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Purpose: We present two patients who developed neurogenic stuttering after long COVID-19 related to SARS-CoV-2 infection. Methods and Results: Both patients experienced both physical (e.g., fatigue) and cognitive difficulties, which led to impaired function of attention, lexical retrieval, and memory consolidation. Both patients had new-onset stuttering-like speech dysfluencies: Blocks and repetitions were especially evident at the initial part of words and sentences, sometimes accompanied by effortful and associated movements (e.g., facial grimaces and oro-facial movements). Neuropsychological evaluations confirmed the presence of difficulties in cognitive tasks, while neurophysiological evaluations (i.e., electroencephalography) suggested the presence of “slowed” patterns of brain activity. Neurogenic stuttering and cognitive difficulties were evident for 4–5 months after negativization of SARS-CoV-2 nasopharyngeal swab, with gradual improvement and near-to-complete recovery. Conclusions: It is now evident that SARS-CoV-2 infection may significantly involve the central nervous system, also resulting in severe and long-term consequences, even if the precise mechanisms are still unknown. In the present report, long COVID-19 resulted in neurogenic stuttering, as the likely consequence of a “slowed” metabolism of (pre)frontal and sensorimotor brain regions (as suggested by the present and previous clinical evidence). As a consequence, the pathophysiological mechanisms related to the appearance of neurogenic stuttering have been hypothesized, which help to better understand the broader and possible neurological consequences of COVID-19.

Background and purpose: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. Methods: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. Results: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. Conclusions: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

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.

Background and objectives: Status epilepticus (SE) is a time-dependent neurological emergency. The current study evaluated the prognostic value of admission neutrophil-to-lymphocyte ratio (NLR) in patients with status epilepticus. Methods: In this retrospective observational cohort study we included all consecutive patients discharged from our neurology unit with the clinical or EEG diagnosis of SE from 2012 to 2022. Stepwise multivariate analysis was conducted to test the association of NLR with length of hospitalization, need for Intensive Care Unit (ICU) admission and 30 days mortality. Receiver operating characteristic (ROC) analysis was performed to identify the best cutoff for NLR to identify patients who will need ICU admission. Results: A total of 116 patients were enrolled in our study. NLR was correlated with length of hospitalization (p = 0.020) and need for ICU admission ( p = 0.046). In addition, the risk of ICU admission increased in patients with intracranial hemorrhage and length of hospitalization was correlated with C-reactive protein-to-albumin ratio (CRP/ALB). ROC analysis identified a NLR of 3.6 as best cutoff value to discriminate need of ICU admission (area under the curve [AUC]=0.678; p = 0.011; Youden's index=0.358; sensitivity, 90.5%, specificity, 45.3%). Discussion: In patients with SE admission NLR could be a predictor of length of hospitalization and need for ICU admission.

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.

Objective Among the clinical manifestations of stroke mimics, isolated aphasia is one of the most challenging due to its aetiopathogenic diagnosis. This short communication describes a specific perfusion and brain oscillatory pattern in a challenging case of prolonged isolated aphasia caused by status epilepticus, jointly investigated by computed tomography (CT) perfusion, single-photon emission computerized tomography (SPECT)/CT and EEG qualitative and quantitative analysis. Methods We discuss the different patterns of perfusion neuroimaging and EEG between SE and ischaemic stroke or postictal (Todd's)-related isolated aphasia, and propose these differences as a basis to support the differential diagnosis. Results The pattern associated with SE was characterized by focal hyperperfusion on CT perfusion maps (the left mean transit time was shorter with10% asymmetry, and left cerebral blood volume and cerebral blood flow increased or slightly altered, relative to the contralateral side) and SPECT (focal left temporal hyperperfusion), without any early ischaemic signs on non-enhanced CT, while the EEG showed a predominant left hemispheric slow delta power. The aforementioned perfusion pattern contrasts with postictal epileptic Todd's phenomenon, which is characterized by hypoperfusion on CT perfusion (the mean transit time is prolonged and cerebral blood volume and cerebral blood flow are reduced, compared to the contralateral hemisphere) and SPECT (focal hypoperfusion), not restricted to the specific vascular territories. Significance CT perfusion patterns may add valuable information to support the differential diagnosis of status epilepticus, rather than acute ischaemic stroke or postictal Todd's phenomenon, in cases with challenging symptoms of prolonged isolated aphasia.

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.

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.

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.

"Long-COVID" is a clinical entity that consists of persisting post-infectious symptoms that last for more than three months after the onset of the first acute COVID-19 symptoms. Among these, a cluster of neurological persisting symptoms defines Neuro-Long-COVID. While the debate about the pathogenesis of Long-COVID is still ongoing, sex differences have been individuated for both the acute and the chronic stage of the infection. We conducted a retrospective study describing sex differences in a large sample of patients with Neuro-Long-COVID. Demographic and clinical data were collected in a specifically designed Neuro-Long-Covid outpatient service. Our sample included 213 patients: 151 were females and 62 were males; the mean age was similar between females (53 y, standard deviation 14) and males (55 y, standard deviation 15); no significant differences was present between the demographic features across the two groups. Despite the prevalence of the specific chronic symptoms between male and females showed no significant differences, the total number of females accessing our service was higher than that of males, confirming the higher prevalence of Neuro-Long-COVID in female individuals. Conversely, a worse acute phase response in males rather than females was confirmed by a significant difference in the rates of acute respiratory symptoms (p = 0.008), dyspnea (p = 0.018), respiratory failure (p = 0.010) and the consequent need for ventilation (p = 0.015), together with other acute symptoms such as palpitations (p = 0.049), headache (p = 0.001) and joint pain (p = 0.049). Taken together, these findings offer a subgroup analysis based on sex-dependent characteristics, which can support a tailored-medicine approach.

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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.

Background: Migrainous aura (MA) represents the third most common stroke mimic (SM). Advanced neuroimaging is pivotal in the assessment of patients with focal neurological acute symptoms. We investigated brain perfusion alterations in MA-SM patients using a novel CT perfusion (CTP)-based quantitative approach in order to improve differential diagnosis between MA and acute stroke. Methods: We processed and analysed the clinical and neuroimaging CTP data, acquired within 4.5 h from symptom onset, of patients with acute focal neurological symptoms receiving a final diagnosis of MA. The differences between ROI, compatible with MA symptoms, and contralateral side were automatically estimated in terms of asymmetry index (AI%) by the newly developed tool for mean transit time (MTT), CBF, and cerebral blood volume (CBV) CTP parameters. The AI% ≥ 10% was considered significant. Results: Out of 923 admitted patients, 14 patients with MA were included. In 13 out of 14 cases, a significant pattern of hypoperfusion was observed by quantitative analysis in at least one of the CTP maps. In 7 patients, all three CTP maps were significantly altered. In particular, MTT-AI% increased in 11 (79%) cases, while CBF-AI% and CBV-AI% decreased in 12 (86%) and in 9 (64%) patients, respectively. All CBV values were above ischemic stroke core threshold and all MTT-AI were below ischemic penumbra threshold. Conclusions: Our data suggest that a novel CTP-quantitative approach may detect during MA a moderate hypoperfusion pattern in the cerebral regions compatible with aura symptoms. The use of this novel tool could support differential diagnosis between MA and acute stroke.

Background:Advanced neuroimaging can identify patients who can most benefit from reperfusion treatment, discriminating between ischemic core and penumbra area in a quick and accurate manner. Despite core-penumbra mismatch being an independent prognostic factor, computed tomography perfusion (CTP) assessment is still debated in hyperacute decision-making. The authors aimed to study a novel CTP mismatch score in emergency settings and to investigate its relation with clinical outcome in acute ischemic stroke patients treated with intravenous thrombolysis (IVT).Methods:Neuroimaging and clinical data of 226 consecutive acute ischemic stroke patients were analyzed. The study population was divided into 5 different CTP scores: (0) without perfusion deficit, (1) only penumbra, (2) penumbra > core, (3) core >= penumbra, (4) only core. For differences in outcome between treated and nontreated patients, and among CTP core-penumbra groups to be assessed, the authors have evaluated the outcome in terms of National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) at discharge and symptomatic intracerebral hemorrhage.Results:A decrease in NIHSS was statistically greater in IVT-treated patients compared to nontreated patients showing only penumbra (Delta NIHSS%: 80.0% vs. 50.0%; P=0.0023) or no perfusion deficit (Delta NIHSS%: 89.4% vs. 61.5%; P=0.027) on CTP maps. The same trend was found in other groups without significant difference. A significant correlation was found in IVT patients between core/penumbra score and outcome in terms of Delta NIHSS (Kendall tau=-0.19; P=0.004).Conclusions:The authors proposed a novel immediate CTP assessment to score perfusion mismatch in emergency settings to guide clinicians' decision-making for aggressive treatment and to prevent stroke-related disability.

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.

Changes in physiological functions after spaceflight and simulated spaceflight involve several mechanisms. Microgravity is one of them and it can be partially reproduced with models, such as head down bed rest (HDBR). Yet, only a few studies have investigated in detail the complexity of neurophysiological systems and their integration to maintain homeostasis. Central nervous system changes have been studied both in their structural and functional component with advanced techniques, such as functional magnetic resonance (fMRI), showing the main involvement of the cerebellum, cortical sensorimotor, and somatosensory areas, as well as vestibular-related pathways. Analysis of electroencephalography (EEG) led to contrasting results, mainly due to the different factors affecting brain activity. The study of corticospinal excitability may enable a deeper understanding of countermeasures' effect, since greater excitability has been shown being correlated with better preservation of functions. Less is known about somatosensory evoked potentials and peripheral nerve function, yet they may be involved in a homeostatic mechanism fundamental to thermoregulation. Extending the knowledge of such alterations during simulated microgravity may be useful not only for space exploration, but for its application in clinical conditions and for life on Earth, as well.

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.

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: The worldwide lockdown in response to COVID-19 pandemics has often led to physical inactivity and social distancing. When combined, these factors may affect quality and life and increase the risk of different diseases. Therefore, assessment of physical activity levels should be encouraged to monitor and identify those at a higher risk of inactivity. Smart technology is a promising tool to assess physical activity and health, and may be particularly useful during a period of general lockdown. METHODS: An online survey was developed and shared among the Italian general population to collect data about physical activity and daily routine changes between January 2020 and the lockdown period from 23rd to 29th of March. Participants were asked to provide data such as daily step count (Steps) or heart rate (HR) measured and collected by their smart technology devices. RESULTS: Four hundred participants were included in the final analysis. During the lockdown, the number of steps dropped from 8,284±4,390 to 3,294±3,994 steps (p< 0.001), while mean peak HR decreased from 61.3±18.2% to 55.9±17.3% (p< 0.001). CONCLUSIONS: These findings provide objective data about the effects of the COVID-19 lockdown on physical activity, thus encouraging the use of smart devices to monitor and promote healthy lifestyles while faced with a confinement condition.

Hypohydration may be associated with vascular diseases, poor prognosis and worse outcomes in stroke. The underlying mechanisms have not yet been completely investigated, although some studies suggested potential associations with brain perfusion and collaterals status. Despite the potentially different mechanisms promoting serum or urine biomarkers of hypohydration, few studies have investigated both markers separately. A prospective descriptive study was conducted in stroke patients admitted to a stroke unit 15 and “underhydrated” (UND) if urine osmolality was >500 mOsm/kg. CTP images were processed to calculate core, penumbra, their mismatch and total hypoperfused volume. Forty-six patients were included and were grouped according to hydration status. Despite no different NIHSS at baseline, at CTP HYP was independently associated with core-penumbra mismatch (β: −0.157, 95% CI: −0.305 to −0.009; p =.04), while UND was independently associated with the total hypoperfused volume (β: 31.502, 95% CI: 8.522‒54.481; p =.01). Using CTP imaging, this study proposes a physiological insight of some possible mechanisms associated with the better outcomes observed in acute stroke patients when properly hydrated. These results suggest different associations between hydration status and CTP parameters depending on serum or urine biomarkers in the hyper-acute phase and encourage the association between hydration status and stroke characteristics.

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.

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

Prognosis in Wake-up ischemic stroke (WUS) is important for guiding treatment and rehabilitation strategies, in order to improve recovery and minimize disability. For this reason, there is growing interest on models to predict functional recovery after acute ischemic events in order to personalize the therapeutic intervention and improve the final functional outcome. The aim of this preliminary study is to evaluate the possibility to predict a good functional outcome, in terms of modified Rankin Scale (mRS ≤ 2), in thrombolysis treated WUS patients by Bayesian analysis of clinical, demographic and neuroimaging data at admission. The study was conducted on 54 thrombolysis treated WUS patients. The Variational Bayesian logistic regression with Automatic Relevance Determination (VB-ARD) was used to produce model and select informative features to predict a good functional outcome (mRS ≤ 2) at discharge. The produced model showed moderately high 10 × 5-fold cross validation accuracy of 71% to predict outcome. The sparse model highlighted the relevance of NIHSS at admission, age, TACI stroke syndrome, ASPECTs, ischemic core CT Perfusion volume, hypertension and diabetes mellitus. In conclusion, in this preliminary study we assess the possibility to model the prognosis in thrombolysis treated WUS patients by using VB ARD. The identified features related to initial neurological deficit, history of diabetes and hypertension, together with necrotic tissue relate ASPECT and CTP core volume neuroimaging features, were able to predict outcome with moderately high accuracy.

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.

Purpose Crossed cerebellar diaschisis (CCD) is a common finding in hyper-acute ischemic stroke, related to supratentorial dysfunction of the contralateral hemisphere. Several studies investigated a possible relationship between CCD and clinical outcomes but still no evidence emerged. We proposed a novel quantitative whole cerebellum analysis using CT perfusion (CTP) imaging to investigate the relationship between CCD and stroke severity, hypoperfused volume and outcome measures. Methods 55 patients with supratentorial ischemic stroke who underwent CTP evaluation within 4.5 h since symptom onset were enrolled. CCD was evaluated by CTP image-processing and by calculating the mean transit time (MTT)-map asymmetry index in the whole cerebellum. MTT asymmetry correlation with ischemic volume and clinical outcomes was investigated. Results MTT asymmetry was found in most of the included patients and significantly correlated with NIH Stroke Scale (NIHSS) score at baseline and CTP ischemic volume. MTT asymmetry was significantly correlated with hemorrhagic transformation, NIHSS and modified Rankin Scale (mRS) score on discharge in treated patients. Conclusions CCD was detectable by CTP in acute supratentorial ischemic stroke by processing the whole cerebellum volume. CCD perfusion asymmetry was significantly correlated with neurological and perfusion deficit on admission as well as with clinical outcomes in treated patients.

Early post-stroke prognosis is important for guiding treatment and rehabilitation strategies in order to improve recovery and minimize disability. Several demographic, clinical and neuroimaging factors were associated with functional outcome. Early prediction of post-stroke outcome is still challenging since there is large inter-subject variability. Thus, biomarkers that can add prognostic information are still needed. This pilot study aimed to investigate the correlation between early stroke-related EEG changes, measured on bedside with wireless EEG device and short-term functional outcome, measured with 7-day National Institutes of Health Stroke Scale (NIHSS), in thrombolysis treated ischemic stroke patients. Delta/alpha power ratio (ρ=0.67, p=0.031) and relative delta power (ρ=0.66, p=0.037) correlated directly with 7-day NIHSS, while relative alpha power (ρ =-0.69, p=0.028) correlated inversely with 7-day NIHSS. In conclusion, in this preliminary study we assessed the correlation between EEG spectral parameters obtained in the pre-treatment hyper-acute phase and short-term functional outcome. These preliminary results highlight the value of hyper-acute EEG as a possible complementary tool in the evaluation of stroke severity and its potential role in the prediction of stroke-related outcome.

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.