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- Wearable Health Technology to Quantify the Functional Impact of Peripheral Neuropathy on Mobility in Parkinson’s Disease: A Systematic ReviewPublication . Corrà, Marta; Warmerdam, Elke; Vila-Chã, Nuno; Maetzler, Walter; Maia, LuisThe occurrence of peripheral neuropathy (PNP) is often observed in Parkinson's disease (PD) patients with a prevalence up to 55%, leading to more prominent functional deficits. Motor assessment with mobile health technologies allows high sensitivity and accuracy and is widely adopted in PD, but scarcely used for PNP assessments. This review provides a comprehensive overview of the methodologies and the most relevant features to investigate PNP and PD motor deficits with wearables. Because of the lack of studies investigating motor impairments in this specific subset of PNP-PD patients, Pubmed, Scopus, and Web of Science electronic databases were used to summarize the state of the art on PNP motor assessment with wearable technology and compare it with the existing evidence on PD. A total of 24 papers on PNP and 13 on PD were selected for data extraction: The main characteristics were described, highlighting major findings, clinical applications, and the most relevant features. The information from both groups (PNP and PD) was merged for defining future directions for the assessment of PNP-PD patients with wearable technology. We established suggestions on the assessment protocol aiming at accurate patient monitoring, targeting personalized treatments and strategies to prevent falls and to investigate PD and PNP motor characteristics.
- Advantages of an Automated Method Compared With Manual Methods for the Quantification of Intraepidermal Nerve Fiber in Skin BiopsyPublication . Corrà, Marta; Sousa, Mafalda; Reis, Inês; Tanganelli, Fabiana; Vila-Chã, Nuno; Sousa, Ana Paula; Magalhães, Rui; Sampaio, Paula; Taipa, Ricardo; Maia, LuisIntraepidermal nerve fiber density (IENFD) measurements in skin biopsy are performed manually by 1-3 operators. To improve diagnostic accuracy and applicability in clinical practice, we developed an automated method for fast IENFD determination with low operator-dependency. Sixty skin biopsy specimens were stained with the axonal marker PGP9.5 and imaged using a widefield fluorescence microscope. IENFD was first determined manually by 3 independent observers. Subsequently, images were processed in their Z-max projection and the intradermal line was delineated automatically. IENFD was calculated automatically (fluorescent images automated counting [FIAC]) and compared with manual counting on the same fluorescence images (fluorescent images manual counting [FIMC]), and with classical manual counting (CMC) data. A FIMC showed lower variability among observers compared with CMC (interclass correlation [ICC] = 0.996 vs 0.950). FIMC and FIAC showed high reliability (ICC = 0.999). A moderate-to-high (ICC = 0.705) was observed between CMC and FIAC counting. The algorithm process took on average 15 seconds to perform FIAC counting, compared with 10 minutes for FIMC counting. This automated method rapidly and reliably detects small nerve fibers in skin biopsies with clear advantages over the classical manual technique.
- Timely and Blood-Based Multiplex Molecular Profiling of Acute StrokePublication . Dias, Alexandre; Silva, Isabel; Pinto, Inês Mendes; Maia, LuisStroke is a leading cause of death and disability in the world. To address such a problem, early diagnosis and tailored acute treatment represent one of the major priorities in acute stroke care. Since the efficacy of reperfusion treatments is highly time-dependent, there is a critical need to optimize procedures for faster and more precise diagnosis. We provide a concise review of the most relevant and well-documented blood-protein biomarkers that exhibit greater potential for translational to clinical practice in stroke differential diagnosis and to differentiate ischemic stroke from hemorrhagic stroke, followed by an overview of the most recent point-of-care technological approaches to address this problem. The integration of fluid-based biomarker profiling, using point-of-care biosensors with demographic, clinical, and neuroimaging parameters in multi-dimensional clinical decision-making algorithms, will be the next step in personalized stroke care.
- Does SARS‐Cov‐2 invade the brain? Translational lessons from animal modelsPublication . Natoli, S.; Oliveira, V.; Calabresi, P.; Maia, Luis; Pisani, A.The current coronavirus disease (COVID-19) outbreak, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised the possibility of potential neurotropic properties of this virus. Indeed, neurological sequelae of SARS-CoV-2 infection have already been reported and highlight the relevance of considering the neurological impact of coronavirus (CoV) from a translational perspective. Animal models of SARS and Middle East respiratory syndrome, caused by structurally similar CoVs during the 2002 and 2012 epidemics, have provided valuable data on nervous system involvement by CoVs and the potential for central nervous system spread of SARS-CoV-2. One key finding that may unify these pathogens is that all require angiotensin-converting enzyme 2 as a cell entry receptor. The CoV spike glycoprotein, by which SARS-CoV-2 binds to cell membranes, binds angiotensin-converting enzyme 2 with a higher affinity compared with SARS-CoV. The expression of this receptor in neurons and endothelial cells hints that SARS-CoV-2 may have higher neuroinvasive potential compared with previous CoVs. However, it remains to be determined how such invasiveness might contribute to respiratory failure or cause direct neurological damage. Both direct and indirect mechanisms may be of relevance. Clinical heterogeneity potentially driven by differential host immune-mediated responses will require extensive investigation. Development of disease models to anticipate emerging neurological complications and to explore mechanisms of direct or immune-mediated pathogenicity in the short and medium term is therefore of great importance. In this brief review, we describe the current knowledge from models of previous CoV infections and discuss their potential relevance to COVID-19.
- The international European Academy of Neurology survey on neurological symptoms in patients with COVID‐19 infectionPublication . Moro, E.; Priori, A.; Beghi, E.; Helbok, R.; Campiglio, L.; Bassetti, C. L.; Bianchi, E.; Maia, Luis; Ozturk, S.; Cavallieri, F.; Zedde, M.; Sellner, J.; Bereczki, D.; Rakusa, M.; Di Liberto, G.; Sauerbier, A.; Pisani, A.; Macerollo, A.; Soffietti, R.; Taba, P.; Crean, M.; Twardzik, A.; Oreja‐Guevara, C.; Bodini, B.; Jenkins, T. M.; Oertzen, T. J.Background and purpose: Although the main clinical features of COVID-19 infection are pulmonary, several associated neurological signs, symptoms and diseases are emerging. The incidence and characteristics of neurological complications are unclear. For this reason, the European Academy of Neurology (EAN) core COVID-19 Task Force initiated a survey on neurological symptoms observed in patients with COVID-19 infection. Methods: A 17-question online survey was made available on the EAN website and distributed to EAN members and other worldwide physicians starting on 9 April 2020. Results: By 27 April 2020, proper data were collected from 2343 responders (out of 4199), of whom 82.0% were neurologists, mostly from Europe. Most responders (74.7%) consulted patients with COVID-19 mainly in emergency rooms and in COVID-19 units. The majority (67.0%) had evaluated fewer than 10 patients with neurological manifestations of COVID-19 (neuro COVID-19). The most frequently reported neurological findings were headache (61.9%), myalgia (50.4%), anosmia (49.2%), ageusia (39.8%), impaired consciousness (29.3%) and psychomotor agitation (26.7%). Encephalopathy and acute cerebrovascular disorders were reported at 21.0%. Neurological manifestations were generally interpreted as being possibly related to COVID-19; they were most commonly recognized in patients with multiple general symptoms and occurred at any time during infection. Conclusion: Neurologists are currently and actively involved in the management of neurological issues related to the COVID-19 pandemic. This survey justifies setting up a prospective registry to better capture the prevalence of patients with neuro COVID-19, neurological disease characteristics and the contribution of neurological manifestations to outcome.
- Gait speed in clinical and daily living assessments in Parkinson’s disease patients: performance versus capacityPublication . Atrsaei, Arash; Corrà, Marta; Dadashi, Farzin; Vila Cha, Nuno; Maia, Luis; Mariani, Benoit; Maetzler, Walter; Aminian, KamiarGait speed often referred as the sixth vital sign is the most powerful biomarker of mobility. While a clinical setting allows the estimation of gait speed under controlled conditions that present functional capacity, gait speed in real-life conditions provides the actual performance of the patient. The goal of this study was to investigate objectively under what conditions during daily activities, patients perform as well as or better than in the clinic. To this end, we recruited 27 Parkinson's disease (PD) patients and measured their gait speed by inertial measurement units through several walking tests in the clinic as well as their daily activities at home. By fitting a bimodal Gaussian model to their gait speed distribution, we found that on average, patients had similar modes in the clinic and during daily activities. Furthermore, we observed that the number of medication doses taken throughout the day had a moderate correlation with the difference between clinic and home. Performing a cycle-by-cycle analysis on gait speed during the home assessment, overall only about 3% of the strides had equal or greater gait speeds than the patients' capacity in the clinic. These strides were during long walking bouts (>1 min) and happened before noon, around 26 min after medication intake, reaching their maximum occurrence probability 3 h after Levodopa intake. These results open the possibility of better control of medication intake in PD by considering both functional capacity and continuous monitoring of gait speed during real-life conditions.
- Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment - the ComOn-studyPublication . Geritz, Johanna; Maetzold, Sara; Steffen, Maren; Pilotto, Andrea; Corrà, Marta; Moscovich, Mariana; Rizzetti, Maria C; Borroni, Barbara; Padovani, Alessandro; Alpes, Annekathrin; Bang, Corinna; Barcellos, Igor; Baron, Ralf; Bartsch, Thorsten; Becktepe, Jos S; Berg, Daniela; Bergeest, Lu M; Bergmann, Philipp; Bouça-Machado, Raquel; Drey, Michael; Elshehabi, Morad; Farahmandi, Susan; Ferreira, Joaquim J; Franke, Andre; Friederich, Anja; Geisler, Corinna; Hüllemann, Philipp; Gierthmühlen, Janne; Granert, Oliver; Heinzel, Sebastian; Heller, Maren K; Hobert, Markus A; Hofmann, Marc; Jemlich, Björn; Kerkmann, Laura; Knüpfer, Stephanie; Krause, Katharina; Kress, Maximilian; Krupp, Sonja; Kudelka, Jennifer; Kuhlenbäumer, Gregor; Kurth, Roland; Leypoldt, Frank; Maetzler, Corina; Maia, Luis; Moewius, Andreas; Neumann, Patricia; Niemann, Katharina; Ortlieb, Christian T; Paschen, Steffen; Pham, Minh H; Puehler, Thomas; Radloff, Franziska; Riedel, Christian; Rogalski, Marten; Sablowsky, Simone; Schanz, Elena M; Schebesta, Linda; Schicketmüller, Andreas; Studt, Simone; Thieves, Martina; Tönges, Lars; Ullrich, Sebastian; Urban, Peter P; Vila-Chã, Nuno; Wiegard, Anna; Warmerdam, Elke; Warnecke, Tobias; Weiss, Michael; Welzel, Julius; Hansen, Clint; Maetzler, WalterBackground: Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany). Methods: This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week's inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters. Discussion: This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.