Catarina Godinho

Technology in Parkinson's disease: Challenges and opportunities

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinsons disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide‐scale and long‐term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the “big data” acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open‐source and/or open‐hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self‐adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed‐loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico‐pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease‐modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD.

A systematic review of the characteristics and validity of monitoring technologies to assess Parkinson’s disease

BackgroundThere is growing interest in having objective assessment of health-related outcomes using technology-based devices that provide unbiased measurements which can be used in clinical practice and scientific research. Many studies have investigated the clinical manifestations of Parkinson’s disease using such devices. However, clinimetric properties and clinical validation vary among the different devices.MethodsGiven such heterogeneity, we sought to perform a systematic review in order to (i) list, (ii) compare and (iii) classify technological-based devices used to measure motor function in individuals with Parkinsons disease into three groups, namely wearable, non-wearable and hybrid devices. A systematic literature search of the PubMed database resulted in the inclusion of 168 studies. These studies were grouped based on the type of device used. For each device we reviewed availability, use, reliability, validity, and sensitivity to change. The devices were then classified as (i) ‘recommended’, (ii) ‘suggested’ or (iii) ‘listed’ based on the following criteria: (1) used in the assessment of Parkinson’s disease (yes/no), (2) used in published studies by people other than the developers (yes/no), and (3) successful clinimetric testing (yes/no).ResultsSeventy-three devices were identified, 22 were wearable, 38 were non-wearable, and 13 were hybrid devices. In accordance with our classification method, 9 devices were ‘recommended’, 34 devices were ‘suggested’, and 30 devices were classified as ‘listed’. Within the wearable devices group, the Mobility Lab sensors from Ambulatory Parkinson’s Disease Monitoring (APDM), Physilog®, StepWatch 3, TriTrac RT3 Triaxial accelerometer, McRoberts DynaPort, and Axivity (AX3) were classified as ‘recommended’. Within the non-wearable devices group, the Nintendo Wii Balance Board and GAITRite® gait analysis system were classified as ‘recommended’. Within the hybrid devices group only the Kinesia® system was classified as ‘recommended’.

New methods for the assessment of Parkinson's disease (2005 to 2015): A systematic review.

The past decade has witnessed a highly dynamic and growing expansion of novel methods aimed at improving the assessment of Parkinsons disease with technology (NAM‐PD) in laboratory, clinical, and home environments. However, the current state of NAM‐PD regarding their maturity, feasibility, and usefulness in assessing the main PD features has not been systematically evaluated.

Cognitive Impairment in Fall-Related Studies in Parkinson’s Disease

Abstract Background: There is increasing evidence to suggest a tight relationship between cognitive impairment and falls in Parkinson’s disease (PD). Here, we draw attention to a potentially significant flaw in the existent falls-related research, namely the apparent exclusion of patients with cognitive impairment or dementia. Objective: Our objective was to review all published, on-going or scheduled fall-related intervention studies, in order to investigate the extent to which cognitively impaired individuals with PD were included in these studies. Methods: We analyzed published controlled trials regarding falls and PD in commonly used databases, as well as relevant ongoing clinical trials registered within the World Health Organization database, clinicaltrials.gov and the European Clinical Trials Database. Results: Fourteen of the fifteen published studies included had explicit cognitive exclusion criteria as part of their study protocol. Most of the 54 on-going PD fall-related studies excluded patients with cognitive impairment. Conclusions: This suggests that individuals with cognitive impairment or dementia are excluded from fall-related research studies. We strongly recommend that future work in this area should include a representative sample of patients with PD, including subjects with cognitive decline.

Speech and Voice Response to a Levodopa Challenge in Late-Stage Parkinson's Disease

Background Parkinson’s disease (PD) patients are affected by hypokinetic dysarthria, characterized by hypophonia and dysprosody, which worsens with disease progression. Levodopa’s (l-dopa) effect on quality of speech is inconclusive; no data are currently available for late-stage PD (LSPD). Objective To assess the modifications of speech and voice in LSPD following an acute l-dopa challenge. Method LSPD patients [Schwab and England score <50/Hoehn and Yahr stage >3 (MED ON)] performed several vocal tasks before and after an acute l-dopa challenge. The following was assessed: respiratory support for speech, voice quality, stability and variability, speech rate, and motor performance (MDS-UPDRS-III). All voice samples were recorded and analyzed by a speech and language therapist blinded to patients’ therapeutic condition using Praat 5.1 software. Results 24/27 (14 men) LSPD patients succeeded in performing voice tasks. Median age and disease duration of patients were 79 [IQR: 71.5–81.7] and 14.5 [IQR: 11–15.7] years, respectively. In MED OFF, respiratory breath support and pitch break time of LSPD patients were worse than the normative values of non-parkinsonian. A correlation was found between disease duration and voice quality (R = 0.51; p = 0.013) and speech rate (R = −0.55; p = 0.008). l-Dopa significantly improved MDS-UPDRS-III score (20%), with no effect on speech as assessed by clinical rating scales and automated analysis. Conclusion Speech is severely affected in LSPD. Although l-dopa had some effect on motor performance, including axial signs, speech and voice did not improve. The applicability and efficacy of non-pharmacological treatment for speech impairment should be considered for speech disorder management in PD.

Substantia Nigra Neuromelanin as an Imaging Biomarker of Disease Progression in Parkinson’s Disease

BACKGROUND A specific T1-weighted magnetic resonance imaging (MRI) sequence has been shown to detect substantia nigra (SN) neuromelanin (NM) signal changes that accurately discriminate Parkinsons disease (PD) patients from controls, even in early disease stages. However, it is unclear what happens to these SN changes in later disease stages and if they can be a marker of disease progression. OBJECTIVE to investigate the pattern of SN-NM area loss and contrast ratio (CR) intensity changes in late-stage PD (LSPD) compared to earlier disease stages. METHODS A comparative cross-sectional study was performed, analyzing SN-NM MRI signal in LSPD (Schwab and England Activities of Daily Living Scale score <50 or Hoehn Yahr Stage [HY] >3), comparing this group with de novo, 2-5 year PD and controls. SN-NM signal area and CR values for the internal and lateral SN regions were obtained with semi-automated methods. RESULTS 13 LSPD, 12 de novo patients with PD, 10 PD patients with a 2-5 year disease duration, and 10 controls were included. NM signal area was significantly decreased in LSPD compared to de novo PD (P-value = 0.005; sensitivity: 75%; specificity 92% and AUC: 0.86). In the lateral SN region, a decrease in the CR was detected in all PD groups compared to controls; despite not reaching statistical significance, a slight increment was observed comparing LSPD to 2-5 year PD. NM signal area significantly correlated with HY (R = -0.37; P < 0.05) and Movement disorder Society Unified Parkinsons Disease Rating Scale part II (MDS-UPDRS) (R = -0.4; P < 0.05) while a weak correlation was found with MDS-UPDRS part III (R = -0.26; P: 0.1). CONCLUSION SN area evaluated by NM-sensitive MRI may be a promising biomarker of nigral degeneration and disease progression in PD patients.

Disability in Activities of Daily Living and Severity of Dyskinesias Determine the Handicap of Parkinson’s Disease Patients in Advanced Stage Selected to DBS

BACKGROUND There is scarce data on the level of handicap in Parkinsons disease (PD) and none in advanced stage PD. OBJECTIVE To assess the handicap in advanced stage PD patients with disabling levodopa-induced motor complications selected to deep brain stimulation (DBS). METHODS Data was prospectively recorded during routine evaluation for DBS. Handicap was measured using London Handicap Scale (LHS) (0 = maximal handicap; 1 = no handicap). Disease severity was evaluated using the Hoehn & Yahr scale and the UPDRS/MDS-UPDRS, during off and on after a supra-maximal dose of levodopa. Schwab and England Scale (S&E) was scored in off and on. Dyskinesias were scored using the modified Abnormal Involuntary Movement Scale (mAIMS). Results concern cross-sectional assessment before DBS. RESULTS 100 PD patients (mean age 61 (±7.6); mean disease duration 12.20 (±4.6) years) were included. Median score of motor MDS-UPDRS was 54 in off and 25 in on. Mean total LHS score was 0.56 (±0.14). Patients were handicapped in several domains with a wide range of severity. Physical Independence and Social Integration were the most affected domains. Determinants of total LHS score were MDS-UPDRS part II off (β= -0.271; p = 0.020), S&E on (β= 0.264; p = 0.005) and off (β= 0.226; p = 0.020), and mAIMS on (β= -0.183; p = 0.042) scores (R2  = 29.6%). CONCLUSIONS We were able to use handicap to measure overall health condition in advanced stage PD. Patients were moderately to highly handicapped and this was strongly determined by disability in ADL and dyskinesias. Change in handicap may be a good patient-centred outcome to assess efficiency of DBS.

Feasibility of using risk prompts to prevent falls, dehydration and pulmonary aspiration in nursing homes: a clinical study protocol

BackgroundEvidence has shown a relationship between dehydration, falls, and pulmonary aspiration among older adults in nursing homes, all of which contribute to loss of independence and quality of life. It is believed that improving communication among healthcare professionals in nursing homes (physicians, nurses, rehabilitation team, psychologist, social workers, dieticians and medical assistants) decreases the number of adverse events in institutionalized patients. This study will evaluate the feasibility of using a set of written signs, designed to caution against the risk of falls, dehydration, and pulmonary aspiration, and will enable the proposal of tailored interventions to manage these events in nursing homes.Methods/DesignAll patients from Campus Neurológico Sénior (CNS) nursing home, at risk of falls and/ordysphagia and/or dehydration will be invited to participate in the study. Patients will undertake a screeningrisk assessment and the corresponding risk prompts will be attributed. Study duration will be a minimum ofthree months per participant, including daily record of falls, dehydration and pulmonary aspiration eventsand monthly interview assessments, conducted by a member of the research team. Data of the events that occur will be compared with historical data extracted retrospectively from medical and nursing charts. This study has been approved by the Ethics Committee of the Medical Academic Center of Lisbon, Faculty of Medicine, University of Lisbon (Ref. 176/15). All participants will give their written informed consent before entering the study.DiscussionThis study is unique in evaluating the feasibility of a communication system in preventing the three major risks in nursing home. Thoughtful selection and display of proper risk prompts in nursing homes could be an essential step along a path toward efficient communication of risks among healthcare teams. We expect that the displays will be easily applicable given their simplicity, low complexity, and minimal physical requirements.Trial registrationNCT03123601. March 7, 2017. Retrospectively registered.

Proliferation of community exercise programs with limited evidence and expertise: Safety implications: Proliferation of community exercise programs

A number of research studies underscore the beneficial effects that physiotherapy and exercise can have on functional activities involving gait, transfers, and balance in Parkinson’s disease (PD). People with Parkinson’s (PwP) can receive this care in a range of settings from various professionals. Evidence is emerging that supports a number of community programs for PwP that incorporate different nonconventional types of group exercises, including dance, boxing, Nordic walking, tai chi, and aquatic exercise. There are reasons to be optimistic that these new initiatives may be a long-term cost-effective and easily accessible care strategy for ongoing exercise for PwP. However, data regarding their true benefits and the best approaches to implementation are still limited. Notably, there is an optimal minimal level of disease-specific expertise necessary, particularly with respect to safely integrating exercises and reducing the risk of falls and other possible safety issues. By prematurely referring PwP to exercise approaches that do not have robust evidence and are led by instructors with a lack of professional expertise, health professionals may favor unnecessary procedures, foster unrealistic expectations in PwP (particularly those with less favorable profiles), and could ultimately be putting patients at risk of falls and/or injury. As such, several important questions regarding the specificity to PD and safety issues are now arising that should fuel future research. First, should we obtain more evidence about these community exercise programs and then implement them within the community setting, or should we start these programs first, even if little evidence is available? Second, taking into account the financial considerations, accessibility, and safety issues and the progressive nature of the disease, who should implement such community programs? Should physiotherapists incorporate boxing, dance, or tai chi into to their clinical practice? Or would it be more feasible while equally effective to train exercise instructors who teach community programs? Safe evidence-based practices must be a priority for care in all settings, including the community. Several courses of action may be needed to address the gap between expertise, evidence, its dissemination, and its implementation into community exercise practices. Programs must be made available and accessible to PwP by reducing critical financial and travel barriers. If evidencebased practices are not covered or are inaccessible, they will simply not be used. Even if PwP may have limited access to evidenced-based care, that care, when delivered, should be delivered by instructors with PD expertise. It is critical to enhance expertise among professionals who deliver these exercise programs through specific training, adequate ongoing educational support, and continuous contact with PwP. In addition, we also need to enhance public and PwP awareness of evidence-based exercise programs and their locations. Increasing public interest in community exercise programs may also potentially positively influence the direction of clinical research and advance clinical practice. All these actions can begin to guide us away from care disparities and promote better care for PwP. Without them, no amount of evidence will matter.

Neuromelanin magnetic resonance imaging of the substantia nigra in LRRK2‐related Parkinson's disease

Specific T1-weighted MRI sequences are able to detect SN neuromelanin (NM) signal changes and accurately discriminate Parkinson’s disease (PD) patients from controls. The study of NM-MRI in PD patients carrying a LRRK2 gene mutation (LRRK2-PD) could contribute to further uncover LRRK2-associated phenotype. Albeit considered to largely overlap idiopathic PD (iPD), differences have been described. Furthermore, the identification of a biomarker of neurodegeneration in LRRK2-PD can eventually support studies in asymptomatic carriers. Castellanos and colleagues found NM-MRI SN volumes significantly reduced in both idiopathic and LRRK2-PD (3 G2019S and 4 R1441G PD patients). Our study aimed to further investigate neuromelanin imaging in LRRK2-PD. We performed a cross-sectional study including LRRK2-PD patients, control individuals with no signs or family history of a neurodegenerative disorder, and PD patients with no LRRK2 mutations identified (referred as iPD). Our primary outcome was SN neuromelanin high signal area obtained with semiautomated methods. LRRK2-PD and iPD patients were identified through previous and recent genetic studies. Clinical assessments were performed in best On. Imaging was acquired using a 3.0 Tesla scanner and NM-sensitive pulse sequence was used as previously described. OsiriX software was used for imaging postprocessing. Data analysis was blinded to clinical and genetic status. Kruskal-Wallis, with pair-wise comparisons (Bonferroni method applied), and Mann-Whitney U tests were used as appropriate (P < 0.05). Nonparametric receiver operating characteristic curves were constructed for calculating NM imaging area sensitivity and specificity for discriminating groups. Thirteen LRRK2-PD patients (10 G2019S, 3 R1441H), 10 controls, and 13 iPD patients were included. No significant differences between groups were identified concerning sex, age at disease onset (59.7 6 12.3 LRRK2-PD vs. 61.8 6 11.8 iPD), disease duration (7.7 6 3.5 LRRK2-PD vs. 10.7 6 4.3 iPD), MDS-UPDRS I, III (36.8 6 13.0 LRRK2-PD; 41.2 6 16.2 iPD), and IV scores, or levodopa equivalent daily dose. Mean age at examination in LRRK2PD (67.4 6 12.9), control (61.2 6 7.4), and iPD (72.5 6 12.7) groups were different. Although when comparing LRRK2-PD versus controls (P 5 0.1640) and LRRK2-PD versus iPD (P 5 0.3220) mean age at examination was not statistically significantly different, iPD group presented a significantly higher mean age at examination when compared to controls (P 5 0.0211), limiting results interpretation. The H & Y (2.0 6 0.1 LRRK2-PD vs. 3.0 6 0.9 iPD) and MDS-UPDRS II scores were significantly worse in iPD. Median SN NM area was significantly decreased in the LRRK2-PD group compared to controls (Fig. 1). Furthermore, when only considering G2019S LRRK2-PD, median SN NM signal area was also significantly decreased compared to controls. No differences were found between LRRK2-PD and iPD groups. High signal area showed 92.3% sensitivity and 100% specificity for discriminating LRRK2-PD patients from controls (cut off: 28.24 mm). In our study, NM-MR imaging of the SN was able to differentiate LRRK2-PD patients from controls, and NM signal