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.

Divergence Between Clinical Trial Evidence and Actual Practice in Use of Dual Antiplatelet Therapy After Transient Ischemic Attack and Minor Stroke.

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 <4 and 252 (74.7%) because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <6 and no symptomatic arterial stenosis. Additionally, 144 (13.5%) patients would have been excluded because of revascularization procedures. Three hundred forty-five patients (32.2%) did not follow the RCT procedures because of late (>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.

Outcome of a Real-World Cohort of Patients Subjected to Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVES: Ischemic stroke is a leading cause of death and disability worldwide. For patients with large vessel occlusion stroke, endovascular treatment is now the most effective treatment. We aimed to assess the outcome of patients undergoing endovascular treatment for large vessel occlusion stroke in a real-world setting, comparing our results with data from randomized clinical trials, and recognizing the factors associated with prognosis. MATERIALS AND METHODS: We retrospectively collected data on endovascular procedures performed in one comprehensive stroke center in consecutive patients presenting with large vessel occlusion stroke from January 2017 to January 2020. Data on baseline clinical, imaging, and treatment-related characteristics were recorded. Selection of patients and treatment approach was not standardized but followed current guidelines for ischemic stroke. Functional outcome was evaluated 3 months after endovascular treatment. Clinical, imaging and treatment-related variables associated to outcome were evaluated with univariate and multivariable analyses. RESULTS: Four hundred twelve patients were included in our study. Three-month functional independence was achieved in 50.5% of patients (50.3% in the anterior stroke and 52.1% in the posterior stroke subgroup). Successful arterial reperfusion was observed in 84.3% of patients. Age (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.20-0.87, p = 0.020]), severe stroke at onset (OR 0.40, 95%CI 0.19-0.83), procedure related complications (OR 0.45, 95%CI 0.20-0.99), and good collateral circulation (OR 2.69, 95%CI 1.17-6.16) were associated with 3-month functional independence in multivariable model. CONCLUSIONS: Our real-world outcome results are in line with data from large randomized clinical trials on endovascular treatment for large vessel occlusion stroke.

Limbic encephalitis in a COVID-19 patient?

We describe the case of a 79-year-old woman infected by SARS-CoV-2 and purely neurological confusional syndrome without clinically relevant respiratory disease and NMR alterations of the limbic system.

Stroke networks and telemedicine: An Italian national survey.

Stroke is the leading cause of disability and death. Nowadays, clinical benefits of stroke units and thrombolysis in ischemic stroke are evidence-based. Also the benefit of endovascular treatment for acute ischemic stroke has been established. Telemedicine has been used to improve access to care by allowing a neurologist at a remote location to interact with the patient and their family members. Prior studies have shown that the use of telemedicine for acute ischemic stroke is not only safe and effective, but it also increases the utilization of tPA, improving patient outcomes. This study aimed to investigate the diffusion of telemedicine in Italian stroke networks with an online questionnaire to assess: type of stroke care setting, Volume of thrombolysis- thrombectomy/year, access to stroke care between different hospitals, the presence of imaging sharing protocols within the network or patients dispatchment screening; type of network solutions. We have interviewed 24 Italian neurologists, working in large urban areas, from north southward, including Italian islands. In particular, these neurologists represented 14 different regions and 20 countries. A majority of neurologists replying to the survey (47.83%) worked in large general hospitals or smaller general hospitals (26%) and a smaller number of physicians (17.3%) were committed in University Hospital or (8.7%) independent foundation hospitals. The 60.87% of stroke networks involved in the survey had a low thrombolysis/year volume while the 30.43% had a thrombolysis/year volume above 100. According to the survey a local stroke network was established in 87.50% of cases. In the 45.83% of cases, the hospitals care is not homogeneous within the network. A network for the consultation of neuroimaging between hospitals is available in 33.33% of cases. Whitin those describing an active network for Teleconsult the 57.14% used personal devices, while only the 25 % use professional teleconference system, and in 25% of cases used medical devices. Our findings demonstrated a relevant diffusion of Teleconsult in Italian stroke networks. The systems adopted are mostly individual solutions not integrated in protocolled pathways. These findings may encourage a systematization of Telemedicine medical curricula to increase larger access to neurological consults.

Botulinum neurotoxin-A does not spread to distant muscles after intragastric injection: A double-blind single-fiber electromyography study.

The purpose of this study was to perform a careful neurophysiological examination to identify subclinical signs of botulinum toxin spread distant to the injection site following intragastric injection for obesity treatment. Single-fiber electromyography of extensor digitorum communis and repetitive stimulation of abductor digiti minimi were performed before and 8 days after multiple intragastric injections of botulinum toxin A (Botox, 200 U per patient) or placebo. The study was performed in a randomized double-blind fashion. No patient in either group displayed results indicative of neuromuscular dysfunction either before or after the treatment. No significant change in muscle jitter was observed when comparing baseline with the after-treatment evaluation in either group, and no significant differences between groups were observed. After intragastric botulinum toxin injection no subclinical sign of distant spread was observed.

Fas-mediated T-cell apoptosis is impaired in patients with chronic inflammatory demyelinating polyneuropathy.

The Fas death receptor is expressed by activated lymphocytes and is involved in switching-off the immune response. Its inherited defects cause auto-immune lymphoproliferative syndrome. Impaired Fas function may also play a role in other auto-immune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The aim of this work was to evaluate Fas function in T cells from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated Fas-induced apoptosis in T-cell lines from 27 patients with CIDP, 12 patients with acute inflammatory demyelinating polyneuropathy (AIDP), and 110 controls. CIDP patients displayed lower Fas function than both AIDP patients and controls, whereas no statistically significant difference was found between AIDP patients and controls. Moreover, Fas function was lower in CIDP patients with progressive course than in those with relapsing-remitting course and lower in CIDP patients with axonal damage than in those with pure demyelination. These data suggest that defective Fas function favours CIDP development and aggressive evolution.

Acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in human immunodeficiency virus patients: an open label study.

Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus (HIV) patients under dideoxynucleoside therapy, benefits only partially from medical therapy, and often leads to drug discontinuation. Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism, eventually related to a reduction of mitochondrial DNA content, and interference with nerve growth factor activity. Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions. Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation. The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients. Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period. Efficacy was evaluated by means of the modified Short Form McGill Pain Questionnaire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit. Mean pain intensity score was significantly reduced during the study, changing from 7.35 +/- 1.98 (mean +/- SD) at baseline to 5.80 +/- 2.63 at week 4 (p = 0.0001). Electrophysiological parameters did not significantly change between baseline and week 4. In this study, acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity. On the contrary, no effect was noted on neurophysiological parameters.

Cutaneous silent period in human immunodeficiency virus-related peripheral neuropathy.

The aim of this work was first to determine whether the cutaneous silent period (CSP), a marker of small-nerve-fibre function, was altered in human immunodeficiency virus (HIV)-positive subjects with predominantly sensory symmetrical polyneuropathy and, second, to assess whether such alterations were predictive of an impairment in the largest calibre sensory and motor nerve fibres of the upper limb (UL) peripheral nerves. CSP was assessed in three groups of subjects: healthy control subjects, HIV-positive subjects with peripheral neuropathy (PN) of the lower limbs, and HIV-positive patients with clinical and neurophysiological involvement of the four limbs. CSP study showed a significant increase of the latency compared to the controls both in HIV-positive cases with no impairment in the UL (p=0.006) and in patients with four-limb neuropathy (p=0.002). CSP study in HIV-positive patients with mild lower limb distal sensory polyneuropathy can detect an early involvement of the UL peripheral nerves. CSP latency increase could therefore be addressed as the first sign of PN spreading to the UL.