Gaëtan Garraux

The objective of this work is to implement and test an innovative single-unit multi-PPG measurement system to assess pulse transit time (PTT) measured between two sites on the forearm as a potential indicator of blood pressure (BP). It aims to provide additional insight into the many non-invasive methods of BP measurement, none of which has yet achieved consensus. We have developed a highly integrated patch-type flexible sensor system consisting of the assembly of a flexible circuit board and flexible materials. It does not apply pressure on the forearm, and it prioritizes user comfort. This system was tested on eleven test subjects to collect PTT related data, including variability and correlation of PTT with BP. Results showed high variability both across subjects and across days within the same subject. Furthermore, we found no correlation between PTT measured along a segment of the forearm and BP. The PPT measured on a single limb does not appear to be a stand-alone indicator of BP.

While inertial measurement unit (IMU)-based systems have shown their potential in quantifying medically significant gait parameters, it remains to be determined whether they can provide accurate and reliable parameters both across various walking conditions and in healthcare settings. Using an IMU-based system we previously developed, with one IMU module on each subject’s heel, we quantify the gait parameters of 55 men and 46 women, all healthy and aged 40–65, in normal, dual-task, and fast walking conditions. We evaluate their intra-session reliability, and we establish a new reference database of such parameters showing good to excellent reliability. ICC(2,1) assesses relative reliability, while SEM% and MDC% assess absolute reliability. The reliability is excellent for all spatiotemporal gait parameters and the stride length (SL) symmetry ratio (ICC ≥ 0.90, SEM% ≤ 4.5%, MDC% ≤ 12.4%) across all conditions. It is good to excellent for the fast walking performance (FWP) indices of stride (Sr), stance (Sa), double-support (DS), and step (St) times; gait speed (GS); and the GS normalized to leg length (GS_n1) and body height (GS_n2) (ICC ≥ 0.91, |SEM%| ≤ 10.0%, |MDC%| ≤ 27.6%). Men have a higher swing time (Sw) and SL across all conditions. The following parameters are gender-independent: (1) Sa, DS, GS_n1, GS_n2; (2) the symmetry ratios of SL and GS, as well as Sa% and Sw% (representing Sa and Sw as percentages of Sr); and (3) the FWPs of Sr, Sa, Sw, DS, St, cadence, Sa% and Sw%. Our results provide reference values with new insights into gender FWP comparisons rarely reported in the literature. The advantages and reliability of our IMU-based system make it suitable in medical applications such as prosthetic evaluation, fall risk assessment, and rehabilitation.

While inertial measurement unit (IMU)-based systems have shown their potential in quantifying medically-significant gait parameters, it remains to be demonstrated that they can provide accurate and reliable parameters both across various walking conditions and in healthcare settings. Using an IMU-based system we have previously developed, with one IMU module on each subject’s heel, we quantify gait parameters in 55 men and 46 women, all healthy and aged 40-65, in normal, dual-task, and fast-walking conditions. We evaluate their intra-session reliability, and we establish a new reference database of such parameters showing good to excellent reliability. ICC(2,1) assesses relative reliability, while SEM% and MDC% evaluate absolute reliability. The reliability is excellent for all spatiotemporal gait parameters and stride length (SL) symmetry ratio (ICC≥0.90, SEM%≤4.5%, MDC%≤12.4%) across all conditions. It is good to excellent for fast-walking performance (FWP) indices of stride (Sr), stance (Sa), double-support (DS), and step (St) times; gait speed (GS), and GS normalized to leg length (GSn1) and body height (GSn2) (ICC≥0.91, |SEM%|≤10.0%, |MDC%|≤27.6%). Men have higher swing time (Sw) and SL across all conditions. The following parameters are gender-independent: (1) Sa, DS, GSn1, GSn2; (2) symmetry ratios of Sa, Sa ratio (Sa%), Sw, Sw ratio (Sw%), SL, GS; and (3) FWPs of Sr, Sa, Sw, DS, St, cadence, Sa%, Sw%. Our results provide reference values with new insights into gender FWP comparisons rarely reported in the literature. The advantages and reliability of our IMU-based system make it suitable in medical applications such as prosthetic evaluation, fall-risk assessment, and rehabilitation.

Alterations in subcortical brain regions are linked to motor and non-motor symptoms in Parkinson’s disease (PD). However, associations between clinical expression and regional morphological abnormalities of the basal ganglia, thalamus, amygdala and hippocampus are not well established. We analyzed 3D T1-weighted brain MRI and clinical data from 2525 individuals with PD and 1326 controls from 22 global sources in the ENIGMA-PD consortium. We investigated disease effects using mass univariate and multivariate models on the medial thickness of 27,120 vertices of seven bilateral subcortical structures. Shape differences were observed across all Hoehn and Yahr (HY) stages, as well as correlations with motor and cognitive symptoms. Notably, we observed incrementally thinner putamen from HY1, caudate nucleus and amygdala from HY2, hippocampus, nucleus accumbens, and thalamus from HY3, and globus pallidus from HY4–5. Subregions of the thalami were thicker in HY1 and HY2. Largely congruent patterns were associated with a longer time since diagnosis and worse motor symptoms and cognitive performance. Multivariate regression revealed patterns predictive of disease stage. These cross-sectional findings provide new insights into PD subcortical degeneration by demonstrating patterns of disease stage-specific morphology, largely consistent with ongoing degeneration.

Background: Deep brain stimulation (DBS) has shown some efficacy in monogenic Parkinson’s disease; however, data about its long-term benefit in SNCA mutations remain scarce. Case report: Subthalamic nucleus DBS was implanted in a 60-year-old female patient with Parkinson’s disease due to SNCA duplication. One year later, the patient walked unassisted and was independent for most activities of daily living, without requiring any anti-Parkinson’s medication. Discussion: To our knowledge, four cases of bilateral subthalamic DBS have been reported previously. This case report adds an additional body of evidence of improved one-year outcome after DBS surgery in a patient with SNCA mutation. Highlights: This is a case report of a patient with genetic parkinsonism due to SNCA duplication undergoing bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. The outcome was favorable one year after implantation, with the patient coming off all anti-Parkinson’s medications. This further clarifies DBS outcome in monogenic Parkinson’s disease.

Parkinson’s disease (PD) is a neurodegenerative synucleinopathy characterized by the degeneration of neuromelanin (NM)-containing dopaminergic neurons and deposition of iron in the substantia nigra (SN). How regional NM loss and iron accumulation within specific areas of SN relate to nigro-striatal dysfunction needs to be clarified. We measured dopaminergic function in pre- and postcommissural putamen by [¹⁸F]DOPA PET in 23 Parkinson’s disease patients and 23 healthy control (HC) participants in whom NM content and iron load were assessed in medial and lateral SN, respectively, by NM-sensitive and quantitative R2* MRI. Data analysis consisted of voxelwise regressions testing the group effect and its interaction with NM or iron signals. In PD patients, R2* was selectively increased in left lateral SN as compared to healthy participants, suggesting a local accumulation of iron in Parkinson’s disease. By contrast, NM signal differed between PD and HC, without specific regional specificity within SN. Dopaminergic function in posterior putamen decreased as R2* increased in lateral SN, indicating that dopaminergic function impairment progresses with iron accumulation in the SN. Dopaminergic function was also positively correlated with NM signal in lateral SN, indicating that dopaminergic function impairment progresses with depigmentation in the SN. A complex relationship was detected between R2* in the lateral SN and NM signal in the medial SN. In conclusion, multimodal imaging reveals regionally specific relationships between iron accumulation and depigmentation within the SN of Parkinson’s disease and provides in vivo insights in its neuropathology.

Background: Brain structure abnormalities throughout the course of Parkinson’s disease (PD) have yet to be fully elucidated. Inconsistent findings across studies may be partly due to small sample sizes and heterogeneous analysis methods. Using a multicenter approach and harmonized analysis methods, we aimed to overcome these limitations and shed light on disease stage-specific profiles of PD pathology as suggested by in vivo neuroimaging. Methods: Individual brain MRI and clinical data from 2,367 PD patients and 1,183 healthy controls were collected from 19 sites, deriving from 20 countries. We analyzed regional cortical thickness, cortical surface area, and subcortical volume using mixed-effect linear models. Patients were grouped according to the Hoehn & Yahr (HY) disease stages and compared to age- and sex-matched controls. Within the PD sample, we investigated associations between Montreal Cognitive Assessment (MoCA) scores and brain morphology. Findings: The main analysis showed a thinner cortex in 38 of 68 regions in PD patients compared to controls ( dmax = −0·25, dmin = −0·13). The bilateral putamen (left: d = −0·16, right: d = −0·16) and left amygdala ( d = −0·15) were smaller in patients, while the left thalamus was larger ( d = 0·17). HY staging indicated that a thinner cortex initially presents in the occipital, parietal and temporal cortex, and extends towards caudally located brain regions with increased disease severity. From HY stage 2 and onwards the bilateral putamen and amygdala were consistently smaller with larger effects denoting each increment. Finally, we found that poorer cognitive performance was associated with widespread cortical thinning as well as lower volumes of core limbic structures. Interpretation: Our findings offer robust and novel imaging signatures that are specific to the disease severity stages and in line with an ongoing neurodegenerative process, highlighting the importance of such multicenter collaborations. Funding: NIH Big Data to Knowledge program, ENIGMA World Aging Center, and ENIGMA Sex Differences Initiative, and other international agencies (listed in full in the Acknowledgments).