Cerebrovascular Complications of COVID-19 and COVID-19 Vaccination.

The risk of stroke and cerebrovascular disease complicating infection with SARS-CoV-2 has been extensively reported since the onset of the pandemic. The striking efforts of many scientists in cooperation with regulators and governments worldwide have rapidly brought the development of a large landscape of vaccines against SARS-CoV-2. The novel DNA and mRNA vaccines have offered great flexibility in terms of antigen production and led to an unprecedented rapidity in effective and safe vaccine production. However, as mass vaccination has progressed, rare but catastrophic cases of thrombosis have occurred in association with thrombocytopenia and antibodies against PF4 (platelet factor 4). This catastrophic syndrome has been named vaccine-induced immune thrombotic thrombocytopenia. Rarely, ischemic stroke can be the symptom onset of vaccine-induced immune thrombotic thrombocytopenia or can complicate the course of the disease. In this review, we provide an overview of stroke and cerebrovascular disease as a complication of the SARS-CoV-2 infection and outline the main clinical and radiological characteristics of cerebrovascular complications of vaccinations, with a focus on vaccine-induced immune thrombotic thrombocytopenia. Based on the available data from the literature and from our experience, we propose a therapeutic protocol to manage this challenging condition. Finally, we highlight the overlapping pathophysiologic mechanisms of SARS-CoV-2 infection and vaccination leading to thrombosis.

PAD4-Induced NETosis Via Cathepsin G-Mediated Platelet-Neutrophil Interaction in ChAdOx1 Vaccine-Induced Thrombosis-Brief Report.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare syndrome characterized by platelet anti-PF4 (platelet-activating antiplatelet factor 4)-related thrombosis. Platelet-neutrophil interaction has been suggested to play a role, but the underlying mechanism has not been fully elucidated. METHODS: The study included 10 patients with VITT after ChAdOx1 (chimpanzee adenovirus Oxford 1) nCoV-19 (Oxford-AstraZeneca) vaccine administration, 10 patients with ischemic stroke (IS), 10 patients with acute deep vein thrombosis, and 10 control subjects in whom blood levels of neutrophil extracellular traps (NETs), soluble TF (tissue factor), and thrombin generation were examined. Furthermore, we performed in vitro studies comparing the effect of serum from patients and controls on NETs formation. Finally, immunohistochemistry was performed in cerebral thrombi retrieved from a patients with VITT and 3 patients with IS. RESULTS: Compared with patients with IS, patients with deep vein thrombosis, controls, and patients with VITT had significantly higher blood values of CitH3 (citrullinated histone H3), soluble TF, D-dimer, and prothrombin fragment 1+2 (P<0.0001). Blood CitH3 significantly correlated with blood soluble TF (Spearman rank correlation coefficient=0.7295; P=0.0206) and prothrombin fragment 1+2 (Spearman rank correlation coefficient=0.6809; P<0.0350) in patients with VITT. Platelet-neutrophil mixture added with VITT plasma resulted in higher NETs formation, soluble TF and thrombin generation, and platelet-dependent thrombus growth under laminar flow compared with IS and deep vein thrombosis plasma; these effects were blunted by PAD4 (protein arginine deiminase 4) and cathepsin G inhibitors, anti-FcγRIIa (Fc receptor for IgG class IIa), and high doses of heparin. Immunohistochemistry analysis showed a more marked expression of PAD4 along with more diffuse neutrophil infiltration and NETs formation as well as TF and cathepsin expression in VITT thrombus compared with thrombi from patients with IS. CONCLUSIONS: Patients with VITT display enhanced thrombogenesis by PAD4-mediated NETs formation via cathepsin G-mediated platelet/neutrophil interaction.

Mechanical thrombectomy in young patients with large vessel occlusion-related ischemic stroke: Data from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND AND PURPOSE: The weight of outcome predictors in acute ischemic stroke (AIS) patients older than 60 years is not necessarily mirrored in the younger population, posing the question of whether outcome determinants specific for the latter might vary. Very few data are available on predictors of outcome in young AIS patients receiving endovascular treatment (EVT). METHODS: We analyzed data for patients aged between 16 and 55 years from the Italian Registry of Endovascular Treatment in Acute Stroke. We divided our population into patients <45 years old and patients aged between 45 and 55 years. After testing the differences between groups in terms of 90-day modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage, we looked for predictors of poor outcome (mRS 3-6), death, and symptomatic intracerebral hemorrhage in the two groups. RESULTS: A total of 438 patients younger than 45 years and 817 aged 45-55 years were included; 284 (34.8%) patients aged 45-55 years and 112 (25.6%) patients younger than 45 years old showed poor 90-day functional outcome (p = 0.001). Predictors of poor outcome in the older group were baseline National Institutes of Health Stroke Scale (NIHSS; p < 0.001), diabetes (p = 0.027), poor collateral status (p = 0.036), and groin puncture-to-recanalization time (p = 0.010), whereas Thrombolysis in Cerebral Infarction (TICI) 2b-3 had an inverse association (p < 0.001). Predictors of poor outcome in patients younger than 45 years were baseline NIHSS (p < 0.001) and groin puncture-to-recanalization time (p = 0.015), whereas an inverse association was found for baseline Alberta Stroke Program Early CT Score (p = 0.010) and TICI 2b-3 (p < 0.001). CONCLUSIONS: Approximately one third of young adults treated with EVT do not reach a good functional outcome. Fast and successful recanalization, rather than common risk factors, has a major role in determining clinical outcome.

A transient magnetic resonance spectroscopy peri-ischemic peak: a possible radiological biomarker of post-stroke neurogenesis.

BACKGROUND AND AIMS: In adult human brain, neurogenesis seems to persist throughout life and ischemic stroke was proved to stimulate this process. Using magnetic resonance spectroscopy (MRS), a 1.28-ppm peak, putative biomarker of neural progenitor cells (NPCs), was identified both in vitro and in vivo, i.e., in normal rat and healthy human brain. The aim of our study was to identify a 1.28-ppm peak in adult human ischemic brain by using 3.0 T multivoxel MRS. METHODS: We studied 10 patients, six males, and four females, with a mean (± SD) age of 59.3 (± 17.3), at three different time points from ischemic stroke onset (T0: < 5 days; T14: 14 ± 2 days; T30: 30 ± 2 days). RESULTS: In all patients except one, a 1.28-ppm peak at T14 was detected at the ischemic boundary (all p values < 0.05). MRS performed on six voluntary age-matched healthy subjects did not detect any 1.28-ppm peak. CONCLUSIONS: The nature of this 1.28-pm peak is uncertain; however, our data support the hypothesis that it might represent a marker of NPCs in post-stroke human brain.

No-reflow phenomenon in acute ischemic stroke: an angiographic evaluation.

BACKGROUND: Futile recanalization (FR) is de fined as a poor 90-day outcome or lack of neurological improvement at 24 h despite successful recanalization in acute ischemic stroke (AIS) with large vessel occlusion (LVO) treated by mechanical throbectomy (MT). The No-reflow phenomenon (NRP) could be a possible cause of FR, but its evidence in AIS patients is scarce. METHODS: We retrospectively analyzed 185 digital subtraction angiographies (DSA) of AIS patients with anterior circulation LVO after endovascular treatment. To better define NRP, we designed a score called the modified capillary index score (mCIS). The score is obtained by dividing the middle cerebral artery territory in three segments. For each segment, we gave 2 points if the capillary blush was present without any delay, 1 if delayed, and 0 if absent. The primary endpoint was to use mCIS to identify NRP on post-interventional DSA and to test whether this marker may predict FR and failure of early neurological improvement (fENI). The secondary endpoint was to search for a correlation between NRP, lesion volume, and hemorrhagic transformation. We used the ROC curve to define mCIS ≤ 3 as the cut-off and marker of NRP. RESULTS: NRP was present in 35.1% of patients. NRP predicted fENI at 24 h (aOR 2.825, 95% CI 1.265-6.308, P = 0.011) and at 7 days (aOR 2.191, 95% CI 1.008-4.762, P = 0.048), but not 90-day FR. Moreover, NRP predicted hemorrhagic transformation (aOR 2.444, 95% CI 1.266-4.717, P = 0.008). CONCLUSIONS: The modified capillary index score (mCIS) seems useful in identifying NRP in AIS. In addition, mCIS was able to predict NRP that correlated with early clinical outcome and hemorrhagic transformation of the ischemic lesion. An external validation of the score is warranted.

Acute ischemic stroke in childhood: a comprehensive review.

This review provides an updated analysis of the main aspects involving the diagnosis and the management of children with acute ischemic stroke. Acute ischemic stroke is an emergency of rare occurrence in children (rate of incidence of 1/3500 live birth in newborns and 1-2/100,000 per year during childhood with peaks of incidence during the perinatal period, under the age of 5 and in adolescence). The management of ischemic stroke in the paediatric age is often challenging because of pleomorphic age-dependent risk factors and aetiologies, high frequency of subtle or atypical clinical presentation, and lacking evidence-based data about acute recanalization therapies. Each pediatric tertiary centre should activate adequate institutional protocols for the optimization of diagnostic work-up and treatments.Conclusion: The implementation of institutional standard operating procedures, summarizing the steps for the selection of candidate for neuroimaging among the ones presenting with acute neurological symptoms, may contribute to shorten the times for thrombolysis and/or endovascular treatments and to improve the long-term outcome. What is Known: •Acute ischemic stroke has a higher incidence in newborns than in older children (1/3500 live birth versus 1-2/100,000 per year). •Randomized clinical trial assessing safety and efficacy of thrombolysis and/or endovascular treatment were never performed in children What is New: •Recent studies evidenced a low risk (2.1% of the cases) of intracranial haemorrhages in children treated with thrombolysis. •A faster access to neuroimaging and hyper-acute therapies was associated with the implementation of institutional protocols for the emergency management of pediatric stroke.

Copeptin Kinetics in Acute Ischemic Stroke May Differ According to Revascularization Strategies: Pilot Data.

Background and Purpose- Prognostic value of copeptin in acute ischemic stroke has been widely reported. This study aimed to evaluate copeptin temporal profile according to revascularization strategies and the development of brain edema and hemorrhagic transformation. Methods- Plasma copeptin and brain edema and hemorrhagic transformation assessed by computed tomography/magnetic resonance imaging were evaluated upon admission (T0), at 24 hours (T1), and between the third and fifth day of hospitalization (T2) in 34 acute ischemic stroke patients. Results- Median copeptin concentration was 50.71 pmol/L at T0, 18.31 pmol/L at T1, and 10.92 pmol/L at T2. Copeptin at T1 was higher in patients with medium/severe brain edema at T2 (32.25 versus 13.67 pmol/L; P=0.038) and hemorrhagic transformation at T1 (93.10 versus 13.67 pmol/L; P<0.003) and T2 (85.70 versus 14.45 pmol/L; P=0.024). Copeptin level drop (CopΔT1-T0) was significantly steeper in patients receiving revascularization, particularly in those undergoing combined therapy (-129.34 versus -5.43 pmol/L; P=0.038). ΔT1-T0 also correlated with Thrombolysis in Cerebral Infarction score (P<0.001). Conclusions- Copeptin resulted associated with brain edema and hemorrhagic transformation in acute ischemic stroke, and its drop at 24 hours may mirror effective brain vessel recanalization.

IER-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Thrombectomy for Stroke.

Background and Purpose- As a reliable scoring system to detect the risk of symptomatic intracerebral hemorrhage after thrombectomy for ischemic stroke is not yet available, we developed a nomogram for predicting symptomatic intracerebral hemorrhage in patients with large vessel occlusion in the anterior circulation who received bridging of thrombectomy with intravenous thrombolysis (training set), and to validate the model by using a cohort of patients treated with direct thrombectomy (test set). Methods- We conducted a cohort study on prospectively collected data from 3714 patients enrolled in the IER (Italian Registry of Endovascular Stroke Treatment in Acute Stroke). Symptomatic intracerebral hemorrhage was defined as any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline ≤24 hours or death. Based on multivariate logistic models, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve. Results- National Institutes of Health Stroke Scale score, onset-to-end procedure time, age, unsuccessful recanalization, and Careggi collateral score composed the IER-SICH nomogram. After removing Careggi collateral score from the first model, a second model including Alberta Stroke Program Early CT Score was developed. The area under the receiver operating characteristic curve of the IER-SICH nomogram was 0.778 in the training set (n=492) and 0.709 in the test set (n=399). The area under the receiver operating characteristic curve of the second model was 0.733 in the training set (n=988) and 0.685 in the test set (n=779). Conclusions- The IER-SICH nomogram is the first model developed and validated for predicting symptomatic intracerebral hemorrhage after thrombectomy. It may provide indications on early identification of patients for more or less postprocedural intensive management.

Can Repetitive Transcranial Magnetic Stimulation (rTMS) Promote Neurogenesis and Axonogenesis in Subacute Human Ischemic Stroke?

BACKGROUND: Ischemic stroke may trigger neuroplastic changes via proliferation, migration towards the lesion, and differentiation of neuroprogenitor cells into mature neurons. Repetitive Transcranial Magnetic Stimulation (rTMS) may promote brain plasticity. This study aimed to assess rTMS's effect on post-stroke endogenous neuroplasticity by dosing plasma miRs 17~92, Netrin-1, Sema3A, and BDNF. METHODS: In this case-controlled study, we randomized 19 ischemic stroke patients within five days from symptoms onset (T0) to neuronavigated-rTMS or sham stimulation. Stimulation was applied on the stroke hemisphere daily between the 7th and 14th day from stroke onset. Blood samples were collected at T0, before the first rTMS section (T7), and at the end of the last rTMS session (T14). Five healthy controls were also enrolled in this study. RESULTS: Of 19 patients, 10 received rTMS and 9 sham stimulation. Compared with the sham group, in the rTMS group, plasma levels of miRs17~92 and Ntn-1 significantly increased whereas Sema3A levels tended to decrease. In multivariate linear regression analyses, rTMS was independently related to Ntn-1 and miR-25 levels at T14. CONCLUSIONS: We found an association between rTMS and neurogenesis/axonogenesis biomarker enhancement. Our preliminary data suggest that rTMS may positively interfere with natural endogenous plasticity phenomena of the post-ischemic human brain.

Phlebological insole: Can it help in the lymphoedema treatment? A scoping review.

BACKGROUND: The treatment of lymphoedema requires a multi-professional and interdisciplinary approach. Despite being prescribed in the management of lymphatic disorders, the effectiveness of the phlebological insoles is still under investigation. AIM: This scoping review aims to identify and analyse evidence regarding the efficacy of phlebological insoles as a conservative intervention for lower limb lymphoedema. METHOD: The following databases were searched up to November 2022: PubMed, Cochrane Library, CINAHL Complete, PEDro and Scopus. Preventive and conservative interventions were considered. Studies considering people with lower limb oedema, of any age and type of oedema, were eligible for inclusion. No restrictions in terms of language, year of publication, study design and type of publication were applied. Additional studies were sought through grey literature. RESULTS: From 117 initial records, 3 studies met the inclusion criteria. Two quasi-experimental studies and one randomised cross-over study were included. The results of the examined studies confirmed the positive effects of insoles usage and foot and ankle mobility on the venous return. CONCLUSION: This scoping review provided an overview of the topic. The studies analysed in this scoping review have shown that insoles seem to be beneficial in reducing the lower limb oedema in healthy individuals. However, there are still no comprehensive trials confirming this evidence on people with lymphoedema. The small number of identified articles, the selection of participants not affected by lymphoedema, the use of heterogeneous devices in terms of modifications and materials highlight the need of further investigations. Future trails should include people affected by lymphoedema, address the choice of materials in manufacturing the insoles and take in consideration the patients' adherence to the device and concordance to the treatment.

Antiphospholipid antibodies in patients with stroke during COVID-19: A role in the signaling pathway leading to platelet activation.

Background: Several viral and bacterial infections, including COVID-19, may lead to both thrombotic and hemorrhagic complications. Previously, it has been demonstrated an "in vitro" pathogenic effect of "antiphospholipid" antibodies (aPLs), which are able to activate a proinflammatory and procoagulant phenotype in monocytes, endothelial cells and platelets. This study analyzed the occurrence of aPL IgG in patients with acute ischemic stroke (AIS) during COVID-19, evaluating the effect of Ig fractions from these patients on signaling and functional activation of platelets. Materials and methods: Sera from 10 patients with AIS during COVID-19, 10 non-COVID-19 stroke patients, 20 COVID-19 and 30 healthy donors (HD) were analyzed for anti-cardiolipin, anti-ß2-GPI, anti-phosphatidylserine/prothrombin and anti-vimentin/CL antibodies by ELISA. Platelets from healthy donors were incubated with Ig fractions from these patients or with polyclonal anti-ß2-GPI IgG and analyzed for phospho-ERK and phospho-p38 by western blot. Platelet secretion by ATP release dosage was also evaluated. Results: We demonstrated the presence of aPLs IgG in sera of patients with AIS during COVID-19. Treatment with the Ig fractions from these patients or with polyclonal anti-ß2-GPI IgG induced a significant increase of phospho-ERK and phospho-p38 expression. In the same vein, platelet activation was supported by the increase of adenyl nucleotides release induced by Ig fractions. Conclusions: This study demonstrates the presence of aPLs in a subgroup of COVID-19 patients who presented AIS, suggesting a role in the mechanisms contributing to hypercoagulable state in these patients. Detecting these antibodies as a serological marker to check and monitor COVID-19 may contribute to improve the risk stratification of thromboembolic manifestations in these patients.

Evidence of SARS-CoV-2 spike protein on retrieved thrombi from COVID-19 patients.

The pathophysiology of COVID-19-associated coagulopathy is complex and not fully understood. SARS-CoV-2 spike protein (SP) may activate platelets and interact with fibrin(ogen). We aimed to investigate whether isolated SP can be present in clots retrieved in COVID-19 patients with acute ischemic stroke (by mechanical thrombectomy) and myocardial infarction. In this pilot study, we could detect SP, but not nucleocapsid protein, on platelets of COVID-19 patients' thrombi. In addition, in all three COVID-19 thrombi analyzed for molecular biology, no SARS-CoV-2 RNA could be detected by real-time polymerase chain reaction. These data could support the hypothesis that free SP, besides the whole virus, may be the trigger of platelet activation and clot formation in COVID-19.

SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke.

Background and purpose: Acute ischemic stroke (AIS) is a fearful complication of Coronavirus Disease-2019 (COVID-19). Aims of this study were to compare clinical/radiological characteristics, endothelial and coagulation dysfunction between acute ischemic stroke (AIS) patients with and without COVID-19 and to investigate if and how the SARS-CoV-2 spike protein (SP) was implicated in triggering platelet activation. Methods: We enrolled AIS patients with COVID-19 within 12 h from onset and compared them with an age- and sex-matched cohort of AIS controls without COVID-19. Neuroimaging studies were performed within 24 h. Blood samples were collected in a subset of 10 patients. Results: Of 39 AIS patients, 22 had COVID-19 and 17 did not. Admission levels of Factor VIII and von Willebrand factor antigen were significantly higher in COVID-19 patients and positively correlated with the infarct volume. In multivariate linear regression analyses, COVID-19 was an independent predictor of infarct volume (B 20.318, Beta 0.576, 95%CI 6.077-34.559; p = 0.011). SP was found in serum of 2 of the 10 examined COVID-19 patients. Platelets from healthy donors showed a similar degree of procoagulant activation induced by COVID-19 and non-COVID-19 patients' sera. The anti-SP and anti-FcγRIIA blocking antibodies had no effect in modulating platelet activity in both groups. Conclusions: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.

Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients.

Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood-brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.

IER-START nomogram for prediction of three-month unfavorable outcome after thrombectomy for stroke.

BACKGROUND: The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance. AIMS: We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy <6 h of stroke onset. METHODS: We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3-6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training (n = 1219) and test (n = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816-0.869) in the training set, and 0.820 (95% CI: 0.786-0.854) in the test set. CONCLUSIONS: The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome.

Dabigatran Reversal with Idarucizumab in an Emergency Lumbar Puncture: A Case Report.

INTRODUCTION: The widespread use of direct oral anticoagulants (DOACs) has been increasing the conditions in which emergency physicians are forced to rapidly reverse anticoagulation in case of life-threatening bleeding or need of urgent surgery or invasive procedures. The recent approval of Idarucizumab, a humanized monoclonal antibody fragment (Fab), offered the opportunity to rapidly and safely neutralize the anticoagulant effect of Dabigatran. However, real-world experience of its effective use in different emergency setting is now required. Lumbar Puncture (LP) is recognized as an invasive procedure at major bleeding risk and is, therefore, contraindicated in anticoagulated patients. CONCLUSION: We report a successful use of Idarucizumab in an emergency LP of a young woman with a possible diagnosis of encephalitis and a previous history of venous thromboembolism on long-term treatment with Dabigatran 150 mg twice a day.

Acute Flaccid Paralysis by Enterovirus D68 Infection: First Italian Description in Adult Patient and Role of Electrophysiology.

A Peruvian woman was admitted to the Emergency Department, due to an acute flaccid paralysis (AFP) of the upper limbs that progressively involved also lower limbs and respiratory muscles. She previously suffered from non-Hodgkin's lymphoma and had to undergo hematopoietic stem cell transplantation. A magnetic resonance imaging showed a T2 hyperintensity in the anterior and central region of the cervical segment with an elective involvement of gray matter. This finding, combined with other clinical, laboratory, and electrophysiological data, led to a diagnosis of AFP. Enterovirus D68 was isolated in the patient's cerebrospinal fluid, plasma, and throat swab. To our knowledge, this is the first Italian case of AFP by Enterovirus D68 infection in an adult. The diagnostic assessment and management of AFP by Enterovirus D68 are discussed.