Current territorial organization for access to revascularization therapies for acute ischemic stroke in the Veneto region (Italy) from 2017 to 2021.

INTRODUCTION: To evaluate the access to treatments with intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT) in acute ischemic stroke patients admitted to stroke units (SUs) of Veneto region (Italy) according to current "hub-and-spoke" model from 2017 to 2021. PATIENTS AND METHODS: We retrospectively analyzed data on treatments with IVT and/or MT for stroke patients admitted to the 23 SUs (6 Hubs and 17 Spokes) of the 6 macro-areas including 9 local sanitary units (LSUs) and 2 hospitals. RESULTS: We reported 6093 treatments with IVT alone, 1114 with IVT plus MT, and 921 with MT alone. Number of stroke unit (SU) beds/100,000 inhabitants ranges from 2.3 to 2.8, and no difference was found among different macro-areas. Number of treatments/100,000 inhabitants/year ranges from 19 to 34 for IVT alone, from 2 to 7 for IVT plus MT, and from 2 to 5 for MT alone. Number of IVT alone/SU bed/year ranges from 9 to 21 in the Hub and from 6 to 12 in the Spokes. Rate of IVT plus MT in patients directly arrived in the same LSU's Hub ranges from 50 to 81%, likewise the one of MT alone ranges from 49 to 84%. CONCLUSIONS: Treatment target rates of IVT and MT set by Action Plan for Stroke in Europe 2018-2030 has been globally exceeded in the Veneto region. However, the target rate of MT and access revascularization treatments is heterogeneous among different macro-areas. Further efforts should be made to homogenize the current territorial organization.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

Acute revascularization treatments for ischemic stroke in the Stroke Units of Triveneto, northeast Italy: time to treatment and functional outcomes.

It is not known whether the current territorial organization for acute revascularization treatments in ischemic stroke patients guarantees similar time to treatment and functional outcomes among different levels of institutional stroke care. We aimed to assess the impact of time to treatment on functional outcomes in ischemic stroke patients who received intravenous thrombolysis (IVT) alone, bridging (IVT plus thrombectomy), or primary thrombectomy in level 1 and level 2 Stroke Units (SUs) in Triveneto, a geographical macroarea in Northeast of Italy. We conducted an analysis of data prospectively collected from 512 consecutive ischemic stroke patients who received IVT and/or mechanical thrombectomy in 25 SUs from September 17th to December 9th 2018. The favorable outcome measures were mRS score 0-1 and 0-2 at 3 months. The unfavorable outcome measures were mRS score 3-5 and death at 3 months. We estimated separately the possible association of each variable for time to treatment (onset-to-door, door-to-needle, onset-to-needle, door-to-groin puncture, needle-to-groin puncture, and onset-to-groin puncture) with 3-month outcome measures by calculating the odds ratios (ORs) with two-sided 95% confidence intervals (CI) after adjustment for pre-defined variables and variables with a probability value ≤ 0.10 in the univariate analysis for each outcome measure. Distribution of acute revascularization treatments was different between level 1 and level 2 SUs (p < 0.001). Among 182 patients admitted to level 1 SUs (n = 16), treatments were IVT alone in 164 (90.1%), bridging in 12 (6.6%), and primary thrombectomy in 6 (3.3%) patients. Among 330 patients admitted to level 2 SUs (n = 9), treatments were IVT alone in 219 (66.4%), bridging in 74 (22.4%), and primary thrombectomy in 37 (11.2%) patients. Rates of excellent outcome (51.4% vs 45.9%), favorable outcome (60.1% vs 58.7%), unfavorable outcome (33.3% vs 33.8%), and death (9.8% vs 11.3%) at 3 months were similar between level 1 and 2 SUs. No significant association was found between time to IVT alone (onset-to-door, door-to-needle, and onset-to-needle) and functional outcomes. After adjustment, door-to-needle time ≤ 60 min (OR 4.005, 95% CI 1.232-13.016), shorter door-to-groin time (OR 0.991, 95% CI 0.983-0.999), shorter needle-to-groin time (OR 0.986, 95% CI 0.975-0.997), and shorter onset-to-groin time (OR 0.994, 95% CI 0.988-1.000) were associated with mRS 0-1. Shorter door-to-groin time (OR 0.991, 95% CI 0.984-0.998), door-to-groin time ≤ 90 min (OR 12.146, 95% CI 2.193-67.280), shorter needle-to-groin time (OR 0.983, 95% CI 0.972-0.995), and shorter onset-to-groin time (OR 0.993, 95% CI 0.987-0.999) were associated with mRS 0-2. Longer door-to-groin time (OR 1.007, 95% CI 1.001-1.014) and longer needle-to-groin time (OR 1.019, 95% CI 1.005-1.034) were associated with mRS 3-5, while door-to-groin time ≤ 90 min (OR 0.229, 95% CI 0.065-0.808) was inversely associated with mRS 3-5. Longer onset-to-needle time (OR 1.025, 95% CI 1.002-1.048) was associated with death. Times to treatment influenced the 3-month outcomes in patients treated with thrombectomy (bridging or primary). A revision of the current territorial organization for acute stroke treatments in Triveneto is needed to reduce transfer time and to increase the proportion of patients transferred from a level 1 SU to a level 2 SU to perform thrombectomy.

Diagnostic features of initial demyelinating events associated with serum MOG-IgG.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-IgG associated disorders are increasingly recognized as a distinct disease entity. However, diagnostic sensitivity and specificity of serum MOG-IgG as well as recommendations for testing are still debated. MATERIALS AND METHODS: Between October 2015 and July 2017 we tested serum MOG-IgG in 91 adult patients (49 females) with a demyelinating event (DE) not fulfilling 2010 McDonald criteria for MS at sampling, negative for neuromyelitis optica (NMO)-IgG and followed-up for at least 12 months. We assessed the sensitivity and specificity of a live-cell MOG-IgG assay for each final diagnosis at last follow-up, for the 2018 international recommendations for MOG-IgG testing, and for other combinations of clinical and laboratory characteristics. RESULTS: Clinical presentations included acute myelitis (n = 48), optic neuritis (n = 36), multifocal encephalomyelitis (n = 4), and brainstem syndrome (n = 3). Twenty-four patients were MOG-IgG positive. Sensitivity and specificity of MOG-IgG test applied to the 2018 international recommendations were 28.4% and 86.7%, while they were 42.1% and 88.6% when applied to DE of unclear aetiology as defined above with two or more among: 1_no periventricular and juxtacortical MS-like lesions on brain MRI; 2_longitudinally extensive MRI optic nerve lesion; 3_no CSF-restricted oligoclonal bands; 4_CSF protein > 50 mg/dl. CONCLUSIONS: Simplified requirements compared to those currently proposed for MOG-IgG testing could facilitate the applicability of the assay in the diagnosis of adults with DEs of unclear aetiology.

Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study.

Anti-myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) recently emerged as a potential biomarker in patients with inflammatory demyelinating diseases of the central nervous system. We here compare the clinical and laboratory findings observed in a cohort of MOG-Ab seropositive and seronegative cases and describe IgG subclass analysis results. Consecutive serum samples referred to Verona University Neuropathology Laboratory for aquaporin-4 (AQP4)-Ab and/or MOG-Ab testing were analysed between March 2014 and May 2017. The presence of AQP4-Ab was determined using a cell-based assay. A live cell immunofluorescence assay was used for the detection of MOG-IgG and IgG subclass analysis. Among 454 analysed samples, 29 were excluded due to AQP4-Ab positivity or to the final demonstration of a disorder not compatible with MOG-Ab. We obtained clinical data in 154 out of 425 cases. Of these, 22 subjects resulted MOG-Ab positive. MOG-Ab positive patients were mainly characterised by the involvement of the optic nerve and/or spinal cord. Half of the cases presented relapses and the recovery was usually partial. Brain MRI was heterogeneous while short lesions were the prevalent observation on spinal cord MRI. MOG-Ab titre usually decreased in non-relapsing cases. In all MOG-IgG positive cases, we observed IgG1 antibodies, which were predominant in most subjects. IgG2 (5/22), IgG3 (9/22) and IgG4 (3/22) antibodies were also detectable. We confirm that MOG-Ab-related syndromes have distinct features in the spectrum of demyelinating conditions, and we describe the possible role of the different IgG subclasses in this condition.

Skin globotriaosylceramide 3 deposits are specific to Fabry disease with classical mutations and associated with small fibre neuropathy.

BACKGROUND: Fabry Disease (FD) is characterized by globotriaosylceramide-3 (Gb3) accumulation in several tissues and a small fibre neuropathy (SFN), however the underlying mechanisms are poorly known. This study aimed to: 1) ascertain the presence of Gb3 deposits in skin samples, by an immunofluorescence method collected from FD patients with classical GLA mutations or late-onset FD variants or GLA polymorphisms; 2) correlate skin GB3 deposits with skin innervation. METHODS: we studied 52 genetically-defined FD patients (32 with classical GLA mutations and 20 with late-onset variants or GLA polymorphisms), 15 patients with SFN associated with a specific cause and 22 healthy controls. Subjects underwent skin biopsy to evaluate Gb3 deposits and epi-dermal innervation. RESULTS: Skin Gb3 deposits were found in all FD patients with classical GLA mutations but never in FD patients with late-onset variants or GLA polymorphisms or in patients with SFN and healthy controls. Abnormal deposits were found inside different skin structures but never inside axons. FD patients with GB3 deposits showed lower skin innervation than FD patients with late-onset variants or polymorphisms. CONCLUSIONS: 1) Skin Gb3 deposits are specific to FD patients with classical GLA mutations; 2) Gb3 deposits were associated with lower skin innervation but they were not found inside axons, suggesting an indirect damage on peripheral small fibre innervation.