Telemedicine in Parkinson's Disease: How to Ensure Patient Needs and Continuity of Care at the Time of COVID-19 Pandemic

Introduction: With the spread of the SARS-CoV2 pandemic, telemedicine has become the safest way to guarantee care continuity, especially for chronic disabling diseases requiring frequent medical consultations and therapeutic adjustments, such as Parkinson's disease (PD). The age-related prevalence of PD, combined with increased vulnerability due to age-related comorbidities, makes PD patients protection a priority. Methodology: We reviewed potentials and limitations of teleneurology in PD and suggested a specific battery of tests, including patient-reported outcomes, smartphone applications, and neurological examination through telemedicine. Conclusions: These tools can provide full neurological consultations, with the engagement of both patients and caregivers, and can support clinicians in defining whether patients need to access diagnostic and therapeutic procedures. Telemedicine will also carry a value in the future, within conventional health care, to support clinicians in decision making, enabling more efficacious follow-up, reducing burden for caregivers, and delivering neurological expertise to local realities. These advantages are very important when there is physical distance between patients and neurologists, and when patients are not recommended to attend in-person consultations

Involvement of cortico-subcortical circuits in normoacousic chronic tinnitus: A source localization EEG study

To better characterize brain circuits dysfunctions in normoacousic tinnitus sufferers. Methods: 17 normoacousic chronic, unilateral high-pitched tinnitus sufferers (6 females, 43.6 ± 9.8 y.o, disease duration 22 ± 35 months) underwent a 29-channel resting-state electroencephalography (EEG – 5 min opened-eyes, 5 min closed-eyes) and auditory oddball paradigm for event-related potentials analyses (ERPs – N1, P2 and P300). Cortical 3D distribution of current source density was computed with sLORETA. Results were compared with 17 controls (9 females, 45.7 ± 15.1 y.o). Results: Eyes opened, tinnitus sufferers had lower alpha and beta sources in the left inferior parietal lobule. Eyes closed, tinnitus sufferers had decreased alpha sources in the left inferior temporal and post-central gyri, and low gamma sources in the left middle temporal gyrus. EEG data did not correlate with tinnitus sufferers’ clinical features. Subjects with tinnitus had shorter N1 and P2 latencies. P300 did not differ between groups. sLORETA solutions showed decreased sources of these ERPs in the left inferior temporal gyrus in the tinnitus group. Conclusions: We showed cortico-thalamo-cortical involvements in normoacousic tinnitus with hyperexcitability of the left auditory cortex and inferior temporal gyrus. Significance: This might reflect processes of maladaptive cortical plasticity and memory consolidation. Further validation is needed to establish the value of this tool in customizing therapeutic approach

Action observation and motor imagery in performance of complex movements: Evidence from EEG and kinematics analysis

Motor imagery (MI) and action observation (AO) are considered effective cognitive tools for motor learning, but little work directly compared their cortical activation correlate in relation with subsequent performance. We compared AO and MI in promoting early learning of a complex four-limb, hand?foot coordination task, using electroencephalographic (EEG) and kinematic analysis. Thirty healthy subjects were randomly assigned into three groups to perform a training period in which AO watched a video of the task, MI had to imagine it, and Control (C) was involved in a distracting computation task. Subjects were then asked to actually perform the motor task with kinematic measurement of error time with respect to the correct motor performance. EEG was recorded during baseline, training and task execution, with task-related power (TRPow) calculation for sensorimotor (alpha and beta) rhythms reactive with respect to rest. During training, the AO group had a stronger alpha desynchronization than the MI and C over frontocentral and bilateral parietal areas. However, during task execution, AO group had greater beta synchronization over bilateral parietal regions than MI and C groups. This beta synchrony furthermore demonstrated the strongest association with kinematic errors, which was also significantly lower in AO than in MI. These data suggest that sensorimotor activation elicited by action observation enhanced motor learning according to motor performance, corresponding to a more efficient activation of cortical resources during task execution. Action observation may be more effective than motor imagery in promoting early learning of a new complex coordination task

Multicentre assessment of motor and sensory evoked potentials in multiple sclerosis : reliability and implications for clinical trials

Motor and sensory evoked potentials (EP) are potential candidate biomarkers for clinical trials in multiple sclerosis.; To determine test -retest reliability of motor EP (MEP) and sensory EP (SEP) and associated EP-scores in patients with multiple sclerosis.; In three centres, 16 relapsing and five progressive multiple sclerosis patients had MEPs and SEPs 1-29 days apart. Five neurophysiologists independently marked latencies by central reading. By variance component analysis, we estimated the critical difference (absolute reliability) for cross-sectional group comparison, comparison of longitudinal group changes, within-subject minimal detectable change and defined within-subject improvement.; Cortical SEP responses and cortico-muscular MEP latencies were more reliable than central conduction times. For comparison of 20 subjects per arm, cross-sectional group difference ranged from 0.7 to 3.9 ms and 1.1 to 1.7, group difference in longitudinal changes from 0.4 to 1.8 ms and 0.36 to 0.62, within-subject minimal detectable change from 1.2 to 5.8 ms and 1.2 to 2.0, within-subject improvement from 0.8 to 3.8ms and 0.8 to 1.3, for single EP modalities and EP scores, respectively.; Multicentre EP assessment with central EP reading is feasible and reliable. The critical difference is reasonably low to detect significant group changes and to define responders. The results support the concept of using EP and EP-scores as candidate response biomarkers for quantification of disease progression and for studying remyelination in multiple sclerosis

Cas9/sgRNA selective targeting of the P23H Rhodopsin mutant allele for treating retinitis pigmentosa by intravitreal AAV9.PHP.B-based delivery

P23H is the most common mutation in the RHODOPSIN (RHO) gene leading to a dominant form of retinitis pigmentosa (RP), a rod photoreceptor degeneration that invariably causes vision loss. Specific disruption of the disease P23H RHO mutant while preserving the wild-type (WT) functional allele would be an invaluable therapy for this disease. However, various technologies tested in the past failed to achieve effective changes and consequently therapeutic benefits. We validated a CRISPR/Cas9 strategy to specifi

Fifteen years of wireless sensors for balance assessment in neurological disorders

Balance impairment is a major mechanism behind falling along with environmental hazards. Under physiological conditions, ageing leads to a progressive decline in balance control per se. Moreover, various neurological disorders further increase the risk of falls by deteriorating specific nervous system functions contributing to balance. Over the last 15 years, significant advancements in technology have provided wearable solutions for balance evaluation and the management of postural instability in patients with neurological disorders. This narrative review aims to address the topic of balance and wireless sensors in several neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and other neurodegenerative and acute clinical syndromes. The review discusses the physiological and pathophysiological bases of balance in neurological disorders as well as the traditional and innovative instruments currently available for balance assessment. The technical and clinical perspectives of wearable technologies, as well as current challenges in the field of teleneurology, are also examined

Impact of treatment with dimethyl fumarate on sleep quality in patients with relapsing-remitting multiple sclerosis: A multicentre Italian wearable tracker study

BackgroundSleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression. ObjectiveTo evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis. MethodsThis was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (n=177) or beta interferon (n=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored. ResultsPatients treated with dimethyl fumarate had significant improvement in the quality of sleep as measured with the Pittsburgh Sleep Quality Index (p<0.001). At all-time points, no significant changes in Pittsburgh Sleep Quality Index score were observed in the interferon group. Total and deep sleep measured by wearable tracker decreased at week 12 with both treatments, then remained stable for the total study duration. Depression significantly improved in patients treated with dimethyl fumarate. No significant changes were observed in mobility, fatigue and quality of life. ConclusionIn patients with relapsing-remitting multiple sclerosis, the treatment with dimethyl fumarate was associated with improvements in patient-reported quality of sleep. Further randomised clinical trials are needed to confirm the benefits of long-term treatment with dimethyl fumarate

An Internet- and Kinect-Based Multiple Sclerosis Fitness Intervention Training With Pilates Exercises: Development and Usability Study

background: balance impairments are common in people with multiple sclerosis (MS), with reduced ability to maintain position and delayed responses to postural adjustments. Pilates is a popular alternative method for balance training that may reduce the rapid worsening of symptoms and the increased risk of secondary conditions (eg, depression) that are frequently associated with physical inactivity.objective: In this paper, we aimed to describe the design, development, and usability testing of MS Fitness Intervention Training (MS-FIT), a Kinect-based tool implementing Pilates exercises customized for MS. methods: MS-FIT has been developed using a user-centered design approach (design, prototype, user feedback, and analysis) to gain the target user's perspective. a team composed of 1 physical therapist, 2 game programmers, and 1 game designer developed the first version of MS-FIT that integrated the knowledge and experience of the team with MS literature findings related to pilates exercises and balance interventions based on exergames. MS-FIT, developed by using the Unity 3D (Unity Technologies) game engine software with kinect Sensor V2 for Windows, implements exercises for breathing, posture, and balance. Feedback from an Italian panel of experts in MS rehabilitation (neurologists, physiatrists, physical therapists, 1 statistician, and 1 bioengineer) and people with MS was collected to customize the tool for use in MS. The context of MS-FIT is traveling around the world to visit some of the most important cities to learn the aspects of their culture through pictures and stories. At each stay of the travel, the avatar of a Pilates teacher shows the user the exercises to be performed. Overall, 9 people with MS (n=4, 44% women; mean age 42.89, SD 11.97 years; mean disease duration 10.19, SD 9.18 years; Expanded Disability Status Scale score 3.17, SD 0.75) were involved in 3 outpatient user test sessions of 30 minutes; MS-FIT's usability was assessed through an ad hoc questionnaire (maximum value=5; higher the score, higher the usability) evaluating easiness to use, playability, enjoyment, satisfaction, and acceptance.Results: A user-centered design approach was used to develop an accessible and challenging tool for balance training. all people with MS (9/9, 100%) completed the user test sessions and answered the ad hoc questionnaire. the average score on each item ranged from 3.78 (SD 0.67) to 4.33 (SD 1.00), which indicated a high usability level. The feedback and suggestions provided by 64% (9/14) of people with MS and 36% (5/14) of therapists involved in the user test were implemented to refine the first prototype to release MS-FIT 2.0. Conclusions: The participants reported that MS-FIT was a usable tool. It is a promising system for enhancing the motivation and engagement of people with MS in performing exercise with the aim of improving their physical status

Loss of Either Rac1 or Rac3 GTPase Differentially Affects the Behavior of Mutant Mice and the Development of Functional GABAergic Networks

Rac GTPases regulate the development of cortical/hippocampal GABAergic interneurons by affecting the early development and migration of GABAergic precursors. We have addressed the function of Rac1 and Rac3 proteins during the late maturation of hippocampal interneurons. We observed specific phenotypic differences between conditional Rac1 and full Rac3 knockout mice. Rac1 deletion caused greater generalized hyperactivity and cognitive impairment compared with Rac3 deletion. This phenotype matched with a more evident functional impairment of the inhibitory circuits in Rac1 mutants, showing higher excitability and reduced spontaneous inhibitory currents in the CA hippocampal pyramidal neurons. Morphological analysis confirmed a differential modification of the inhibitory circuits: deletion of either Rac caused a similar reduction of parvalbumin-positive inhibitory terminals in the pyramidal layer. Intriguingly, cannabinoid receptor-1-positive terminals were strongly increased only in the CA1 of Rac1-depleted mice. This increase may underlie the stronger electrophysiological defects in this mutant. Accordingly, incubation with an antagonist for cannabinoid receptors partially rescued the reduction of spontaneous inhibitory currents in the pyramidal cells of Rac1 mutants. Our results show that Rac1 and Rac3 have independent roles in the formation of GABAergic circuits, as highlighted by the differential effects of their deletion on the late maturation of specific populations of interneurons

Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets: A MAGNIFY-MS Substudy.

BACKGROUND AND OBJECTIVES Cladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS). METHODS Immunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+ B cells, CD4+ and CD8+ T cells, CD16+ natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed. RESULTS The full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%-87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period. DISCUSSION Cladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence. TRIAL REGISTRATION INFORMATION ClinicalTrials.gov Identifier: NCT03364036. Date registered: December 06, 2017