Objective
Whether bridging therapy (intravenous thrombolysis IVT followed by endovascular treatment) is superior to IVT alone in minor stroke with large vessel occlusion (LVO) is unknown.
Methods
...Multicentric retrospective observational study including, in intention‐to‐treat, consecutive IVT‐treated minor strokes (National Institutes of Health Stroke Scale NIHSS ≤ 5) with LVO, with or without additional mechanical thrombectomy. Propensity‐score (inverse probability of treatment weighting) was used to reduce baseline between‐groups differences. The primary outcome was excellent outcome, that is, modified Rankin score 0 to 1 at 3 months follow‐up.
Results
Overall, 598 patients were included (214 and 384 in the bridging therapy and IVT groups, respectively). Following propensity‐score weighting, the distribution of baseline clinical and radiological variables was similar across the two patient groups. Compared with IVT alone, bridging therapy was not associated with excellent outcome (odds ratio OR = 0.96; 95% confidence interval CI = 0.75–1.24; p = 0.76), but was associated with symptomatic intracranial hemorrhage (OR = 3.01; 95% CI = 1.77–5.11; p < 0.0001). Occlusion site was a strong modifier of the effect of bridging therapy on outcome (pinteraction < 0.0001), with bridging therapy associated with higher odds of excellent outcome in proximal M1 (OR = 3.26; 95% CI = 1.67–6.35; p = 0.0006) and distal M1 (OR = 1.69; 95% CI = 1.01–2.82; p = 0.04) occlusions, but with lower odds of excellent outcome for M2 (OR = 0.53; 95% CI = 0.38–0.75; p = 0.0003) occlusions. Bridging therapy was associated with higher rates of symptomatic intracranial hemorrhage in M2 occlusions only (OR = 4.40; 95% CI = 2.20–8.83; p < 0.0001).
Interpretation
Although overall outcomes were similar in intended bridging therapy as compared to intended IVT alone in minor strokes with LVO, our results suggest that intended bridging therapy may be beneficial in M1 occlusions, whereas the benefit–risk profile may favor IVT alone in M2 occlusions. ANN NEUROL 2020 ANN NEUROL 2020;88:160–169
•Alpha-synuclein deposits are found in the gut in PD.•Alpha-synuclein expression levels and phosphorylation status were analyzed by biochemical means in 17 PD patients.•No differences in the ...expression levels, phosphorylation and aggregation status of alpha-synuclein was observed between controls and PD.•Our study suggests that the biochemical methods tested are not adequate for the prediction of PD using gastrointestinal biopsies.
Lewy bodies and neurites, the pathological hallmarks found in the brain of Parkinson’s disease (PD) patients, are primarily composed of aggregated and hyperphosphorylated alpha-synuclein. The observation that alpha-synuclein inclusions are also found in the gut of the vast majority of parkinsonian patients has led to an increasing number of studies aimed at developing diagnostic procedures based on the detection of pathological alpha-synuclein in gastrointestinal biopsies. The previous studies, which have all used immunohistochemistry for the detection of alpha-synuclein, have provided conflicting results. In the current survey, we used a different approach by analyzing the immunoreactivity pattern of alpha-synuclein separated by one- and two-dimensional electrophoresis, in colonic biopsies from PD subjects and healthy individuals. We did not observe any differences between controls and PD in the expression levels, phosphorylation or aggregation status of alpha-synuclein. Overall, our study suggests that the two biochemical methods tested here are not adequate for the prediction of PD using gastrointestinal biopsies. Further studies, using other biochemical approaches, are warranted to test whether there exists specific forms of pathological alpha-synuclein that distinguish PD from control subjects.
To assess the risk of recurrence of cervical artery dissection (CAD) during pregnancy and puerperium in women with a history of CAD and then help physicians with providing medical information to ...women who wish to become pregnant.
Women aged 16-45 years who were admitted to our center for a CAD between 2005 and 2017 were identified from the hospital database, and those with spontaneous and symptomatic CAD were included. They were then contacted to answer a questionnaire that was specifically designed in regard to the recurrence of CAD and pregnancies after the primary CAD.
Ninety-one patients satisfied our inclusion criteria, and 89 were included in the analysis. During a median follow-up of 7.0 years, 4 women (4.4%) had recurrent CAD, although none during pregnancy or puerperium. Eighteen women (20%) had a total of 20 full-term pregnancies, occurring at least 6 months after CAD. Of these 20 pregnancies, 13 (65%) were vaginal deliveries, and 7 (35%) were cesarean sections. The reason for the absence of pregnancies after the initial CAD was unrelated to the vascular event in 89% of cases, but 8% of the women had been advised by a physician to avoid any future pregnancy or they had been recommended to undergo abortion or sterilization.
In this study, there were no CAD recurrences during subsequent pregnancies or postpartum, irrespective of the type of delivery. Thus, pregnancy after a history of CAD appears to be safe.
Abstract only Introduction One potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre‐interventional reperfusion. Currently, there is a paucity of data ...regarding the occurrence of pre‐interventional reperfusion in patients randomized to IVT or no‐IVT before MT. Methods SWIFT DIRECT was a randomized controlled trial including acute ischemic stroke IVT‐eligible patients being directly admitted to a comprehensive stroke center, with allocation to either MT alone or IVT + MT. Primary endpoint of this analysis was the occurrence of pre‐interventional reperfusion defined as pre‐interventional expanded Thrombolysis in Cerebral Infarction score ≥ 2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Out of the 396 patients analyzed, pre‐interventional reperfusion occurred in 20 (10.0%) of patients randomized to IVT+MT, and 7 (3.6%) of patients randomized to MT alone. Receiving IVT favored the occurrence of pre‐interventional reperfusion (aOR 2.91 95% CI 1.23 – 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre‐interventional reperfusion with different strata of Randomization‐to‐Groin‐Puncture (p for interaction = 0.33), although the effect tended to be stronger in patients with Randomization‐to‐Groin‐Puncture >28 minutes (aOR 4.65 95% CI 1.16 – 18.68). There were no significant difference in rates of functional outcomes between patients with and without pre‐interventional reperfusion. Conclusions Even for patients with proximal large vessel occlusions and direct access to MT, IVT leads towards an absolute increase of 6.9% (95% CI 1.7‐12.2%) in the rates of pre‐interventional reperfusion. The effect of IVT tended to be more pronounced when Randomization‐to‐Groin‐Puncture intervals were longer, but this heterogeneity did not reach statistical significance.
Background and hypothesis
There is no consensus on the optimal endovascular management of the extracranial internal carotid artery steno-occlusive lesion in patients with acute ischemic stroke due to ...tandem occlusion. We hypothesized that intracranial mechanical thrombectomy plus emergent internal carotid artery stenting (and at least one antiplatelet therapy) is superior to intracranial mechanical thrombectomy alone in patients with acute tandem occlusion.
Study design
TITAN is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of acute ischemic stroke, pre-stroke modified Rankin Scale (mRS)≤2 (no upper age limit), National Institutes of Health Stroke Scale (NIHSS)≥6, Alberta Stroke Program Early Computed Tomography Score (ASPECTS)≥6, and tandem occlusion on the initial catheter angiogram. Tandem occlusion is defined as large vessel occlusion (intracranial internal carotid artery , M1 and/or M2 segment) and extracranial severe internal carotid artery stenosis ≥90% (NASCET) or complete occlusion. Patients are randomized in two balanced parallel groups (1:1) to receive either intracranial mechanical thrombectomy plus internal carotid artery stenting (and at least one antiplatelet therapy) or intracranial mechanical thrombectomy alone within 8 h of stroke onset. Up to 432 patients are randomized after tandem occlusion confirmation on angiogram.
Study outcomes
The primary outcome measure is complete reperfusion rate at the end of endovascular procedure, assessed as a modified Thrombolysis in Cerebral Infarction (mTICI) 3, and ≥4 point decrease in NIHSS at 24 h. Secondary outcomes include infarct growth, recurrent clinical ischemic event in the ipsilateral carotid territory, type and dose of antiplatelet therapy used, mRS at 90 (±15) days and 12 (±1) months. Safety outcomes are procedural complications, stent patency, intracerebral hemorrhage, and death. Economics analysis includes health-related quality of life, and costs utility comparison, especially with the need or not of endarterectomy.
Discussion
TITAN is the first randomized trial directly comparing two types of treatment in patients with acute ischemic stroke due to anterior circulation tandem occlusion, and especially assessing the safety and efficacy of emergent internal carotid artery stenting associated with at least one antiplatelet therapy in the acute phase of stroke reperfusion.
Trial registration
ClinicalTrials.gov NCT03978988
Dysautonomia in Parkinson's disease (PD) has been shown to be associated with disease severity and especially with the occurrence of dementia. One proposed explanation for this finding is that ...phosphorylated alpha-synuclein histopathology (PASH), the characteristic pathological feature of PD is more diffuse in dysautonomia-associated PD than in disease without dysautonomia, not only in the central nervous system but also in peripheral autonomic networks. The aim of this study was therefore to determine if colonic alpha-synuclein histopathology is associated with dysautonomia in PD.
A total of 43 PD patients participated in this study. For each patient, two biopsies were taken in the sigmoid colon and analyzed by immunohistochemistry with antibodies against phosphorylated alpha-synuclein and PGP 9.5. All patients had a complete neuropsychological and neurological assessment along with a comprehensive evaluation of dysautonomia with questionnaires (SCOPA-Aut, NMS-Quest, Rome III constipation criteria and dry eye symptoms) and functional tests (pupillometry, Saxon and Schirmer's tests, heart rate variability, orthostatic blood pressure measure and sympathetic skin response).
Colonic PASH was observed in 20/43 PD patients. No differences were observed in autonomic symptoms and testing between patients with and without PASH.
Although frequent in PD, autonomic dysfunction is not related to colonic PASH. In addition to the existing literature, our findings further suggest that each dysautonomic symptom in PD might not be associated with a more severe or diffuse PASH not only in the central nervous system but also in the peripheral autonomic nervous systems.
•47% of PD patients exhibited alpha-synuclein neuropathology in the sigmoid colon.•There was no association between colonic neuropathology and dysautonomia.•Dysautonomia in PD might not be associated with a more diffuse alpha-synuclein pathology.
Background
Although acute central retinal artery occlusion is as a stroke in the carotid territory (retinal artery), its management remains controversial. The aim of this study was to assess the ...feasibility and safety of intravenous thrombolysis delivered within 6 h of central retinal artery occlusion in French stroke units.
Methods
We performed a retrospective analysis of patients treated with intravenous alteplase (recombinant tissue-plasminogen activator), based on stroke units thrombolysis registers from June 2005 to June 2015, and we selected those who had acute central retinal artery occlusion. The feasibility was assessed by the ratio of patients that had received intravenous alteplase within 6 h after central retinal artery occlusion onset among those who had been admitted to the same hospital for acute central retinal artery occlusion. All adverse events were documented.
Results
Thirty patients were included. Visual acuity before treatment was limited to “hand motion”, or worse, in 90% of the cases. The mean onset-to-needle time was 273 min. The individuals treated with intravenous alteplase for central retinal artery occlusion represented 10.2% of all of the patients hospitalized for central retinal artery occlusion in 2013 and 2014. We observed one occurrence of major bleeding, a symptomatic intracerebral hemorrhage.
Conclusion
When applied early on, intravenous thrombolysis appears to be feasible and safe, provided that contraindications are given due consideration. Whether intravenous thrombolysis is more effective than conservative therapy remains to be determined. In order to conduct a well-designed prospective randomized control trial, an organized network should be in place.
Différencier la maladie de Parkinson idiopathique (MPI) des autres syndromes parkinsoniens tels que atrophie multi-systématisée (AMS) ou paralysie supranucléaire progressive (PSP) peut être difficile ...pour les cliniciens experts.
L’objectif de cette étude était d’évaluer la corrélation entre la conclusion des experts et celle des scintigraphies myocardiques au 123-I-MIBG pour le diagnostic différentiel entre MPI et PSP ou AMS.
Les 10 patients qui ont bénéficié d’une scintigraphie myocardique au CHU de Nantes entre février 2012 et septembre 2013 pour un syndrome parkinsonien atypique ont été inclus. L’examen d’imagerie était interprété selon 3 plans d’analyse : taux de fixation cardiaque globale aux temps précoce et tardif, rapports cœur/médiastin aux 2 temps et taux de relargage du traceur. Un examen anormal était en faveur d’une dénervation dopaminergique post-ganglionnaire, compatible avec le diagnostic de MPI.
La scintigraphie myocardique était réalisée entre un et dix huit ans après le début des symptômes. Deux de nos patients avaient une MPI, 3 une AMS et 4 une PSP. L’examen était interprété comme normal chez 3 patients (aucun avec une MPI), pathologique chez 4 patients (dont 1 AMS et 1 PSP), et douteux chez 2 patients. La sensibilité de notre examen d’imagerie était de 100 %. La spécificité (calculée en incluant AMS et PSP) était proche de 60 %. Elle était meilleure pour différencier la MPI de la l’AMS.
Nous avons retrouvé une scintigraphie myocardique au 123-I-MIBG pathologique chez la totalité des patients parkinsoniens. Cet examen était normal chez près de 60 % des patients avec syndrome parkinsonien atypique. Ainsi un examen normal éliminerait formellement le diagnostic de MPI. Le nombre élevé de faux positifs peut s’expliquer par les différentes pathologies et médicaments qui peuvent altérer les neurones sympathiques post-ganglionnaires.
Au total, notre étude a retrouvé des performances diagnostiques comparables à celles de la littérature concernant l’utilisation des scintigraphies myocardiques au 123-I-MIBG pour le diagnostic différentiel entre MPI et AMS ou PSP.
Les Lymphomes T cérébraux primitifs sont une pathologie rare et représentent moins de 2 % des lymphomes cérébraux. La difficulté diagnostique (IRM et anatomopathologique) est probablement à l’origine ...d’une sous-estimation de cette pathologie.
Un patient de 54 ans sans antécédent est hospitalisé dans le service de neurologie pour des troubles phasiques accompagnés de céphalées d’apparition progressive sur quelques mois. L’IRM cérébrale initiale retrouve des lésions hémorragiques multiples limitées au cortex avec prises de contraste hétérogènes et œdème péri lésionnel sans effet de masse significatif. L’analyse du LCR met en évidence une méningite lymphocytaire (15 elts/mm3) aseptique avec un immunophénotypage lymphocytaire négatif, et une synthèse intrathécale de béta-2-microglobuline. Le bilan exhaustif inflammatoire et infectieux revient négatif, notamment le TEP-TDM. Devant la gravité et l’extension rapide des lésions à l’imagerie, une première biopsie cérébrale est réalisée, et met en évidence des infiltrats lymphocytaires T périvasculaires et interstitiels, associé à des plages de nécroses pouvant évoquer une vascularite ou une encéphalomyélite aiguë disséminée hémorragique. Devant ces hypothèses, le patient est traité par de fortes doses de cyclophosphamide mensuelles. La mauvaise évolution clinique et radiologique incite à une deuxième biopsie cérébrale qui permet finalement le diagnostic de lymphome-T cérébral primitif (CD3+, CD8+, CD5+, phénotype cytotoxique activé, population lymphoïde T monoclonale identifiée en PCR). Un traitement par méthotrexate intrathécal est débuté et est actuellement en cours.
Le diagnostic de Lymphome cérébral T primitif est particulièrement difficile, et cette pathologie est très probablement sous diagnostiquée ; en cause, l’hétérogénéité IRM des lésions, mais aussi le manque de spécificité de l’analyse anatomopathologique initiale. Malgré l’absence de marqueurs de surface spécifique de cette pathologie, la perte du CD7 doit faire évoquer ce diagnostic, confirmé ensuite par l’étude de la clonalité T en biologie moléculaire.
Le diagnostic de lymphome-T primitif cérébral est difficile et l’étude de la clonalité par PCR est indispensable au diagnostic. Cette pathologie d’évolution rapide est de mauvais pronostic et nécessite une prise en charge précoce.
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