Effects of immediate thrombolytic treatment in imaging area on functional outcome in patients with acute ischemic stroke.

INTRODUCTION: Door-to-needle time (DNT) is an established predictor of outcome in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Several strategies have been proposed to streamline in-hospital pathways, among which treatment at CT/MR bed. AIM: To explore the impact of treatment at CT/MR bed, here defined as imaging area (IA), on functional outcome in stroke patients treated with IVT alone. METHODS: All AIS patients treated with IVT alone at our center in 2020, 2021, and 2022 were included. Patients with any previous disability were excluded. The cohort was divided into two groups, depending on the treatment site. One group received IVT at IA, the other at emergency room or stroke unit (non-IA). Regression analysis assessed the association between treatment site and 3-month outcome. RESULTS: A total of 327 patients who received IVT alone were included in the analysis. One hundred thirty-three (40.7%) were in the IA group and 194 (59.3%) in the non-IA group. The groups showed similar baseline characteristics. In the IA group, DNT was 45 min shorter. Despite similar rates of functional independence (mRS 0-2), the IA group showed higher rates of excellent outcome (mRS 0-1) compared to the non-IA group (60.1% vs 42.8%, p<0.01). Immediate treatment at IA was independently associated to excellent outcome (OR 1.78 [1.03-3.08]). CONCLUSIONS: Thrombolytic treatment at IA lowers DNT and is an independent predictor of excellent outcome after AIS. Our study emphasizes the importance of immediate thrombolytic treatment at IA, soon after radiological eligibility is confirmed. Immediate treatment at IA should be a standard-of-care for AIS.

Effect of Treatment of the Cholinergic Precursor Choline Alphoscerate in Mild Cognitive Dysfunction: A Randomized Controlled Trial.

Background and Objectives: The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer's disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer's disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. Materials and Methods: This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. Discussion: This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. Registration: EudraCT number: 2020-000576-38.

Models of care in emergency neurology: from the Neuro Fast Track to the emergency neurologist-a position paper of the Italian Association for Emergency Neurology (ANEU).

I n the context of an adequate health care organization, the figure of the neurologist as an emergency operator (in the emergency room-ER-and/or in a dedicated outpatient clinic) is crucial for an effective functional connection with the territory (and therefore with general practitioners), a reduction in inappropriate ER accesses, specific diagnostic and therapeutic approaches to neurological emergencies in the ER and a reduction in nonspecific or even unnecessary instrumental investigations. In this position paper of the Italian Association of Emergency Neurology (ANEU: Associazione Neurologia dell'Emergenza Urgenza), these issues are addressed, and two important organizational solutions are proposed: 1) The Neuro Fast Track, as an outpatient organization approach strongly linked to general practitioners and non-neurological specialists and dedicated to cases with deferrable urgency (to be assessed within 72 h) 2) The identification of an emergency neurologist, who is engaged in ER assessments as a consultant and involved in the management of the semi-intensive care unit of the emergency neurology and the stroke unit according to an appropriate rotation, as well as in consultations for patients with neurological emergencies in inpatient wards The possibility of computerizing the screening of patients with deferrable urgency in the Neuro Fast Track is described. A dedicated app represents an important tool that can facilitate the identification of patients for whom deferred assessment is appropriate, the scheduling of neurological examinations and reductions in the booking time through a more rapid approach to specialist assessment and subsequent investigations.

Trends of recanalization therapies and state of art for ischemic stroke treatment in Campania region, Italy.

BACKGROUND: According to the last Italian report by the Ministry of Health in 2018, the estimated number of acute ischemic strokes (AIS) in Campania is 10,000/year, with an expected number of 1390 intravenous thrombolysis (IVT) and 694 mechanical thrombectomies (MT). In 2017, only 1.5% of expected patients received IVT and 0.2% MT. This study analyzed the trend of IVT and MT in 2019-2020 and depicted the state of art of Stroke Care in Campania. METHODS: From the regional health task force, we obtained the hospital discharge forms from all private and public hospitals in Campania; we selected patients with a principal diagnosis of AIS and measured the rate of patients admitted to neurology units and the rate of IVT, MT, and IVT + MT for both 2019 and 2020. RESULTS: In 2019, we observed 4817 admissions for AIS; 2858/4817 (59.3%) patients were admitted to neurology units. Out of 4817 patients, 192 received IVT, 165 MT, and 131 IVT + MT (488 treated patients; 10.1%). In 2020, we observed 4129 admissions for AIS; 2502/4129 (62.7%) patients were admitted to neurology units. Out of 4129 patients, 198 received IVT, 250 MT, and 180 IVT + MT (628 treated patients; 15.2%). These results showed that despite a reduction of AIS admissions in 2020, the relative and absolute rate of recanalization treatments increased. However, the number of patients who were not admitted to neurology units nor received acute treatments remained dramatically high. CONCLUSION: Despite the development of acute treatments, the Campania Stroke Network still needs significative efforts to improve.

Hyperkinetic manifestations in superficial siderosis: evidence for pathogenic network disruption.

Superficial siderosis (SS) of central nervous system is a rare condition characterized by hemosiderin deposition diffusely involving supratentorial and infratentorial compartments. SS usually manifests with ataxia and sensorineural hearing loss. Basal ganglia are almost always spared by the degenerative process, and movement disorders are only rarely reported. We describe the case of an aged woman with apparently idiopathic SS presenting with cerebellar ataxia, hearing loss, and orofacial dyskinesias. Together with some previously reported patients affected by SS and presenting with dystonic manifestations, our case reinforces the current hypothesis supporting a wide network disruption, rather than a direct basal ganglia damage, as the likely underlying cause of some dystonic syndromes.

The Impact of Covid-19 Lockdown on Stroke Admissions and Treatments in Campania.

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.

Circulating MiRNA-195-5p and -451a in Diabetic Patients with Transient and Acute Ischemic Stroke in the Emergency Department.

(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.

Comparison of injective related reactions following ofatumumab and ocrelizumab in patients with multiple sclerosis: data from the European spontaneous reporting system.

Introduction: In 2021 ofatumumab, a recombinant human anti-CD20 monoclonal antibody (mAb) already authorized for the treatment of chronic lymphocytic leukemia, received the marketing approval for the treatment of relapsing forms of multiple sclerosis (MS). Differently from ocrelizumab, that is administered intravenously, ofatumumab if the first anti-CD20 mAb to be administered subcutaneously without a premedication. Methods and objectives: In this study we aimed to describe and compare the main characteristics of Individual Case Safety Reports (ICSRs) describing the occurrence of Injective Related Reactions (IRRs) following the treatment with ocrelizumab and ofatumumab reported in the Eudravigilance (EV) database during years 2021-2023. Results: A total of 860 ICSRs with either ofatumumab and ocrelizumab as suspected drug were retrieved from Eudravigilance, of which 51% associated with ofatumumab and 49% with ocrelizumab. The majority of patients who experienced IRRs following ocrelizumab belonged to the age group of 18-64 years (73%), while the age-group was mostly not specified (55%) in ICSRs reporting ofatumumab as suspected. The distribution of gender was almost similar in the two groups, with the majority of ICSRs related to female patients. "Pyrexia" was the Preferred Term (PT) most reported for ofatumumab, while "Infusion related reaction" were more frequently reported with ocrelizumab. Premedication drugs were reported in 148 ICSRs. Out of 89 ICSRs for which the Time to Event (TTE) was calculated, 74 reported IRRs that occurred the same day of the drug administration. Discussion: Based on the results of this study, although a risk of ofatumumab-induced IRRs cannot be excluded, it should be considered as manageable considering that the drug seems to be mostly associated with the occurrence of fever. Thus, it is important to continue to closely monitor the use of these in clinical practice to improve the knowledge on their long-term safety.

Neurovascular Issues in Antiphospholipid Syndrome: Arterial Vasculopathy from Small to Large Vessels in a Neuroradiological Perspective.

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition characterized by venous thromboembolism, arterial thrombosis, and pregnancy morbidity. Among neurological manifestations, arterial thrombosis is only one of the possible associated clinical and neuroradiological features. The aim of this review is to address from a neurovascular point of view the multifaceted range of the arterial side of APS. A modern neurovascular approach was proposed, dividing the CNS involvement on the basis of the size of affected arteries, from large to small arteries, and corresponding clinical and neuroradiological issues. Both large-vessel and small-vessel involvement in APS were detailed, highlighting the limitations of the available literature in the attempt to derive some pathomechanisms. APS is a complex disease, and its neurological involvement appears multifaceted and not yet fully characterized, within and outside the diagnostic criteria. The involvement of intracranial large and small vessels appears poorly characterized, and the overlapping with the previously proposed inflammatory manifestations is consistent.

Beyond RCTs: Short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack.

BACKGROUND AND PURPOSE: Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs. METHODS: READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment. RESULTS: We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding. CONCLUSIONS: In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.

Immediate and progressive neurological damage after electrical injury: A pediatric case report.

BACKGROUND: An electrical injury can cause multiple consequences, especially to the nervous system, both peripheral and central. Such consequences may present immediately as well as later on. AIMS OF THE STUDY: To report on a case of a 5-year-old boy with focal refractory status epilepticus after an electrical injury. METHODS: Clinical history, electroencephalography, neuroimaging, and laboratory data of a patient admitted to our emergency department. RESULTS: A 5-year-old male received an electrical shock by contact with an alternating current source after coming out of the pool. When reaching our emergency department, focal seizures was observed in the same site affected by the electrical insult, with progressive structural changes in the related brain area. In the days after, his neurological conditions dramatically evolved leading to brain death. CONCLUSIONS: Based on our knowledge, this is the first report on refractory status epilepticus in a child after electrical injury. The possible underlying pathogenetic mechanisms are not yet clear.

Investigating the association between neoplasms and MOG antibody-associated disease.

Introduction: The association of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease (MOGAD) and tumors has seldom been reported. We aim to investigate the occurrence of tumors in a cohort of patients with MOGAD and to describe their clinical features, in addition to previously reported cases. Methods: We retrospectively identified patients with MOGAD (i.e., compatible clinical phenotype and positive MOG antibodies analysed with a live cell-based assay) from 1/1/2015 to 1/1/2023 who had a neoplasm diagnosed within 2 years from MOGAD onset. Furthermore, we performed systematic review of literature to identify previously reported cases. Clinical, paraclinical and oncological findings were collected and reported as median (range) or number (percentage). Results: Two of 150 MOGAD patients (1%) had a concomitant neoplasm in our cohort. Fifteen additional cases were retrieved from literature. Median age was 39 (16-73) years-old, 12 patients were female. ADEM (n = 4;23.5%), encephalomyelitis (n = 3;17.6%), and monolateral optic neuritis (n = 2;11.8%) were the most frequent phenotypes. Median number of treatments was 1 (range 1-4), improvement was reported in 14/17 cases (82.4%). Oncological accompaniments were teratoma (n = 4), CNS (n = 3), melanoma (n = 2), lung (n = 2), hematological (n = 2), ovary (n = 1), breast (n = 1), gastrointestinal (n = 1), and thymic (n = 1) neoplasms. Median time from tumor diagnosis to MOGAD onset was 0 (range - 60 to 20) months. MOG expression in neoplastic tissue was reported in 2/4 patients. Median PNS-CARE score was 3 (range 0-7): 11 patients were classified as "non-PNS," 5 as "possible PNS," and 1 as "probable PNS." Discussion: Our study confirms that MOG is a low-risk antibody for paraneoplastic neurological syndromes and that the clinical presentation and oncological accompaniments are extremely variable. Most of these patients were classified as non-PNS, whereas only a minority was diagnosed with possible/probable PNS, frequently in association with ovarian teratoma. These findings support the notion that MOGAD is not a paraneoplastic disease.

Initial Experience Using the New pHLO 0.072-inch Large-Bore Catheter for Direct Aspiration Thrombectomy in Acute Ischemic Stroke.

PURPOSE: A direct aspiration, first pass technique (ADAPT) has been introduced as a rapid and safe thrombectomy strategy in patients with intracranial large vessel occlusion (LVO). The aim of the study is to determine the technical feasibility, safety, and functional outcome of ADAPT using the newly released large bore pHLO 0.072-inch aspiration catheter (AC; Phenox). MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively (October 2019-November 2021) from 2 comprehensive stroke centers. Accessibility of the thrombus, vascular recanalization, time to recanalization, and procedure-related complications were evaluated. National Institutes of Health stroke scale scores at presentation and discharge and the modified Rankin scale (mRS) score at 90 days post-procedure were recorded. RESULTS: Twenty-five patients (14 female, 11 male) with occlusions of the anterior circulation were treated. In 84% of cases, ADAPT led to successful recanalization with a median procedure time of 28 minutes. In the remaining cases, successful recanalization required (to a total of 96%; modified thrombolysis in cerebral infarction score 2b/3) the use of stent retrievers. No AC-related complications were reported. Other complications included distal migration of the thrombus, requiring a stent-retriever, and symptomatic PH2 hemorrhage in 16% and 4%, respectively. After 3 months, 52% of the patients had mRS scores of 0-2 with an overall mortality rate of 20%. CONCLUSION: Results from our retrospective case series revealed that thrombectomy of LVOs with pHLO AC is safe and effective in cases of large-vessel ischemic stroke. Rates of complete or near-complete recanalization after the first pass with this method might be used as a new benchmark in future trials.

Three Doses of COVID-19 Vaccines: A Retrospective Study Evaluating the Safety and the Immune Response in Patients with Multiple Sclerosis.

Since the beginning of the mass immunization of patients with multiple sclerosis (MS), many data on the efficacy and safety of COVID-19 vaccines have been produced. Considering that MS is an autoimmune disease and that some disease-modifying therapies (DMTs) could decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety of these vaccines in terms of AEFI occurrence and the antibody response after MS patients had received the third dose. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. Third doses were administered from October 2021 to January 2022. The majority of patients (n = 193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs.

Intra-Arterial Thrombolysis to Improve Final Thrombolysis in Cerebral Infarction Score after Thrombectomy: A Case-Series Analysis.

Endovascular thrombectomy is the standard treatment in selected patients with acute ischemic stroke and large vessel occlusion, but continuous improvement in angiographic and clinical outcome is still needed. Intra-arterial thrombolysis has been tested as a possible rescue tool in unsuccessful thrombectomy, or as an adjuvant therapy after the endovascular procedure, to pursue complete recanalization. Here we present a case series analysis of intra-arterial alteplase administration (5 mg bolus, repeated up to 15 mg if Thrombolysis in Cerebral Infarction (TICI) scale ≥2c is not achieved) in 15 consecutive anterior circulation stroke patients after unsuccessful thrombectomy, defined as TICI score ≤2b after at least 3 passes or if unsuitable for further endovascular attempts, with the aim of improving recanalization. An improvement of final TICI score was achieved in 10 of 15 patients (66.7%). TICI score ≥2c was achieved after 5 mg intra-arterial tissue plasminogen activator (iaTPA) in 4 patients, and after 10 mg iaTPA in 5 cases. Six of 15 patients received 15 mg iaTPA: 1 of 6 showed angiographical improvement. A major effect of intra-arterial alteplase was observed for distally migrated emboli. None of the patients experienced any symptomatic hemorrhagic transformation or other major bleeding. Our report shows, in a very small cohort, a high rate of final TICI score improvement, encouraging the development of randomized controlled trials of rescue intra-arterial thrombolysis in patients with suboptimal angiographic results after mechanical thrombectomy.

Thrombolysis after dabigatran reversal: A nation-wide Italian multicentre study, systematic review and meta-analysis.

Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.

Risk of disease relapse following COVID-19 vaccination in patients with AQP4-IgG-positive NMOSD and MOGAD.

Post-vaccination disease relapses have been reported in patients with MOGAD and AQP4-IgG+NMOSD. In this retrospective multicenter Italian study we assessed the frequency of relapses after SARS-CoV-2 vaccination. We included 56 cases: MOGAD, 30; AQP4-IgG+NMOSD, 26. Vaccines received were BNT162b2-Pfizer-BioNTech in 42 patients and mRNA-1273-Moderna in 14 patients. Six patients had a history of SARS-CoV-2 infection; two of them experienced a post-infection disease relapse (MOGAD). The frequency of relapses within one month of SARS-CoV-2 vaccination was 4% (1/26) in the AQP4-IgG+NMOSD group and 0% in the MOGAD group. In these patients the potential benefits of vaccination overcome the risk of relapses.

Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study.

INTRODUCTION: Cladribine administration has been approved for the treatment of relapsing-remitting multiple sclerosis (MS) in 2017; thus, data on cladribine in a real-world setting are still emerging. METHODS: We report on cladribine effectiveness, safety profile, and treatment response predictors in 243 patients with MS followed at eight tertiary MS centers. Study outcomes were: (1) No Evidence of Disease Activity-3 (NEDA-3) status and its components (absence of clinical relapses, MRI activity, and sustained disability worsening); (2) development of grade III/IV lymphopenia. The relationship between baseline features and the selected outcomes was tested via multivariate logistic models. RESULTS: Of the 243 subjects included in the study (66.5% female, age 34.2 ± 10 years, disease duration 6.6 ± 9.6 years), 64% showed NEDA-3 at median follow-up (22 months). Patients with higher number of previous treatments had lower probability to retain NEDA-3 [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41-0.98, p = 0.04] and were more prone to experience clinical relapses (OR 1.6, 95% CI 1-2.6, p = 0.04). The presence of active lesions at baseline was associated with follow-up magnetic resonance imaging (MRI) activity (OR 1.92, 95% CI 1.04-3.55, p = 0.04). Patients with higher rate of relapses in the year prior to cladribine start were at higher risk of developing sustained disability worsening (OR 2.95% CI 1-4.2, p = 0.04). Lymphopenia grade III/IV over the follow-up was associated with baseline lymphocyte count (OR 0.998, 95% CI 0.997-0.999, p = 0.01). CONCLUSION: In this large cohort, we confirm previous data about cladribine effectiveness on disease activity and disability worsening and provide information on response predictors that might inform therapeutic choices.

Long term persistence of SARS-CoV-2 humoral response in multiple sclerosis subjects.

BACKGROUND & OBJECTIVES: The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients. METHODS: 96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5-6 months (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose. The anti-Spike IgG titre from MS subjects was compared with 21 age- and sex-matched healthy controls (HC). RESULTS: When compared with SARS-CoV-2 IgG levels at T2 in HC, we observed comparable levels in interferon-ß 1a-, dimethyl fumarate-, teriflunomide- and natalizumab-treated MS subjects, but an impaired humoral response in MS subjects undergoing glatiramer acetate-, cladribine-, fingolimod- and ocrelizumab-treatments. Moreover, comparison between SARS-CoV-2 IgG Spike titre at T1 and T2 revealed a faster decline of the humoral response in patients undergoing dimethyl fumarate-, interferon-ß 1a- and glatiramer acetate-therapies, while those receiving teriflunomide and natalizumab showed higher persistence compared to healthy controls. CONCLUSION: The prominent decline in humoral response in MS subjects undergoing dimethyl fumarate-, interferon-ß 1a- and glatiramer acetate-therapies should be considered when formulating booster regimens as these subjects would benefit of early booster vaccinations.

The Safety Profile of COVID-19 Vaccines in Patients Diagnosed with Multiple Sclerosis: A Retrospective Observational Study.

In the current COVID-19 pandemic, patients diagnosed with multiple sclerosis (MS) are considered to be one of the highest priority categories, being recognized as extremely vulnerable people. For this reason, mRNA-based COVID-19 vaccines are strongly recommended for these patients. Despite encouraging results on the efficacy and safety profile of mRNA-based COVID-19 vaccines, to date, in frail populations, including patients diagnosed with MS, this information is rather limited. We carried out a retrospective observational study with the aim to evaluate the safety profile of mRNA-based COVID-19 vaccines by retrieving real-life data of MS patients who were treated and vaccinated at the Multiple Sclerosis Center of the Hospital A.O.R.N. A. Cardarelli. Three-hundred and ten medical records of MS patients who received the first dose of the mRNA-based COVID-19 vaccine were retrieved (63% female; mean age: 45.9 years). Of these patients, 288 also received the second dose. All patients received the Pfizer-BioNTech vaccine. Relapsing-Remitting Multiple Sclerosis (RRSM) was the most common form of MS. The Expanded Disability Status Scale (EDSS) values were <3.0 in 70% of patients. The majority of patients received a Disease Modifying Therapy (DMT) during the study period, mainly interferon beta 1-a, dimethyl fumarate, and natalizumab and fingolimod. Overall, 913 AEFIs were identified, of which 539 were after the first dose of the vaccine and 374 after the second dose. The majority of these AEFIs were classified as short-term since they occurred within the first 72 h. The most common identified adverse events were pain at injection site, flu-like symptoms, and headache. Fever was reported more frequently after the second dose than after the first dose. SARS-CoV-2 infection occurred in 3 patients after the first dose. Using historical data of previous years (2017−2020), the relapses' rate during 2021 was found to be lower. Lastly, the results of the multivariable analysis that assessed factors associated with the occurrence of AEFIs revealed a statistical significance for age, sex, and therapy with ocrelizumab (p < 0.05). In conclusion, our results indicated that Pfizer-BioNTech vaccine was safe for MS patients, being associated with AEFIs already detected in the general population. Larger observational studies with longer follow-up and epidemiological studies are strongly needed.