Complications During Inter-Hospital Transfer of Patients with Acute Ischemic Stroke for Endovascular Therapy.

Purpose: Few data are available on complications occurring during inter-hospital transfer from a primary stroke center (PSC) to a comprehensive stroke center (CSC) for endovascular treatment (EVT) after large vessel occlusion (LVO). Therefore, we prospectively studied data from consecutive patients transferred from our PSC to the next CSC during 4 years to determine the incidence and risk factors of complications during transfer. Methods: This observational, single-center study included consecutive patients transferred from January 1, 2015 to December 31, 2018. During inter-hospital transfer, all medical incidents were systematically recorded. A new complete clinical examination was performed on arrival at the CSC. Results: Among the 253 patients transferred to the CSC during the study period, 68 (26.9%) had one or more complications. In 11 patients (4.3%) these were life-threatening and required emergency intervention by a physician. Baseline characteristics were not different between patients with and without complications, except for the LVO location. Specifically, basilar artery (BA) occlusion was strongly associated with complications during the transport (p < 0.0005). Conclusion: Complications occurred in 26.9% of patients during transfer. Only BA occlusion could predict complication during transfer. Future studies should identify variables to help stratifying patients at high and low risk of complications during transportation.

A Clinico-Radiological Study of Cerebral Amyloid Angiopathy-Related Inflammation.

OBJECTIVE: To describe the clinico-radiological features and long-term prognosis in patients with cerebral amyloid angiopathy-related inflammation (CAA-ri). METHODS: Twenty-eight CAA-ri patients were recruited retrospectively from 6 neurological centers. We recorded the clinico-radiological and biological data, at baseline and during follow-up. Baseline characteristics associated with relapse risk and prognosis were assessed. RESULTS: Five patients had pathologically confirmed CAA-ri whereas 23 had probable (n = 21) or possible (n = 2) CAA-ri. The mean age was 72 years; main clinical symptoms included confusion (54%), hemiparesis (36%), and aphasia (29%). Cerebral MRI disclosed a brain parenchymal lesion (89%), which was usually multifocal (82%) and bilateral (89%). It was associated with gadolinium enhancement (84%), small ischemic lesions (39%), cortical superficial siderosis (CSS; 50%), and a high number of microbleeds (mean 240 ± 277). An isolated leptomeningeal involvement was observed in 3 patients with pathological confirmation. Despite a favorable initial evolution after treatment, we observed a 42% risk of relapse, mostly within the first year (83%). After a mean follow-up of 2 years, 29% died and 25% had a marked disability. Disseminated CSS was associated with death. CONCLUSION: Despite an apparently favorable initial evolution, CAA-ri is characterized by a poor prognosis. Diagnostic criteria should consider patients with isolated leptomeningeal involvement.

Which Patients Require Physician-Led Inter-Hospital Transport in View of Endovascular Therapy?

INTRODUCTION: The current guidelines advocate the implementation of stroke networks to organize endovascular treatment (ET) for patients with acute ischemic stroke due to large vessel occlusion (LVO) after transfer from a Primary Stroke Centre (PSC) to a Comprehensive Stroke Centre (CSC). In France and in many other countries around the world, these transfers are carried out by a physician-led mobile medical team. However, with the recent broadening of ET indications, their availability is becoming more and more critical. Here, we retrospectively analysed data of patients transferred from a PSC to a CSC for potential ET to identify predictive factors of major complications (MC) at departure and during transport that absolutely require the presence of a physician during interhospital transfer. METHODS: This observational, single-centre study included patients with evidence of intracranial LVO transferred for ET from Perpignan to a 156 km-distant CSC between January 1, 2015 and -December 31, 2018. We compared 2 groups: MC group (patients who required emergency intervention by the medical team due to life-threatening complications, including need of mechanical ventilation at departure) and non-MC group (all other patients who experienced no or only minor complications that could be managed by the emergency paramedics alone). RESULTS: Among the 253 patients who were transferred to the CSC, 185 (73.1%) had no complication, 57 (22.6%) minor complications, and 11 (4.3%) had MC. In multivariate analysis, MC was associated with basilar artery (BA) occlusion (p < 0.0001), initial National Institute of Health Stroke Scale (NIHSS) score >22 (p < 0.005), and history of atrial fibrillation (p < 0.04). Among the 168 patients treated with intravenous thrombolysis (IVT), only 1 patient (0.6%) had MC due to an IVT-related adverse event during transfer. CONCLUSIONS: Physician-led inter-hospital transports are warranted for patients with BA occlusion, initial NIHSS score >22, or history of atrial fibrillation. For the other patients, transfer without a physician may be considered, even if treated with IVT.

Mechanical Recanalization after Transfer from a Distant Primary Stroke Center: Effectiveness and Future Directions.

INTRODUCTION: Little is known about the effectiveness of endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) admitted to a primary stroke center (PSC). The aim of this study was to assess EVT effectiveness after transfer from a PSC to a distant (156 km apart; 1.5 hour by car) comprehensive stroke center (CSC), and to discuss perspectives to improve access to EVT, if indicated. PATIENTS AND METHOD: Analysis of the data collected in a 6-year prospective registry of patients admitted to a PSC for AIS due to LVO and selected for transfer to a distant CSC for EVT. The rate of transfer, futile transfer, EVT, reperfusion (thrombolysis in cerebral infarction score ≥2b-3), and relevant time measures were determined. RESULTS: Among the 529 patients eligible, 278 (52.6%) were transferred and 153 received EVT (55% of transferred patients) followed by reperfusion in 115 (overall reperfusion rate: 21.7%). Median times (interquartile range) were: 90 minutes (76-110) for PSC-door-in to PSC-door-out, 88 minutes (65-104) for PSC-door-out to CSC-door-in, 262 minutes (239-316) for PSC-imaging to reperfusion, and 393 minutes (332-454) for symptom onset to reperfusion. At 3 months, rates of favorable outcome (modified Rankin Scale 0-2) were not significantly different between patients eligible for EVT (42.4%), transferred patients (49.1%) and patients who underwent EVT (34.1%). DISCUSSION AND CONCLUSIONS: Our study suggests that transfer to a distant CSC is associated with reduced access to early EVT. These results argue in favor of on-site EVT at high volume PSCs that are distant from the CSC.

Target Door-to-Needle Time for Tissue Plasminogen Activator Treatment with Magnetic Resonance Imaging Screening Can Be Reduced to 45 min.

OBJECTIVE: The purpose of this study was to demonstrate that the median door-to-needle (DTN) time for intravenous tissue plasminogen activator (tPA) treatment can be reduced to 45 min in a primary stroke centre with MRI-based screening for acute ischaemic stroke (AIS). METHODS: From February 2015 to February 2017, the stroke unit of Perpignan general hospital, France, implemented a quality-improvement (QI) process. During this period, patients who received tPA within 4.5 h after AIS onset were included in the QI cohort. Their clinical characteristics and timing metrics were compared each semester and also with those of 135 consecutive patients with AIS treated by tPA during the 1-year pre-QI period (pre-QI cohort). RESULTS: In the QI cohort, 274 patients (92.5%) underwent MRI screening. While the demographic and baseline characteristics were not significantly different between cohorts, the median DTN time was significantly lower in the QI than in the pre-QI cohort (52 vs. 84 min; p < 0.00001). Within the QI cohort, the median DTN time for each semester decreased from 65 to 44 min (p < 0.00001) and the proportion of treated patients with a DTN time ≤45 min increased from 25 to 58.9% (p < 0.0001). Overall, DTN time improvement was associated with a better outcome at 3 months (patients with a modified Rankin Scale score between 0 and 2: 61.8% in the QI vs. 39.3% in the pre-QI cohort; p < 0.0001). CONCLUSIONS: A QI process can reduce the DTN within 45 min with MRI as a screening tool.

Punctate and curvilinear gadolinium enhancing lesions in the brain: a practical approach.

INTRODUCTION: Cerebral punctate and curvilinear gadolinium enhancements (PCGE) correspond to opacification of small vessel lumen or its perivascular areas in case of blood-brain barrier (BBB) disruption. We will discuss the possible causes of intra-parenchymal central nervous system PCGE. METHODS: Our review is based on French database including patients presenting with central nervous system PCGE and literature search using PubMed database with the following keywords: punctate enhancement, linear enhancement, and curvilinear enhancement. Disorders which displayed linear leptomeningeal or periventricular enhancements without intra-parenchymal PCGE are excluded of this review. RESULTS: Among our 39 patients with PCGE, 16 different diagnoses were established. After combining our PCGE causes with those described in the literature, we propose a practical approach. Besides physiologic post-contrast enhancement of small vessels, three pathologic conditions may exhibit PCGE: (1) small collateral artery network seen in Moyamoya syndrome, (2) small veins congestions related to developmental or acquired venous outflow disturbance, and (3) disorders causing small vessels BBB disruption indicated by T2 and FLAIR hyperintensities in the corresponding areas of PCGE. Disruption of the BBB could be caused by a direct injury of the endothelial cell, as in posterior reversible encephalopathy syndrome, Susac syndrome, and radiochemotherapy-induced injuries, or by an angiocentric cellular infiltrate, as in inflammatory disorders, demyelinating diseases, host immune responses fighting against infections, prelymphoma states, lymphoma, and in CLIPPERS. CONCLUSION: PCGE may conceal several causes, including physiological and pathological conditions. Nevertheless, a practical approach could improve its management and limit the indications of brain biopsy to very specific situations.

Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. METHODS: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. RESULTS: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). CONCLUSION: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Usefulness of a single-parameter tool for the prediction of large vessel occlusion in acute stroke.

BACKGROUND: In acute stroke, large vessel occlusion (LVO) should be promptly identified to guide patient's transportation directly to comprehensive stroke centers (CSC) for mechanical thrombectomy (MT). In many cases, prehospital multi-parameter scores are used by trained emergency teams to identify patients with high probability of LVO. However, in several countries, the first aid organization without intervention of skilled staff precludes the on-site use of such scores. Here, we assessed the accuracy of LVO prediction using a single parameter (i.e. complete hemiplegia) obtained by bystander's telephone-based witnessing. PATIENTS AND METHODS: This observational, single-center study included consecutive patients who underwent intravenous thrombolysis at the primary stroke center and/or were directly transferred to a CSC for MT, from January 1, 2015 to March 1, 2020. We defined two groups: patients with initial hemiplegia (no movement in one arm and leg and facial palsy) and patients without initial hemiplegia, on the basis of a bystander's witnessing. RESULTS: During the study time, 874 patients were included [mean age 73 years (SD 13.8), 56.7% men], 320 with initial hemiplegia and 554 without. The specificity of the hemiplegia criterion to predict LVO was 0.88, but its sensitivity was only 0.53. CONCLUSION: Our results suggest that the presence of hemiplegia as witnessed by a bystander can predict LVO with high specificity. This single criterion could be used for decision-making about direct transfer to CSC for MT when the absence of emergency skilled staff precludes the patient's on-site assessment, especially in regions distant from a CSC.

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera.

INTRODUCTION: IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. METHODS: 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. RESULTS: IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). CONCLUSIONS: Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.

Futile inter-hospital transfer for mechanical thrombectomy in a semi-rural context: analysis of a 6-year prospective registry.

BACKGROUND AND PURPOSE: Inter-hospital transfer for mechanical thrombectomy (MT) might result in the transfer of patients who finally will not undergo MT (ie, futile transfers [FT]). This study evaluated FT frequency in a primary stroke center (PSC) in a semi-rural area and at 156 km from the comprehensive stroke center (CSC). METHODOLOGY: Retrospective analysis of data collected in a 6-year prospective registry concerning patients admitted to our PSC within 4.5 hours of acute ischemic stroke (AIS) symptom onset, with MR angiography indicating the presence of large vessel occlusion (LVO) without large cerebral infarction (DWI-ASPECT ≥5), and selected for transfer to the CSC to undergo MT. Futile transfer rate and reasons were determined, and the relevant time measures recorded. RESULTS: Among the 529 patients screened for MT, 278 (52.6%) were transferred to the CSC. Futile transfer rate was 45% (n=125/278) and the three main reasons for FT were: clinical improvement and reperfusion on MRI on arrival at the CSC (58.4% of FT); clinical worsening and/or infarct growth (16.8%); and longer than expected inter-hospital transfer time (11.2%). Predictive factors of FT due to clinical improvement/reperfusion on MRI could not be identified. Baseline higher NIHSS (21 vs 17; P=0.01) and lower DWI-ASPECT score (5 vs 7; P=0.001) were associated with FT due to clinical worsening/infarct growth on MRI. CONCLUSIONS: In our setting, 45% of transfers for MT were futile. None of the baseline factors could predict FT, but the initial symptom severity was associated with FT caused byclinical worsening/infarct growth.

Pathologic and MRI analysis in acute atypical inflammatory demyelinating lesions.

BACKGROUND: The diagnosis of atypical inflammatory demyelinating lesions can be difficult. Brain biopsy is often required to exclude neoplasms. Moreover, the relationship between these lesions and multiple sclerosis and NMOSD is not clear. OBJECTIVES: Our objectives were to describe radiological and pathological characteristics of patients with acute inflammatory demyelinating lesions. METHODS: We retrospectively identified patients with brain biopsy performed for diagnostic uncertainty revealing a demyelinating lesion. A complete clinical, biological, radiological and pathological analysis was performed. RESULTS: Twenty patients (15 with a single lesion) were included. MRI disclosed a wide range of lesions including infiltrative lesions (40%), ring-like lesion (15%) Baló-like lesion (15%) and acute haemorrhagic leukoencephalitis (20%). In spite of a marked heterogeneity, some findings were common: a peripheral B1000 hyperintense rim (70%), a slight oedema with mild mass effect (75%) and an open-rim peripheral enhancement (75%). Histopathology revealed that all cases featured macrophages distributed throughout, extensive demyelination, axonal preservation and absence of haemorrhagic changes. In the majority of cases, macrophages were the predominant inflammatory infiltrate and astrocytes were reactive and dystrophic. Aquaporin-4 staining was systematically preserved. After a mean follow-up of 5 years (1-12), 16/20 patients had a diagnosis of monophasic acute atypical inflammatory demyelinating lesion. One patient was diagnosed with MS and 3 with AQP4 negative NMOSD. DISCUSSION: Although imaging findings in patients with atypical inflammatory demyelinating lesions are heterogeneous, some common features such as peripheral DWI hyperintense rim with open-rim enhancement and absence of oedema argue in favour of a demyelinating lesion and should preclude a brain biopsy. In this context, AQP4 staining is systematically preserved and argues against an AQP4-positive NMOSD. Moreover, long-term follow-up is characterized by low recurrence rate.

Therapeutic Approaches in CLIPPERS.

OPINION STATEMENT: CLIPPERS for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a steroid-sensitive and steroid-dependent brainstem inflammatory disease of unknown origin. Since its first description in 2010, about 60 cases have been reported throughout the world. The mean age at onset is 50 years and men seem to be more frequently affected. In patients without chronic corticosteroid therapy or immunosuppressive agents, the disease had a relapsing remitting course, and the mean annualized relapse rate was 0.5. During attacks, although clinical and radiological improvement after high doses of corticosteroids was systematically observed, patients could display subsequent disability and hindbrain atrophy. Since no progressive course was observed, clinical and radiological sequelae were correlated with previous severe attacks. Therefore, maintaining the disease in remission may prevent the accumulation of disability. In the literature, no relapse occurred when chronic corticosteroid therapy was maintained above 20 mg per day. However, steroids side effects led to propose corticosteroid-sparing therapies. Unfortunately, no controlled therapy studies for CLIPPERS have been performed yet, and no therapeutic recommendations exist. Using the PubMed database, all articles having the following keywords "chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids" and "CLIPPERS" have been analysed. Considering that the mean annual relapse rate was 0.5, and that no relapse occurred when corticosteroid therapy was maintained above 20 mg per day, the therapeutic efficiency of corticosteroid-sparing agents was considered as "probable" when patients had a relapse-free period ≥24 months, in the absence of concomitant corticosteroid therapy. Corticosteroid-sparing agents whose efficiency is "probable" are methotrexate in two cases, cyclophosphamide in one case and hydroxychloroquine in one case. Considering the risk benefit ratio of corticosteroid-sparing agents, methotrexate seems to be the most suitable. Nevertheless, randomized controlled trials testing the different corticosteroid-sparing agents in CLIPPERS are necessary.