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.

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.

Sustained Tumor Control With MAPK Inhibition in BRAF V600-Mutant Adult Glial and Glioneuronal Tumors.

OBJECTIVE: To assess whether RAF and MEK inhibitors (RAFi/MEKi) can provide long-term clinical benefit in adult patients with BRAF V600-mutant glial and glioneuronal tumors (GGNTs), we analyzed tumor response and long-term outcome in a retrospective cohort. METHODS: We performed a retrospective search in the institutional databases of 6 neuro-oncology departments for adult patients with recurrent or disseminated BRAF V600-mutant GGNTs treated with RAFi/MEKi. RESULTS: Twenty-eight adults with recurrent or disseminated BRAF V600-mutant gangliogliomas (n = 9), pleomorphic xanthoastrocytomas (n = 9), and diffuse gliomas (n = 10) were included in the study. At the time that treatment with RAFi/MEKi was started, all tumors displayed radiologic features of high-grade neoplasms. Thirteen patients received RAFi as single agents (vemurafenib [n = 11], dabrafenib [n = 2]), and 15 received combinations of RAFi/MEKi (vemurafenib + cobimetinib [n = 5], dabrafenib + trametinib [n = 10]). Eleven patients achieved a partial or complete response (11 of 28, 39%), with a median reduction of -78% in their tumor burden. Responders experienced a median increase of 10 points in their Karnofsky Performance Status (KPS) score and a median progression-free survival of 18 months, which was longer than achieved with first-line treatment (i.e., 7 months, p = 0.047). Responders had better KPS score (p = 0.018) and tended to be younger (p = 0.061) and to be treated earlier (p = 0.099) compared to nonresponders. Five patients were rechallenged with RAFi/MEKi at progression, with novel tumor responses in 2. On univariate and multivariate analyses, response to RAFi/MEKi was an independent predictor of overall survival. CONCLUSIONS: Our study highlights the long-term clinical benefits of RAFi/MEKi in adult patients with BRAF V600-mutant GGNTs and encourages rechallenge in responders. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that, for adult patients with BRAF V600-mutant GGNT, RAFi/MEKi can reduce tumor burden and provide clinical benefit.

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.

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.

Optic Nerve Infiltration in Primary Central Nervous System Lymphoma.

Importance: Visual impairment in primary central nervous system lymphoma (PCNSL) is caused mostly by intraocular lymphomatous involvement (vitritis and retinal infiltration), whereas optic nerve infiltration (ONI) is a rare condition. Objective: To describe the clinical presentation of ONI, its imaging characteristics, and outcome. Design, Setting and Participants: A total of 752 patients diagnosed with PCNSL were retrospectively identified from the databases of 3 French hospitals from January 1, 1998, through December 31, 2014. Of these, 7 patients had documented ONI. Exclusion criteria were intraocular involvement, orbital lymphoma, or other systemic lymphoma. Clinical presentation, neuroimaging, biological features, treatment, and outcomes were assessed. Main Outcomes and Measures: Treatment response was evaluated clinically and radiologically on follow-up magnetic resonance imaging (MRI) according to the International PCNSL Collaborative Group response criteria. Results: The 7 patients included 5 women and 2 men. Median age at diagnosis was 65 years (range, 49-78 years). Two patients had initial ONI at diagnosis, and 5 had ONI at relapse. Clinical presentation was marked by rapidly progressive and severe visual impairment for all patients. The MRI findings showed optic nerve enlargement in 3 patients and contrast enhancement of the optic nerve in all patients. Additional CNS lesions were seen in 4 patients. Examination of cerebrospinal fluid samples detected lymphomatous meningitis in 2 patients. Clinical outcome was poor and marked by partial recovery for 2 patients and persistent severe low visual acuity or blindness for 5 patients. Median progression-free survival after optic nerve infiltration was 11 months (95% CI, 9-13 months), and median overall survival was 18 months (95% CI, 9-27 months). Conclusions and Relevance: Optic nerve infiltration is an atypical and challenging presentation of PCNSL. Its visual and systemic prognosis is particularly poor compared with vitreoretinal lymphomas even in response to chemotherapy. Although intraocular involvement is frequent in PCNSL and clinically marked by slowly progressive visual deterioration, lymphomatous ONI is rare and characterized by rapidly progressive severe visual impairment.

The CSF IL-10 concentration is an effective diagnostic marker in immunocompetent primary CNS lymphoma and a potential prognostic biomarker in treatment-responsive patients.

INTRODUCTION: We aimed to confirm the diagnostic value and to evaluate the pre- and post-therapeutic prognostic value of cerebrospinal fluid (CSF) concentrations of interleukin (IL)-10 and IL-6 in patients with diffuse large B-cell primary central nervous system lymphoma (PCNSL). PATIENTS AND METHODS: IL-10 and IL-6 concentrations were measured in 79 patients with PCNSL at diagnosis and in 40 control individuals. Fifty-four PCNSL patients underwent repeat assessments starting at diagnosis. RESULTS: The IL-10 concentration distinguished PCNSL from other neurologic diseases with a sensitivity of 88.6% and a specificity of 88.9% with a cutoff of 4 pg/ml. In a multivariate analysis of PCNSL patients, CSF involvement was associated with a higher IL-10 concentration (mean log (IL-10) of 4.4 versus 2.5 pg/ml, respectively, p = 0.0004). The pre-therapeutic IL-10 concentration had no prognostic impact on outcome. The IL-10 concentration decreased after treatment for most patients tested. Among patients with complete remission or partial remission, as evaluated by magnetic resonance imaging (MRI), a persistent detectable IL-10 level in the CSF at the end of treatment was associated with a negative impact on progression-free survival (PFS) (1-year PFS: 15%, 95% confidence interval [CI]: 2.5-38% versus 59%, 95% CI: 32-78%, respectively, p = 0.0004). CONCLUSION: Our study confirmed that IL-10 is a useful biomarker for the diagnosis of PCNSL. We highlight new findings showing that the IL-10 level in the CSF could be used as a surrogate marker for CSF involvement and that the post-treatment IL-10 concentration could complement standard MRI for therapeutic response assessment in PCNSL.