Publications by authors named "Letizia Leocani"

121 Publications

Walking on common ground: a cross-disciplinary scoping review on the clinical utility of digital mobility outcomes.

NPJ Digit Med 2021 Oct 14;4(1):149. Epub 2021 Oct 14.

Insigneo Institute, Department of Mechanical Engineering, University of Sheffield, Sheffield, UK.

Physical mobility is essential to health, and patients often rate it as a high-priority clinical outcome. Digital mobility outcomes (DMOs), such as real-world gait speed or step count, show promise as clinical measures in many medical conditions. However, current research is nascent and fragmented by discipline. This scoping review maps existing evidence on the clinical utility of DMOs, identifying commonalities across traditional disciplinary divides. In November 2019, 11 databases were searched for records investigating the validity and responsiveness of 34 DMOs in four diverse medical conditions (Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, hip fracture). Searches yielded 19,672 unique records. After screening, 855 records representing 775 studies were included and charted in systematic maps. Studies frequently investigated gait speed (70.4% of studies), step length (30.7%), cadence (21.4%), and daily step count (20.7%). They studied differences between healthy and pathological gait (36.4%), associations between DMOs and clinical measures (48.8%) or outcomes (4.3%), and responsiveness to interventions (26.8%). Gait speed, step length, cadence, step time and step count exhibited consistent evidence of validity and responsiveness in multiple conditions, although the evidence was inconsistent or lacking for other DMOs. If DMOs are to be adopted as mainstream tools, further work is needed to establish their predictive validity, responsiveness, and ecological validity. Cross-disciplinary efforts to align methodology and validate DMOs may facilitate their adoption into clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41746-021-00513-5DOI Listing
October 2021

Retinal Optical Coherence Tomography in Neuromyelitis Optica.

Neurol Neuroimmunol Neuroinflamm 2021 Nov 15;8(6). Epub 2021 Sep 15.

From the Experimental and Clinical Research Center (F.C.O., Svenja Specovius, H.G.Z., C.C., S.M., C.B., A.U.B., F.P.), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany: NeuroCure Clinical Research Center (F.C.O., Svenja Specovius, H.G.Z., C.C., S.M., C.B., A.U.B., F.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Germany; Department of Neurology (F.C.O., A.J.G.), University of California San Francisco, CA; Department of Pediatrics (L.C.), University of Utah, Salt Lake City; CIEM MS Research Center (M.A.L.P., M.A.F.), University of Minas Gerais, Medical School, Belo Horizonte, Brazil; Department of Neurology (H.J.K., J.-W.H.), National Cancer Center, Goyang, Republic of Korea; Department of Neurology (J.P., A.R.-F., M.I.L.), and Department of Ophthalmology (Srilakshmi Sharma), and Department of Ophthalmology (Srilakshmi Sharma), Oxford University Hospitals, National Health Service Trust, UK; Kashani MS Center (F.A.), School of Advanced Technologies in Medicine and Medical Image and Signal Processing Research Center (R.K.), Department of Ophthalmology, Isfahan Eye Research Center (A.D., Mohsen Pourazizi), Isfahan University of Medical Sciences, Iran; Department of Neurology (L.P., A.D'C.), KS Hegde Medical Academy, Nitte University, Mangalore, India; Department of Neurology (O.A., Marius Ringelstein, P.A.), Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Swedish Neuroscience Institute Neuro-Ophthalmology (E.M., C.T.), Seattle, WA; Experimental Neurophysiology Unit (L.L., Marco Pisa, Marta Radaelli), Institute of Experimental Neurology (INSPE) Scientific Institute Hospital San Raffaele and University Vita-Salute San Raffaele, Milan, Italy; Hospital Clinic of Barcelona-Institut d'Investigacions (E.H.M.-L.), Biomèdiques August Pi Sunyer, (IDIBAPS), Spain; Sackler School of Medicine (H.S.-K.), Tel Aviv University, Israel; Neuro-Ophthalmology Division (H.S.-K.), Department of Ophthalmology, Rabin Medical Center, Petah Tikva, Israel; Division of Neurology (Sasitorn Siritho), Department of Medicine, Siriraj Hospital and Bumrungrad International Hospital, Bangkok, Thailand; Neurology Service (J.d.S., Thomas Senger), University Hospital of Strasbourg, France; Institute of Clinical Neuroimmunology (J.H.), Biomedical Center and University Hospital, Ludwig-Maximilians Universitaet Muenchen, Munich, Germany; Neurology (R.M., A.C.C.), Multiple Sclerosis, Myelin Disorders and Neuroinflammation, Pierre Wertheimer Neurological Hospital, Hospices Civils de Lyon, France; Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (A.C.C.), Department of Neurology/Neuroimmunology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Department of Neurology and Neurosurgery (D.B., I.M.T.), Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil; Departments of Neurology (N.A.), Slagelse Hospitals, Institute of Regional Health Research, University of Southern Denmark, Odense; Institute of Regional Health Research (N.A., K.S.), University of Southern Denmark, Odense; Department of Neurology (A.A., U.T.), and Department of Ophthalmology (R.Y.), Cerrahpasa Medical Faculty, Istanbul University, Turkey; The Walton Centre for Neurology and Neurosurgery (A.J., S.H.), Liverpool, UK; The Cleveland Clinic Abu Dhabi (A.J.), United Arab Emirates; NYU Multiple Sclerosis Comprehensive Care Center (Z.R., A.R.), Department of Neurology, NYU School of Medicine, New York; Department of Neurology (Y.M.-D.), University of Michigan Medical School, Ann Arbor; Department of Neurology (I.S.C.), Hospital Clínico de Maracaibo, Venezuela; Moorfield's Eye Hospital (A.P.), University College London, UK; Department of Medicine (M.R.Y.), Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles (UCLA) Medical Center, Torrance, CA, United States of America; Department of Medicine (M.R.Y.), David Geffen School of Medicine at UCLA, Los Angeles, CA, United States of America; Departments of Ophthalmology and Visual Sciences (Terry Smith), Kellogg Eye Center, University of Michigan Medical School, Ann Arbor, United States of America; Division of Metabolism (Terry Smith), Endocrine and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor; Department of Neurology (A.U.B.), University of California, Irvine; and Department of Neurology (F.P.), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany.

Background And Objectives: To determine optic nerve and retinal damage in aquaporin-4 antibody (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) in a large international cohort after previous studies have been limited by small and heterogeneous cohorts.

Methods: The cross-sectional Collaborative Retrospective Study on retinal optical coherence tomography (OCT) in neuromyelitis optica collected retrospective data from 22 centers. Of 653 screened participants, we included 283 AQP4-IgG-seropositive patients with NMOSD and 72 healthy controls (HCs). Participants underwent OCT with central reading including quality control and intraretinal segmentation. The primary outcome was thickness of combined ganglion cell and inner plexiform (GCIP) layer; secondary outcomes were thickness of peripapillary retinal nerve fiber layer (pRNFL) and visual acuity (VA).

Results: Eyes with ON (NMOSD-ON, N = 260) or without ON (NMOSD-NON, N = 241) were assessed compared with HCs (N = 136). In NMOSD-ON, GCIP layer (57.4 ± 12.2 μm) was reduced compared with HC (GCIP layer: 81.4 ± 5.7 μm, < 0.001). GCIP layer loss (-22.7 μm) after the first ON was higher than after the next (-3.5 μm) and subsequent episodes. pRNFL observations were similar. NMOSD-NON exhibited reduced GCIP layer but not pRNFL compared with HC. VA was greatly reduced in NMOSD-ON compared with HC eyes, but did not differ between NMOSD-NON and HC.

Discussion: Our results emphasize that attack prevention is key to avoid severe neuroaxonal damage and vision loss caused by ON in NMOSD. Therapies ameliorating attack-related damage, especially during a first attack, are an unmet clinical need. Mild signs of neuroaxonal changes without apparent vision loss in ON-unaffected eyes might be solely due to contralateral ON attacks and do not suggest clinically relevant progression but need further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/NXI.0000000000001068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448522PMC
November 2021

Myasthenia gravis and telemedicine: a lesson from COVID-19 pandemic.

Neurol Sci 2021 Aug 26. Epub 2021 Aug 26.

I Division of Neurology and Neurophysiopathology, Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

COVID-19 pandemic has induced an urgent reorganization of the healthcare system to ensure continuity of care for patients affected by chronic neurological diseases including myasthenia gravis (MG). Due to the fluctuating nature of the disease, early detection of disease worsening, adverse events, and possibly life-threatening complications is mandatory. This work analyzes the main unresolved issues in the management of the myasthenic patient, the possibilities offered so far by digital technologies, and proposes an online evaluation protocol based on 4 simple tests to improve MG management. Telemedicine and Digital Technology might help neurologists in the clinical decision-making process of MG management, avoiding unnecessary in presence consultations and allowing a rational use of the time and space reduced by the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05566-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390022PMC
August 2021

The 4-Hole-Board Test for Assessment of Long-Term Spatial Memory in Mice.

Curr Protoc 2021 Aug;1(8):e228

Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, IRCCS-San Raffaele Hospital, Milan, Italy.

The hole-board test has been used in rodents since the early 60s to measure exploratory behavior, locomotor activity and cognitive function. The test is based on rodents' natural curiosity and attraction for novelty. Basically, the hole-board consists of a small square arena with an extractable platform as floor, which has a set of equally spaced circular holes on its surface. In this article, we describe the protocol of a 4-hole-board test allowing the assessment of long-term spatial memory in mice without the employment of water or food restriction, painful stimuli (as electrical shocks) or any aversive condition (as forced swimming or exposure to intense light). Four holes are present on the floor of the square arena (one for each of its four quadrants). Mice released in the arena spontaneously approach the holes and explore them by briefly inserting the snout inside, a behavior defined as nose-poking (or head-dipping). If, after 24 hr, rodents are re-exposed to the hole-board, the novelty of the holes decreases. Animals with an intact long-term memory will show a reduction of the frequency of nose-poking into the holes. The total number of nose-pokes on day 1 is an index of exploration, while the percentage of decrease in nose-poking on day 2 represents an index of long-term spatial memory. Number of quadrant crossings is scored as a control measure for locomotor activity, which with the present protocol should remain stable across the days of testing. Indeed, the 4-hole-board test represents a stress-free and animal-friendly option to evaluate long-term spatial memory. In the present paper, we provide detailed description of the hole-board apparatus and step-by-step protocol for assessment of spatial memory in mice. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Validation of the 4-hole-board Basic Protocol 2: Evaluation of long-term spatial memory through the 4-hole-board test.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cpz1.228DOI Listing
August 2021

Optical Coherence Tomography and Visual Evoked Potentials as Prognostic and Monitoring Tools in Progressive Multiple Sclerosis.

Front Neurosci 2021 5;15:692599. Epub 2021 Aug 5.

Experimental Neurophysiology Unit, San Raffaele Hospital, Institute of Experimental Neurology (INSPE), Milan, Italy.

Understanding the mechanisms underlying progression and developing new treatments for progressive multiple sclerosis (PMS) are among the major challenges in the field of central nervous system (CNS) demyelinating diseases. Over the last 10 years, also because of some technological advances, the visual pathways have emerged as a useful platform to study the processes of demyelination/remyelination and their relationship with axonal degeneration/protection. The wider availability and technological advances in optical coherence tomography (OCT) have allowed to add information on structural neuroretinal changes, in addition to functional information provided by visual evoked potentials (VEPs). The present review will address the role of the visual pathway as a platform to assess functional and structural damage in MS, focusing in particular on the role of VEPs and OCT, alone or in combination, in the prognosis and monitoring of PMS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2021.692599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374170PMC
August 2021

Digital work engagement among Italian neurologists.

Ther Adv Chronic Dis 2021 20;12:20406223211029616. Epub 2021 Jul 20.

Department of Advanced Medical and Surgical Sciences, II Clinic of Neurology, University of Campania 'Luigi Vanvitelli,' Caserta, Italy.

Background: Digital health, including telemedicine, is increasingly recommended for the management of chronic neurological disorders, and it has changed the roles of patients and clinicians.

Methods: In this cross-sectional study we aimed to investigate the digital work engagement of Italian neurologists through a survey collected between September 2020 and January 2021. Questionnaires were anonymous and collected demographic characteristics, attitudes towards digital devices and social media, and details about the clinician-patient relationship. We used logistic-regression models to identify characteristics associated with the propensity to communicate with patients using social media.

Results: Among the 553 neurologists who participated to the study, smartphones and computers were widely preferred compared with tablets; wearable devices were not common, although some neurologists desired them. A total of 48% of participants reported communicating with patients using social media but only a few were in favor of social friendship with patients; WhatsApp was the social media most popular for professional (86%) and personal (98%) purposes. Propensity to communicate with social media was significantly higher among those who were older ( < 0.001) and lived in regions outside northern Italy (center:  = 0.006; south and the islands:  < 0.001). For 58% of responders, social media improved their relationship with patients, but 72% usually warned patients about unreliable websites.

Conclusions: The preferred social media were those which were rapid and which safeguard privacy more effectively; neurologists made many efforts to disprove fake news circulating online, providing help to patients in various ways. This analysis can help direct future interventions for the management of chronic neurological disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/20406223211029616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299881PMC
July 2021

The hypometabolic state: a good predictor of a better prognosis in amyotrophic lateral sclerosis.

J Neurol Neurosurg Psychiatry 2021 Aug 5. Epub 2021 Aug 5.

NeuroMuscular Omnicentre (NeMO)-Fondazione Serena Onlus, Milano, Italy

Background: Malnutrition and weight loss are negative prognostic factors for survival in patients with amyotrophic lateral sclerosis (ALS). However, energy expenditure at rest (REE) is still not included in clinical practice, and no data are available concerning hypometabolic state in ALS.

Objective: To evaluate in a referral cohort of patients with ALS the prevalence of hypometabolic state as compared with normometabolic and hypermetabolic states, and to correlate it with clinical phenotype, rate of progression and survival.

Design: We conducted a retrospective study examining REE measured by indirect calorimetry in patients with ALS referred to Milan, Limoges and Tours referral centres between January 2011 and December 2017. Hypometabolism and hypermetabolism states were defined when REE difference between measured and predictive values was ≤-10% and ≥10%, respectively. We evaluated the relationship between these metabolic alterations and measures of body composition, clinical characteristics and survival.

Results: Eight hundred forty-seven patients with ALS were recruited. The median age at onset was 63.79 years (IQR 55.00-71.17). The male/female ratio was 1.26 (M/F: 472/375). Ten per cent of patients with ALS were hypometabolic whereas 40% were hypermetabolic. Hypometabolism was significantly associated with later need for gastrostomy, non-invasive ventilation and tracheostomy placement. Furthermore, hypometabolic patients with ALS significantly outlived normometabolic (HR=1.901 (95% CI 1.080 to 3.345), p=0.0259) and hypermetabolic (HR=2.138 (95% CI 1.154 to 3.958), p=0.0157) patients.

Conclusion: Hypometabolism in ALS is not uncommon and is associated with slower disease progression and better survival than normometabolic and hypermetabolic subjects. Indirect calorimetry should be performed at least at time of diagnosis because alterations in metabolism are correlated with prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jnnp-2021-326184DOI Listing
August 2021

How to manage with telemedicine people with neuromuscular diseases?

Neurol Sci 2021 Sep 25;42(9):3553-3559. Epub 2021 Jun 25.

1st Clinic of Neurology, Italian Society of Neurology, AOU University of Campania "Luigi Vanvitelli", Caserta, Italy.

Introduction: COVID-19 pandemic radically transformed our daily clinical practice, raising the need not to lose close contact with patients without being able to see them face-to-face. These issues are even more felt and evident in fragile patients, as those affected by neuromuscular disease. An important help came from new digital technologies that allow clinicians to remotely monitor health status and any deterioration of chronically ill patients.

Methods: In this mini-review, an initiative of the "Digital Technologies, Web and Social Media Study Group" of the Italian Society of Neurology, we propose to analyze the approach to neuromuscular patients by looking over raising evidence on the main cornerstones of Telemedicine (TM): clinician-patient interaction, remote clinical assessment, remote monitoring, and digital therapeutics. In particular, we explored the strategies developed by researchers and their impact on the physical and emotional status of the patients, with particular focusing on their adherence to the program of virtual monitoring.

Results: TM plays an important role in each of four stages of approach to neuromuscular disease, having demonstrated validity in keep close clinical patient interaction, clinical assessment, remote monitoring, and telerehabilitation. Nevertheless, there is no remote alternative to electrophysiological testing neither validate tools to assess disability.

Conclusion: The role of TM in neuromuscular care is yet underestimated but is crucial, beyond the pandemic era. Further development of TM is advisable, through making specific apps, remotely controlled by clinicians, and making more engaging clinicians-patients interaction. Last, it is necessary to ensure adequate internet access to everyone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-021-05396-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232560PMC
September 2021

APOSTEL 2.0 Recommendations for Reporting Quantitative Optical Coherence Tomography Studies.

Neurology 2021 07 28;97(2):68-79. Epub 2021 Apr 28.

From the Department of Neurology, Medical Faculty (A.A., O.A., H.-P.H., O.M., S.M., M.R., P.A.), Heinrich-Heine University Düsseldorf, Germany; Department of Neurology (A.C.-H., A.J.G.), University of California San Francisco; Departments of Neurology, Population Health, and Ophthalmology (L.J.B., R.K.), NYU Grossman School of Medicine, New York, NY; Mulier Institute (L.B.), Centre for Research on Sports in Society, Utrecht, the Netherlands; Scientific Institute San Raffaele (P.B.), Milan, Italy; Centre for Public Health (A.A.B.), Queen's University Belfast, Northern Ireland, UK; Division of Neuroimmunology (P.A.C., S. Saidha), Johns Hopkins University, Baltimore, MD; Departments of Clinical Neurosciences and Surgery (F.C.), University of Calgary, Alberta, Canada; Institut d'Investigacións Biomediques August Pi iSunyer (IDIBAPS) and Hospital Clinic (B.S.-D., E.H.M.-L., P.V.), University of Barcelona, Spain; Bascom Palmer Eye Institute (D.C.D.), University of Miami Miller School of Medicine, FL; Department of Ophthalmology (N.F.), University Medical Center, Göttingen; Department of Ophthalmology (R.P.F., F.G.H.), University of Bonn, Germany; Department of Neurology (J.L.F., G.P.-J.), Rigshospitalet Glostrup and University of Copenhagen, Denmark; Laboratory of Neuroimmunology (E.F., T.F.), Stanford University School of Medicine, CA; Institute of Ophthalmology (D.G.-H.), National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (D.G.-H.), London, UK; Biocruces Bizkaia Health Research Institute (I.G.), Barakaldo, Spain; Department of Neurosciences (J.S.G.), University of California, San Diego; Brain and Mind Centre (H.-P.H.), University of Sydney, Australia; Department of Neurology (H.-P.H.), Medical University of Vienna, Austria; Institute of Clinical Neuroimmunology (J.H.), LMU Hospital, Ludwig-Maximilians Universität München, Germany; UConn Health Comprehensive MS Center, Division of Multiple Sclerosis and Neuroimmunology, Department of Neurology (J.I.), University of Connecticut School of Medicine, Farmington; Faculty of Medicine and Health Sciences (A.K.), Macquarie University, Sydney, Australia; Department of Neurology (B.K., T.K.), Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Germany; Department of Medicine and Radiology (S.K.), University of Melbourne, Australia; Department of Neurology with Institute of Translational Neurology (J.K.), University of Münster; Eye Center, Medical Center, Faculty of Medicine (W.A.L.), University of Freiburg, Germany; Experimental Neurophysiology Unit (L.L.), Institute of Experimental Neurology (INSPE), IRCCS San Raffaele, University Vita-Salute San Raffaele, Milan, Italy; Lille Neurosciences & Cognition (O.O.), Univ Lille, Inserm, CHU Lille, U1172-LilNCog (JPARC), France; Experimental and Clinical Research Center (F.P., H.G.Z., A.U.B.), Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany; Moorfields Eye Hospital (A.P.), The National Hospital for Neurology and Neurosurgery, Queen Square, UCL Institute of Neurology, London, UK; Neuro-ophthalmology Expert Center (A.P.), Amsterdam UMC, the Netherlands; Department of Neurology, First Faculty of Medicine (J.L.P.), Charles University and General University Hospital in Prague, Czech Republic; Department of Ophthalmology (G.R.), Ramon y Cajal Hospital, Medicine University of Alcalá, Madrid, Spain; Department of Neurology (M.R.), Center for Neurology and Neuropsychiatry, LVR-Klinikum, Heinrich-Heine-University Düsseldorf, Germany; Department of Neurology (S. Schippling), University Hospital Zurich, Switzerland; Departments of Ophthalmology, Neuroscience, and Physiology (J.S.S.), NYU Langone Health, NYU Grossman School of Medicine, New York; Departments of Biomedical Engineering, Electrical and Computer Engineering (J.S.S.), NYU Tandon School of Engineering, Brooklyn, NY; Thomas Jefferson University Medical College (R.C.S.), Philadelphia, PA; Queen Square MS Centre, Department of Neuroinflammation (A.T.), UCL Institute of Neurology, University College London, UK; Departments of Ophthalmology and Clinical Research (S.W.), Bern University Hospital, University of Bern, Switzerland; Division of Neurology, Department of Pediatrics (E.A.Y.), Hospital for Sick Children, Division of Neurosciences and Mental Health SickKids Research Institute, University of Toronto, Canada; Department of Clinical Neurosciences (P.Y.-W.-M.), University of Cambridge; Moorfields Eye Hospital (P.Y.-W.-M.), London, UK; University of California (A.U.B.), Irvine; and IMSVISUAL (A.A., A.C.-H., O.A., L.J.B., L.B., P.A.C., F.C., J.L.F., E.F., T.F., I.G., J.S.G., A.J.G., H.-P.H., J.H., J.I., R.K., A.K., B.K., T.K., J.K., L.L., E.H.M.-L., S.M., O.O., F.P., A.P., G.P.-J., J.L.P., M.R., S. Saidha, S. Schippling, R.C.S., P.V., E.A.Y., H.G.Z., A.U.B., P.A.), International Multiple Sclerosis Visual System Consortium, Middleton, WI.

Objective: To update the consensus recommendations for reporting of quantitative optical coherence tomography (OCT) study results, thus revising the previously published Advised Protocol for OCT Study Terminology and Elements (APOSTEL) recommendations.

Methods: To identify studies reporting quantitative OCT results, we performed a PubMed search for the terms "quantitative" and "optical coherence tomography" from 2015 to 2017. Corresponding authors of the identified publications were invited to provide feedback on the initial APOSTEL recommendations via online surveys following the principle of a modified Delphi method. The results were evaluated and discussed by a panel of experts and changes to the initial recommendations were proposed. A final survey was recirculated among the corresponding authors to obtain a majority vote on the proposed changes.

Results: A total of 116 authors participated in the surveys, resulting in 15 suggestions, of which 12 were finally accepted and incorporated into an updated 9-point checklist. We harmonized the nomenclature of the outer retinal layers, added the exact area of measurement to the description of volume scans, and suggested reporting device-specific features. We advised to address potential bias in manual segmentation or manual correction of segmentation errors. References to specific reporting guidelines and room light conditions were removed. The participants' consensus with the recommendations increased from 80% for the previous APOSTEL version to greater than 90%.

Conclusions: The modified Delphi method resulted in an expert-led guideline (evidence Class III; Grading of Recommendations, Assessment, Development and Evaluations [GRADE] criteria) concerning study protocol, acquisition device, acquisition settings, scanning protocol, funduscopic imaging, postacquisition data selection, postacquisition analysis, nomenclature and abbreviations, and statistical approach. It will be essential to update these recommendations to new research and practices regularly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000012125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279566PMC
July 2021

Subclinical anterior optic pathway involvement in early multiple sclerosis and clinically isolated syndromes.

Brain 2021 04;144(3):848-862

Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE), San Raffaele Scientific Institute, Milan, Italy.

Optical coherence tomography (OCT) is gaining increasing relevance in the assessment of patients with multiple sclerosis. Converging evidence point to the view that neuro-retinal changes, in eyes without acute optic neuritis, reflect inflammatory and neurodegenerative processes taking place throughout the CNS. The present study aims at exploring the usefulness of OCT as a marker of inflammation and disease burden in the earliest phases of the disease. Thus, a cohort of 150 consecutive patients underwent clinical, neurophysiological and brain MRI assessment as well as lumbar puncture as part of their diagnostic workup for a neurological episode suggestive of inflammatory CNS disorder; among those 32 patients had another previous misdiagnosed episode. For the present study, patients also received a visual pathway assessment (OCT, visual evoked potentials, visual acuity), measurement of CSF inflammatory markers (17 cytokines-chemokines, extracellular vesicles of myeloid origin), and dosage of plasma neurofilaments. Subclinical optic nerve involvement is frequently found in clinically isolated syndromes by visual evoked potentials (19.2%). OCT reveals ganglion cell layer asymmetries in 6.8% of patients; retinal fibre layer asymmetries, despite being more frequent (17.8%), display poor specificity. The presence of subclinical involvement is associated with a greater disease burden. Second, ganglion cell layer thinning reflects the severity of disease involvement even beyond the anterior optic pathway. In fact, the ganglion cell layer in eyes without evidence of subclinical optic involvement is correlated with Expanded Disability Status Scale, low contrast visual acuity, disease duration, brain lesion load, presence of gadolinium enhancing lesions, abnormalities along motor and somatosensory evoked potentials, and frequency of CSF-specific oligoclonal bands. Third, the inner nuclear layer thickens in a post-acute (1.1-3.7 months) phase after a relapse, and this phenomenon is counteracted by steroid treatment. Likewise, a longitudinal analysis on 65 patients shows that this swelling is transient and returns to normal values after 1 year follow-up. Notwithstanding, the clinical, MRI, serological and CSF markers of disease activity considered in the study are strictly associated with one another, but none of them are associated with the inner nuclear layer. Our findings challenge the current hypothesis that the inner nuclear layer is an acute phase marker of inflammatory activity. The present study suggests that instrumental evidence of subclinical optic nerve involvement is associated with a greater disease burden in clinically isolated syndrome. Neuro-retinal changes are present since the earliest phases of the disease and yield important information regarding the neurodegenerative and inflammatory processes occurring in the CNS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/brain/awaa458DOI Listing
April 2021

Repetitive Transcranial Magnetic Stimulation With H-Coil in Alzheimer's Disease: A Double-Blind, Placebo-Controlled Pilot Study.

Front Neurol 2020 18;11:614351. Epub 2021 Feb 18.

University Vita-Salute San Raffaele, Milan, Italy.

Focal repetitive transcranial magnetic stimulation (rTMS) has been applied to improve cognition in Alzheimer's disease (AD) with conflicting results. We applied rTMS in AD in a pilot placebo-controlled study using the H2-coil. H-coils are suitable for targeting wider neuronal structures compared with standard focal coils, in particular the H2-coil stimulates simultaneously the frontal-parietal-temporal lobes bilaterally. Thirty patients (mean age 70.9 year, SD 8.1; mean MMSE score 16.9, SD 5.5) were randomized to sham or real 10 Hz rTMS stimulation with the H2-coil. Each patient underwent 3 sessions/week for 4 weeks, followed by 4 weeks with maintenance treatment (1 session/week). Primary outcome was improvement of ADAS-cog at 4 and 8 weeks compared with baseline. A trend toward an improved ADAS-cog score over time was observed for patients undergoing real rTMS, with actively treated patients experiencing a mean decrease of -1.01 points at the ADAS-Cog scale score per time point (95% CIs -0.02 to -3.13, < 0.04). This trend was no longer evident 2 months after the end of treatment. Real rTMS showed no significant effect on MMSE and BDI changes over time. These preliminary findings suggest that rTMS with H-coil is feasible and safe in patients with probable AD and might provide beneficial, even though transient, effects on cognition. This study prompts larger studies in the early stages of AD, combining rTMS and cognitive rehabilitation. www.ClinicalTrials.gov, identifier: NCT04562506.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.614351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930223PMC
February 2021

Bilateral Repetitive Transcranial Magnetic Stimulation With the H-Coil in Parkinson's Disease: A Randomized, Sham-Controlled Study.

Front Neurol 2020 18;11:584713. Epub 2021 Feb 18.

Experimental Neurophysiology Unit, Institute of Experimental Neurology - INSPE, Scientific Institute Hospital San Raffaele, Milan, Italy.

Pilot open-label application of high-frequency repetitive transcranial magnetic stimulation (rTMS) with H-coil in Parkinson's Disease (PD) have shown promising results. To evaluate safety and efficacy of high-frequency rTMS with H-coil in PD in a double-blind, placebo-controlled, randomized study. Sixty patients with PD were randomized into 3 groups: M1-PFC (real stimulation on primary motor-M1 and pre-frontal cortices-PFC), M1 (real rTMS on M1, sham on PFC), Sham (apparent stimulation). Primary outcome was baseline-normalized percent improvement in UPDRS part III OFF-therapy at the end of treatment (12 rTMS sessions, 4 weeks). Secondary outcomes were improvement in UPDRS part III sub-scores, timed tests, and neuropsychological tests. Statistical analysis compared improvement following real and sham stimulation at the end of the protocol using either a -test or a Mann-Whitney test. All patients tolerated the treatment and concluded the study. One patient from M1-PFC group was excluded from the analysis due to newly discovered uncontrolled diabetes mellitus. No serious adverse effect was recorded. At the end of treatment, patients receiving real rTMS (M1-PFC and M1 combined) showed significantly greater improvement compared to sham in UPDRS part III total score ( = 0.007), tremor subscore ( = 0.011), and lateralized sub-scores ( = 0.042 for the more affected side; = 0.012 for the less affected side). No significant differences have been oserved in safety and efficacy outcomes between the two real rTMS groups. Notably, mild, not-distressing and transient dyskinesias occurred in 3 patients after real rTMS in OFF state. The present findings suggest that high-frequency rTMS with H-coil is a safe and potentially effective procedure and prompt larger studies for validation as add-on treatment in PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.584713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930321PMC
February 2021

Training in the practice of noninvasive brain stimulation: Recommendations from an IFCN committee.

Clin Neurophysiol 2021 03 3;132(3):819-837. Epub 2020 Dec 3.

Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife and Department of Neurology, Harvard Medical School, Boston, MA, USA; Guttmann Brain Health Institute, Institut Guttmann, Universitat Autonoma, Barcelona, Spain. Electronic address:

As the field of noninvasive brain stimulation (NIBS) expands, there is a growing need for comprehensive guidelines on training practitioners in the safe and effective administration of NIBS techniques in their various research and clinical applications. This article provides recommendations on the structure and content of this training. Three different types of practitioners are considered (Technicians, Clinicians, and Scientists), to attempt to cover the range of education and responsibilities of practitioners in NIBS from the laboratory to the clinic. Basic or core competencies and more advanced knowledge and skills are discussed, and recommendations offered regarding didactic and practical curricular components. We encourage individual licensing and governing bodies to implement these guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.11.018DOI Listing
March 2021

Facing the urgency of therapies for progressive MS - a Progressive MS Alliance proposal.

Nat Rev Neurol 2021 Mar 22;17(3):185-192. Epub 2021 Jan 22.

Department of Neurosciences, Mental Health and Sensory Organs, Centre for Experimental Neurological Therapies (CENTERS), Faculty of Medicine and Psychology, Sapienza University, Rome, Italy.

Therapies for infiltrative inflammation in multiple sclerosis (MS) have advanced greatly, but neurodegeneration and compartmentalized inflammation remain virtually untargeted as in other diseases of the nervous system. Consequently, many therapies are available for the relapsing-remitting form of MS, but the progressive forms remain essentially untreated. The objective of the International Progressive MS Alliance is to expedite the development of effective therapies for progressive MS through new initiatives that foster innovative thinking and concrete advancements. Based on these principles, the Alliance is developing a new funding programme that will focus on experimental medicine trials. Here, we discuss the reasons behind the focus on experimental medicine trials, the strengths and weaknesses of these approaches and of the programme, and why we hope to advance therapies while improving the understanding of progression in MS. We are soliciting public and academic feedback, which will help shape the programme and future strategies of the Alliance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41582-020-00446-9DOI Listing
March 2021

CSF extracellular vesicles and risk of disease activity after a first demyelinating event.

Mult Scler 2021 09 19;27(10):1606-1610. Epub 2021 Jan 19.

Clinical Neuroimmunology Unit, Institute of Experimental Neurology, Division of Neuroscience, IRCCS San Raffaele Hospital, Milan, Italy.

Background: Extracellular vesicles (EVs), a recently described mechanism of cell communication, are released from activated microglial cells and macrophages and are a candidate biomarker in diseases characterized by chronic inflammatory process such as multiple sclerosis (MS).

Methods: We explored cerebrospinal fluid extracellular vesicle (CSF EV) of myeloid origin (MEVs), cytokine and chemokine levels in patients with clinically isolated syndrome (CIS).

Results: We found that CSF MEVs were significantly higher in CIS patients than in controls and were inversely correlated to CSF CCL2 levels. MEVs level were significantly associated with an shorter time to evidence of disease activity (hazard ratio: 1.01, 95% confidence interval: 1.00-1.02,  < 0.01) independently from other known prognostic markers.

Conclusion: After a first demyelinating event, CSF EVs may improve risk stratification of these patients and allow more targeted intervention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520987542DOI Listing
September 2021

Stroke and digital technology: a wake-up call from COVID-19 pandemic.

Neurol Sci 2021 Mar 12;42(3):805-809. Epub 2021 Jan 12.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Introduction: The pandemic has implemented the need for new digital technologies as useful tools during the emergency and the long recovery phase that will follow. SARS-CoV-2 has strongly impacted stroke care with significant contraction in a number of patients treated.

Methods: This mini-review is an initiative of the "Digital Technologies, Web and Social Media Study Group" of the Italian Society of Neurology and briefly discusses digital tools for managing the acute phase and the rehabilitation after stroke, even considering the new apps that will improve the process of remote monitoring of patients after discharge at home.

Results: Telemedicine and digital technologies could play a role in each of the three stroke-belt stages: hyperacute treatment and reperfusion, acute care, etiological classification and secondary prevention and rehabilitation.

Conclusion: The global emergency represented by the COVID-19 pandemic can be the stimulus to accelerate the digitalization process in the field of stroke for the use of new methods on a large scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04993-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801773PMC
March 2021

Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert Guidelines.

Clin Neurophysiol 2021 01 24;132(1):269-306. Epub 2020 Oct 24.

Berenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA.

This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinph.2020.10.003DOI Listing
January 2021

The Danger of Walking with Socks: Evidence from Kinematic Analysis in People with Progressive Multiple Sclerosis.

Sensors (Basel) 2020 Oct 29;20(21). Epub 2020 Oct 29.

Neurorehabilitation Department and Experimental Neurophysiology Unit, INSPE-Institute of Experimental Neurology, San Raffaele Hospital, 20132 Milan, Italy.

Multiple sclerosis (MS) is characterized by gait impairments and severely impacts the quality of life. Technological advances in biomechanics offer objective assessments of gait disabilities in clinical settings. Here we employed wearable sensors to measure electromyography (EMG) and body acceleration during walking and to quantify the altered gait pattern between people with progressive MS (PwPMS) and healthy controls (HCs). Forty consecutive patients attending our department as in-patients were examined together with fifteen healthy controls. All subjects performed the timed 10 min walking test (T10MW) using a wearable accelerator and 8 electrodes attached to bilateral thighs and legs so that body acceleration and EMG activity were recorded. The T10MWs were recorded under three conditions: standard (wearing shoes), reduced grip (wearing socks) and increased cognitive load (backward-counting dual-task). PwPMS showed worse kinematics of gait and increased muscle coactivation than controls at both the thigh and leg levels. Both reduced grip and increased cognitive load caused a reduction in the cadence and velocity of the T10MW, which were correlated with one another. A higher coactivation index at the thigh level of the more affected side was positively correlated with the time of the T10MW (r = 0.5, < 0.01), Expanded Disability Status Scale (EDSS) (r = 0.4, < 0.05), and negatively correlated with the cadence (r = -0.6, < 0.001). Our results suggest that excessive coactivation at the thigh level is the major determinant of the gait performance as the disease progresses. Moreover, demanding walking conditions do not influence gait in controls but deteriorate walking performances in PwPMS, thus those conditions should be prevented during hospital examinations as well as in homecare environments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s20216160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662955PMC
October 2020

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO).

BMJ Open 2020 10 29;10(10):e035397. Epub 2020 Oct 29.

Neurological Department and Institute of Experimental Neurology (INSPE) Scientific Institute, Hospital San Raffaele; and University Vita-Salute San Raffaele, Milan, Italy.

Purpose: Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD.

Participants: The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices.

Findings To Date: The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline.

Future Plans: We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-035397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597491PMC
October 2020

Two-year macular volume assessment in multiple sclerosis patients treated with fingolimod.

Neurol Sci 2021 Feb 8;42(2):731-733. Epub 2020 Oct 8.

Multiple Sclerosis Center, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Background: Fingolimod (FNG) is associated with the development of symptomatic macular edema (ME) in a small subset of multiple sclerosis (MS) patients. By using spectral domain optical coherence tomography (SD-OCT), an increase in the total macular volume (TMV) was rarely detected during the first months of treatment.

Objectives: The objective of this study is to assess whether FNG treatment leads to long-term macular changes in a real-life setting.

Methods: Sixty RRMS patients starting FNG, according to therapeutic indication, were enrolled at three Italian MS centers and followed for 2 years.

Results: The mean TMV did not change between baseline and the follow-up. No patients experienced visual acuity drop during the follow-up.

Conclusions: Initiation of FNG in MS is associated with a modest, not significant, increase in macular volume followed by no further significant changes over 2 years, highlighting the good safety profile of such treatment in MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04802-xDOI Listing
February 2021

Telemedicine for management of patients with amyotrophic lateral sclerosis through COVID-19 tail.

Neurol Sci 2021 Jan 6;42(1):9-13. Epub 2020 Oct 6.

Department of Advanced Medical and Surgical Sciences, I Clinic of Neurology, University of Campania "Luigi Vanvitelli", Naples, Italy.

Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04783-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538170PMC
January 2021

Intensive Care Admission and Early Neuro-Rehabilitation. Lessons for COVID-19?

Front Neurol 2020 25;11:880. Epub 2020 Aug 25.

Acute Neuro-Rehabilitation Unit and Neurology Unit, Department of Clinical Neurosciences, Lausanne University Hospital-CHUV, Lausanne, Switzerland.

Coronavirus disease 2019 (COVID-19) requires admission to intensive care (ICU) for the management of acute respiratory distress syndrome in about 5% of cases. Although our understanding of COVID-19 is still incomplete, a growing body of evidence is indicating potential direct deleterious effects on the central and peripheral nervous systems. Indeed, complex and long-lasting physical, cognitive, and functional impairments have often been observed after COVID-19. Early (defined as during and immediately after ICU discharge) rehabilitative interventions are fundamental for reducing the neurological burden of a disease that already heavily affects lung function with pulmonary fibrosis as a possible long-term consequence. In addition, ameliorating neuromuscular weakness with early rehabilitation would improve the efficiency of respiratory function as respiratory muscle atrophy worsens lung capacity. This review briefly summarizes the polymorphic burden of COVID-19 and addresses possible early interventions that could minimize the neurological and systemic impact. In fact, the benefits of early multidisciplinary rehabilitation after an ICU stay have been shown to be advantageous in several clinical conditions making an early rehabilitative approach generalizable and desirable to physicians from a wide range of different specialties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2020.00880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477378PMC
August 2020

Intracortical motor conduction is associated with hand dexterity in progressive multiple sclerosis.

Mult Scler 2021 07 25;27(8):1222-1229. Epub 2020 Sep 25.

University Vita-Salute San Raffaele, Milan, Italy/Department of Neurorehabilitation, IRCCS Ospedale San Raffaele, Milan, Italy/Experimental Neurophysiology Unit, The Institute of Experimental Neurology (INSPE), IRCCS Ospedale San Raffaele, Milan, Italy.

Background: Hand dexterity dysfunction is a key feature of disability in people with progressive multiple sclerosis (PMS). It underlies corticospinal tract (CST) and cerebellar integrity, as well as disruption of cortical networks, which are hardly assessed by standard techniques. Transcranial magnetic stimulation is a promising tool for evaluating the integrity of intracortical motor pathways.

Objective: To investigate neurophysiological correlates of motor hand impairment in PMS.

Methods: Antero-posterior (AP) stimulation of the primary motor cortex activates the CST indirectly through polysynaptic pathways, while a direct CST activation occurs with latero-medial (LM) directed current. Thirty PMS and 15 healthy controls underwent dominant hand motor evoked potentials (MEP) using AP and LM-directed stimulation, and a clinical assessment of dexterity (nine-hole peg test) and strength (MRC scale, grip and pinch).

Results: PMS with AP-LM latency difference 2.5 standard deviation above the mean of controls (33%) showed worse dexterity but no difference in upper limb strength. Accordingly, AP-LM latency shortening predicted dexterity (R = 0.538,  < 0.001), but not strength impairment. On the contrary, absolute MEP latencies only correlated with strength (grip: R = 0.381,  = 0.014; MRC: R = 0.184,  = 0.041).

Conclusion: AP-LM latency shortening may be used to assess the integrity polysynaptic intracortical networks implicated in dexterity impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1352458520960374DOI Listing
July 2021

Neuro-Retina Might Reflect Alzheimer's Disease Stage.

J Alzheimers Dis 2020 ;77(4):1455-1468

Experimental Neurophysiology Unit, Institute of Experimental Neurology-INSPE, IRCCS San Raffaele Hospital, Milan, Italy.

Background: Alzheimer's disease (AD) pathological hallmarks were found in retinas of AD patients. Several studies showed a significant reduction of neuro-retina thickness measured through optical coherence tomography (OCT) in AD patients, but possible correlations between retina morphology, cognition, and cerebrospinal fluid (CSF) AD biomarkers (Aβ42, t-tau, and p-tau) have been poorly investigated so far.

Objective: In the present cross-sectional study, we measured the thickness of neuro-retinal layers through OCT searching for possible correlations with patients' cognitive performances and CSF AD biomarkers.

Methods: 137 consecutive subjects [43 with AD, 37 with mild cognitive impairment (MCI), and 57 healthy controls (HC)], received an OCT scan acquisition to measure the peripapillary retinal nerve fiber layer (RNFL) thickness. In a subsample of 21 AD, 18 MCI, and 18 HC, the macular volume of ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer was computed. A comprehensive neuropsychological assessment and CSF AD biomarkers' concentrations were available in AD and MCI patients.

Results: Peripapillary RNFL, global, and in superior quadrant was significantly thinner in AD and MCI patients when compared to HC, while macular GCL volume was significantly reduced only in AD. RNFL thickness in nasal and inferior quadrants was correlated with single CSF AD biomarker concentrations, but no differences were found in retina morphology depending on the presence of a CSF profile typical for AD. Memory performances were positively associated with GCL and IPL volume.

Conclusion: Our findings might propose OCT as a reliable and easy to handle tool able to detect neuro-retinal atrophy in AD in relation with cognitive performances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-200043DOI Listing
September 2021

Using Smartphones and Wearable Devices to Monitor Behavioral Changes During COVID-19.

J Med Internet Res 2020 09 25;22(9):e19992. Epub 2020 Sep 25.

The RADAR-CNS Consortium, London, United Kingdom.

Background: In the absence of a vaccine or effective treatment for COVID-19, countries have adopted nonpharmaceutical interventions (NPIs) such as social distancing and full lockdown. An objective and quantitative means of passively monitoring the impact and response of these interventions at a local level is needed.

Objective: We aim to explore the utility of the recently developed open-source mobile health platform Remote Assessment of Disease and Relapse (RADAR)-base as a toolbox to rapidly test the effect and response to NPIs intended to limit the spread of COVID-19.

Methods: We analyzed data extracted from smartphone and wearable devices, and managed by the RADAR-base from 1062 participants recruited in Italy, Spain, Denmark, the United Kingdom, and the Netherlands. We derived nine features on a daily basis including time spent at home, maximum distance travelled from home, the maximum number of Bluetooth-enabled nearby devices (as a proxy for physical distancing), step count, average heart rate, sleep duration, bedtime, phone unlock duration, and social app use duration. We performed Kruskal-Wallis tests followed by post hoc Dunn tests to assess differences in these features among baseline, prelockdown, and during lockdown periods. We also studied behavioral differences by age, gender, BMI, and educational background.

Results: We were able to quantify expected changes in time spent at home, distance travelled, and the number of nearby Bluetooth-enabled devices between prelockdown and during lockdown periods (P<.001 for all five countries). We saw reduced sociality as measured through mobility features and increased virtual sociality through phone use. People were more active on their phones (P<.001 for Italy, Spain, and the United Kingdom), spending more time using social media apps (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), particularly around major news events. Furthermore, participants had a lower heart rate (P<.001 for Italy and Spain; P=.02 for Denmark), went to bed later (P<.001 for Italy, Spain, the United Kingdom, and the Netherlands), and slept more (P<.001 for Italy, Spain, and the United Kingdom). We also found that young people had longer homestay than older people during the lockdown and fewer daily steps. Although there was no significant difference between the high and low BMI groups in time spent at home, the low BMI group walked more.

Conclusions: RADAR-base, a freely deployable data collection platform leveraging data from wearables and mobile technologies, can be used to rapidly quantify and provide a holistic view of behavioral changes in response to public health interventions as a result of infectious outbreaks such as COVID-19. RADAR-base may be a viable approach to implementing an early warning system for passively assessing the local compliance to interventions in epidemics and pandemics, and could help countries ease out of lockdown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/19992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527031PMC
September 2020

Repetitive Transcranial Magnetic Stimulation With H-Coil Coupled With Cycling for Improving Lower Limb Motor Function After Stroke: An Exploratory Study.

Neuromodulation 2021 Jul 29;24(5):916-922. Epub 2020 Jul 29.

Neurorehabilitation Department, Hospital San Raffaele, Milan, Italy.

Background/objectives: Repetitive transcranial magnetic stimulation (rTMS) has been recognized as a promising intervention for the treatment of post-stroke motor deficits. Here, we explore safety, feasibility, and potential effectiveness of high-frequency rTMS (HF-rTMS) delivered with the Hesed coil (H-coil) during active cycling on paretic lower extremity (LE) motor function in chronic stroke.

Materials And Methods: Twelve subjects with a first-ever stroke were recruited in this double-blind, placebo controlled, crossover study. Eleven sessions of HF-rTMS (40 2s-trains of 20 Hz at 90% resting leg motor threshold) were delivered over the LE motor areas using the H-coil during active cycling for three weeks. Each subject underwent both real and sham rTMS treatments separated by a four-week washout period, in a random sequence. Vital signs were recorded before and after each rTMS session. Any discomfort related to stimulation and side effects were recorded. LE function was also evaluated with Fugl-Meyer assessment (FMA-LE), spasticity was assessed with modified-Ashworth scale and measures of gait speed and endurance (10-meter and 6-min walk tests, respectively) were recorded.

Results: No participant reported serious adverse effects. During real rTMS, 4 of 12 subjects reported mild side effects including transitory dizziness and muscle twitches on shoulder, so that intensity of stimulation initially set at 90% of RMT was reduced to 80% of RMT on average in these four subjects. Only real treatment was associated with a significant and sustained improvement in FMA-LL (67% responders vs. 9% of the sham). Spasticity significantly ameliorated only after the real rTMS. Real treatment did not offer advantages on walking timed measures when compared with sham.

Conclusions: This exploratory study suggests that bilateral HF-rTMS combined with cycling is safe and potentially effective in ameliorating paretic LE motor function and spasticity, rather than gait speed or endurance, in chronic stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.13228DOI Listing
July 2021

Walking-related digital mobility outcomes as clinical trial endpoint measures: protocol for a scoping review.

BMJ Open 2020 07 19;10(7):e038704. Epub 2020 Jul 19.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

Introduction: Advances in wearable sensor technology now enable frequent, objective monitoring of real-world walking. Walking-related digital mobility outcomes (DMOs), such as real-world walking speed, have the potential to be more sensitive to mobility changes than traditional clinical assessments. However, it is not yet clear which DMOs are most suitable for formal validation. In this review, we will explore the evidence on discriminant ability, construct validity, prognostic value and responsiveness of walking-related DMOs in four disease areas: Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease and proximal femoral fracture.

Methods And Analysis: Arksey and O'Malley's methodological framework for scoping reviews will guide study conduct. We will search seven databases (Medline, CINAHL, Scopus, Web of Science, EMBASE, IEEE Digital Library and Cochrane Library) and grey literature for studies which (1) measure differences in DMOs between healthy and pathological walking, (2) assess relationships between DMOs and traditional clinical measures, (3) assess the prognostic value of DMOs and (4) use DMOs as endpoints in interventional clinical trials. Two reviewers will screen each abstract and full-text manuscript according to predefined eligibility criteria. We will then chart extracted data, map the literature, perform a narrative synthesis and identify gaps.

Ethics And Dissemination: As this review is limited to publicly available materials, it does not require ethical approval. This work is part of Mobilise-D, an Innovative Medicines Initiative Joint Undertaking which aims to deliver, validate and obtain regulatory approval for DMOs. Results will be shared with the scientific community and general public in cooperation with the Mobilise-D communication team.

Registration: Study materials and updates will be made available through the Center for Open Science's OSFRegistry (https://osf.io/k7395).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-038704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371223PMC
July 2020

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

Telemed J E Health 2020 12 13;26(12):1533-1536. Epub 2020 Jul 13.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli," Naples, Italy.

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. 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. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/tmj.2020.0184DOI Listing
December 2020

Real-time assessment of COVID-19 prevalence among multiple sclerosis patients: a multicenter European study.

Neurol Sci 2020 Jul 2;41(7):1647-1650. Epub 2020 Jul 2.

Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, via Olgettina 60, 20132, Milan, Italy.

We assessed the prevalence and impact of COVID-19 among multiple sclerosis (MS) patients across Europe by leveraging participant data collected as part of the ongoing EU IMI2 RADAR-CNS major programme aimed at finding new ways of monitoring neurological disorders using wearable devices and smartphone technology. In the present study, 399 patients of RADAR-MS have been included (mean age 43.9 years, 60.7% females) with 87/399 patients (21.8%) reporting major symptoms suggestive of COVID-19. A trend for an increased risk of COVID-19 symptoms under alemtuzumab and cladribine treatments in comparison to injectables was observed. Remote monitoring technologies may support health authorities in monitoring and containing the ongoing pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-020-04519-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331489PMC
July 2020
-->