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Background: The assessment of treatment response is a crucial step for patients with relapsing-remitting multiple sclerosis on disease-modifying therapies (DMTs). We explored whether a scoring system developed within the MAGNIMS (MRI in Multiple Sclerosis) network to evaluate treatment response to injectable drugs can be adopted also to oral DMTs., Methods: A multicentre dataset of 1200 patients who started three oral DMTs (fingolimod, teriflunomide and dimethyl fumarate) was collected within the MAGNIMS network. Disease activity after the first year was classified by the 'MAGNIMS' score based on the combination of relapses (0-≥2) and/or new T2 lesions (<3 or ≥3) on brain MRI. We explored the association of this score with the following 3-year outcomes: (1) confirmed disability worsening (CDW); (2) treatment failure (TFL); (3) relapse count between years 1 and 3. The additional value of contrast-enhancing lesions (CELs) and lesion location was explored., Results: At 3 years, 160 patients experienced CDW: 12% of them scored '0' (reference), 18% scored '1' (HR=1.82, 95% CI 1.20 to 2.76, p=0.005) and 37% scored '2' (HR=2.74, 95% CI 1.41 to 5.36, p=0.003) at 1 year. The analysis of other outcomes provided similar findings. Considering the location of new T2 lesions (supratentorial vs infratentorial/spinal cord) and the presence of CELs improved the prediction of CDW and TFL, respectively, in patients with minimal MRI activity alone (one or two new T2 lesions)., Conclusions: Early relapses and substantial MRI activity in the first year of treatment are associated with worse short-term outcomes in patients treated with some of the oral DMTs., Competing Interests: Competing interests: SR has received honoraria from Biogen, MS, Novartis and Teva for consulting services, speaking and/or travel support. LP has received consulting fees from Biogen, Novartis and Roche; speaker honoraria from Biogen, Genzyme, Merck Serono, Novartis and Teva; travel grants from Biogen, Genzyme, Novartis and Teva; research grants from the Italian MS Society (Associazione Italiana Sclerosi Multipla) and Genzyme. SA-A reports no disclosure relevant to the manuscript. POA received honoraria for lecturing and participation in advisory boards, and/or travel expenses for attending congresses and meetings from Almirall, Biogen, BMS-Celgene, Janssen, Merck, Mylan, Novartis, Roche Sanofi-Genzyme and Teva. AB received speaker honoraria and/or compensation for consulting service and/or speaking activities from Biogen, Roche, Merck, Celgene and Genzyme. OC receives research grant support from the Multiple Sclerosis Society of Great Britain and Northern Ireland, the NIHR and the NIHR UCLH Biomedical Research Centre. She is the Deputy Editor of Neurology, for which she receives an honorarium. NDS has received honoraria from Biogen-Idec, Bristol Myers Squibb, Celgene, Genzyme, Immunic, Merck Serono, Novartis, Roche and Teva for consulting services and speaking; serves on advisory boards for Merck, Novartis, Biogen-Idec, Roche, Genzyme and Immunic; has received research grant support from the Italian MS Society. MF is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche and Sanofi; speaking activities from Bayer, Biogen, Celgene, Chiesi Italia, Eli Lilly, Genzyme, Janssen, Merck Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda and Teva; participation in advisory boards for Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme and Takeda; scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol Myers Squibb, Lilly, Novartis and Sanofi-Genzyme; receives research support from Biogen Idec, Merck Serono, Novartis, Roche, the Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA). VF reports no disclosure relevant to the manuscript. NE has served as a member of advisory boards for Biogen, Merck, Novartis and Roche; has received grant income from the UK Multiple Sclerosis Society, MRC, PCORI and NIHR. CE has received funding for travelling and speaker honoraria from Biogen Idec and Bayer Schering. AGal has received honoraria from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi-Genzyme and Teva for consulting services, speaking and/or travel support. AGar has received funding from the UK Multiple Sclerosis Society and has received speaker honoraria from the Multiple Sclerosis Academy. SG reports no disclosure relevant to the manuscript. SH has received travel funding and/or speaker honoraria from Biogen, Roche, Genzyme, Novartis, Bial, CSL Behring and Merck Serono. MK has received funding for travel and speaker honoraria from Bayer, Novartis, Merck, Biogen Idec and Teva Pharmaceutical Industries; and serves on scientific advisory boards for Biogen Idec, Merck Serono, Roche, Novartis and Gilead. ML has received honoraria from Biogen, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Almirall and Bayer for consulting services, speaking and/or travel support. MM has served on scientific advisory boards for Bayer Schering, Biogen, Sanofi-Genzyme, Merck, Novartis, Teva, Mylan and Almirall; and has received consulting and/or speaker fees, research support or travel grants from Almirall, Bayer Schering, Biogen, CSL Behring, Sanofi-Genzyme, Merck, Novartis, Teva, Roche and Ultragenix. XM has received speaking honoraria and travel expenses for participation in scientific meetings, has been a steering committee member of clinical trials or participated in advisory boards of clinical trials in the past years with Abbvie, Actelion, Alexion, Biogen, Bristol Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS. CP has served on scientific advisory boards and received consulting and/or speaker fees from Almirall, Alexion, Biogen, Janssen, Roche, Merck and Novartis; and has received research support from Almirall, Biogen, Roche, Merck and Novartis. PP received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Genzyme; has received research support from the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. JR has received speaking honoraria and personal compensation for participating in advisory boards from Biogen-Idec, Genzyme, Merck Serono, Mylan, Novartis, Roche, Teva and Sanofi-Aventis. MAR received consulting fees from Biogen, Bristol Myers Squibb, Eli Lilly, Janssen and Roche; received speaker honoraria from AstraZeneca, Biogen, Bristol Myers Squibb, Bromatech, Celgene, Genzyme, Horizon Therapeutics Italy, Merck Serono, Novartis, Roche, Sanofi and Teva; and receives research support from the MS Society of Canada, the Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. She is Associate Editor for Multiple Sclerosis and Related Disorders. AR serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Synthetic MR, TensorMedical, Roche, Biogen and OLEA Medical; and has received speaker honoraria from Bayer, Sanofi-Genzyme, Merck Serono, Teva Pharmaceutical Industries, Novartis, Roche, Bristol Myers and Biogen. MLS reports no disclosure relevant to the manuscript. MZ has received honoraria for lecturing or participating in advisory boards, or financial support for attending scientific meetings from Alexion, Biogen, BMS-Celgene, Janssen, Genzyme, Merck, Novartis and Sanofi. CT received honoraria for speaking and travel grants from Biogen, Sanofi-Aventis, Merck Serono, Bayer-Schering, Teva, Genzyme, Almirall and Novartis. CG has received speaker honoraria and/or travel expenses for attending meetings from Bayer Schering Pharma, Sanofi-Aventis, Merck, Biogen, Novartis and Almirall., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Endovascular therapy (EVT) has been established as a major component in the acute treatment of large vessel occlusion stroke. However, it is unclear whether outcome and other treatment-related factors differ if patients are treated within or outside core working hours., Methods: We analyzed data from the prospective nationwide Austrian Stroke Unit Registry capturing all consecutive stroke patients treated with EVT between 2016 and 2020. Patients were trichotomized according to the time of groin puncture into treatment within regular working hours (08:00-13:59), afternoon/evening (14:00-21:59) and night-time (22:00-07:59). Additionally, we analyzed 12 EVT treatment windows with equal patient numbers. Main outcome variables included favorable outcome (modified Rankin Scale scores of 0-2) 3 months post-stroke as well as procedural time metrics, recanalization status and complications., Results: We analyzed 2916 patients (median age 74 years, 50.7% female) who underwent EVT. Patients treated within core working hours more frequently had a favorable outcome (42.6% vs 36.1% treated in the afternoon/evening vs 35.8% treated at night-time; p=0.007). Similar results were found when analyzing 12 treatment windows. All these differences remained significant in multivariable analysis adjusting for outcome-relevant co-factors. Onset-to-recanalization time was considerably longer outside core working hours, which was mainly explained by longer door-to-groin time (p<0.001). There was no difference in the number of passes, recanalization status, groin-to-recanalization time and EVT-related complications., Conclusions: The findings of delayed intrahospital EVT workflows and worse functional outcomes outside core working hours in this nationwide registry are relevant for optimization of stroke care, and might be applicable to other countries with similar settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increased middle cerebral artery (MCA) blood flow velocities on transcranial duplex sonography (TCD) were recently reported in individual patients after successful mechanical thrombectomy (MT) and were related to intracranial hemorrhage and poor outcome. However, the retrospective study design of prior studies precluded elucidation of the underlying pathomechanisms, and the relationship between TCD and brain parenchymal perfusion still remains to be determined., Methods: We prospectively investigated consecutive patients with stroke successfully recanalized by MT with TCD and MRI including contrast-enhanced perfusion sequences within 48 hours post-intervention. Increased MCA flow on TCD was defined as >30% mean blood flow velocity in the treated MCA compared with the contralateral MCA. MRI blood flow maps served to assess hyperperfusion rated by neuroradiologists blinded to TCD., Results: A total of 226 patients recanalized by MT underwent post-interventional TCD and 92 patients additionally had perfusion MRI. 85 patients (38%) had increased post-interventional MCA flow on TCD. Of these, 10 patients (12%) had an underlying focal stenosis. Increased TCD blood flow in the recanalized MCA was associated with larger infarct size, vasogenic edema, intracranial hemorrhage and poor 90-day outcome (all p≤0.005). In the subgroup for which both TCD and perfusion MRI were available, 29 patients (31%) had increased ipsilateral MCA flow velocities on TCD. Of these, 25 patients also showed parenchymal hyperperfusion on MRI (sensitivity 85%; specificity 62%). Hyperperfusion severity on MRI correlated with MCA flow velocities on TCD (r s =0.379, p<0.001)., Conclusions: TCD is a reliable bedside tool to identify post-reperfusion hyperperfusion, correlates well with perfusion MRI, and indicates risk of reperfusion injury after MT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Objective: To determine if vascular risk factor (VRF), that is, smoking, arterial hypertension (HT), dyslipidaemia and diabetes, have an effect on multiple sclerosis (MS) pathology as measured by MS typical brain lesions, we have compared brain MRIs from patients with MS with and without VRF age-matched and sex-matched., Methods: Brain MRIs from five centres were scored for the presence of Dawson's fingers (DF) and juxtacortical lesions (JCL). A regression model was built to predict the effect of each individual VRF on DF and JCL, considering age and disease duration., Results: 92 MS cases without VRF and 106 MS with one or more VRF (80 ever-smokers, 43 hypertensives, 25 dyslipidaemics and 10 diabetics) were included. Ever-smoking associated with a higher burden of DF (Exp(B)=1.29, 95% CI 1.10 to 1.51, p<0.01) and JCL (Exp(B)=1.38, 95% CI 1.21 to 1.57, p<0.01). No other VRF had an impact on DF. Dyslipidaemia associated with increased JCL (Exp(B)=1.30, 95% CI 1.10 to 1.56, p<0.01) but HT did not associate with any of the outcomes., Conclusions: Individual VRF appear to affect MS-specific lesions differently. An increase in MS lesions was mainly seen in smokers; however, this VRF is most likely to be present from onset of MS, and other VRF effects may be partly mitigated by treatment. Our findings support that treating VRF and cessation of smoking may be important in the management of MS., Competing Interests: Competing interests: RG has received support for scientific meetings and courses or honoraria for advisory work from Wolfson College, by the EAN, Bayer, Biogen, Merck and Novartis. GdP has received scholarships from the ECTRIMS, the World Federation of Neurology and Novartis; funding for research from Biogen, Novartis and Roche; travel grants from Roche, Sanofi-Genzyme and Teva and fees for editorial content from Bayer, Merck Serono and Roche. KC has received honoraria for speaking at meetings, advisory work or support to attend meetings from Teva, Biogen Idec and Roche. JS-G reports in the last 36 months grants and personal fees from Genzyme, personal fees from: Biogen, Bayer, Merck, Almirall, Bial, Novartis, Roche, TEVA, Celgene; he is Director of Revista de Neurologia, for which he does not receive any compensation, and serves of Editorial Board of Multiple Sclerosis Journal, for which he receives a compensation. CE has received funding for travel and speaker honoraria from Biogen, Bayer, Genzyme, Merck, Novartis, Shire and Teva, research support from Biogen, Merck and Teva, and has served on scientific advisory boards for Bayer, Biogen, Merck, Novartis, Roche and Teva. DTC has received, in the last 3 years, honoraria (paid to his employer) from Excemed for faculty-led education work; had meeting expenses funded by EAN, ECTRIMS, Novartis and Société des Neurosciences. He has received research funding from the International Progressive MS Alliance, the MS society of Great Britain and Northern Ireland and the Institute for Health Research (NIHR), University College London Hospitals (UCLH) Biomedical Research Centre. GCD is supported by the NIHR Biomedical Research Centre (BRC), Oxford and has research funding from the Oxford BRC, MRC (UK) and Merck-Serono. He has received travel expenses from Bayer Schering, Biogen Idec, Genzyme, Merck Serono and Novartis and honoraria as an invited speaker for Bayer Schering and Novartis. JP is partly funded by highly specialised services to run a national congenital myasthenia service and a neuromyelitis service. She has received support for scientific meetings and honorariums for advisory work from Merck Serono, Biogen Idec, Novartis, Teva, Chugai Pharma and Bayer Schering, Alexion, Roche, Genzyme, MedImmune, EuroImmune, MedDay, Abide and ARGENX, and grants from Merck Serono, Novartis, Biogen Idec, Teva, Abide and Bayer Schering. She has received grants from the MS society and Guthie Jackson Foundation for research studies. FB serves as a consultant for Biogen, Bayer, Genzyme, Jansen Research, Merck, Novartis, Roche, Synthon BV and Teva. CG has received compensation for consulting from Bayer and Biogen and speaker's fees for lectures from Biogen, Bayer, Genzyme, Merck, Novartis and Teva. AR serves on scientific advisory boards for Novartis, Sanofi-Genzyme, Icometrix, SyntheticMR, Bayer, Biogen and OLEA Medical and has received speaker honoraria from Bayer, Sanofi-Genzyme, Bracco, Merck-Serono, Teva Pharmaceutical Industries Ltd, Novartis, Roche and Biogen., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Cerebral hyperperfusion has been related to the risk of intracranial hemorrhage (ICH) in stroke patients after vessel recanalization therapy. We hypothesized that after successful mechanical thrombectomy for acute anterior circulation stroke, hemodynamics detectable by transcranial Duplex (TCD) sonography would vary, and that increased blood flow velocities would be associated with ICH., Methods: We retrospectively identified all ischemic stroke patients with successful endovascular recanalization for anterior circulation vessel occlusion (Thrombolysis in Cerebral Infarction 2b-3) between 2010 and 2017. We reviewed their postinterventional TCD examinations for mean blood flow (MBF) velocities of the recanalized and contralateral middle cerebral artery (MCA) and searched for an association with postinterventional ICH and clinical outcome., Results: 123 stroke patients (mean age 63±14 years, 40% women) with successful anterior circulation thrombectomy were analyzed. Of those, 18 patients had postinterventional ICH. ICH patients had an increased MCA MBF velocity index (=MBF velocity of the recanalized divided by the contralateral MCA) compared with non-ICH patients (1.32±0.39 vs 1.02±0.32, P<0.001). In multivariate analysis, a higher MCA MBF velocity index was associated with postinterventional ICH and poor 90 day outcome., Conclusions: A high MCA MBF velocity index on TCD after successful recanalization therapy for anterior circulation stroke indicates a risk for postinterventional ICH and worse prognosis., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological mechanism involving mitochondrial dysfunction., Objective: The primary aim was to define MRI features of LMS and LHON, and to assess the proportions of individuals displaying features typical of MS. Secondarily, we investigated the effect of gender on the risk of developing white matter lesions in the context of LHON., Methods: A blinded standardised review of conventional brain MRIs of 30 patients with MS, 31 patients with LHON and 11 patients with LMS was conducted by three independent experts in the field. MS-like MRI features were assessed., Results: All patients with LMS and 26% of patients with LHON had white matter lesions. Of these, all patients with LMS and 25% with LHON were found to have an MRI appearance typical of MS. Female patients with LHON had a significantly greater risk of having white matter lesions consistent with MS compared with male patients (relative risk 8.3)., Conclusions: A blinded review of conventional brain MRIs shows that patients with LMS have a scan appearance indistinguishable from MS. Mitochondrial dysfunction could be a common pathophysiological pathway in the formation of white matter lesions. There appears to be a strong female influence on the radiological appearance as well as clinical development of MS in patients with LHON., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)