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Swallowing disorders are common in neurological diseases, with dysphagia representing one of the most prevalent complications that may cause poor quality of life, reduce independence, and increase mortality. Rapid identification of dysphagia is necessary to reduce the risk of penetration and aspiration, and to early start rehabilitation protocols. Among the methods that can be used to evaluate dysphagia and its components, ultrasound imaging has been suggested to support the evaluation of dysphagia by providing measures of both static and dynamic anatomical components. The aim of this systematic review is to evaluate the usefulness of ultrasonography in neurogenic dysphagia according to current literature. From 2000 to 2020, 633 studies with the appropriate search terms for ultrasound and dysphagia were identified. After screening them, 10 studies were included in the qualitative analysis. Patients with the following neurologic conditions were studied with ultrasonography for dysphagia: Parkinson’s disease, muscle dystrophy, amyotrophic lateral sclerosis, and stroke. The main outcomes of ultrasonography were swallowing muscles thickness (e.g., tongue), and dynamic measures such as hyoid displacement. The different protocols used in the studies, as well as their outcomes, did not allow to provide standard procedures and normative or cut-off values in the presented diseases. Because there are a variety of tools, methods, and techniques that have been used in the studies that were reviewed, it is difficult to evaluate them using established standards. However, ultrasonography correlates well with clinical evaluation of dysphagia and therefore has prognostic and rehabilitation potential. Future studies should aim to develop and utilize a common interdisciplinary protocol that includes standard procedures and outcomes to define normative values applicable in the different conditions.

Actigraphy is a tool used to describe limb motor activity. Some actigraphic parameters, namely Motor Activity (MA) and Asymmetry Index (AR), correlate with stroke severity. However, a long-lasting actigraphic monitoring was never performed previously. We hypothesized that MA and AR can describe different clinical conditions during the evolution of the acute phase of stroke. We conducted a multicenter study and enrolled 69 stroke patients. NIHSS was assessed every hour and upper limbs’ motor activity was continuously recorded. We calculated MA and AR in the first hour after admission, after a significant clinical change (NIHSS ± 4) or at discharge. In a control group of 17 subjects, we calculated MA and AR normative values. We defined the best model to predict clinical status with multiple linear regression and identified actigraphic cut-off values to discriminate minor from major stroke (NIHSS ≥ 5) and NIHSS 5–9 from NIHSS ≥ 10. The AR cut-off value to discriminate between minor and major stroke (namely NIHSS ≥ 5) is 27% (sensitivity = 83%, specificity = 76% (AUC 0.86 p < 0.001), PPV = 89%, NPV = 42%). However, the combination of AR and MA of the non-paretic arm is the best model to predict NIHSS score (R2: 0.482, F: 54.13), discriminating minor from major stroke (sensitivity = 89%, specificity = 82%, PPV = 92%, NPV = 75%). The AR cut-off value of 53% identifies very severe stroke patients (NIHSS ≥ 10) (sensitivity = 82%, specificity = 74% (AUC 0.86 p < 0.001), PPV = 73%, NPV = 82%). Actigraphic parameters can reliably describe the overall severity of stroke patients with motor symptoms, supporting the addition of a wearable actigraphic system to the multi-parametric monitoring in stroke units.

The autonomic nervous system (ANS) can be affected by COVID-19, and dysautonomia may be a possible complication in post-COVID individuals. Orthostatic hypotension (OH) and postural tachycardia syndrome (POTS) have been suggested to be common after SARS-CoV-2 infection, but other components of ANS function may be also impaired. The Composite Autonomic Symptom Scale 31 (COMPASS-31) questionnaire is a simple and validated tool to assess dysautonomic symptoms. The aim of the present study was to administer the COMPASS-31 questionnaire to a sample of post-COVID patients with and without neurological complaints. Participants were recruited among the post-COVID ambulatory services for follow-up evaluation between 4 weeks and 9 months from COVID-19 symptoms onset. Participants were asked to complete the COMPASS-31 questionnaire referring to the period after COVID-19 disease. Heart rate and blood pressure were manually taken during an active stand test for OH and POTS diagnosis. One-hundred and eighty participants were included in the analysis (70.6% females, 51 ± 13 years), and OH was found in 13.8% of the subjects. Median COMPASS-31 score was 17.6 (6.9–31.4), with the most affected domains being orthostatic intolerance, sudomotor, gastrointestinal and pupillomotor dysfunction. A higher COMPASS-31 score was found in those with neurological symptoms (p p p p p

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID‐19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin‐6 (IL‐6) and IL−8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL‐6 and IL‐8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL‐8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL‐6 and IL‐8 as prognostic biomarkers in COVID‐19.

Background 123I-Metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy is a useful technique to differentiate Parkinson's disease (PD) from atypical parkinsonisms, since it is generally abnormal in PD and normal in the latter. Reduction of myocardial MIBG uptake is a supportive feature in the latest PD diagnostic criteria. Objectives To explore the clinical contribution of myocardial scintigraphy in discriminating different forms of parkinsonisms, especially when atypical features are present. Methods Forty-one patients with parkinsonism underwent a 123I-MIBG myocardial scintigraphy in our Movement Disorders Center. Disease evolution was reviewed by applying the latest disease criteria for PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as appropriate. Three diagnostic times were defined: T1 (before scintigraphy execution), T2 (immediately after the exam) and T3 (two years later). Early and delayed heart/mediastinum (H/M) ratios and washout rate (WR) were analyzed. Results Myocardial scintigraphy showed impaired MIBG uptake in 12 out of 15 patients with a definite PD diagnosis, while normal uptake was found in 20 of 26 patients with no-PD. Early and delayed H/M ratios were significantly lower in PD compared to overall no-PD patients and MSA patients. 123I-MIBG myocardial scintigraphy was abnormal in all PD patients with dysautonomia. After 123I-MIBG myocardial scintigraphy (T2), in 9 patients (22%) an improvement of diagnostic accuracy was reached. Conclusions Diagnostic accuracy of myocardial scintigraphy in distinguishing PD from atypical parkinsonism was suboptimal. Nevertheless, this study confirmed the relevance of 123I-MIBG myocardial scintigraphy for the discrimination of PD from atypical parkinsonism, especially when dysautonomic symptoms are present.

Owing to the large inter-subject variability, early post-stroke prognosis is challenging, and objective biomarkers that can provide further prognostic information are still needed. The relation between quantitative EEG parameters in pre-thrombolysis hyper-acute phase and outcomes has still to be investigated. Hence, possible correlations between early EEG biomarkers, measured on bedside wireless EEG, and short-term/long-term functional and morphological outcomes were investigated in thrombolysis-treated strokes. EEG with a wireless device was performed in 20 patients with hyper-acute (

COVID-19 may increase the risk of heat-related symptoms during hot weather since vulnerable populations, including the elderly and those with neurological disabilities, must continue to self-isolate, often indoors. Within the chronic neurological patient population, indoor conditions in summer months present a hazard because of impaired and/or altered thermoregulation, including poor hydration status due to both autonomic and behavioral dysfunction(s). To address this increased risk, telemedicine protocols should include an assessment of the patient's environmental parameters, and when combined with physiological data from wearable devices, identify those with neurological diseases who are at higher risk of heat illness. Personalized medicine during times of self-isolation must be encouraged, and using smart technology in ambient assisted living solutions, including e-health to monitor physiological parameters are highly recommended, not only during extreme weather conditions but also during times of increased isolation and vulnerability.

We report the case of a 70-year-old man coming to our attention for new onset refractory status epilepticus (NORSE) in a rapidly evolving CJD during SARS-CoV-2 co-infection. Our case report describes a fulminant CJD evolution associated with SARS-CoV-2 infection, which led to patient death after 15 days from admission. First EEG presented continuous diffuse spikes, sharp waves and sharp-and-slow wave complexes, pattern consistent with a non-convulsive status epilepticus (NORSE). Our case supports how CJD with SARS-CoV-2 co-infection could be characterized by an accelerated evolution, as already hypothesize for others microorganism infections, and how the diagnosis might be more challenging due to its uncommon presentations, such as NORSE.

Background The COVID-19 lockdown has influenced people lifestyle, behaviour, physical activity (PA), and working habits as well as, possibly, migraine. The aim of the study was to assess the impact of lockdown on the burden of migraine attacks during COVID-19 lockdown. Methods Patients were interviewed, and data about demographics, PA, daily behaviour, working habits, disability (HIT-6) and characteristics of migraine and drugs consumption were compared between the first month of the lockdown in Italy (March 2020), and a reference month prior the lockdown (January 2020). Results 37 patients were analysed, classified as migraine without aura (MwoA) (n = 26) and migraine with aura (MwA) plus migraine with and without aura (MwA/MwoA) (n = 11). During the lockdown, a greater proportion of patients with insufficient PA (65% vs 31%; p = 0.012) were found. Reduced mean headache duration [3 h, (2–12) vs 2 h (1–8); p = 0.041] and HIT score [59 (51–63) vs 50 (44–57); p = 0.001] were found in MwoA patients during the lockdown, while no changes found in patients with MwA + MwA/MwoA. Conclusions Lockdown induced significant changes in PA and working habits of people with migraine and was found to be associated with improved migraine-related symptoms which might depend by different lifestyle habits.

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Outcome prediction in wake-up ischemic stroke (WUS) is important for guiding treatment strategies, in order to improve recovery and minimize disability. We aimed at producing an interpretable model to predict a good outcome (NIHSS 7-day

Objective Orthostatic hypotension (OH) represents a frequent but under-recognized phenomenon in Parkinson’s disease (PD). During COVID-19 pandemic, Information and Communication Technologies (ICT) have become pivotal in the management of chronic diseases like PD, not only to assess motor impairment, but also for vital signs monitoring. This pilot study aimed to propose a real-time remote home-monitoring system and protocol for PD patients with OH. Methods Vital parameters were acquired by wireless devices and transmitted to an ICT platform, providing data and smart notifications to the healthcare provider through an interactive web portal. Eight patients with idiopathic PD and OH underwent 5-day monitoring. Data about OH episodes, therapeutic interventions, impact on daily activities, and patient satisfaction were collected and analyzed. Results The proposed solution allowed the identification of 65 OH episodes and subsequent medical interventions. Thirty-five episodes were asymptomatic, especially in the postprandial and in the afternoon recordings. Systolic-blood-pressure (SBP) and diastolic-blood-pressure (DBP) were significantly lower in symptomatic episodes, while the pressure drops resulted significantly higher in presence of symptoms. High usability and patient satisfaction scores were observed. Conclusion The proposed home-monitoring system and protocol have proved to provide useful information and to allow prompt interventions in the management of PD patients with OH during COVID-19 pandemic.

OBJECTIVE: The objective of this study was to evaluate skin wetness perception and thermal sensitivity in people with migraine and similar healthy controls.BACKGROUND: Environmental triggers, such as cold and humidity, are known triggers for pain in people with migraine. Sensory inputs might be implicated in such heightened responses to cold-humid environments, such that a migraine-induced hypersensitivity to cold wetness could be present in people with migraine. However, we lack empirical evidence on skin thermal and wetness sensitivity across skin sites commonly associated with reported pain in migraine, such as the forehead.METHODS: This prospective cross-sectional observational study, conducted in a university hospital setting, evaluated skin wetness perceptions and thermal sensations to wet non-noxious warm-wet, neutral-wet, and cold-wet stimuli applied to the forehead, the posterior neck, and the index finger pad of 12 patients with migraine (mean and standard deviation for age 44.5 ± 13.2 years, 7/12 [58%] women) and 36 healthy controls (mean and standard deviation for age 39.4 ± 14.6 years, 18/36 [50%] women).RESULTS: On the forehead, people with migraine reported a significantly higher wetness perception than healthy controls across all thermal stimulus (15.1 mm, 95% confidence interval [CI]: 1.8 to 28.5, p = 0.027, corresponding to ~ 15% difference), whereas no significant differences were found on the posterior neck nor on the index finger pad. We found no differences among groups in overall thermal sensations (-8.3 mm, 95% CI: -24.0 to 7.3, p = 0.291; -7.8 mm, 95% CI: -25.3 to 9.7, p = 0.375; and 12.4 mm, 95% CI: -4.0 to 28.9, p = 0.133; forehead, posterior neck, and index finger, respectively).CONCLUSION: These findings indicate that people with migraine have a heightened sensitivity to skin wetness on the forehead area only, which is where pain attacks occur. Future studies should further explore the underlying mechanisms (e.g., TRPM8-mediated cold-wet allodynia) that lead to greater perception of wetness in people with migraine to better understand the role of environmental triggers in migraine.

Neurological manifestations may be common in COVID-19 patients. They may include several syndromes, such as a suggested autoimmune abnormal response, which may result in encephalitis and new-onset refractory status epilepticus (NORSE). Quickly recognizing such cases and starting the most appropriate therapy is mandatory due to the related rapid worsening and bad outcomes. This case series describes two adult patients admitted to the university hospital and positive to novel coronavirus 2019 (SARS-CoV-2) infection who developed drug-resistant status epilepticus. Both patients underwent early electroencephalography (EEG) assessment, which showed a pathological EEG pattern characterized by general slowing, rhythmic activity and continuous epileptic paroxysmal activity. A suspected autoimmune etiology, potentially triggered by SARS-CoV-2 infection, encouraged a rapid work-up for a possible autoimmune encephalitis diagnosis. Therapeutic approach included the administration of 0.4 g/kg intravenous immunoglobulin, which resulted in a complete resolution of seizures after 5 and after 10 days, respectively, without adverse effects and followed by a normalization of the EEG patterns.

Purpose The fear of COVID-19 infection may discourage patients from going to the hospital even in case of sudden onset of disabling symptoms. There is growing evidence of the reduction of stroke admissions and higher prevalence of severe clinical presentation. Yet, no studies have investigated the perfusion pattern of acute strokes admitted during the lockdown. We aimed to evaluate the effects of the COVID-19 pandemic on hyper-acute stroke CT perfusion (CTP) pattern during the first months of the pandemic in Italy. Methods In this retrospective observational study, we analyzed CTP images and clinical data of ischemic stroke patients admitted between 9 March and 2 June 2020 that underwent CTP (n = 30), to compare ischemic volumes and clinical features with stroke patients admitted during the same period in 2019 (n = 51). In particular, CTP images were processed to calculate total hypoperfused volumes, core volumes, and mismatch. The final infarct volumes were calculated on follow-up CT. Results Significantly higher total CTP hypoperfused volume (83.3 vs 18.5 ml, p = 0.003), core volume (27.8 vs 1.0 ml, p < 0.001), and unfavorable mismatch (0.51 vs 0.91, p < 0.001) were found during the COVID-19 period compared to no-COVID-19 one. The more unfavorable perfusion pattern at admission resulted in higher infarct volume on follow-up CT during COVID-19 (35.5 vs 3.0 ml, p < 0.001). During lockdown, a reduction of stroke admissions (− 37%) and a higher prevalence of severe clinical presentation (NIHSS ≥ 10; 53% vs 36%, p = 0.029) were observed. Conclusion The results of CTP analysis provided a better insight in the higher prevalence of major severity stroke patients during the COVID-19 period.

Brain electrical activity in acute ischemic stroke is related to the hypoperfusion of cerebral tissue as manifestation of neurovascular coupling. EEG could be applicable for bedside functional monitoring in emergency settings. We aimed to investigate the relation between hyper-acute ischemic stroke EEG changes, measured with bedside wireless-EEG, and hypoperfused core-penumbra CT-perfusion (CTP) volumes. In addition, we investigated the association of EEG and CTP parameters with neurological deficit measured by NIHSS. We analyzed and processed EEG, CTP and clinical data of 31 anterior acute ischemic stroke patients registered within 4.5 h from symptom onset. Delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DTABR) and relative delta power correlated directly (ρ = 0.72; 0.63; 0.65, respectively), while alpha correlated inversely (ρ = − 0.66) with total hypoperfused volume. DAR, DTBAR and relative delta and alpha parameters also correlated with ischemic core volume (ρ = 0.55; 0.50; 0.59; − 0.51, respectively). The same EEG parameters and CTP volumes showed significant relation with NIHSS at admission. The multivariate stepwise regression showed that DAR was the strongest predictor of NIHSS at admission (p < 0.001). The results of this study showed that hyper-acute alterations of EEG parameters are highly related to the extent of hypoperfused tissue highlighting the value of quantitative EEG as a possible complementary tool in the evaluation of stroke severity and its potential role in acute ischemic stroke monitoring.

There is growing research interest on identification of CT Perfusion (CTP) parameters that predict the outcome in acute ischemic stroke patients. The aim of this study is to produce the model, based on core-penumbra related parameters assessed by CTP processing and commonly used clinical prediction factors, to predict the final infarct volume in thrombolysis-treated anterior circulation wake-up stroke (WUS) patients. The study was conducted on 51 consecutive wake-up ischemic stroke patients. The model for the predictive estimation of final ischemic volume was determined by using the Least Absolute Shrinkage and Selection Operator (LASSO) regularized least-squares regression. The results showed that CTP core volume and CTP total ischemic volume at admission, together with ASPECT score predict the final infarct lesion volume. In particular, the identified model presented 5-fold cross-validation root mean square error RMSE of 8.1 ml and the coefficient of determination (R2=0.94) on our dataset. The results should be confirmed in a lager study. In conclusion, in this study we preliminarily identified a predictive model to estimate final ischemic lesion volume in thrombolysis treated wake-up stroke patients.

Background: When it comes to critical early post-acute TIA/stroke phase, there is a lack of a comprehensive multi-parametric telemonitoring system. The COVID-19 emergency, its related global mobility restrictions and fear of hospitalization further highlighted the need of a comprehensive solution. Objective: We aimed to design and test a pragmatic e-Health system based on multiparametric telemonitoring to support of TIA/stroke patients in sub-acute phase during the COVID-19 pandemic. Methods: We proposed a telemonitoring system and protocol for TIA/minor stroke patients during COVID-19 pandemic for patients at risk of stroke recurrence. This system involves the use of portable devices for BP/HR/SpO2/temperature sensing, panic-button, gateway, and a dedicated ICT platform. The protocol is a 14-day multiparametric telemonitoring, therapy, and emergency intervention based on vital sign alteration notifications. We conducted a proof-of-concept validation test on 8 TIA/minor stroke patients in the early post-acute phase (< 14 days from ischemic event). Results: The proposed solution allowed to promptly and remotely identify vital sign alterations at home during the early post-acute phase, allowing therapy and behavioral intervention adjustments. Also, we observed a significant improvement of quality of life, as well as a significant reduction of anxiety and depression status. TUQ showed ease of use, good interface quality and high user satisfaction of the proposed solution. The 3-month follow-up showed total adherence of prescribed therapy and no stroke/TIA recurrence or other emergency department admissions. Conclusion: The proposed e-Health solution and telemonitoring protocol may be highly useful for early post-acute remote patient management, thus supporting constant monitoring and patient adherence to the treatment pathway, especially during the COVID-19 emergency.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) is rapidly spreading worldwide, and the WHO declared its pandemic nature on 11th March 20201. The outbreak has hit Europe and, as of April 19, 2020, Italy has the third largest number of confirmed cases, namely a total of 175,925 cases and 23,227 deaths according to the John Hopkins University 2. This is the largest health and economic emergency of our country since the post‐war period, and many hospitals are now dedicated exclusively to COVID‐19 assistance. Our University Hub Stroke Unit of Cattinara Hospital is in the northeaster Italian region of Friuli Venezia Giulia which enlisted 2,731 cases and 222 deaths at the time of writing3.

Objective: Advanced neuroimaging has proved to be pivotal in the management of acute ischemic stroke. The use of CT perfusion (CTP) core and penumbra parameters to predict the outcome in wake-up stroke (WUS) patients in everyday clinical scenarios has not yet been investigated. The aim of our study was to investigate the predictive power of CTP parameters on functional and morphological outcomes in WUS patients treated with recombinant tissue plasminogen activator (rTPA). Approach: We analyzed clinical data and processed CTP images of 83 consecutive WUS patients treated with rTPA. The predictive power of whole-brain CTP features and of the clinical stroke-related parameters to predict the National Institutes of Health Stroke Scale (NIHSS) score at the seventh day and ischemic lesion volume outcome was investigated by means of multivariate regression analysis as well as least absolute shrinkage and selection operator (LASSO) modeling. Main results: Multivariate analysis showed that CTP core volume (β = 0.403, p = 0.000), NIHSS at admission (β = 0.323, p = 0.005) and Alberta Stroke Program Early CT (ASPECT) score (β = -0.224, p = 0.012) predict NIHSS at 7 days, while total hypoperfused volume (β = 0.542, p = 0.000) and core volume on CTP (β =0.441, p = 0.000) predict infarct lesion volume at follow-up CT. The LASSO modeling approach confirmed the significant predictive power of CTP core volume, total hypoperfused CTP volume, NIHSS at baseline and ASPECT score, producing a sparse model with adequate reliability (the root mean square error on a previously unseen testing dataset was 3.68). Significance: Our findings highlight the importance of CT multimodal imaging features for decision-making and prediction in the hyperacute phase of WUS. The predictive model supports the hypothesis that an irreversible necrotic core rather than the extent of the penumbra is the main prognostic factor in WUS patients treated with rTPA.

Background and purpose: Diagnosis of posterior circulation stroke may be challenged. National Institutes of Health Stroke Scale (NIHSS) and brain imaging (non-contrast brain computed tomography-CT) are used for diagnosis; evaluation on posterior circulation stroke remains a limit of NIHSS, and the value of non-contrast CT (NCCT) is limited due to artifacts caused by the bones of the base of the skull. We tested the validity and prognostic value of posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) in patients with posterior circulation stroke. Methods: Pc-ASPECTS allots the posterior circulation 10 points. We studied 50 patients with posterior circulation stroke. We applied pc-ASPECTS to NCCT, CT angiography, and CT Perfusion. We evaluated the correlation of pc-ASPECT with outcome parameters for stroke. Results: Out of 50 patients, CTP showed abnormalities in 34 cases. The pc-ASPECT score calculated on brain CT and on the brain CT + angio CT had a sensibility of 24%, calculated on brain CT, angio CT and CTPerfusion gain a sensibility of 72%. Pc-ASPECT MTT resulted to be the more reliable parameter: outcome given by NIHSS score at discharge, mRS at discharge, and at 3 months was more severe in patients with Pc-ASPECT MTT alteration. Outcome given by NIHSS score at discharge and mRS at discharge and 1 at 3 months was more severe in patients with higher NIHSS score at admission. Conclusion: We evaluated the usefulness of pc-ASPECTS on CTP in predicting functional outcome in acute posterior circulation stroke that appears to be a powerful marker for predicting functional outcome.

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The pathological deposition of the transactive response DNA-binding protein of 43 kDa occurs in the majority (∼97%) of amyotrophic lateral sclerosis and in around 45% of frontotemporal lobar degeneration cases. Amyotrophic lateral sclerosis and frontotemporal lobar degeneration clinically overlap, presenting a continuum of phenotypes. Both amyotrophic lateral sclerosis and frontotemporal lobar degeneration lack treatments capable of interfering with the underlying pathological process and early detection of transactive response DNA-binding protein of 43 kDa pathology would facilitate the development of disease-modifying drugs. The real-time quaking-induced conversion reaction showed the ability to detect prions in several peripheral tissues of patients with different forms of prion and prion-like diseases. Despite transactive response DNA-binding protein of 43 kDa displays prion-like properties, to date the real-time quaking-induced conversion reaction technology has not yet been adapted to this protein. The aim of this study was to adapt the real-time quaking-induced conversion reaction technique for the transactive response DNA-binding protein of 43 kDa substrate and to exploit the intrinsic ability of this technology to amplify minute amount of mis-folded proteins for the detection of pathological transactive response DNA-binding protein of 43 kDa species in the cerebrospinal fluid of amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients. We first optimized the technique with synthetic transactive response DNA-binding protein of 43 kDa–pre-formed aggregates and with autopsy-verified brain homogenate samples and subsequently analysed CSF samples from amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients and controls. Transactive response DNA-binding protein of 43 kDa real-time quaking-induced conversion reaction was able to detect as little as 15 pg of transactive response DNA-binding protein of 43 kDa aggregates, discriminating between a cohort of patients affected by amyotrophic lateral sclerosis and frontotemporal lobar degeneration and age-matched controls with a total sensitivity of 94% and a specificity of 85%. Our data give a proof-of-concept that transactive response DNA-binding protein of 43 kDa is a suitable substrate for the real-time quaking-induced conversion reaction. Transactive response DNA-binding protein of 43 kDa real-time quaking-induced conversion reaction could be an innovative and useful tool for diagnosis and drug development in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. The cerebrospinal fluid detection of transactive response DNA-binding protein of 43 kDa pathological aggregates may be exploited as a disease biomarker for amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients., We adapted the RT-QuIC (real-time quaking-induced conversion reaction) technology to the TDP-43 substrate. TDP-43 RT-QuIC detected as little as 15 pg of TDP-43 synthetic aggregates and reached 94% of sensitivity and 85% of specificity in the analysis of CSF from amyotrophic lateral sclerosis and frontotemporal lobar degeneration patients and age-matched controls., Graphical Abstract Graphical Abstract

Neuroimaging is crucial for stroke diagnosis and to establish the feasibility of reperfusion therapy, but is not practical for the assessment of continuous evolution of brain ischemia. Electroencephalography (EEG) in the early phase of brain ischemia could be a feasible instrument of functional monitoring. In this context, it would be of great research and clinical interest to assess the relation between EEG parameters and the hypoperfused volume measured by Computed Tomography Perfusion (CTP), as possible real-time surrogate parameters for extent of brain ischemia. This preliminary study aimed at investigating the relation between stroke-related EEG changes, measured on bedside with wireless EEG device, and the extent of hypoperfused volume assessed on CTP during the hyper-acute phase. We studied 12 consecutive ischemic stroke patients who underwent CTP assessment and EEG recording with wireless device within 4.5 hours from symptom onset. Total hypoperfused volume correlated significantly with the delta/alpha power ratio (ρ=0.72; p

Hypohydration has been suggested increasing the risk of vascular diseases, and it is associated with poor prognosis and worse functional outcome in stroke. Most studies have used blood parameters to determine patients’ hydration status. The aim of this study was to measure urine osmolality (uOsm) and its influence on stroke severity and independence. A prospective descriptive study was conducted in stroke patients admitted to a stroke unit. All patients underwent neurological evaluation at admission and discharge using the National Institute of Health Stroke Scale (NIHSS). Independence at discharge was evaluated with the Barthel Index (BI) and the modified Rankin Scale (mRS). uOsm was measured at admission. Patients were grouped in “poor fluid intake” (PF) and “euhydration” (EU), the latter if uOsm ≤ 500 mOsm/kg. Among 119 included patients, the prevalence of PF was 52%, with no difference observed between groups in demographics or blood samples analyses. PF had higher chances of NIHSS > 8 at admission (OR: 4.7 95% CI: 1.3–17.0; p = 0.02), lower BI at discharge (β: −15.3 95% CI: −26.7 to −3.8; p = 0.01), and worse mRS at discharge (OR: 4.01 95% CI: 1.2–14.0; p = 0.02). These findings are consistent with previous results, suggesting that uOsm may be a factor significantly associated with stroke severity and independence outcome after acute ischemic stroke.

Background The COVID-19 pandemics required several changes in stroke management and it may have influenced some clinical or functional characteristics. We aimed to evaluate the effects of the COVID-19 pandemics on stroke management during the first month of Italy lockdown. In addition, we described the emergency structured pathway adopted by an Italian University Hub Stroke Unit in the cross-border Italy-Slovenia area. Methods We analyzed admitted patients' clinical features and outcomes between 9th March 2020 and 9th April 2020 (first month of lockdown), and compared them with patients admitted during the same period in 2019. Results Total admissions experienced a reduction of 45% during the lockdown compared to the same period in 2019 (16 vs 29, respectively), as well as a higher prevalence of severe stroke (NIHSS>10) at admission (n = 8, 50% vs n = 8, 28%). A dramatic prevalence of stroke of unknown symptom onset was observed in 2020 (n = 8, 50% vs n = 3, 10%). During lockdown, worse functional and independence outcomes were found, despite the similar proportion of reperfused patients. Similar ‘symptoms alert-to-admission’ and ‘door-to-treatment’ times were observed. During lockdown hospitalization was shorter and fewer patients completed the stroke work-up. Conclusion In conclusion, the adopted strategies for stroke management during the COVID-19 emergency have suggested being effective, while suffering a reduced and delayed reporting of symptoms. Therefore, we recommend raising awareness among the population against possible stroke symptoms onset. Thus, think F.A.S.T. and do not stay-at-home at all costs.

Introduction: Recombinant tissue plasminogen activator (rt-PA) is the first-line therapy demonstrated to be safe and effective in acute ischemic stroke. People with pre-existing severe dementia or physical disability are usually excluded from rt-PA. The aim of our study was to investigate rt-PA safety and effectiveness in acute stroke with pre-existing disability (mRS ≥ 2). Methods: The study encompassed 35 acute ischemic stroke patients with mRS ≥ 2 treated with rt-PA. In order to assess the differences in clinical outcome in three disability groups (mRS = 2; 3; 4/5), the following parameters were evaluated: intracerebral hemorrhage, mortality, NIHSS, ΔNIHSS and mRS. Results: Baseline-NIHSS and age were not significantly different among groups. Mortality was higher in the pre-morbid mRS 4/5 group (44%) than in the pre-morbid mRS 2 (16.7%) and mRS 3 groups (21.4%). In survived patients, median ΔNIHSS% was higher in the mRS 2 and 3 groups (-63.3% and −92.3%, respectively) than in the mRS 4/5 group (−9.1%). The 247 rt-PA treated subjects with mRS < 2 in the same period showed lower mortality rate (4.7%), lower sICH (5%), lower mRS at discharge (median 1; range 0–6) and similar ΔNIHSS% (−75%). Conclusion: Patients with mRS 2 and 3 may benefit from rt-PA with a moderate risk of sICH and mortality.

Backgrounds: Wake-Up Stroke (WUS) patients are generally excluded from thrombolytic therapy (rTPA) due to the unknown time of stroke onset. This study aimed to investigate the effects of rTPA in WUS patients during every day clinical scenarios, by measuring ischemic lesion volume and functional outcomes compared to non-treated WUS patients. Methods: We retrospectively analyzed clinical and imaging data of 149 (75 rTPA; 74 non-rTPA) patients with acute ischemic WUS. Ischemic volume was calculated on follow-up CT and functional outcomes were the NIHSS and mRS comparing rTPA and non-rTPA WUS. Patients were selected using ASPECTS > 6 on CT and/or ischemic penumbra > 50% of hypoperfused tissue on CTP. Results: A reduced volume was measured on the follow-up CT for rTPA (1 mL, 0-8) compared to the non-rTPA patients (10 mL, 0-40; p = 0.000). NIHSS at 7 days from admission was significantly lower in the rTPA (1, 0-4) compared to non-rTPA group (3, 1-9; p = 0.015), as was the percentage of improvement (ΔNIHSS) (70% vs 50%; p = 0.002). A higher prevalence of mRS 0-2 was observed in the rTPA compared to the non-rTPA (54% vs 39%; p = 0.060). Multivariate analysis showed that NIHSS at baseline and rTPA treatment are significant predictors of good outcome both in terms of NIHSS at 7 days and ischemic lesion volume on follow-up CT (p < 0.05). Conclusions: rTPA in WUS patients selected with CT and/or CTP resulted in reduced ischemic infarct volume on follow-up CT and better functional outcome without increment of intracranial hemorrhages and in-hospital mortality.

COVID-19 pandemics required a reorganisation of social spaces to prevent the spread of the virus. Due to the common presence of fever in the symptomatic patients, temperature measurement is one of the most common screening protocols. Indeed, regulations in many countries require temperature measurements before entering shops, workplaces, and public buildings. Due to the necessity of providing rapid non-contact and non-invasive protocols to measure body temperature, infra-red thermometry is mostly used. Many countries are now facing the need to organise the return to school and universities in the COVID-19 era, which require solutions to prevent the risk of contagion between students and/or teachers and technical/administrative staff. This paper highlights and discusses some of the strengths and limitations of infra-red cameras, including the site of measurements and the influence of the environment, and recommends to be careful to consider such measurements as a single "safety rule" for a good return to normality.

Proper hydration and nutrition have been found to be contributing factors to a better recovery in patients after stroke. A better knowledge of factors influencing fluid and energy intake may contribute to a better care of the acute stroke patient. Aim of this study was to describe hydration status, fluid intake, and energy intake of stroke patients during acute hospitalization in a stroke unit. A retrospective descriptive study was conducted in stroke patients admitted to a stroke unit. All patients received neurological evaluation and urinary osmolality (uOsm) measure at admission and discharge. During stroke unit stay patients received a day-by-day diary to record data about beverages, food, and therapy. Water and energy content were then reported based on a national nutritional database. Ninety-five patients were included in the analysis. uOsm did not differ between patients with or without dysphagia, with uOsm > 500 mosm/kg in 58.1% at admission and 57.8% at discharge. Inadequate fluid intake was found in 41.2% of the sample with no difference between groups. Insufficient energy intake was found in 95.6% of the sample, with no patients with dysphagia reaching the minimum suggested amount. Our results suggest that a relevant proportion of stroke patients with and without dysphagia may not improve their hydration status during the first days after admission. Diet and therapy were insufficient to achieve recommended fluid intake and energy intake in a large proportion of patients, suggesting a more careful monitoring of hydration and nutrition needs.

Background Parkinson's disease (PD) patients who are treated with dopamine replacement therapy are at risk of developing impulse control disorders (ICDs) (such as gambling, binge eating, and others). According to recent evidence, compulsive reward seeking in ICDs may arise from an excessive attribution of incentive salience (or ‘wanting’) to rewards. Objectives In this study, we tested this hypothesis in patients with PD who developed binge eating (BE). Methods Patients with BE, patients without BE, and healthy controls performed different experimental tasks assessing food liking and wanting. Participants first rated the degree of liking and wanting for different foods using explicit self-report measures. They then performed an affective priming task that measured participants' affective reactions towards foods (liking), and a grip-force task that assessed their motivation for food rewards (wanting). All participants also completed several questionnaires assessing impulsivity, reward sensitivity, anxiety and depression, and underwent a neuropsychological evaluation. Results Patients with BE displayed an altered liking for sweet foods compared to controls but not to patients without BE. Furthermore, this difference emerged only when implicit measures were used. Importantly, an increased wanting was not associated with binge eating even if wanting, but not liking scores significantly correlated with LED levodopa, confirming the hypothesis of a distinction between the two components of rewards. Lastly, binge eating was associated with depression and lower working memory scores. Conclusions Take together these results suggest that binge eating in PD is associated with cognitive abnormalities, and to lesser extent affective abnormalities, but not with an increased incentive salience.

Background Aphasia is one of the most devastating stroke-related consequences for social interaction and daily activities. Aphasia recovery in acute stroke depends on the degree of reperfusion after thrombolysis or thrombectomy. As aphasia assessment tests are often time-consuming for patients with acute stroke, physicians have been developing rapid and simple tests. The aim of our study is to evaluate the improvement of language functions in the earliest stage in patients treated with thrombolysis and in nontreated patients using our rapid screening test. Materials and Methods Our study is a single-center prospective observational study conducted at the Stroke Unit of the University Medical Hospital of Trieste (January-December 2016). Patients treated with thrombolysis and nontreated patients underwent 3 aphasia assessments through our rapid screening test (at baseline, 24 hours, and 72 hours). The screening test assesses spontaneous speech, oral comprehension of words, reading aloud and comprehension of written words, oral comprehension of sentences, naming, repetition of words and a sentence, and writing words. Results The study included 40 patients: 18 patients treated with thrombolysis and 22 nontreated patients. Both groups improved over time. Among all language parameters, spontaneous speech was statistically significant between 24 and 72 hours (P value = .012), and between baseline and 72 hours (P value = .017). Conclusions Our study demonstrates that patients treated with thrombolysis experience greater improvement in language than the nontreated patients. The difference between the 2 groups is increasingly evident over time. Moreover, spontaneous speech is the parameter marked by the greatest improvement.