA). The distribution of CMBs in thirty-two post-mortem brains, consisting of 12 AD, 8 AD-CAA and 12 controls, was mutually compared on T2*-GRE MRI of six coronal sections of a cerebral hemisphere. The mean numbers of CMBs were determined in twenty-two different gyri. As a whole there was a trend of more CMBs on GRE MRI in the prefrontal section of the AD, the AD-CAA as well as of the control brains. Compared to controls AD brains had significantly more CMBs in the superior frontal, the inferior temporal, the rectus and the cinguli gyrus, and in the insular cortex. In AD-CAA brains CMBs were increased in all gyri with exception of the medial parietal gyrus and the hippocampus. AD-CAA brains showed a highly significant increase of CMBs in the inferior parietal gyrus (p value: 0.001) and a significant increase in the precuneus and the cuneus (p value: 0.01) compared to the AD brains. The differences in topographic distribution of CMBs between AD and AD-CAA brains should be further investigated on MRI in clinically suspected patients.

Anemia in young patients with ischaemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of anemia on admission with ischaemic stroke (IS), stroke severity and early functional outcome in patients with cervical artery dissection (CeAD) or with IS of other causes (non-CeAD-IS patients). METHODS: The study sample comprised all patients from the Cervical Artery Dissection and Ischaemic Stroke Patients (CADISP) study without pre-existing disability and with documentation of stroke severity and hemoglobin (Hb) concentration on admission. Anemia was classified as mild (Hb < 12 g/dl in women and Hb < 13 g/dl in men) or moderate to severe (Hb < 10 g/dl in women and Hb < 11 g/dl in men). Stroke severity on admission was assessed with the National Institutes of Health Stroke Scale (NIHSS). Outcome after 3 months was assessed with the modified Rankin Scale (mRS-3mo). Unfavorable outcome was defined as mRS-3mo ≥ 3. RESULTS: Amongst 1206 study patients (691 CeAD and 515 non-CeAD), 87 (7.2%) had anemia, which was moderate to severe in 18 (1.5%) patients. Anemia was associated with female sex in both study samples, but no further associations with risk factors or comorbidities were observed. In CeAD patients, anemia was associated with occurrence of stroke (P = 0.042). In both study samples, anemic patients had more severe strokes (CeAD, P = 0.023; non-CeAD, P = 0.005). Functional outcome was not associated with anemia in general, but moderate to severe anemia was significantly associated with unfavorable outcome (P = 0.004). CONCLUSION: Anemia on admission was associated with stroke in CeAD patients and with more severe strokes in both study samples. Moderate to severe anemia may predict unfavorable outcome.

Post-mortem 7.0-tesla magnetic resonance study of cortical microinfarcts in neurodegenerative diseases and vascular dementia with neuropathological correlates.

BACKGROUND: Until recently cortical microinfarcts (CMIs) were considered as the invisible lesions in clinical-radiological correlation studies that rely on conventional structural magnetic resonance imaging. The present study investigates the presence of CMIs on 7.0-T magnetic resonance imaging (MRI) in post-mortem brains with different neurodegenerative and cerebrovascular diseases. MATERIALS AND METHODS: One hundred-seventy five post-mortem brains, composed of 37 with pure Alzheimer's disease (AD), 12 with AD associated to cerebral amyloid angiopathy (AD-CAA), 38 with frontotemporal lobar degeneration, 12 with amyotrophic lateral sclerosis, 16 with Lewy body disease (LBD), 21 with progressive supranuclear palsy, 18 with vascular dementia (VaD) and 21 controls were examined. According to their size several types of CMIs were detected on 3 coronal sections of a cerebral hemisphere with 7.0-T MRI and compared to the mean CMI load observed on histological examination of one standard separate coronal section of a cerebral hemisphere at the level of the mamillary body. RESULTS: Overall CMIs were significantly prevalent in those brains with neurodegenerative and cerebrovascular diseases associated to CAA compared to those without CAA. VaD, AD-CAA and LBD brains had significantly more CMIs compared to the controls. While all types of CMIs were increased in VaD and AD-CAA brains, a predominance of the smallest ones was observed in the LBD brains. CONCLUSIONS: The present study shows that 7.0-T MRI allows the detection of several types of MICs and their contribution to the cognitive decline in different neurodegenerative and cerebrovascular diseases.

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.