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Background: Randomized controlled trials (RCTs) proved that short-term (21–90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. Methods: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. Results: We evaluated 1070 patients, who had 72 (interquartile range, 62–79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score 24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. Conclusions: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05476081.

Anti-myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are new emerging diseases with heterogeneous course, treatment, response, and prognosis. We herein present 2 cases with antibodies to MOG, one with a cerebellar/brainstem monophasic syndrome which partially improved after treatment, and the other with an optic neuritis onset then relapsed with cortical encephalitis and presented a subsequent complete recovery. We further discuss elements possibly associated with disease heterogeneity and influencing treatment choices. MOGAD is an extremely variable disease which can relapse and accumulate disability over time. An early diagnosis and correct timely treatment is fundamental to improve clinical outcome.

Background Dabigatran is a direct competitive thrombin inhibitor approved for stroke prevention in non-valvular atrial fibrillation. At full-dose, dabigatran showed similar rates of bleedings and higher efficacy compared to warfarin. Case summary We report a case of acute ischaemic stroke in a patient treated with dabigatran 150 mg b.i.d. for atrial fibrillation. After an off-label treatment with idarucizumab, a humanized monoclonal antibody approved for dabigatran reversal, we performed a successful intravenous thrombolysis (IVT). Transoesophageal echocardiography showed a left atrial appendage (LAA) thrombus, despite full-dose dabigatran and an adequate therapy adherence. Discussion There are few cases of LAA thrombus during dabigatran treatment reported in literature till date. We analyse the possible pathogenetic mechanisms involved in dabigatran failure, including drug interactions and unexpected genetic variations interfering with dabigatran serum levels suggesting periodical assessment of direct Oral Anticoagulant levels. Furthermore, we confirm initial reports of safety and efficacy of intravenous thrombolysis after idarucizumab, in case of dabigatran failure.

Background Several concerns exist on the immunogenicity of SARS-CoV-2 vaccines in multiple sclerosis (MS) subjects due to their immunomodulating disease modifying therapies (DMTs). Here we report a comparison of the humoral response to BNT162b2-mRNA coronavirus (COVID)-19 vaccine and the immunological phenotype in a cohort of 125 MS subjects undergoing different DMTs, with no history of SARS-CoV-2 infection. Methods We collected serum and blood samples at the first day of vaccine (T0) and 21 days after the second vaccine dose (T1) from 125 MS subjects, undergoing eight different DMTs. Sera were tested using the Elecsys anti-SARS-CoV-2-IgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgG titres from MS subjects were compared with 24 age- and sex-matched healthy controls (HC). Percentage and absolute number of B and T lymphocytes were evaluated by cytofluorimetric analysis in the same study cohort. Results When compared with SARS-CoV-2 IgG levels in HC (n = 24, median 1089 (IQR 652.5–1625) U/mL), we observed an increased secretion of SARS-CoV-2 IgG in interferon-beta 1a (IFN)-treated MS subjects (n = 22, median 1916 (IQR 1024–2879) U/mL) and an impaired humoral response in MS subjects undergoing cladribine (CLAD) (n = 10, median 396.9 (IQR 37.52–790.9) U/mL), fingolimod (FTY) (n = 19, median 7.9 (IQR 4.8–147.6) U/mL) and ocrelizumab (OCRE) (n = 15, median 0.67 (IQR 0.4–5.9) U/mL) treatment. Moreover, analysis of geometric mean titre ratio (GMTR) between different DMT's groups of MS subjects revealed that, when compared with IFN-treated MS subjects, intrinsic antibody production was impaired in teriflunomide (TERI)-, natalizumab (NAT)-, CLAD-, FTY- and OCRE-, while preserved in DMF- and GA-treated MS subjects. Conclusion Humoral response to BNT162b2-mRNA-vaccine was increased in IFN-treated MS subjects while clearly blunted in those under CLAD, FTY and OCRE treatment. This suggests that the DMTs could have a key role in the protection from SARS-CoV-2 related disease and complication in MS subjects, underlying a novel aspect that should be considered in the selection of the most appropriate therapy under COVID-19 pandemic.

A 68-year-old man with a 9-year history of relapsing-remitting multiple sclerosis previously treated with natalizumab and fingolimod achieved clinical and radiologic stability with alemtuzumab. Sixteen months after administration of the second cycle, he developed behavioral changes and focal seizures, characterized by aphasia and motor automatisms. Seizures were refractory to multiple antiepileptic drugs and evolved into epilepsia partialis continua and, after 1 week, into generalized status epilepticus (see timeline, [doi.org/10.5061/dryad.pvmcvdnht][1]). EEG showed bilateral temporal slowing and epileptiform discharges. Brain MRI revealed new large multifocal nonenhancing cortical/subcortical abnormalities involving bilaterally the frontal and temporal lobes (figure 1, A and B). Routine blood analyses were unremarkable, except for a reduced lymphocyte count (730/μL; B cells 50%, T cells 36%). CSF analysis showed pleocytosis (12 cells/μL) and increased proteins (53.8 mg/dL), whereas extensive screening for infections (including JC virus, herpes simplex virus 1-2-6, varicella-zoster virus, cytomegalovirus, Enterovirus , Listeria , Haemophilus , Cryptococcus , and bacterial and fungi cultures) yielded negative results. Fixed cell-based and Western Blot commercial assays (Euroimmun, Lubeck) excluded the presence of neuronal antibodies, including Hu, Yo, Ri, Tr, GAD65, CV2/CRMP5, Ma2, SOX1, amphiphysin, N-methyl-D-aspartate receptor, LGI1, CASPR2, AMPAR1/2, gamma-aminobutyric acid-B receptor, and dipeptidyl peptidase-like protein 6. Whole-body computed axial tomography did not show any malignancies. A right parietal brain biopsy showed unspecific gliosis without inflammatory infiltrates. [1]: https://doi.org/10.5061/dryad.pvmcvdnht

Objectives The enforcement of complete lockdown with home confinement has been necessary to limit SARS-CoV-2 contagions in Italy, one the most affected countries worldwide. Simultaneously, in several Emergency Departments, a reduction in cardio- and cerebrovascular presentations was noticed. This study analyses the impact of Covid-19 pandemic and lockdown measures on the incidence of stroke, in Campania, the most densely-populated region in Italy. Materials and Methods We retrospectively analyzed data regarding acute stroke patients presenting at 5 Campania stroke hubs, before and after the issue of lockdown in Italy on March 9th, 2020. Results Compared to the pre-lockdown, we observed a significant reduction in the number of acute reperfusion treatments in stroke (P for interact 0.001); however the global number of patients presenting with acute stroke did not significantly differ. The time to reach medical attention was significantly longer in the lockdown phase (230 versus 154 min, P 0.016). For patients who underwent acute reperfusion treatment we also observed significantly longer time-to-imaging (30 versus 40 min, P 0.0005) and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin. Conclusions This study showed the reduction in acute reperfusion treatments for acute ischemic stroke and the slowdown of stroke pathways, during the lockdown phase of Covid-19 pandemic, in Campania, the third-most-populous and the most-densely populated Italian Region. In the next future, the risk for high-grade disability and death, due to delayed or even avoided hospital presentation due to fear of contagion, may be high.

Background/Aims. Ocular motor disorders (OMDs) are a common feature of multiple sclerosis (MS). In clinical practice, if not reported by patients, OMDs are often underdiagnosed and their prevalence is underestimated.Methods. We studied 163 patients (125 women, 76.7%, 38 men, 23.3%; median age 45.0 years; median disease duration 10 years; median EDSS 3.5) with definite MS (n=150, 92%) or clinically isolated syndrome (n=13, 8%) who underwent a thorough clinical examination of eye movements. Data on localization of previous relapses, MS subtype, and MRI findings were collected and analyzed.Results. Overall, 111/163 (68.1%) patients showed at least one abnormality of eye movement. Most frequent OMDs were impaired smooth pursuit (42.3%), saccadic dysmetria (41.7%), unilateral internuclear ophthalmoplegia (14.7%), slowing of saccades (14.7%), skew deviation (13.5%), and gaze evoked nystagmus (13.5%). Patients with OMDs had more severe disability(P=0.0005)and showed more frequently infratentorial MRI lesions(P=0.004). Localization of previous relapses was not associated with presence of OMDs.Conclusion. OMDs are frequent in patients with stable (no relapses) MS. A precise bedside examination of eye motility can disclose abnormalities that imply the presence of subclinical MS lesions and may have a substantial impact on definition of the diagnosis and on management of MS patients.

BACKGROUND Recent studies suggest that alterations in the cerebrospinal venous system may play a role in multiple sclerosis (MS) and that chronic cerebrospinal venous insufficiency correlates with clinical features of MS patients. OBJECTIVES To evaluate the vascularization of optic nerve (ONr) and measure ONe thickness by color Doppler ultrasonography in MS patients with and without previous optic neuritis (ONe). SUBJECTS AND METHODS We assessed flow variables in the ophthalmic artery, central retinal artery, and central retinal vein and measured the diameter of ONe in 46 relapsing-remitting MS patients and 37 healthy controls (HC). Twenty-two MS patients had previous ONe and 24 MS patients had not. Patients with acute ONe were not included. We examined and compared 63 unaffected and 29 affected eyes of MS patients with 74 control eyes. RESULTS Regarding flow variables, we did not find any significant difference between HC, MS affected, and unaffected eyes. Comparing ONr diameters, we found a progressive significant thinning of the ONr from HC to MS patients without and with past ONe. CONCLUSIONS We found no significant alteration in the arterial-venous vascularization of both affected and unaffected ONr compared with HC. We demonstrated the possibility to detect ONr atrophy in MS patients.

Summary Background Optic Neuritis (ONe) is common in Multiple Sclerosis (MS). The aim of this study was to evaluate the Optic Nerve (ONr) and its vascularisation in MS patients with and without previous ONe and in Healthy Controls (HC). Methods We performed high-resolution echo-color ultrasound examination in 50 subjects (29 MS patients and 21 HC). By a suprabulbar approach we measured the ONr diameter at 3 mm from the retinal plane and at another unfixed point. We assessed the flow velocities of Ophthalmic Artery (OA), Central Retinal Artery (CRA) and Central Retinal Vein (CRV) measuring the Peak Systolic Velocity (PSV) and the End Diastolic Velocity (EDV) for the arteries and the Maximal Velocity (MaxV), Minimal Velocity (MinV) and mean Velocity (mV) for the veins. The Pulsatility Index (PI) and the Resistive Index (RI) were also calculated. Results No significant variation for OA supply was found as well as no significant variation for CRA supply, while significant higher PI in the CRV of non-ONe MS eyes vs. both HC and ONe MS eyes was measured. We found that ONr diameter was decreased significantly from HC to non-ONe MS eyes and ONe MS eyes. Conclusions Ultrasound examination of ONr and its vascularisation is feasible and can demonstrate ON atrophy. The increase of CRV PI in unaffected eyes of MS patients is intriguing and seems not associated to ONr atrophy. Larger studies are needed to confirm these results.