In-vivo characterization of macro- and microstructural injury of the subventricular zone in relapsing-remitting and progressive multiple sclerosis.

Introduction: The subventricular zone (SVZ) represents one of the main adult brain neurogenesis niche. In-vivo imaging of SVZ is very challenging and little is known about MRI correlates of SVZ macro- and micro-structural injury in multiple sclerosis (MS) patients. Methods: The aim of the present study is to evaluate differences in terms of volume and microstructural changes [as assessed with the novel Spherical Mean Technique (SMT) model, evaluating: Neurite Signal fraction (INTRA); Extra-neurite transverse (EXTRATRANS) and mean diffusivity (EXTRAMD)] in SVZ between relapsing-remitting (RR) or progressive (P) MS patients and healthy controls (HC). We are also going to explore whether SVZ microstructural injury correlate with caudate (a nucleus that is in the vicinity of the SVZ) or thalamus (another well-defined grey matter area which is further from SVZ than caudate) volume and clinical disability. Clinical and brain MRI data were prospectively acquired from 20 HC, 101 RRMS, and 50 PMS patients. Structural and diffusion metrics inside the global SVZ, normal appearing (NA-) SVZ, caudate and thalamus were collected. Results: We found a statistically significant difference between groups in terms of NA-SVZ EXTRAMD (PMS>RRMS>HC; p = 0.002), EXTRATRANS (PMS>RRMS>HC; p<0.0001), and INTRA (HC>RRMS>PMS; p = 0.009). Multivariable models showed that NA-SVZ metrics significantly predicted caudate (R 2 = 0.21, p < 0.0001), but not thalamus, atrophy. A statistically significant correlation between EXTRAMD and EXTRATRANS of the NA-SVZ and EDSS (r=0.25, p=0.003 and r=0.24, p = 0.003, respectively) was found. These findings were confirmed in analyses restricted to RRMS, but not to PMS patients. Discussion: In conclusion, the microstructural damage we observed within the NA-SVZ of MS patients - reflecting higher free water content (higher EXTRAMD), cytoarchitecture disruption and astrogliosis (higher EXTRATRANS and lower INTRA) - was more evident in the progressive as compared to the relapsing phases of MS. These abnormalities were significantly associated with a more pronounced caudate atrophy and higher clinical disability scores. Our findings may support the neuroprotective role of SVZ in MS patients.

Endovascular treatment of patients with acute ischemic stroke and tandem occlusion due to internal carotid artery dissection: A multicenter experience.

BACKGROUND: The optimal management of patients with acute ischemic stroke (AIS) due to tandem occlusion (TO) and underlying carotid dissection (CD) remains unclear. OBJECTIVE: We present our multicenter-experience of endovascular treatment (EVT) approach used and outcomes for AIS patients with CD-related TO (CD-TO). METHODS: Consecutive AIS patients underwent EVT for CD-TO at five Italian Neuro-interventional Tertiary Stroke Centers were retrospectively identified. TO from atherosclerosis and other causes of, were excluded from the final analysis. Primary outcome was successful (mTICI 2b-3) and complete reperfusion (mTICI 3); secondary outcome was patients' 3-months functional independence (mRS≤2). RESULTS: Among 214 AIS patients with TO, 45 presented CD-TO. Median age was 54 years (range 29-86), 82.2% were male. Age <65 years (p < 0.0001), lower baseline NIHSS score (p = 0.0002), and complete circle of Willis (p = 0.0422) were associated with mRS ≤ 2 at the multivariate analysis. Comparisons between antegrade and retrograde approaches resulted in differences for baseline NIHSS scores (p = 0.001) and number of EVT attempts per-procedure (p = 0.001). No differences in terms of recanalization rates were observed between antegrade and retrograde EVT approaches (p = 0.811) but higher rates of mTICI3 revascularization was observed with the retrograde compared to the antegrade approach (78.6% vs 73.3%), anyway not statistically significant. CD management technique (angioplasty vs aspiration vs emergent stenting) did not correlate with 3-months mRS≤2. CONCLUSION: AIS patients with CD-TO were mostly treated with the retrograde approach with lower number of attempts per-procedure but it offered similar recanalization rates compared with the antegrade approach. Emergent carotid artery stenting (CAS) proved to be safe for CD management but it does not influence 3-months patients' clinical outcomes.

18F-FDG-PET correlates of aging and disease course in ALS as revealed by distinct PVC approaches.

PURPOSE: The partial volume effect (PVE) complicates PET studies of neurodegenerative diseases, since a decreased 18F-FDG retention might be influenced by atrophy-related changes of cortical regions. Multiple partial volume correction (PVC) methods have been therefore developed, but their application in amyotrophic lateral sclerosis (ALS) is still rare. Additionally, even if metabolic changes have been established in ALS, no study yet has investigated how these may be influenced by aging and disease course. The aim of the present study was therefore to apply and compare multiple PVC approaches to explore aging and disease course-related hypometabolism in ALS. METHODS: PET and MRI data from 15 ALS patients were analyzed using PETSurfer to implement 4 distinct PVC methods: noPVC, Meltzer (MZ), Müller-Gärtner (MG) and Symmetric Geometric Transfer Matrix (SGTM). For each method and Region of Interest (ROI), the 18F-FDG value was regressed against subject age and disease duration. RESULTS: MG/SGTM application almost halved the number of regions showing a significant age-related hypometabolism, while the same effect was not observed for disease course, where only the distribution of identified regions varied. Three distinct patterns emerged: regions showing a significant age/disease course-related effect across all the different methods, regions yielding significance only with MG/SGTM application, and regions maintaining significance only with noPVC/MZ application. CONCLUSIONS: Significant changes in the distribution of aging and disease course-related hypometabolism were observed when the effect of the underlying structural status was considered, supporting the need for investigate the impact of PVE on PET-assessed metabolic changes in clinical and research settings.

Mechanical thrombectomy in acute ischemic stroke with tandem occlusions: impact of extracranial carotid lesion etiology on endovascular management and outcome.

OBJECTIVE: Different etiologies of extracranial internal carotid artery steno-occlusive lesions (ECLs) in patients with acute ischemic stroke (AIS) and tandem occlusion (TO) have been pooled together in randomized trials. However, carotid atherosclerosis (CA) and carotid dissection (CD), the two most common ECL etiologies, are distinct nosological entities. The authors aimed to determine if ECL etiology has impacts on the endovascular management and outcome of patients with TO. METHODS: A multicenter, retrospective study of prospectively collected data was conducted. AIS patients were included who had TO due to internal CA or CD and ipsilateral M1 middle cerebral artery occlusion and underwent endovascular treatment (EVT). Comparative analyses including demographic data, safety, successful recanalization rates, and clinical outcome were performed according to EVT and ECL etiology. RESULTS: In total, 214 AIS patients with TOs were included (77.6% CA related, 22.4% CD related). Patients treated with a retrograde approach were more often functionally independent at 3 months than patients treated with an antegrade approach (OR 0.6, 95% CI 0.4-0.9). Patients with CD-related TOs achieved 90-day clinical independence more often than patients with CA-related TOs (OR 1.4, 95% CI 1.1-2.0). Emergency stenting use was associated with good 3-month clinical outcome only in patients with CA-related TOs (OR 1.4, 95% CI 1.1-2.1). Symptomatic intracranial hemorrhage (sICH) occurred in 10.7% of patients, without differences associated with ECL etiology. CONCLUSIONS: ECL etiology impacts both EVT approach and clinical outcome in patients with TOs. Patients with CD-related TO achieved higher 3-month functional independence rates than patients with CA-related TOs. A retrograde approach can be desirable for both CA- and CD-related TOs, and emergency stenting is likely better justified in CA-related TOs.

Age at symptom onset influences cortical thinning distribution and survival in amyotrophic lateral sclerosis.

PURPOSE: The lifetime risk of developing amyotrophic lateral sclerosis (ALS) increases in the elderly, and greater age at symptom onset has been identified as a negative prognostic factor in the disease. However, the underlying neurobiological mechanisms are still poorly investigated. We hypothesized that older age at symptom onset would have been associated with greater extra-motor cortical damage contributing to worse prognosis, so we explored the relationship between age at symptom onset, cortical thinning (CT) distribution, and clinical markers of disease progression. METHODS: We included 26 ALS patients and 29 healthy controls with T1-weighted magnetic resonance imaging (MRI). FreeSurfer 6.0 was used to identify regions of cortical atrophy (CA) in ALS, and to relate age at symptom onset to CT distribution. Linear regression analyses were then used to investigate whether MRI metrics of age-related damage were predictive of clinical progression. MRI results were corrected using the Monte Carlo simulation method, and regression analyses were further corrected for disease duration. RESULTS: ALS patients exhibited significant CA mainly encompassing motor regions, but also involving the cuneus bilaterally and the right superior parietal cortex (p < 0.05). Older age at symptom onset was selectively associated with greater extra-motor (frontotemporal) CT, including pars opercularis bilaterally, left middle temporal, and parahippocampal cortices (p < 0.05), and CT of these regions was predictive of shorter survival (p = 0.004, p = 0.03). CONCLUSION: More severe frontotemporal CT contributes to shorter survival in older ALS patients. These findings have the potential to unravel the neurobiological mechanisms linking older age at symptom onset to worse prognosis in ALS.

Delayed Treatment (≥5 Days) by Flow Diversion of Ruptured Blister-Like Cerebral Aneurysms : Case Series of 8 Consecutive Patients.

BACKGROUND AND PURPOSE: Ruptured blister-like aneurysms (BLAs) are challenging lesions to treat, without any consensus on their management. Few studies have evaluated the safety and effectiveness of flow diverter stents (FDS) for this indication, with promising results. The goal was to evaluate the safety and effectiveness of a delayed (≥5 days) flow diversion strategy for the treatment of ruptured intracranial BLAs. MATERIAL AND METHODS: A monocentric retrospective analysis of a prospectively collected database of intracranial aneurysms was performed. Eight consecutive patients with 9 ruptured intracranial BLAs from November 2010 to June 2018 were included in the study. The BLA treatment with FDS was delayed from the rupture (minimum rupture to treatment delay = 5 days, mean = 16.9 ± 9.2 days). Procedure-related complications were systematically recorded. Rebleeding occurrences were systematically assessed. Long-term clinical and angiographic follow-ups were recorded. RESULTS: No procedure-related death was recorded. Neither early nor late rebleeding was observed and one (12.5%) major procedure-related complication occurred (ischemic stroke). Most of the patients (5/8; 62.5%) had an mRS <2 at discharge. The immediate periprocedural control angiogram showed a complete exclusion of the aneurysm in one patient (12.5%) but at follow-up (mean delay = 19.8 months) all patients had a complete aneurysm occlusion. All patients had a long-term mRS <2. CONCLUSION: This case series suggests that a delayed treatment (≥5 days after the hemorrhagic event) of ruptured BLAs with FDS is feasible, and may be safe and effective in terms of rebleeding prevention and long-term angiographic outcome.

Occlusion Rate and Visual Complications With Flow-Diverter Stent Placed Across the Ophthalmic Artery's Origin for Carotid-Ophthalmic Aneurysms: A Meta-Analysis.

BACKGROUND: Flow-diverter stents (FDSs) have recently gained acceptance for the treatment of intracranial aneurysms, especially for carotid-ophthalmic aneurysms (COAs). However, complications have been reported after coverage of side branches, especially the ophthalmic artery (OA). OBJECTIVE: To evaluate, through a meta-analysis, the occlusion rate, and the ophthalmic complications after treatment of COA by FDS. METHODS: We reviewed on MEDLINE via PubMed, Embase via Ovid, and Cochrane central database via CENTRAL. We included all case series with at least 15 patients and clinical trials about flow diversion of aneurysms close to the OA's origin. Among these studies, we only included articles with aneurysm occlusion rate and rate of new ophthalmic symptoms. RESULTS: We included 16 studies with 913 COA treated by FDSs and covering the OA with a mean follow-up of 16.4 mo. The random-effect modeling analysis concerning the overall rate of new ophthalmic complications, after FDS deployment covering the OA, was 3.0% (CI95% 1.0-6.0). There was medium-high heterogeneity in the study reports P < .01, I2 = 70.2% [50.4%; 82.1%]. We were not able to statistically explain this heterogeneity with the performed analysis, which could be related to the design of the included studies. We found an overall aneurysm occlusion rate of 85.0% (95% CI 80.0-89.0). CONCLUSION: Our meta-analysis found a high aneurysm occlusion rate (85%) and low rate of iatrogenic visual complications, with only 3.0% of new visual symptoms, after treatment of COA by FDS.

Medina embolization device for the treatment of intracranial aneurysms: 18 months' angiographic results.

BACKGROUND AND PURPOSE: The Medina embolization device (MED) is a new flow disruption device combining the design of a detachable coil with an intrasaccular flow disrupter. Safety and short-term angiographic effectiveness of this device have recently been reported. However, long-term angiographic results are lacking. We report herein the 18 months' angiographic outcome in patients treated for a wide-neck intracranial aneurysm with the MED. MATERIALS AND METHODS: Nineteen patients (17 female, mean age 50 years) with 20 wide-neck intracranial aneurysms (six ruptured; 14 unruptured) were treated by the MED between January 2015 and June 2016. Procedure-related complications were systematically recorded; discharge and 6-9 months' follow-up modified Rankin Scale scores were assessed. Angiographic mid-term and long-term follow-up were performed with a mean delay of 6.4±1.5 months (n=16 aneurysms) and 17.7±4.2 months (n=15 aneurysms), respectively. Occlusion rates were evaluated after the procedure and at the mid-term and long-term follow-up using the Roy-Raymond scale. RESULTS: Embolization with the MED was feasible in all except two cases (2/20, 10%). One per-procedural perforation was recorded (1/20, 5%) and one MED deployment failed because of the aneurysm's shape (1/20, 5%). Three cases of thromboembolic complications were observed (3/20, 15%). Only one thromboembolic complication was responsible for clinical sequelae. Grade A occlusion rate was 61% (11/18) after the procedure, 75% at 6 months' follow-up (12/16), and 80% (12/15) at long-term follow-up. Two cases (2/18, 11%) of recanalization at mid-term were documented angiographically. No recanalization occurred between the mid-term and long-term follow-up. CONCLUSION: MED is a hybrid embolization device, combining properties of a conventional coil with those of an intrasaccular flow disrupter. Our series focusing on long-term angiographic follow-up shows a satisfactory long-term occlusion rate. Larger series with longer angiographic follow-up times are warranted to confirm these preliminary results.