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In 2011, a discrepancy between the values of the Planck constant measured by counting Si atoms and by comparing mechanical and electrical powers prompted a review, among others, of the measurement of the spacing of 28Si {220} lattice planes, either to confirm the measured value and its uncertainty or to identify errors. This exercise confirmed the result of the previous measurement and yields the additional value d220 = 192 014 711.98(34) am having a reduced uncertainty. [ABSTRACT FROM AUTHOR]

Abstract: Background: Over 795 000 US people per year experience a stroke, and 10% are younger than 50 years. After a stroke, posttraumatic stress disorder (PTSD) affects 10% to 30% of those patients and may compromise a survivor's secondary prevention compliance. At an inner-city clinic in Maryland where up to 300 young adult stroke survivors are followed, zero patients were screened for PTSD. A quality improvement project was implemented to screen for PTSD in a young adult stroke survivor clinic and to provide them with psychotherapy referrals and follow-up. Methods: Over 15 weeks in the fall of 2023, all patients presenting to the young adult stroke survivor clinic were screened for PTSD using the Posttraumatic Stress Disorder Checklist-5 validated screening tool. Providers and medical staff were all educated on the tool before implementation. Results: During the 15-week implementation period, 72 patients presented to the clinic. Posttraumatic stress disorder screening was completed for 88.9% (64/72). Of those, 32.8% (21/64) completed the Posttraumatic Stress Disorder Checklist-5 via the electronic health record, and 67.2% (43/64) completed it by in-person screening. Of the 64 patients screened, 12 patients screened positive for PTSD (18.8%, 12/64). Among those screening positive, 75% (9/12) were given a referral for psychotherapy. Conclusions: Literature reports that PTSD compromises stroke survivors' ability to optimize their health after a stroke. Screening identifies those experiencing symptoms of PTSD, providing an opportunity for referral and treatment. Results show that routine care of young stroke survivors can effectively include screening for PTSD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 American Association of Neuroscience Nurses.)

Objective: Locomotion is an automated voluntary movement sustained by coordinated neural synchronization across a distributed brain network. The cerebral cortex is central for adapting the locomotion pattern to the environment and alterations of cortical network dynamics can lead to gait impairments. Gait problems are a common symptom with a still unclear pathophysiology and represent an unmet therapeutical need in Parkinson's disease. Little is known about the cortical network dynamics of locomotor control in these patients., Methods: We studied the cortical basis of parkinsonian gait by combining metabolic brain imaging with high-density EEG recordings and kinematic measurements performed at rest and during unperturbed overground walking., Results: We found significant changes in functional connectivity between frontal, sensorimotor, and visuomotor cortical areas during walking as compared to resting. Specifically, hypokinetic gait was associated with poor information flow from the supplementary motor area (SMA) to precuneus and from calcarine to lingual gyrus, as well as high information flow from calcarine to cuneus., Interpretation: Our findings support a role for visuomotor integration processes in PD-related hypokinetic gait and suggest that reinforcing visual information may act as a compensatory strategy to allow SMA-mediated feedforward locomotor control in PD., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Conventional DBS (cDBS) for Parkinson's disease uses constant, predefined stimulation parameters, while the currently available adaptive DBS (aDBS) provides the possibility of adjusting current amplitude with respect to subthalamic activity in the beta band (13-30 Hz). This preliminary study on one patient aims to describe how these two stimulation modes affect basal ganglia dynamics and, thus, behavior in the long term. We collected clinical data (UPDRS-III and -IV) and subthalamic recordings of one patient with Parkinson's disease treated for one year with aDBS, alternated with short intervals of cDBS. Moreover, after nine months, the patient discontinued all dopaminergic drugs while keeping aDBS. Clinical benefits of aDBS were superior to those of cDBS, both with and without medications. This improvement was paralleled by larger daily fluctuations of subthalamic beta activity. Moreover, with aDBS, subthalamic beta activity decreased during asleep with respect to awake hours, while it remained stable in cDBS. These preliminary data suggest that aDBS might be more effective than cDBS in preserving the functional role of daily beta fluctuations, thus leading to superior clinical benefit. Our results open new perspectives for a restorative brain network effect of aDBS as a more physiological, bidirectional, brain-computer interface.

Gait disturbance is a common and severe symptom of Parkinson's disease that severely impairs quality of life. Current treatments provide only partial benefits with wide variability in outcomes. Also, deep brain stimulation of the subthalamic nucleus (STN-DBS), a mainstay treatment for bradykinetic-rigid symptoms and parkinsonian tremor, is poorly effective on gait. We applied a novel DBS paradigm, adjusting the current amplitude linearly with respect to subthalamic beta power (adaptive DBS), in one parkinsonian patient with gait impairment and chronically stimulated with conventional DBS. We studied the kinematics of gait and gait initiation (anticipatory postural adjustments) as well as subthalamic beta oscillations with both conventional and adaptive DBS. With adaptive DBS, the patient showed a consistent and long-lasting improvement in walking while retaining benefits on other disease-related symptoms. We suggest that adaptive DBS can benefit gait in Parkinson's disease possibly by avoiding overstimulation and dysfunctional entrainment of the supraspinal locomotor network., Competing Interests: IUI is Newronika S.p.A. consultant. IUI is Adjunct Professor at the Department of Neurology, NYU Grossman School of Medicine. IUI and LB received research fundings (paid to the Institution) by Newronika S.p.A. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Isaias, Caffi, Borellini, Ampollini, Locatelli, Pezzoli, Mazzoni and Palmisano.)

Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for granular phenotyping. Instrumented neurophysiological analyses have proven useful, but are highly resource-intensive and lack broad accessibility. In contrast, bedside scores are simple to administer, but lack the granularity to capture subtle but relevant tremor features. We utilise the open-source computer vision pose tracking algorithm Mediapipe to track hands in clinical video recordings and use the resulting time series to compute canonical tremor features. This approach is compared to marker-based 3D motion capture, wrist-worn accelerometry, clinical scoring and a second, specifically trained tremor-specific algorithm in two independent clinical cohorts. These cohorts consisted of 66 patients diagnosed with essential tremor, assessed in different task conditions and states of deep brain stimulation therapy. We find that Mediapipe-derived tremor metrics exhibit high convergent clinical validity to scores (Spearman's ρ = 0.55-0.86, p≤ .01) as well as an accuracy of up to 2.60 mm (95% CI [-3.13, 8.23]) and ≤0.21 Hz (95% CI [-0.05, 0.46]) for tremor amplitude and frequency measurements, matching gold-standard equipment. Mediapipe, but not the disease-specific algorithm, was capable of analysing videos involving complex configurational changes of the hands. Moreover, it enabled the extraction of tremor features with diagnostic and prognostic relevance, a dimension which conventional tremor scores were unable to provide. Collectively, this demonstrates that current computer vision algorithms can be transformed into an accurate and highly accessible tool for video-based tremor analysis, yielding comparable results to gold standard tremor recordings., (© 2024. The Author(s).)

Objective: Both blinking and walking are altered in Parkinson's disease and both motor outputs have been shown to be linked in healthy subjects. Additionally, studies suggest an involvement of basal ganglia activity and striatal dopamine in blink generation. We investigated the role of the basal ganglia circuitry on spontaneous blinking and if this role is dependent on movement state and striatal dopamine., Methods: We analysed subthalamic nucleus (STN) activity in seven chronically implanted patients for deep brain stimulation (DBS) with respect to blinks and movement state (resting state and unperturbed walking). Neurophysiological recordings were combined with individual molecular brain imaging assessing the dopamine reuptake transporter (DAT) density for the left and right striatum separately., Results: We found a significantly higher blink rate during walking compared to resting. The blink rate during walking positively correlated with the DAT density of the left caudate nucleus. During walking only, spontaneous blinking was followed by an increase in the right STN beta power and a bilateral subthalamic phase reset in the low frequencies. The right STN blink-related beta power modulation correlated negatively with the DAT density of the contralateral putamen. The left STN blink-related beta power correlated with the DAT density of the putamen in the less dopamine-depleted hemisphere. Both correlations were specific to the walking condition and to beta power following a blink., Conclusion: Our findings show that spontaneous blinking is related to striatal dopamine and has a frequency specific deployment in the STN. This correlation depends on the current movement state such as walking., Significance: This work indicates that subcortical activity following a motor event as well as the relationship between dopamine and motor events can be dependent on the motor state. Accordingly, disease related changes in brain activity should be assessed during natural movement., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Analysis of coupling between the phases and amplitudes of neural oscillations has gained increasing attention as an important mechanism for large-scale brain network dynamics. In Parkinson's disease (PD), preliminary evidence indicates abnormal beta-phase coupling to gamma-amplitude in different brain areas, including the subthalamic nucleus (STN). We analyzed bilateral STN local field potentials (LFPs) in eight subjects with PD chronically implanted with deep brain stimulation electrodes during upright quiet standing and unperturbed walking. Phase-amplitude coupling (PAC) was computed using the Kullback-Liebler method, based on the modulation index. Neurophysiological recordings were correlated with clinical and kinematic measurements and individual molecular brain imaging studies ([ 123 I]FP-CIT and single-photon emission computed tomography). We showed a dopamine-related increase in subthalamic beta-gamma PAC from standing to walking. Patients with poor PAC modulation and low PAC during walking spent significantly more time in the stance and double support phase of the gait cycle. Our results provide new insights into the subthalamic contribution to human gait and suggest cross-frequency coupling as a gateway mechanism to convey patient-specific information of motor control for human locomotion., (© 2024. The Author(s).)

Studies have shown that beta band activity is not tonically elevated but comprises exaggerated phasic bursts of varying durations and magnitudes, for Parkinson's disease (PD) patients. Current methods for detecting beta bursts target a single frequency peak in beta band, potentially ignoring bursts in the wider beta band. In this study, we propose a new robust framework for beta burst identification across wide frequency ranges. Chronic local field potential at-rest recordings were obtained from seven PD patients implanted with Medtronic SenSight™ deep brain stimulation (DBS) electrodes. The proposed method uses wavelet decomposition to compute the time-frequency spectrum and identifies bursts spanning multiple frequency bins by thresholding, offering an additional burst measure, ∆f, that captures the width of a burst in the frequency domain. Analysis included calculating burst duration, magnitude, and ∆f and evaluating the distribution and likelihood of bursts between the low beta (13-20 Hz) and high beta (21-35 Hz). Finally, the results of the analysis were correlated to motor impairment (MDS-UPDRS III) med off scores. We found that low beta bursts with longer durations and larger width in the frequency domain (∆f) were positively correlated, while high beta bursts with longer durations and larger ∆f were negatively correlated with motor impairment. The proposed method, finding clear differences between bursting behavior in high and low beta bands, has clearly demonstrated the importance of considering wide frequency bands for beta burst behavior with implications for closed-loop DBS paradigms., (© 2023. The Author(s).)

Background: Speech impairment is commonly reported in Parkinson's disease and is not consistently improved by available therapies - including deep brain stimulation of the subthalamic nucleus (STN-DBS), which can worsen communication performance in some patients. Improving the outcome of STN-DBS on speech is difficult due to our incomplete understanding of the contribution of the STN to fluent speaking., Objective: To assess the relationship between subthalamic neural activity and speech production and intelligibility., Methods: We investigated bilateral STN local field potentials (LFPs) in nine parkinsonian patients chronically implanted with DBS during overt reading. LFP spectral features were correlated with clinical scores and measures of speech intelligibility., Results: Overt reading was associated with increased beta-low ([1220) Hz) power in the left STN, whereas speech intelligibility correlated positively with beta-high ([2030) Hz) power in the right STN., Conclusion: We identified separate contributions from frequency and brain lateralization of the STN in the execution of an overt reading motor task and its intelligibility. This subcortical organization could be exploited for new adaptive stimulation strategies capable of identifying the occurrence of speaking behavior and facilitating its functional execution., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Low-frequency oscillatory patterns of pallidal local field potentials (LFPs) have been proposed as a physiomarker for dystonia and hold the promise for personalized adaptive deep brain stimulation. Head tremor, a low-frequency involuntary rhythmic movement typical of cervical dystonia, may cause movement artifacts in LFP signals, compromising the reliability of low-frequency oscillations as biomarkers for adaptive neurostimulation. We investigated chronic pallidal LFPs with the Percept TM PC (Medtronic PLC) device in eight subjects with dystonia (five with head tremors). We applied a multiple regression approach to pallidal LFPs in patients with head tremors using kinematic information measured with an inertial measurement unit (IMU) and an electromyographic signal (EMG). With IMU regression, we found tremor contamination in all subjects, whereas EMG regression identified it in only three out of five. IMU regression was also superior to EMG regression in removing tremor-related artifacts and resulted in a significant power reduction, especially in the theta-alpha band. Pallido-muscular coherence was affected by a head tremor and disappeared after IMU regression. Our results show that the Percept PC can record low-frequency oscillations but also reveal spectral contamination due to movement artifacts. IMU regression can identify such artifact contamination and be a suitable tool for its removal.

Gait disturbances are common manifestations of Parkinson's disease (PD), with unmet therapeutic needs. Inertial measurement units (IMUs) are capable of monitoring gait, but they lack neurophysiological information that may be crucial for studying gait disturbances in these patients. Here, we present a machine learning approach to approximate IMU angular velocity profiles and subsequently gait events using electromyographic (EMG) channels during overground walking in patients with PD. We recorded six parkinsonian patients while they walked for at least three minutes. Patient-agnostic regression models were trained on temporally embedded EMG time series of different combinations of up to five leg muscles bilaterally (i.e., tibialis anterior, soleus, gastrocnemius medialis, gastrocnemius lateralis, and vastus lateralis). Gait events could be detected with high temporal precision (median displacement of <50 ms), low numbers of missed events (<2%), and next to no false-positive event detections (<0.1%). Swing and stance phases could thus be determined with high fidelity (median F1-score of ~0.9). Interestingly, the best performance was obtained using as few as two EMG probes placed on the left and right vastus lateralis. Our results demonstrate the practical utility of the proposed EMG-based system for gait event prediction, which allows the simultaneous acquisition of an electromyographic signal to be performed. This gait analysis approach has the potential to make additional measurement devices such as IMUs and force plates less essential, thereby reducing financial and preparation overheads and discomfort factors in gait studies.

Freezing of gait (FOG) is a sudden episodic inability to produce effective stepping despite the intention to walk. It typically occurs during gait initiation (GI) or modulation and may lead to falls. We studied the anticipatory postural adjustments (imbalance, unloading, and stepping phase) at GI in 23 patients with Parkinson's disease (PD) and FOG (PDF), 20 patients with PD and no previous history of FOG (PDNF), and 23 healthy controls (HCs). Patients performed the task when off dopaminergic medications. The center of pressure (CoP) displacement and velocity during imbalance showed significant impairment in both PDNF and PDF, more prominent in the latter patients. Several measurements were specifically impaired in PDF patients, especially the CoP displacement along the anteroposterior axis during unloading. The pattern of segmental center of mass (SCoM) movements did not show differences between groups. The standing postural profile preceding GI did not correlate with outcome measurements. We have shown impaired motor programming at GI in Parkinsonian patients. The more prominent deterioration of unloading in PDF patients might suggest impaired processing and integration of somatosensory information subserving GI. The unaltered temporal movement sequencing of SCoM might indicate some compensatory cerebellar mechanisms triggering time-locked models of body mechanics in PD.

Background: The prospective DIabetes and CATaract Study II (DICAT II) was performed to characterise the risks of cataract surgery to the retinae of patients with early diabetic macular oedema (E-DMO)., Methods: DICAT II was a prospective, comparative, multicentre, observational study involving six Italian clinics. Patients were aged ≥55 years, had type 1 or 2 diabetes with spectral-domain optical coherence tomography evidence of ESASO classification Early DMO. Group 1 eyes (78 eyes, 78 patients) underwent phacoemulsification-based cataract surgery. Group 2 eyes (65 eyes, 65 patients) had E-DMO and either clear media or had undergone uncomplicated cataract surgery ≥1 year previously. Central subfield thickness (CST) and best-corrected visual acuity (BCVA) were assessed in both groups., Results: The negative impact of surgery on CST was evident after the first postoperative week; CST peaked during the first month, then rapidly decreased. CST worsening ≥10 µm was observed in 63/78 eyes (80.7%) and 29/65 eyes (44.6%) in Groups 1 and 2, respectively (p < 0.0001). CST worsening of ≥50 µm was observed in 51 eyes (65.4%) and 10 eyes (15.4%) in Groups 1 and 2, respectively (p < 0.0001). Mean CST worsening was lower in Group 2 than in Group 1 (38.6 ± 30.4 µm vs 85.5 ± 55.3 µm, p < 0.0001) with a lower BCVA loss (-2.6 ± 3.5 letters vs -8.2 ± 6.2 letters, p < 0.0001). Higher glycaemic levels and HBA1c levels were significantly associated with the risk of >50 μm CST worsening in eyes from both groups., Conclusion: Early DMO is associated with poorer outcomes after cataract surgery and requires close pre- and postoperative monitoring., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

New radioimaging techniques, exploiting the quantitative variables of imaging, permit to identify an hypothetical pathological tissue. We have applied this potential in a series of 72 adrenal incidentalomas (AIs) followed at our center, subdivided in functioning and non-functioning using laboratory findings. Each AI was studied in the preliminary non-contrast phase with a specific software (Mazda), surrounding a region of interest within each lesion. A total of 314 features were extrapolated. Mean and standard deviations of features were obtained and the difference in means between the two groups was statistically analyzed. Receiver Operating Characteristic (ROC) curves were used to identify an optimal cutoff for each variable and a prediction model was constructed via multivariate logistic regression with backward and stepwise selection. A 11-variable prediction model was constructed, and a ROC curve was used to differentiate patients with high probability of functioning AI. Using a threshold value of >-275.147, we obtained a sensitivity of 93.75% and a specificity of 100% in diagnosing functioning AI. On the basis of these results, computed tomography (CT) texture analysis appears a promising tool in the diagnostic definition of AIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Maggio, Messina, D’Arrigo, Maccagno, Lardo, Palmisano, Poggi, Monti, Matarazzo, Laghi, Pugliese and Stigliano.)

Deep brain stimulation (DBS) of the subthalamic nucleus or the globus pallidus is an established treatment for Parkinson's disease (PD) that yields a marked and lasting improvement of motor symptoms. Yet, DBS benefit on gait disturbances in PD is still debated and can be a source of dissatisfaction and poor quality of life. Gait disturbances in PD encompass a variety of clinical manifestations and rely on different pathophysiological bases. While gait disturbances arising years after DBS surgery can be related to disease progression, early impairment of gait may be secondary to treatable causes and benefits from DBS reprogramming. In this review, we tackle the issue of gait disturbances in PD patients with DBS by discussing their neurophysiological basis, providing a detailed clinical characterization, and proposing a pragmatic programming approach to support their management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pozzi, Palmisano, Reich, Capetian, Pacchetti, Volkmann and Isaias.)

Objective : Gait adaptation to environmental challenges is fundamental for independent and safe community ambulation. The possibility of precisely studying gait modulation using standardized protocols of gait analysis closely resembling everyday life scenarios is still an unmet need. Methods : We have developed a fully-immersive virtual reality (VR) environment where subjects have to adjust their walking pattern to avoid collision with a virtual agent (VA) crossing their gait trajectory. We collected kinematic data of 12 healthy young subjects walking in real world (RW) and in the VR environment, both with (VR/A+) and without (VR/A-) the VA perturbation. The VR environment closely resembled the RW scenario of the gait laboratory. To ensure standardization of the obstacle presentation the starting time speed and trajectory of the VA were defined using the kinematics of the participant as detected online during each walking trial. Results : We did not observe kinematic differences between walking in RW and VR/A-, suggesting that our VR environment per se might not induce significant changes in the locomotor pattern. When facing the VA all subjects consistently reduced stride length and velocity while increasing stride duration. Trunk inclination and mediolateral trajectory deviation also facilitated avoidance of the obstacle. Conclusions : This proof-of-concept study shows that our VR/A+ paradigm effectively induced a timely gait modulation in a standardized immersive and realistic scenario. This protocol could be a powerful research tool to study gait modulation and its derangements in relation to aging and clinical conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Palmisano, Kullmann, Hanafi, Verrecchia, Latoschik, Canessa, Fischbach and Isaias.)

Aim: To compare perioperative parameters of one-handed rotational phacoemulsification technique (one-handed phaco-roll) with each of other two techniques, "Divide et Conquer" and femtosecond laser-assisted cataract surgery (FLACS)., Methods: In this retrospective and comparative cohort study, eyes with uncomplicated cataract (nuclear density grade 2 to 3) treated routinely with one-handed phaco-roll ( n =23; Group 1) or "Divide et Conquer" ( n =23; Group 2) or FLACS ( n =23; Group 3) were enrolled. Intraoperative parameters including effective phaco-time (EPt), ultrasound time (USt), aspiration time, surgical time, phacoemulsification (phaco)-power, balanced salt solution (BSS) use, cumulative dissipated energy (CDE) were recorded and compared. Clinical outcomes including best corrected visual acuity (BCVA), corneal endothelial cell density (ECD), endothelial cell loss (ECL), central corneal thickness (CCT) and central macular thickness (CMT), were assessed and compared pre-operatively and at 1mo after surgery., Results: Aspiration and surgical time, and BSS used were lower in Group 1 ( P <0.01) than other groups. EPt, phaco-power and CDE were lower in Group 1 ( P <0.05) than Group 2 but not significantly different from Group 3. In Group 1, USt was lower ( P <0.05) than Group 2 but higher ( P <0.05) than Group 3. BCVA improved in all groups without significant difference between Group 1 and the other ones. No significant differences regarding all post-operative morphologic outcomes (ECD, ECL, CCT, CMT) were reported. No clinical complications occurred., Conclusion: One-handed phaco-roll seems to be less time-consuming than "Divide et Conquer" and FLACS and less energy-consuming than "Divide et Conquer". Furthermore, one-handed phaco-roll seems to have an equal safety profile compared to the other two techniques., (International Journal of Ophthalmology Press.)

Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Giordano, Canesi, Isalberti, Marfia, Campanella, Vincenti, Cereda, Ranghetti, Palmisano, Isaias, Benti, Marotta, Lazzari, Montemurro, Viganò, Budelli, Montelatici, Lavazza, Rivera-Ordaz and Pezzoli.)

Background: Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability., Objectives: Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity., Methods: Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination., Results: The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination., Conclusions: Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective . Technical advances in deep brain stimulation (DBS) are crucial to improve therapeutic efficacy and battery life. We report the potentialities and pitfalls of one of the first commercially available devices capable of recording brain local field potentials (LFPs) from the implanted DBS leads, chronically and during stimulation. The aim was to provide clinicians with well-grounded tips on how to maximize the capabilities of this novel device, both in everyday practice and for research purposes. Approach . We collected clinical and neurophysiological data of the first 20 patients (14 with Parkinson's disease (PD), five with dystonia, one with chronic pain) that received the Percept™ PC in our centres. We also performed tests in a saline bath to validate the recordings quality. Main results . The Percept PC reliably recorded the LFP of the implanted site, wirelessly and in real time. We recorded the most promising clinically useful biomarkers for PD and dystonia (beta and theta oscillations) with and without stimulation. Furthermore, we provide an open-source code to facilitate export and analysis of data. Critical aspects of the system are presently related to contact selection, artefact detection, data loss, and synchronization with other devices. Significance . New technologies will soon allow closed-loop neuromodulation therapies, capable of adapting stimulation based on real-time symptom-specific and task-dependent input signals. However, technical aspects need to be considered to ensure reliable recordings. The critical use by a growing number of DBS experts will alert new users about the currently observed shortcomings and inform on how to overcome them., (Creative Commons Attribution license.)

Excessive beta-band oscillations in the subthalamic nucleus are key neural features of Parkinson's disease. Yet the distinctive contributions of beta low and high bands, their dependency on striatal dopamine, and their correlates with movement kinematics are unclear. Here, we show that the movement phases of the reach-to-grasp motor task are coded by the subthalamic bursting activity in a maximally-informative beta high range. A strong, three-fold correlation linked beta high range bursts, imbalanced inter-hemispheric striatal dopaminergic tone, and impaired inter-joint movement coordination. These results provide new insight into the neural correlates of motor control in parkinsonian patients, paving the way for more informative use of beta-band features for adaptive deep brain stimulation devices.

Inflammatory bowel diseases (IBD), that includes ulcerative colitis and Crohn's disease, can affect not only the gastrointestinal tract but a wide spectrum of organs. The extra-intestinal manifestations (EIMs) are one of the most challenging aspect of IBD, playing a significant role for the lifetime care and the quality of life of patients. Ocular manifestations are the third most frequent EIMs, preceded by articular and dermatological ones. The aim of this narrative review is to describe the different types of ocular involvements, focusing on their clinical management. Uveitis and episcleritis are the most common ocular EIMs, differing for many aspects. Uveitis are unrelated with IBD activity and they even precede the onset of the intestinal disease, while episcleritis are common defined as a good mark of IBD activity. Pain is uncommon in most cases of episcleritis, while severe eye pain and photophobia are the most frequent onset of anterior uveitis. Less common but even more severe, are orbital pseudotumor or posterior segment involvement. Most of the ocular EIMs can be successfully treated with topic and oral steroids and the underlying therapy for IBD can reduce or cut out at all the recurrence of these manifestations. Symptoms are commonly not specific, in some cases being unnoticed for years leading to permanent ocular consequences. Cooperation between different specialists is crucial to avoid all the possible consequences of a non-treated EIMs, especially for ocular ones.

Background: Abnormal beta band activity in the subthalamic nucleus (STN) is known to be exaggerated in patients with Parkinson's disease, and the amplitude of such activity has been associated with akinetic rigid symptoms. New devices for deep brain stimulation (DBS) that operate by adapting the stimulation parameters generally rely on the detection of beta activity amplitude modulations in these patients. Movement-related frequency modulation of beta oscillatory activity has been poorly investigated, despite being an attractive variable for extracting information about basal ganglia activity., Objective: We studied the STN oscillatory activity associated with locomotion and proposed a new approach to extract movement related information from beta band activity., Methods: We recorded bilateral local field potential of the STN in eight parkinsonian patients implanted with DBS electrodes during upright quiet standing and unperturbed walking. Neurophysiological recordings were combined with kinematic measurements and individual molecular brain imaging studies. We then determined the information carried by the STN oscillatory activity about locomotion and we identified task-specific biomarkers., Results: We found a gait-related peak frequency modulation of the beta band of STN recordings of parkinsonian patients. This novel biomarker and the associated power modulations were highly informative to detect the walking state (with respect to standing) in each single patient., Conclusion: Frequency modulation in the human STN represents a fundamental aspect of information processing of locomotion. Our information-driven approach could significantly enrich the spectrum of Parkinson's neural markers, with input signals encoding ongoing tasks execution for an appropriate online tuning of DBS delivery., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Activa PC+S® system and the related hardware and software for programming and readout were provided under a request for application agreement by Medtronic, PLC. The companies had no impact on study design, patient selection, data analysis, or reporting of the results., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Lateral displacement and impaired cerebral autoregulation are associated with worse outcomes following acute brain injury, but their effect on long-term clinical outcomes remains unclear. We assessed the relationship between lateral displacement, disturbances to cerebral autoregulation, and clinical outcomes in acutely comatose patients., Design: Retrospective analysis of prospectively collected data., Setting: Neurocritical care unit of the Johns Hopkins Hospital., Patients: Acutely comatose patients (Glasgow Coma Score ≤ 8)., Interventions: None., Measurements and Main Results: Cerebral oximetry index, derived from near-infrared spectroscopy multimodal monitoring, was used to evaluate cerebral autoregulation. Associations between lateral brain displacement, global cerebral autoregulation, and interhemispheric cerebral autoregulation asymmetry were assessed using mixed random effects models with random intercept. Patients were grouped by functional outcome, determined by the modified Rankin Scale. Associations between outcome group, lateral displacement, and cerebral oximetry index were assessed using multivariate linear regression. Increasing lateral brain displacement was associated with worsening global cerebral autoregulation (p = 0.01 septum; p = 0.05 pineal) and cerebral autoregulation asymmetry (both p < 0.001). Maximum lateral displacement during the first 3 days of coma was significantly different between functional outcome groups at hospital discharge (p = 0.019 pineal; p = 0.008 septum), 3 months (p = 0.026; p = 0.007), 6 months (p = 0.018; p = 0.010), and 12 months (p = 0.022; p = 0.012). Global cerebral oximetry index was associated with functional outcomes at 3 months (p = 0.019) and 6 months (p = 0.013)., Conclusions: During the first 3 days of acute coma, increasing lateral brain displacement is associated with worsening global cerebral autoregulation and cerebral autoregulation asymmetry, and poor long-term clinical outcomes in acutely comatose patients. The impact of acute interventions on outcome needs to be explored.

Objective: Outcome prediction in comatose patients with acute brain injury remains challenging. Regional cerebral oxygenation (rSO2) derived from near-infrared spectroscopy (NIRS) is a surrogate for cerebral blood flow and can be used to calculate cerebral autoregulation (CA) continuously at the bedside from the derived cerebral oximetry index (COx). We hypothesized that COx derived thresholds for CA are associated with outcomes in patients with acute coma from neurological injury., Methods: A prospective cohort study was conducted in 88 acutely comatose adults with heterogenous brain injury diagnoses who were continuously monitored with COx for up to 3 consecutive days. Multivariable logistic regression was performed to investigate association between averaged COx and short (in-hospital and 3 mo) and long-term (6 mo) outcomes., Results: Six month mortality rate was 62%. Median COx in nonsurvivors at hospital discharge was 0.082 [interquartile range, IQR: 0.045 to 0.160] compared with 0.042 [IQR: -0.005 to 0.110] in survivors (P=0.012). At 6 months, median COx was 0.075 [IQR: 0.27 to 0.158] in nonsurvivors compared with 0.029 [IQR: -0.015 to 0.077] in survivors (P=0.02). In the multivariable logistic regression model adjusted for confounders, average COx ≥0.05 was associated with both in-hospital mortality (adjusted odds ratio [OR]=2.9, 95% confidence interval [CI]=1.15-7.33, P=0.02), mortality at 6 months (adjusted OR=4.4, 95% CI=1.41-13.7, P=0.01), and severe disability (modified Rankin Score ≥4) at 6 months (adjusted OR=4.4, 95% CI=1.07-17.8, P=0.04). Area under the receiver operating characteristic curve for predicting mortality and severe disability at 6 months were 0.783 and 0.825, respectively., Conclusions: Averaged COx ≥0.05 is independently associated with short and long-term mortality and long-term severe disability in acutely comatose adults with neurological injury. We propose that COx ≥0.05 represents an accurate threshold to predict long-term functional outcome in acutely comatose adults.

Purpose: To report on the prevalence of diabetes, diabetic macula oedema (DME) and retinopathy and their respective grading in a large cohort of patients undergoing cataract surgery., Methods: Data on previous diagnosis of diabetes, fasting glucose, glycated haemoglobin, presence and type of retinopathy and other maculopathy of 3657 patients over 55 years of age undergoing cataract surgery in 13 centres scattered throughout Italy were analysed., Results: A total of 20.4% of patients were known diabetics and 27.9% of diabetics showed signs of retinopathy. Haemoglobin A1C was higher than 48 mmol/L (6.5%) in 32% of diabetics and 2.4% non-diabetics. Fasting blood glucose level was higher than 120 mg/dL in 4.3% non-diabetics and 50% diabetics. Duration of diabetes did not significantly correlate with either fasting glucose or glycated haemoglobin, while higher grades of diabetic retinopathy were significantly more prevalent as duration of disease increased. DME was present in almost 40% of diabetics and 22% of patients showed non-diabetic maculopathy., Discussion: Diabetic retinopathy and DME worsen after cataract extraction thus complicating long-term prognosis and requiring expensive injective therapy. Since unknown diabetics represent 2-4% of the many million cataract candidates and even known diabetics show poor metabolic control and high rates of DME, preoperative medical testing and accurate retinopathy screening may prove both ethically necessary and cost-effective.

Pathophysiological understanding of gait and balance disorders in Parkinson's disease is insufficient and late recognition of fall risk limits efficacious follow-up to prevent or delay falls. We show a distinctive reduction of glucose metabolism in the left posterior parietal cortex, with increased metabolic activity in the cerebellum, in parkinsonian patients 6-8 months before their first fall episode. Falls in Parkinson's disease may arise from altered cortical processing of body spatial orientation, possibly predicted by abnormal cortical metabolism., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson's disease (PD). Still, the contribution of the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI [imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment., (Copyright © 2020 Palmisano, Brandt, Vissani, Pozzi, Canessa, Brumberg, Marotta, Volkmann, Mazzoni, Pezzoli, Frigo and Isaias.)

Background: The purpose of this study is to determine the prevalence of diabetes and diabetic macular edema in patients undergoing senile cataract surgery in Italy., Methods: It is a prospective, multicenter, cross-sectional study. Thirteen ophthalmic units equally distributed across the Italian territory have been involved in the study. For a period of 3 months, all subjects undergoing phacoemulsification received an Optical Coherence Tompgraphy (OCT) scan and were screened for the anamnestic presence of diabetes. In addition, five selected units collected blood samples from all their patients to measure glycated hemoglobin (HbA1c) levels and detect the presence of occult diabetes (HbA1c > 6.5%). In diabetic patients, levels of retinopathy were measured and diabetic macular edema was considered significant (clinically significant macular edema) when foveal thickness was above 30% of normal levels., Results: A total number of 3657 subjects have been screened. Among them, 20.4% were diabetics. Prevalence of diabetes was significantly higher in males (24.7%) than in females (17%). Levels of HbA1c were tested in a representative sample of 1216 consecutive subjects, and occult diabetes was diagnosed in 4.8% of cases. No significant differences were observed between age groups or different geographic areas. Among diabetic patients, diabetic macular edema of any kind was present in 27.5% (clinically significant macular edema (6.6%)). No significant differences were seen in the prevalence of diabetic macular edema between males and females or between age groups. Among the 745 diabetic patients, no signs of retinopathy were seen in 537 subjects (76.3%), while 101 patients (14.3%) had nonproliferative retinopathy, 13 (1.7%) had nontreated proliferative diabetic retinopathy, and 53 (7.5%) had laser-treated retinopathy. In the entire sample of 3657 subjects, a normal macula was present in 90.9% of cases, diabetic macular edema of any kind in 5.4%, and other maculopathies in 3.4%., Conclusion: In this large cohort study on patients undergoing cataract surgery, more than one-fourth were diabetics and more than one-fourth of these had diabetic macular edema. These high prevalences suggest the opportunity to plan an adequate preoperative assessment in all patients in order to reduce the risk of postoperative development or worsening of a sight-threatening complication such as chronic diabetic macular edema.

The initiation of gait is a highly challenging task for the balance control system, and can be used to investigate the neural control of upright posture maintenance during whole-body movement. Gait initiation is a centrally-mediated motion achieved in a principled, controlled manner, including predictive mechanisms (anticipatory postural adjustments, APA) that destabilize the antigravitary postural set of body segments for the execution of functionally-optimized stepping. Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by early impairment of balance and frequent falls. The neural correlates of postural imbalance and falls in PSP are largely unknown. We biomechanically assessed the APA at gait initiation (imbalance, unloading, and stepping phases) of 26 patients with PSP and 14 age-matched healthy controls. Fourteen of 26 enrolled patients were able to perform valid gait initiation trials. The influence of anthropometric and base-of-support measurements on the biomechanical outcome variables was assessed and removed. Biomechanical data were correlated with clinical findings and, in 11 patients, with brain metabolic abnormalities measured using positron emission tomography and 2-deoxy-2-[18F]fluoro-D-glucose. Patients with PSP showed impaired modulation of the center of pressure displacement for a proper setting of the center of mass momentum and subsequent efficient stepping. Biomechanical measurements correlated with "Limb motor" and "Gait and midline" subscores of the Progressive Supranuclear Palsy Rating Scale. Decreased regional glucose uptake in the caudate nucleus correlated with impaired APA programming. Hypometabolism of the caudate nucleus, supplementary motor area, cingulate cortex, thalamus, and midbrain was associated with specific biomechanical resultants of APA. Our findings show that postural instability at gait initiation in patients with PSP correlates with deficient APA production, and is associated with multiple and distinctive dysfunctioning of different areas of the supraspinal locomotor network. Objective biomechanical measures can help to understand fall-related pathophysiological mechanisms and to better monitor disease progression and new interventions., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigated whether comatose patients with greater duration and magnitude of clinically observed mean arterial pressure outside optimal mean arterial blood pressure have worse outcomes than those with mean arterial blood pressure closer to optimal mean arterial blood pressure calculated by bedside multimodal cerebral autoregulation monitoring using near-infrared spectroscopy., Design: Prospective observational study., Setting: Neurocritical Care Unit of the Johns Hopkins Hospital., Subjects: Acutely comatose patients secondary to brain injury., Interventions: None., Measurements and Main Results: The cerebral oximetry index was continuously monitored with near-infrared spectroscopy for up to 3 days. Optimal mean arterial blood pressure was defined as that mean arterial blood pressure at the lowest cerebral oximetry index (nadir index) for each 24-hour period of monitoring. Kaplan-Meier analysis and proportional hazard regression models were used to determine if survival at 3 months was associated with a shorter duration of mean arterial blood pressure outside optimal mean arterial blood pressure and the absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure. A total 91 comatose patients were enrolled in the study. The most common etiology was intracerebral hemorrhage. Optimal mean arterial blood pressure could be calculated in 89 patients (97%), and the median optimal mean arterial blood pressure was 89.7 mm Hg (84.6-100 mm Hg). In multivariate proportional hazard analysis, duration outside optimal mean arterial blood pressure of greater than 80% of monitoring time (adjusted hazard ratio, 2.13; 95% CI, 1.04-4.41; p = 0.04) and absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure of more than 10 mm Hg (adjusted hazard ratio, 2.44; 95% CI, 1.21-4.92; p = 0.013) were independently associated with mortality at 3 months, after adjusting for brain herniation, admission Glasgow Coma Scale, duration on vasopressors and midline shift at septum., Conclusions: Comatose neurocritically ill adults with an absolute difference between clinically observed mean arterial blood pressure and optimal mean arterial blood pressure greater than 10 mm Hg and duration outside optimal mean arterial blood pressure greater than 80% had increased mortality at 3 months. Noninvasive near-infrared spectroscopy-based bedside calculation of optimal mean arterial blood pressure is feasible and might be a promising tool for cerebral autoregulation oriented-therapy in neurocritical care patients.