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Phantom Limb Syndrome (PLS) can be defined as the disabling or painful sensation of the presence of a body part that is no longer present after its amputation. Anatomical changes involved in Phantom Limb Syndrome, occurring at peripheral, spinal and brain levels and include the formation of neuromas and scars, dorsal horn sensitization and plasticity, short-term and long-term modifications at molecular and topographical levels. The molecular reorganization processes of Phantom Limb Syndrome include NMDA receptors hyperactivation in the dorsal horn of the spinal column leading to inflammatory mechanisms both at a peripheral and central level. At the brain level, a central role has been recognized for sodium channels, BDNF and adenosine triphosphate receptors. In the paper we discuss current available pharmacological options with a final overview on non-pharmacological options in the pipeline. [ABSTRACT FROM AUTHOR]

• This article traces the development of ECT from its origin until today. • The advent of rTMS in the neuropsychiatric field is described. • ECT and rTMS play a complementary role in treatment of neuropsychiatric disorders. Electroconvulsive therapy (ECT) was applied for the first time in humans in 1938: after 80 years, it remains conceptually similar today except for modifications of the original protocol aimed to reduce adverse effects (as persistent memory deficits) without losing clinical efficacy. We illustrate the stages of development as well as ups and downs of ECT use in the last eighty years, and the impact that it still maintains for treatment of certain psychiatric conditions. Targeted, individualized and safe noninvasive neuromodulatory interventions are now possible for many neuropsychiatric disorders thanks to repetitive transcranial magnetic stimulation (rTMS) that injects currents in the brain through electromagnetic induction, powerful enough to depolarize cortical neurons and related networks. Although ECT and rTMS differ in basic concepts, mechanisms, tolerability, side effects and acceptability, and beyond their conceptual remoteness (ECT) or proximity (rTMS) to "precision medicine" approaches, the two brain stimulation techniques may be considered as complementary rather than competing in the current treatment of certain neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Objective: We investigated for the first time the presence of chronic changes in the functional organization of sensorimotor brain areas induced by prolonged training with a bidirectional hand prosthesis. Methods: A multimodal neurophysiological and neuroimaging evaluation of brain functional changes occurring during training in five consecutive amputees participating to experimental trials with robotic hands over a period of 10 years was carried out. In particular, modifications to the functional anatomy of sensorimotor brain areas under resting conditions were explored in order to check for eventual changes with respect to baseline. Results: Full evidence is provided to demonstrate brain functional changes, and some of them in both the hemispheres and others restricted to the hemisphere contralateral to the amputation/prosthetic hand. Conclusions: The study describes a unique experimental experience showing that brain reactions to the prolonged use of an artificial hand can be tracked for a tailored approach to a fully embedded artificial upper limb for future chronic uses in daily activities. [ABSTRACT FROM AUTHOR]

Objective The aim of the paper is to objectively demonstrate that amputees implanted with intraneural interfaces are truly able to feel a sensation in the phantom hand by recording “phantom” somatosensory evoked potentials from the corresponding brain areas. Methods We implanted four transverse intrafascicular multichannel electrodes, available with percutaneous connections to a multichannel electrical stimulator, in the median and ulnar nerves of two left trans-radial amputees. Two channels of the implants that were able to elicit sensations during intraneural nerve stimulation were chosen, in both patients, for recording somatosensory evoked potentials. Results We recorded reproducible evoked responses by stimulating the median and the ulnar nerves in both cases. Latencies were in accordance with the arrival of somatosensory information to the primary somatosensory cortex. Conclusion Our results provide evidence that sensations generated by intraneural stimulation are truly perceived by amputees and located in the phantom hand. Moreover, our results strongly suggest that sensations perceived in different parts of the phantom hand result in different evoked responses. Significance Somatosensory evoked potentials obtained by selective intraneural electrical stimulation in amputee patients are a useful tool to provide an objective demonstration of somatosensory feedback in new generation bidirectional prostheses. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a non-invasive technique able to modulate cortical excitability in a polarity-dependent way. At present, only few studies investigated the effects of tDCS on the modulation of functional connectivity between remote cortical areas. The aim of this study was to investigate—through graph theory analysis—how bipolar tDCS modulate cortical networks high-density EEG recordings were acquired before and after bipolar cathodal, anodal and sham tDCS involving the primary motor and pre-motor cortices of the dominant hemispherein 14 healthy subjects. Results showed that, after bipolar anodal tDCS stimulation, brain networks presented a less evident “small world” organization with a global tendency to be more random in its functional connections with respect to prestimulus condition in both hemispheres. Results suggest that tDCS globally modulates the cortical connectivity of the brain, modifying the underlying functional organization of the stimulated networks, which might be related to changes in synaptic efficiency of the motor network and related brain areas. This study demonstrated that graph analysis approach to EEG recordings is able to intercept changes in cortical functions mediated by bipolar anodal tDCS mainly involving the dominant M1 and related motor areas. Concluding, tDCS could be an useful technique to help understanding brain rhythms and their topographic functional organization and specificity. [ABSTRACT FROM AUTHOR]

The goal of this review is to show how transcranial magnetic stimulation (TMS) techniques can make a contribution to the study of brain networks. Brain networks are fundamental in understanding how the brain operates. Effects on remote areas can be directly observed or identified after a period of stimulation, and each section of this review will discuss one method. EEG analyzed following TMS is called TMS-evoked potentials (TEPs). A conditioning TMS can influence the effect of a test TMS given over the motor cortex. A disynaptic connection can be tested also by assessing the effect of a pre-conditioning stimulus on the conditioning-test pair. Basal ganglia-cortical relationships can be assessed using electrodes placed in the process of deep brain stimulation therapy. Cerebellar-cortical relationships can be determined using TMS over the cerebellum. Remote effects of TMS on the brain can be found as well using neuroimaging, including both positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The methods complement each other since they give different views of brain networks, and it is often valuable to use more than one technique to achieve converging evidence. The final product of this type of work is to show how information is processed and transmitted in the brain. [ABSTRACT FROM AUTHOR]

In a recent study, analyzing the modulation of γ-band oscillations, Naro and colleagues demonstrated that transcranial alternating current stimulation could drive the gamma rhythms in the human EEG in cognitive healthy elderly subjects but not in mild cognitive impairment (MCI) prodromal to Alzheimer's disease (AD) and in early AD patients. Therefore, this method is proposed to intercept early in the disease course those MCI subjects who are in a pre-symptomatic stage of an already established AD. This prediction index may help the clinician to adopt a better prevention/follow-up strategy. In this direction, the novel advances in EEG analysis for the evaluation of brain reactivity and connectivity-namely via innovative mathematical approach, i.e., graph theory-represent a promising tool for a non-invasive and easy-to-perform neurophysiological marker that could be used for the pre-symptomatic diagnosis of AD and to predict MCI progression to dementia. [ABSTRACT FROM AUTHOR]

Head CT scan showed no obvious new-onset ischemic lesions and the CT angiography showed no signs of major vessel occlusion. The emergency CT scan was negative for ischemic/hemorrhagic events, and the CT angiography showed no signs of major vessel occlusion. The pulmonary interstitial disease, seen with the CT scan, and the pachymeningitis, seen with the MRI, were linked to the RA, and a targeted treatment was started. [Extracted from the article]

Background: Automated pupillometry (AP) is a handheld, non-invasive tool that is able to assess pupillary light reflex dynamics and is useful for the detection of intracranial hypertension. Limited evidence is available on acute ischemic stroke (AIS) patients. The primary objective was to evaluate the ability of AP to discriminate AIS patients from healthy subjects (HS). Secondly, we aimed to compute a predictive score for AIS diagnosis based on clinical, demographic, and AP variables. Methods: We included 200 consecutive patients admitted to a comprehensive stroke center who underwent AP assessment through NPi-200 (NeurOptics®) within 72 h of stroke onset and 200 HS. The mean values of AP parameters and the absolute differences between the AP parameters of the two eyes were considered in the analyses. Predictors of stroke diagnosis were identified through univariate and multivariate logistic regressions; we then computed a nomogram based on each variable's β coefficient. Finally, we developed a web app capable of displaying the probability of stroke diagnosis based on the predictive algorithm. Results: A high percentage of pupil constriction (CH, p < 0.001), a low constriction velocity (CV, p = 0.002), and high differences between these two parameters (p = 0.036 and p = 0.004, respectively) were independent predictors of AIS. The highest contribution in the predictive score was provided by CH, the Neurological Pupil Index, CV, and CV absolute difference, disclosing the important role of AP in the discrimination of stroke patients. Conclusions: The results of our study suggest that AP parameters, and in particular, those concerning pupillary constriction, may be useful for the early diagnosis of AIS. [ABSTRACT FROM AUTHOR]

Background and purpose: Post‐stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS). Methods: We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months. Results: None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs. Conclusion: Post‐stroke movement disorders are not uncommon in long‐term follow‐up of successfully reperfused AIS. Follow‐up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke. Methods: This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019. Results: The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min, p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13, p = 0.033), a non-significant increase of thrombectomy (15 vs 9, p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min, p = 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted. Conclusions: Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances. [ABSTRACT FROM AUTHOR]

The amputation of a hand (as of any other body part) is followed by a cascade of plastic changes on the motor and somatosensory pathways; such changes are probably contributing to the Phantom limb syndrome, a distressing situation affecting the vast majority of amputees. Although many effort, a clear explanation of the phantom syndrome is still missing and it could be considered the result of multiple contributing mechanisms acting both at peripheral and central nervous system. The typical feature of cortical plastic reorganization following limb amputations is the invasion of the “deafferented” cortex by neighbouring areas in both the primary somatosensory and the motor cortices. The degree of cortical reorganization was directly related to the magnitude of pain: the greater the remapping, the more severe the pain. On the other side, some novel evidences indicate the persistence of a certain degree of functionality of the somatosensory and motor cortices corresponding to the amputated part and recent evidences showed a correlation between the amount of functional persistence and phantom limb pain, more persistence causing more phantom limb pain. Moreover, it was recently suggested a link between this hypotheses and the aberrant peripheral activity characterized by ectopic evoked and spontaneous nerve activity. Almost all previously cited evidences are the results of non-longitudinal studies, where one or more groups of patients are analysed in a resting situation. Very few information are reported in literature explaining how plastic changes evolve during the use of prosthesis and this is particularly true considering new prototypes of bidirectional neurally hand prosthesis. These implanted neural interfaces for the peripheral nervous system have shown a remarkable potential as tools to restore the bidirectional communication between the hand prosthesis and the nerves in the residuum. In the frame of European founded projects we assessed neuroplastic changes of brain sensorimotor organization (through the assessment of cortical SEPs, MEPs, EEG source analysis, connectivity analysis and fMRI) following the use of a robotic hand during trainings of different durations (4–24 weeks) in four human amputees, providing new advancements in the understanding of the complex phenomena of phantom limb syndrome. [ABSTRACT FROM AUTHOR]

Background: There is a growing body of evidence suggesting a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF). The primary objective of this study is to evaluate the association between OSA and AF in acute ischemic stroke. The secondary objective is to describe the clinical features of patients with acute ischemic stroke and concomitant OSA. Methods: We enrolled consecutive patients with acute ischemic stroke. All patients underwent full-night cardiorespiratory polygraphy. To determine if there is an association between AF and OSA, we compared the observed frequency of this association with the expected frequency from a random co-occurrence of the two conditions. Subsequently, patients with and without OSA were compared. Results: A total of 174 patients were enrolled (mean age 67.3 ± 11.6 years; 95 males). OSA and AF were present in 89 and 55 patients, respectively. The association OSA + AF was observed in 33/174 cases, which was not statistically different compared to the expected co-occurrence of the two conditions. Patients with OSA showed a higher neck circumference and body mass index, a higher prevalence of hypertension and dysphagia, and a higher number of central apneas/hypoapneas. In the multivariate analysis, dysphagia and hypertension were independent predictors of OSA. A positive correlation was observed between OSA severity, BMI, and neck circumference. The number of central apneas/hypoapneas was positively correlated with stroke severity. Conclusions: Our data suggest that OSA and AF are highly prevalent but not associated in acute stroke. Our findings support the hypothesis that OSA acts as an independent risk factor for stroke. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether and how COVID-19 vaccination may affect the outcome of patients with acute ischemic stroke (AIS). We investigated this potential association in a retrospective study by comparing previously vaccinated (VAX) versus unvaccinated (NoVAX) stroke patients. Methods: We collected clinical reports for all consecutive AIS patients admitted to our hospital and evaluated the outcome predictors in VAX and NoVAX groups. Adjustments were made for possible confounders in multivariable logistic regression analysis, and adjusted hazard ratios were calculated. Results: A total of 466 AIS patients (287 VAX and 179 NoVAX) were included in this study. The NIHSS score at discharge and mRS score at a 3-month follow-up visit were significantly lower in VAX patients compared to NoVAX patients (p < 0.001). Good outcomes (mRS 0–2) were significantly associated with COVID-19 vaccination before AIS (adjusted hazard ratio, 0.400 [95% CI = 0.216–0.741]). Conclusions: The observation that COVID-19 vaccination can influence the outcome of AIS provides support for further studies investigating the role of immunity in ischemic brain damage. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 outbreak highly impacted the acute ischemic stroke care management. The primary end point of the study was to evaluate the impact of the COVID-19 outbreak and the following lockdown measures on our hub-and-spoke network; the secondary end point was to evaluate if the impact of the COVID-19 outbreak was different in hub-and-spoke centers. Methods: This was a retrospective multicenter observational study conducted at the Stroke Units of Policlinico Gemelli, Ospedale San Filippo Neri, Ospedale di Belcolle, and Ospedale San Camillo de Lellis. We collected clinical reports of all consecutive patients admitted with diagnosis of acute ischemic stroke or transient ischemic attack (TIA) during the phase 1 of the lockdown period (11 March 2020–4 May 2020). As controls, we used all consecutive patients admitted for acute ischemic stroke or TIA in the same period of the previous year. Results: A total of 156 and 142 clinical reports were collected in 2019 and 2020, respectively. During the COVID-19 outbreak, we observed a reduction of number of thrombolysis, a reduction of the length of hospitalization, and an increase of pneumonia. Regarding performance indicators, we observed an increase in onset-to-door time and in door-to-groin time. We did not observe any statistically significant interaction between year (2019 vs 2020) and facility of admission (hub vs spoke) on all variables analyzed. Discussion: Our observational study, involving hub-and-spoke stroke network of a wide regional area, indicates that the COVID-19 outbreak impacted on the acute stroke management. This impact was equally observed in hub as well as in spoke centers. [ABSTRACT FROM AUTHOR]

Humans rely on their sense of touch to interact with the environment. Thus, restoring lost tactile sensory capabilities in amputees would advance their quality of life. In particular, texture discrimination is an important component for the interaction with the environment, but its restoration in amputees has been so far limited to simplified gratings. Here we show that naturalistic textures can be discriminated by trans-radial amputees using intraneural peripheral stimulation and tactile sensors located close to the outer layer of the artificial skin. These sensors exploit the morphological neural computation (MNC) approach, i.e., the embodiment of neural computational functions into the physical structure of the device, encoding normal and shear stress to guarantee a faithful neural temporal representation of stimulus spatial structure. Two trans-radial amputees successfully discriminated naturalistic textures via the MNC-based tactile feedback. The results also allowed to shed light on the relevance of spike temporal encoding in the mechanisms used to discriminate naturalistic textures. Our findings pave the way to the development of more natural bionic limbs. [ABSTRACT FROM AUTHOR]

• The brain operates in networks and clinical neurophysiology can assess these networks. • Methods include EEG, MEG, and functional MRI. • Neurological and psychiatric disorders cause a breakdown in brain networks. This manuscript is the second part of a two-part description of the current status of understanding of the network function of the brain in health and disease. We start with the concept that brain function can be understood only by understanding its networks, how and why information flows in the brain. The first manuscript dealt with methods for network analysis, and the current manuscript focuses on the use of these methods to understand a wide variety of neurological and psychiatric disorders. Disorders considered are neurodegenerative disorders, such as Alzheimer disease and amyotrophic lateral sclerosis, stroke, movement disorders, including essential tremor, Parkinson disease, dystonia and apraxia, epilepsy, psychiatric disorders such as schizophrenia, and phantom limb pain. This state-of-the-art review makes clear the value of networks and brain models for understanding symptoms and signs of disease and can serve as a foundation for further work. [ABSTRACT FROM AUTHOR]

Cerebral post-stroke plasticity has been repeatedly investigated via functional neuroimaging techniques mainly based on blood flow/metabolism. However, little is known on predictive value of topological properties of widely distributed neural networks immediately following stroke on rehabilitation outcome and post-stroke recovery measured by early functional outcome. The utility of EEG network parameters (i.e. small world organization) analysis as a potential rough and simple biomarker for stroke outcome has been little explored and needs more validation. A total of 139 consecutive patients within a post-stroke acute stage underwent EEG recording. A group of 110 age paired healthy subjects constituted the control group. All patients were clinically evaluated with 3 scales for stroke: NIHSS, Barthel and ARAT. As a first result, NIHSS, Barthel and ARAT correlated with Small World index as provided by the proportional increment/decrement of low (delta) and viceversa of high (beta2 and gamma) EEG frequency bands. Furthermore, in line with the aim of the present study, we found a strong correlation between NIHSS at follow up and gamma Small World index in the acute post-stroke period, giving SW index a significant weight of recovery prediction. This study aimed to investigate possible correlations between functional abnormalities of brain networks, measured by small world characteristics detected in resting state EEG source investigation, and early post-stroke clinical outcome in order to find a possible predictive index of functional recovery to address and/or correct the rehabilitation program. • NIHSS, Barthel and ARAT correlated with Small World index. • Strong correlation between NIHSS at follow up and gamma Small World in acute period • SW index has a significant weight of recovery prediction. [ABSTRACT FROM AUTHOR]

Levodopa-induced dyskinesias (LIDs) are a common complication in patients with Parkinson's disease (PD). A complex cascade of electrophysiological and molecular events that induce aberrant plasticity in the cortico-basal ganglia system plays a key role in the pathophysiology of LIDs. In the striatum, multiple neurotransmitters regulate the different forms of physiological synaptic plasticity to provide it in a bidirectional and Hebbian manner. In PD, impairment of both long-term potentiation (LTP) and long-term depression (LTD) progresses with disease and dopaminergic denervation of striatum. The altered balance between LTP and LTD processes leads to unidirectional changes in plasticity that cause network dysregulation and the development of involuntary movements. These alterations have been documented, in both experimental models and PD patients, not only in deep brain structures but also at motor cortex. Invasive and non-invasive neuromodulation treatments, as deep brain stimulation, transcranial magnetic stimulation, or transcranial direct current stimulation, may provide strategies to modulate the aberrant plasticity in the cortico-basal ganglia network of patients affected by LIDs, thus restoring normal neurophysiological functioning and treating dyskinesias. In this review, we discuss the evidence for neuroplasticity impairment in experimental PD models and in patients affected by LIDs, and potential neuromodulation strategies that may modulate aberrant plasticity. • Aberrant neuroplasticity plays a key role in the pathophysiology of dyskinesias. • Plasticity changes occur both in basal ganglia and motor cortex of PD patients. • Neuromodulation strategies may modulate aberrant plasticity and treat dyskinesias. [ABSTRACT FROM AUTHOR]

Objective: Hand amputation is a highly disabling event, which significantly affects quality of life. An effective hand replacement can be achieved if the user, in addition to motor functions, is provided with the sensations that are naturally perceived while grasping and moving. Intraneural peripheral electrodes have shown promising results toward the restoration of the sense of touch. However, the long-term usability and clinical relevance of intraneural sensory feedback have not yet been clearly demonstrated.Methods: To this aim, we performed a 6-month clinical study with 3 transradial amputees who received implants of transverse intrafascicular multichannel electrodes (TIMEs) in their median and ulnar nerves. After calibration, electrical stimulation was delivered through the TIMEs connected to artificial sensors in the digits of a prosthesis to generate sensory feedback, which was then used by the subjects while performing different grasping tasks.Results: All subjects, notwithstanding their important clinical differences, reported stimulation-induced sensations from the phantom hand for the whole duration of the trial. They also successfully integrated the sensory feedback into their motor control strategies while performing experimental tests simulating tasks of real life (with and without the support of vision). Finally, they reported a decrement of their phantom limb pain and a general improvement in mood state.Interpretation: The promising results achieved with all subjects show the feasibility of the use of intraneural stimulation in clinical settings. ANN NEUROL 2019;85:137-154. [ABSTRACT FROM AUTHOR]

In recent years, several studies have reported a relatively high frequency of polyneuropathy in patients with Parkinson's disease (PD), in particular, in patients receiving levodopa-carbidopa intestinal gel (LCIG) infusion. In spite of the several patients investigated with nerve conduction studies, no study has prospectively explored a possible central nervous system involvement of patients receiving LCIG infusion. We prospectively evaluated eight PD patients receiving LCIG infusion, who underwent neurophysiological evaluations with nerve conduction studies, visual, somatosensory and motor evoked potentials before LCIG infusion, and 1 and 6 months after. At 6 months follow-up, we found significant reduction in sural nerve SNAP amplitude, increase of central sensory conduction time N22-P40, and increases of central motor conduction time recorded from I dorsal interosseous and tibialis anterior. In PD patients with LCIG infusion, we found a subclinical neurophysiological impairment of both peripheral and central nervous system. [ABSTRACT FROM AUTHOR]

Abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare, high grade extranodal B-cell lymphoma, characterized by the proliferation of tumoral cells in the lumen of small vessels of several organs without the tendency for tumor formation in other areas usually affected by lymphomas, such as lymph nodes, bone marrow, or peripheral blood. Diagnosis is generally delayed by variable presentation with non-specific constitutional and neurological symptoms, lack of reliable ancillary tests and it is often obtained only at autopsy. We report a case of IVLBCL presenting with a slowly progressing isolated paraparesis without any evidence of spinal damage at MRI though neurophysiological examinations showed signs of spinal cord injury. Laboratory findings showed markedly elevated levels of lactate dehydrogenase, low albumin values, raised ESR, mild thrombocytopenia and progressive impairment of hepatic function. Bone marrow examinations and total body CT scans were negative. Although clinical history appeared too long, we considered the hypothesis of IVLBCL on the basis of the laboratory constellation and proposed a liver biopsy, but the patient refused the procedure. The diagnosis was confirmed only at autopsy. Our case should make us aware that the disease has to be considered in the differential diagnosis of unexplained paraparesis associated with elevated level of lactate dehydrogenase and only relatively non-specific laboratory findings even without any spinal cord abnormalities at MRI. [Copyright &y& Elsevier]

New direct oral anticoagulants are recommended for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). However, no data are available regarding the optimal time to start oral anticoagulation after acute stroke. The aim of our study was to evaluate the occurrence of symptomatic bleedings within 90 days from acute cardioembolic stroke in patients who received early treatment with Edoxaban. The study was conducted according to an observational prospective uncontrolled design. Secondary endpoints were the incidence of major bleeding (MB), hemorrhagic transformation within the first week of Edoxaban treatment, minor bleeding, and recurrent stroke. We included patients with Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≥ 6, NVAF, no previous treatment with any other anticoagulant, preserved swallowing function. Patients with estimated Glomerular Filtration Rate < 50 mL/min, body weight < 60 kg, receiving cyclosporine, dronedarone, erythromycin, ketoconazole, or previous treatment with any other anticoagulant were excluded. We enrolled 75 elderly patients with moderate disability. We did not observe any symptomatic intracranial bleeding or recurrent stroke after 3 months of treatment with early administration of Edoxaban, while two gastrointestinal MB, and 11 minor bleedings were reported. Asymptomatic bleeding was evaluated with a brain Magnetic Resonance Imaging performed 5 days after starting anticoagulant treatment with Edoxaban. Specifically, we observed small petechiae in 12% of the patients, confluent petechiae in 6.6% of the patients, and small hematoma of the infarcted area in 2.7% of the patients. No intralesional hematoma or hemorrhagic lesion outside the infarcted area were observed. According to our data, the early use of Edoxaban seems to be safe in patients after cardioembolic stroke. However, due to the small size of the study sample, and the short follow-up period, further studies are needed. [ABSTRACT FROM AUTHOR]

Although thrombectomy is beneficial for most stroke patients with large vessel occlusion (LVO), it has added new issues in acute management due to intensive care support. In this prospective cohort study, we described the patients admitted to our neuro-intensive care unit (NICU) after thrombectomy in order to assess factors linked to functional outcomes. The outcome was independency assessed for stroke patients consecutively admitted to NICU for an ischemic stroke due to LVO of the anterior cerebral circulation that underwent intra-arterial mechanical thrombectomy (IAMT), either in combination with intravenous thrombolysis (IVT) in eligible patients or alone in patients with contraindications for IVT. Overall, 158 patients were enrolled. IVT (odds ratio (OR), 3.78; 95% confidence interval (CI), 1.20–11.90; p = 0.023) and early naso-gastric tube removal (OR, 3.32; 95% CI, 1.04–10.59 p = 0.042) were associated with good outcomes, whereas a high baseline National Institutes of Health Stroke Scale (NIHSS) score (OR, 0.72 for each point of increase; 95% CI, 0.61–0.85; p < 0.001) was a predictor of poor outcomes at 3 months. Older age (OR, 0.95 for each year of increase; 95% CI, 0.92–0.99; p = 0.020) and hemorrhagic transformation (OR, 0.31; 95% CI, 0.11–0.84; p = 0.022) were predictors of poor outcomes after IAMT, whereas a modified Treatment in Cerebral Infarction (mTICI) score of 2b/3 was a predictor of good outcomes (OR, 7.86; 95% CI, 1.65–37.39; p = 0.010) at 6 months. Our results show that acute stroke patients with LVO who require NICU management soon after IAMT may show specific clinical factors influencing short- and long-term neurologic independency. [ABSTRACT FROM AUTHOR]

Abstract: Background context: Cervical spondylotic myelopathy (CSM) is a common disorder, but its management and the role of surgery are still a matter of controversy. The assessment of surgical outcome is complicated by the lack of reliable and objective methods to assess the severity of the myelopathy and its evolution. Motor-evoked potentials (MEPs) are a useful and reliable tool to measure noninvasively the involvement of the corticospinal tract in patients with CSM. Recent evidence suggests that MEPs could also have a role in monitoring the effect of surgical therapy. Purpose: The aim of the present study is to use MEPs for the functional assessment of spinal cord before and after surgery and to correlate changes in MEPs with clinical findings. Study design/setting: This is a retrospective cohort study. Patient sample: Thirty-eight patients affected by CSM who underwent surgical intervention. Outcome measures: We used the 18-point modified Japanese Orthopedic Association (mJOA) score for clinical evaluation and the central motor conduction time (CMCT) for the study of MEPs. Methods: All patients were evaluated both clinically and neurophysiologically before (7–15 days) and after (6–12 months) surgery. MEPs were recorded from the biceps, abductor digiti minimi, and tibialis anterior muscles bilaterally. Results: After surgery, the 18-point mJOA score increased significantly from 10.1 to 15.1, and the value of CMCT for tibialis anterior muscles showed a slight but significant reduction, more evident in patients with mild to moderate symptoms. Conclusions: Early surgical intervention for CSM could produce a beneficial effect on spinal cord functionality that can be detected by MEPs. [Copyright &y& Elsevier]

Prognosis of patients with acute ischemic stroke is strictly related to the patency and prominence of the collateral leptomeningeal pathways distal to the arterial occlusion. The gold standard for assessment of collateral circulation is conventional angiography, but it is invasive and used in selected cases. To date, the most reliable technique is multiphase CTA; currently, the available classifications of collateral circles are often complex, time-consuming, and require a trained observer. The purpose of our work is to establish the effectiveness of a new semi-automatic post-processing software (ColorViz FastStroke, GE Healthcare, Milwaukee, Wisconsin) in evaluation of collateral circulation compared to the six-point classifications of multiphase CTA already validated in literature. We selected 86 patients with anterior ischemic stroke symptoms who underwent multiphasic CTA in our emergency department. Two radiologists separately evaluated the collateral leptomeningeal vessels, analyzing respectively, the multiphase CTA (using the six-point scale and its trichotomized form) and ColorViz (using a three-point scale). Then the results were matched. We found a good correlation between the two different analyses; the main advantage of ColorViz is that, while maintaining fast diagnostic times, it allows a simpler and more immediate evaluation of collateral circulation, especially for less experienced radiologists. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown that neural stimulation can be used to provide artificial sensory feedback to amputees eliciting sensations referred on the amputated hand. The temporal properties of the neural stimulation modulate aspects of evoked sensations that can be exploited in a bidirectional hand prosthesis.Methods: We previously collected evidence that the derivative of the amplitude of the stimulation (intra-digit temporal dynamics) allows subjects to recognize object compliance and that the time delay among stimuli injected through electrodes implanted in different nerves (inter-digit temporal distance) allows to recognize object shapes. Nevertheless, a detailed characterization of the subjects' sensitivity to variations of intra-digit temporal dynamic and inter-digit temporal distance of the intraneural tactile feedback has not been executed. An exhaustive understanding of the overall potentials and limits of intraneural stimulation to deliver sensory feedback is of paramount importance to bring this approach closer and closer to the natural situation. To this aim, here we asked two trans-radial amputees to identify stimuli with different temporal characteristics delivered to the same active site (intra-digit temporal Dynamic Recognition (DR)) or between two active sites (inter-digit Temporal distance Recognition (TR)). Finally, we compared the results achieved for (simulated) TR with conceptually similar experiments with real objects with one subject.Results: We found that the subjects were able to identify stimuli with temporal differences (perceptual thresholds) larger than 0.25 s for DR and larger than 0.125 s for TR, respectively. Moreover, we also found no statistically significant differences when the subjects were asked to identify three objects during simulated 'open-loop' TR experiments or real 'closed-loop' tests while controlling robotic hand.Conclusions: This study is a new step towards a more detailed analysis of the overall potentials and limits of intraneural sensory feedback. A full characterization is necessary to develop more advanced prostheses capable of restoring all lost functions and of being perceived more as a natural limb by users. [ABSTRACT FROM AUTHOR]

Neurodegenerative processes of various types of dementia start years before symptoms, but the presence of a "neural reserve", which continuously feeds and supports neuroplastic mechanisms, helps the aging brain to preserve most of its functions within the "normality" frame. Mild cognitive impairment (MCI) is an intermediate stage between dementia and normal brain aging. About 50% of MCI subjects are already in a stage that is prodromal-to-dementia and during the following 3 to 5 years will develop clinically evident symptoms, while the other 50% remains at MCI or returns to normal. If the risk factors favoring degenerative mechanisms are modified during early stages (i.e., in the prodromal), the degenerative process and the loss of abilities in daily living activities will be delayed. It is therefore extremely important to have biomarkers able to identify—in association with neuropsychological tests—prodromal-to-dementia MCI subjects as early as possible. MCI is a large (i.e., several million in EU) and substantially healthy population; therefore, biomarkers should be financially affordable, largely available and non-invasive, but still accurate in their diagnostic prediction. Neurodegeneration initially affects synaptic transmission and brain connectivity; methods exploring them would represent a 1st line screening. Neurophysiological techniques able to evaluate mechanisms of synaptic function and brain connectivity are attracting general interest and are described here. Results are quite encouraging and suggest that by the application of artificial intelligence (i.e., learning-machine), neurophysiological techniques represent valid biomarkers for screening campaigns of the MCI population. [ABSTRACT FROM AUTHOR]