Clinicopathological study of dementia with grains presenting with parkinsonism compared with a typical case.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

Precision Balance Assessment in Parkinson's Disease: Utilizing Vision-Based 3D Pose Tracking for Pull Test Analysis.

Postural instability is a common complication in advanced Parkinson's disease (PD) associated with recurrent falls and fall-related injuries. The test of retropulsion, consisting of a rapid balance perturbation by a pull in the backward direction, is regarded as the gold standard for evaluating postural instability in PD and is a key component of the neurological examination and clinical rating in PD (e.g., MDS-UPDRS). However, significant variability in test execution and interpretation contributes to a low intra- and inter-rater test reliability. Here, we explore the potential for objective, vision-based assessment of the pull test (vPull) using 3D pose tracking applied to single-sensor RGB-Depth recordings of clinical assessments. The initial results in a cohort of healthy individuals (n = 15) demonstrate overall excellent agreement of vPull-derived metrics with the gold standard marker-based motion capture. Subsequently, in a cohort of PD patients and controls (n = 15 each), we assessed the inter-rater reliability of vPull and analyzed PD-related impairments in postural response (including pull-to-step latency, number of steps, retropulsion angle). These quantitative metrics effectively distinguish healthy performance from and within varying degrees of postural impairment in PD. vPull shows promise for straightforward clinical implementation with the potential to enhance the sensitivity and specificity of postural instability assessment and fall risk prediction in PD.

Unraveling the Twist: Spatial Navigational Challenges in Cervical Dystonia.

BACKGROUND: Cervical dystonia (CD) is an intricate neurological condition with motor and nonmotor symptoms. These include disruptions in visual perception, self-orientation, visual working memory, and vestibular functions. However, the specific impact of CD on perceiving self-motion direction, especially with isolated visual or vestibular stimuli, remains largely unexplored. OBJECTIVE: This study aimed to examine the effects of CD on linear motion perception, hypothesizing impaired heading discrimination in both vestibular and visual tasks, and that such deficits correlate with the disease severity. METHODS: We employed a cutting-edge motion platform to precisely control whole-body linear motion. Through repeated two-alternative forced-choice tasks, we assessed vestibular heading direction discrimination. Participants observed dynamic star clouds in immersive virtual reality and indicated their perceived self-motion direction, evaluating visual heading direction discrimination. Sensitivity to direction variations and response accuracy errors were analyzed using robust Gaussian cumulative distribution psychometric functions. RESULTS: Heading perception is impaired in individuals with CD, particularly evident in vestibular heading discrimination. CD severity correlated with elevated thresholds for both vestibular and visual heading discrimination. Surprisingly, lateralized CD did not introduce bias in either system, suggesting widespread disruption over localized effects. CONCLUSIONS: Contrary to previous beliefs, our findings challenge the idea that CD-related heading discrimination issues mainly arise from peripheral vestibular effects. Instead, abnormal proprioceptive input from dystonic neck muscles introduces noise into the central mechanism integrating visual, vestibular, and proprioceptive signals. These insights into spatial navigation deficits have implications for future CD research. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Does Head Tremor Predict Postural Instability After Bilateral Thalamic Stimulation in Essential Tremor?

Essential tremor (ET) may present with head tremor (HT), of presumed cerebellar nature. Deep brain stimulation (DBS) targeting the ventral intermediate (Vim) nucleus of the thalamus is a highly effective therapy for medication-refractory ET. However, stimulation-related side effects may include cerebellar abnormalities, such as postural instability. This retrospective cohort study evaluated the risk of post-Vim DBS postural instability (primary outcome measure) in patients with versus without head tremor (HT vs. nHT). The primary outcome measure, namely post-DBS postural instability, was assessed in both groups using a Wilcoxon rank sum t-test. The time to postural instability was determined using Cox proportional hazards regression analysis adjusted for age and sex. Out of 30 patients analyzed during the follow up period, there was similar postural instability detected in HT (9/14, 64%) and nHT patients (11/16, 69%) at 24 months post-Vim DBS (p=0.82), adjusted hazard ratio[aHR]=0.82, p=0.69). These data suggest that the presence or absence of HT does not have an impact on postural instability after bilateral Vim DBS in patients with ET.

Impact of deep brain stimulation therapy on the vertebral sagittal balance in Parkinson's disease patients.

Parkinson's disease (PD) is characterized by cardinal motor signs: 4-6 Hz resting tremor, rigidity, and bradykinesia. In addition, 3-18% of PD patients have camptocormia, an abnormal forward flexion of the thoracolumbar spine, which may have a negative impact on patients' quality of life. Different possible treatments have been suggested for such a condition, but no one is resolutive. This study aims to define the possible impact of DBS, with selective targeting on the dorsal-lateral region of the STN, on the sagittal balance of patients affected by PD. Among all patients that have undergone DBS procedures in our institution, we selected eight subjects, four females and four males, with selective targeting on the dorsal-lateral region of the subthalamic nucleus (STN) because of camptocormia and other severe postural changes. Radiological assessments of spinal balance parameters before surgery and at 6 and 12 months postoperatively were carried out. Comparison of preoperative and postoperative spine X-ray data showed a statistically significant improvement in dorsal kyphosis angle (D-Cobb) 12 months after the operation. Deep brain stimulation with selective targeting of the dorsal lateral part of the STN may induce changes of the posture in patients with Parkinson's disease 12 months after the operation, which appears to improve in this small sample size, but larger observational and controlled trials would be required to confirm this observation.

A Deep Learning Approach for Automatic and Objective Grading of the Motor Impairment Severity in Parkinson's Disease for Use in Tele-Assessments.

Wearable sensors provide a tool for at-home monitoring of motor impairment progression in neurological conditions such as Parkinson's disease (PD). This study examined the ability of deep learning approaches to grade the motor impairment severity in a modified version of the Movement Disorders Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) using low-cost wearable sensors. We hypothesized that expanding training datasets with motion data from healthy older adults (HOAs) and initializing classifiers with weights learned from unsupervised pre-training would lead to an improvement in performance when classifying lower vs. higher motor impairment relative to a baseline deep learning model (XceptionTime). This study evaluated the change in classification performance after using expanded training datasets with HOAs and transferring weights from unsupervised pre-training compared to a baseline deep learning model (XceptionTime) using both upper extremity (finger tapping, hand movements, and pronation-supination movements of the hands) and lower extremity (toe tapping and leg agility) tasks consistent with the MDS-UPDRS. Overall, we found a 12.2% improvement in accuracy after expanding the training dataset and pre-training using max-vote inference on hand movement tasks. Moreover, we found that the classification performance improves for every task except toe tapping after the addition of HOA training data. These findings suggest that learning from HOA motion data can implicitly improve the representations of PD motion data for the purposes of motor impairment classification. Further, our results suggest that unsupervised pre-training can improve the performance of motor impairment classifiers without any additional annotated PD data, which may provide a viable solution for a widely deployable telemedicine solution.

Resting-state functional magnetic resonance imaging study comparing tremor-dominant and postural instability/gait difficulty subtypes of Parkinson's disease.

PURPOSE: The symptom-specific intrinsic neural mechanisms underlying Parkinson's disease (PD) subtypes (tremor dominant [TD] and postural instability gait difficulty [PIGD]) remain unclarified. We examined spontaneous brain activity patterns in TD and PIGD. MATERIAL AND METHODS: We included 49 patients with PD (21 with TD/28 with PIGD) and 32 healthy controls (HCs) in this study. We conducted analysis of variance and post-hoc analyses of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values of the three groups, with age, sex, and gray matter volume as covariates, and a relationship analysis of the ALFF and ReHo values with clinical variables. RESULTS: In comparison with HCs, PIGD PD patients had increased ALFF values in the right middle occipital gyrus and left superior occipital gyrus and decreased values primarily in the bilateral inferior frontal gyrus (triangular part). TD PD patients had lower ALFF values in the right inferior frontal gyrus (triangular part) and left insula. In comparison to TD PD patients, PIGD PD patients had higher ALFF values in the left middle occipital gyrus and left superior occipital gyrus. In contrast to HCs, TD PD patients demonstrated a reduction of ReHo values in the left middle temporal gyrus, and PIGD patients showed a decrease of ReHo values in the left inferior temporal gyrus. CONCLUSION: ALFF values increased in the occipital gyrus of the PIGD PD patients, thus providing evidence of a compensatory mechanism of altered motor function in comparison with the TD PD patients.

Wearable sensors-based postural analysis and fall risk assessment among patients with diabetic foot neuropathy.

AIMS: To investigate the cross-sectional association between deep and superficial diabetic neuropathy, postural impairment assessed by wearable inertial sensors, and the risk of fall among patients with diabetic foot. METHODS: Diabetic patients attending a University Podiatric Clinic were evaluated for the presence of deep and superficial peripheral neuropathy in sensory tests. Postural impairment was assessed using a wearable inertial sensor, and the evaluation of balance/gait and risk of fall was determined by the Tinetti Scale and Downton Index, respectively. Glycemic control was measured by glycated haemoglobin concentration and fasting glycaemia. The postural parameters measured were the anteroposterior and medio-lateral sway of the center of mass (CoM) and the sway area (area traveled by the CoM per second). The results were analyzed through a logistic regression model to assess those posture variables mostly significantly associated with neuropathy and risk of fall scales. RESULTS: A total of 85 patients were evaluated. Spearman's rank correlation coefficients showed a strong and significant relationship (p < 0.05) between deep diabetic neuropathy assessed by Semmes-Weinstein monofilament, diapason and biothensiometer and postural alterations, whereas no significant correlations between superficial (painful sensitivity) neuropathy and the postural parameters. The sway path of the displacement along the anterior-posterior axis recorded during tests performed with eyes open and feet close together were significantly (p < 0.05) correlated with a poor glycemic (glycated haemoglobin concentration) control and each other with all diabetic neuropathy tests, fall risk scales, muscular weakness, ankle joint limitation and history of ulcers. CONCLUSIONS: The results support the existence of a strong association between alterations of the deep somato-sensitive pathway (although depending on the tool used to measure peripheral neuropathy), glycemic control and balance impairments assessed using a wearable sensors. Wearable-based postural analysis might be part of the clinical assessment that enables the detection of balance impairments and the risk of fall in diabetic patients with diabetic peripheral neuropathy.

Using kinematics to re-define the pull test as a quantitative biomarker of the postural response in normal pressure hydrocephalus patients.

Quantitative biomarkers are needed for the diagnosis, monitoring and therapeutic assessment of postural instability in movement disorder patients. The goal of this study was to create a practical, objective measure of postural instability using kinematic measurements of the pull test. Twenty-one patients with normal pressure hydrocephalus and 20 age-matched control subjects were fitted with inertial measurement units and underwent 10-20 pull tests of varying intensities performed by a trained clinician. Kinematic data were extracted for each pull test and aggregated. Patients participated in 103 sessions for a total of 1555 trials while controls participated in 20 sessions for a total of 299 trials. Patients were separated into groups by MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pull test score. The center of mass velocity profile easily distinguished between patient groups such that score increases correlated with decreases in peak velocity and later peak velocity onset. All patients except those scored as "3" demonstrated an increase in step length and decrease in reaction time with increasing pull intensity. Groups were distinguished by differences in the relationship of step length to pull intensity (slope) and their overall step length or reaction time regardless of pull intensity (y-intercept). NPH patients scored as "normal" on the MDS-UPDRS scale were kinematically indistinguishable from age-matched control subjects during a standardized perturbation, but could be distinguished from controls by their response to a range of pull intensities. An instrumented, purposefully varied pull test produces kinematic metrics useful for distinguishing clinically meaningful differences within hydrocephalus patients as well as distinguishing these patients from healthy, control subjects.

Quantitative trunk sway analysis under challenging gait conditions in early and untreated Parkinson's disease.

INTRODUCTION: Even experienced clinicians may encounter difficulties in making a definitive diagnosis in the early motor stages of Parkinson's disease (PD). We investigated whether quantitative biomechanical trunk sway analysis could support the diagnosis of PD early on. METHODS: We quantified trunk sway performance using body-worn sensors during a test battery of six challenging gait conditions in a cohort of 17 early and untreated PD patients (with evidence of reduced tracer uptake in the basal ganglia on dopamine transporter scans) and 17 age- and sex-matched healthy controls (HCs). RESULTS: Compared to HC, the PD group (Hoehn & Yahr ≤ 2, Unified Parkinson's Disease Rating Scale motor score: mean 13.7 ± 3.5 points) showed significant trunk rigidity in five challenging gait tasks (decreased medio-lateral direction and sway angle area). Post hoc receiver operating characteristic analysis of the significant parameters revealed excellent discrimination with high sensitivity and specificity. CONCLUSION: In the early and untreated motor stages of PD, patients exhibit significant trunk rigidity during challenging gait tasks. Trunk sway motion recorded with body-worn sensors might be a useful tool to disclose a sometimes hard-to-trace cardinal motor sign of PD and support an early clinical diagnosis.

Digitizing a Therapeutic: Development of an Augmented Reality Dual-Task Training Platform for Parkinson's Disease.

Augmented reality (AR) may be a useful tool for the delivery of dual-task training. This manuscript details the development of the Dual-task Augmented Reality Treatment (DART) platform for individuals with Parkinson's disease (PD) and reports initial feasibility, usability, and efficacy of the DART platform in provoking dual-task interference in individuals with PD. The DART platform utilizes the head-mounted Microsoft HoloLens2 AR device to deliver concurrent motor and cognitive tasks. Biomechanical metrics of gait and cognitive responses are automatically computed and provided to the supervising clinician. To assess feasibility, individuals with PD (N = 48) completed a bout of single-task and dual-task walking using the DART platform. Usability was assessed by the System Usability Scale (SUS). Dual-task interference was assessed by comparing single-task walking and walking during an obstacle course while performing a cognitive task. Average gait velocity decreased from 1.06 to 0.82 m/s from single- to dual-task conditions. Mean SUS scores were 81.3 (11.3), which placed the DART in the "good" to "excellent" category. To our knowledge, the DART platform is the first to use a head-mounted AR system to deliver a dual-task paradigm and simultaneously provide biomechanical data that characterize cognitive and motor performance. Individuals with PD were able to successfully use the DART platform with satisfaction, and dual-task interference was provoked. The DART platform should be investigated as a platform to treat dual-task declines associated with PD.

Machine Learning and Wearable Sensors for the Early Detection of Balance Disorders in Parkinson's Disease.

Dynamic posturography combined with wearable sensors has high sensitivity in recognizing subclinical balance abnormalities in patients with Parkinson's disease (PD). However, this approach is burdened by a high analytical load for motion analysis, potentially limiting a routine application in clinical practice. In this study, we used machine learning to distinguish PD patients from controls, as well as patients under and not under dopaminergic therapy (i.e., ON and OFF states), based on kinematic measures recorded during dynamic posturography through portable sensors. We compared 52 different classifiers derived from Decision Tree, K-Nearest Neighbor, Support Vector Machine and Artificial Neural Network with different kernel functions to automatically analyze reactive postural responses to yaw perturbations recorded through IMUs in 20 PD patients and 15 healthy subjects. To identify the most efficient machine learning algorithm, we applied three threshold-based selection criteria (i.e., accuracy, recall and precision) and one evaluation criterion (i.e., goodness index). Twenty-one out of 52 classifiers passed the three selection criteria based on a threshold of 80%. Among these, only nine classifiers were considered "optimum" in distinguishing PD patients from healthy subjects according to a goodness index ≤ 0.25. The Fine K-Nearest Neighbor was the best-performing algorithm in the automatic classification of PD patients and healthy subjects, irrespective of therapeutic condition. By contrast, none of the classifiers passed the three threshold-based selection criteria in the comparison of patients in ON and OFF states. Overall, machine learning is a suitable solution for the early identification of balance disorders in PD through the automatic analysis of kinematic data from dynamic posturography.

Predicting Axial Impairment in Parkinson's Disease through a Single Inertial Sensor.

BACKGROUND: Current telemedicine approaches lack standardised procedures for the remote assessment of axial impairment in Parkinson's disease (PD). Unobtrusive wearable sensors may be a feasible tool to provide clinicians with practical medical indices reflecting axial dysfunction in PD. This study aims to predict the postural instability/gait difficulty (PIGD) score in PD patients by monitoring gait through a single inertial measurement unit (IMU) and machine-learning algorithms. METHODS: Thirty-one PD patients underwent a 7-m timed-up-and-go test while monitored through an IMU placed on the thigh, both under (ON) and not under (OFF) dopaminergic therapy. After pre-processing procedures and feature selection, a support vector regression model was implemented to predict PIGD scores and to investigate the impact of L-Dopa and freezing of gait (FOG) on regression models. RESULTS: Specific time- and frequency-domain features correlated with PIGD scores. After optimizing the dimensionality reduction methods and the model parameters, regression algorithms demonstrated different performance in the PIGD prediction in patients OFF and ON therapy (r = 0.79 and 0.75 and RMSE = 0.19 and 0.20, respectively). Similarly, regression models showed different performances in the PIGD prediction, in patients with FOG, ON and OFF therapy (r = 0.71 and RMSE = 0.27; r = 0.83 and RMSE = 0.22, respectively) and in those without FOG, ON and OFF therapy (r = 0.85 and RMSE = 0.19; r = 0.79 and RMSE = 0.21, respectively). CONCLUSIONS: Optimized support vector regression models have high feasibility in predicting PIGD scores in PD. L-Dopa and FOG affect regression model performances. Overall, a single inertial sensor may help to remotely assess axial motor impairment in PD patients.

Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology.

There are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.

Falls in individuals with type 2 diabetes; a cross-sectional study on the impact of motor dysfunction, postural instability and diabetic polyneuropathy.

AIM: To estimate the incidence of falls in individuals with type 2 diabetes compared to healthy controls and to describe the characteristics of fallers with type 2 diabetes in relation to motor dysfunction, postural instability and diabetic polyneuropathy (DPN). METHODS: This is a cross-sectional study of individuals with type 2 diabetes with DPN (n = 54), without DPN (n = 38) and healthy controls (n = 39). Falls were recorded within the preceding year. DPN was defined by clinical scores and nerve conduction studies. Motor function was assessed by a 6-min walk test (6 MWT), five-time sit-to-stand test (FTSST) and isokinetic dynamometry at the non-dominant ankle and knee. An instability index (ST) was measured using static posturography. Univariate and bivariate descriptive statistics were used for group comparisons. RESULTS: Compared with healthy controls, individuals with diabetes had a higher incidence of falls 36%, (n = 33) versus 15%, (n = 6), p = 0.02. There were no differences in falls when comparing individuals with and without DPN. Fallers had an impaired 6 MWT versus non-fallers (450 ± 153 m vs. 523 ± 97 m respectively), a slower FTSST (11.9 ± 4.2 s vs. 10.3 ± 2.9 s respectively) and a higher ST (53 ± 29 vs. 41 ± 17 respectively), p < 0.02 for all. CONCLUSION: Individuals with type 2 diabetes reported a higher number of falls within the preceding year compared to healthy controls, irrespective of the presence of DPN. The main factors associated with falls were increased postural instability, lower walking capacity and slower sit-to-stand movements. The 6 MWT, FTSST and posturography should be considered in future screening programs in identification of individuals at risk for falls.

Clinical and laboratory measures of balance and comparison of balance performances according to postural instability and gait disorders in individuals with Parkinson's disease.

PURPOSE/AIM: Primary aim was to investigate the association between laboratory measures of balance and clinical balance tests in individuals with Parkinson's disease (PD). The secondary aim was to compare the balance performances according to postural instability and gait disorders (PIGD). MATERIALS AND METHODS: Sixty-four individuals with PD were included in the study. Clinical data were investigated using modified Hoehn and Yahr Scale and Unified Parkinson's Disease Rating Scale (UPDRS). Berg Balance Scale (BBS), Timed Up&Go Test (TUG), Five Times Sit-to-Stand Test (FTSST) were used for clinical measures of balance. Laboratory measures of balance were evaluated by Balance Master System including the modified Clinical Test of Sensory Interaction of Balance (mCTSIB), Limits of Stability Test (LOS), Sit to Stand Test (STS), and Tandem Walk Test (TW). The relationship between clinical and laboratory measures of balance was determined. After participants were divided into two groups based on UPDRS: patients with and without PIGD, their balance performance was compared. RESULTS: There were significant correlations between BBS and mCTSIB, LOS-Movement Velocity, and LOS-Endpoint Excursion. FTSST was correlated with STS-Weight Transfer and STS-Rising Index, and TUG was correlated with TW-Speed. Patients with PIGD had worse scores of balance assessments including FTSST, LOS-Movement Velocity, STS-Rising Index. CONCLUSION: Laboratory measures are associated with clinical balance tests and they may reflect clinical balance outcome measures. Furthermore, PIGD may negatively affect balance performance in patients with PD.

Local field potentials of subthalamic nucleus contain electrophysiological footprints of motor subtypes of Parkinson's disease.

Although motor subtypes of Parkinson's disease (PD), such as tremor dominant (TD) and postural instability and gait difficulty (PIGD), have been defined based on symptoms since the mid-1990s, no underlying neural correlates of these clinical subtypes have yet been identified. Very limited data exist regarding the electrophysiological abnormalities within the subthalamic nucleus (STN) that likely accompany the symptom severity or the phenotype of PD. Here, we show that activity in subbands of local field potentials (LFPs) recorded with multiple microelectrodes from subterritories of STN provide distinguishing neurophysiological information about the motor subtypes of PD. We studied 24 patients with PD and found distinct patterns between TD (n = 13) and PIGD (n = 11) groups in high-frequency oscillations (HFOs) and their nonlinear interactions with beta band in the superior and inferior regions of the STN. Particularly, in the superior region of STN, the power of the slow HFO (sHFO) (200-260 Hz) and the coupling of its amplitude with beta-band phase were significantly stronger in the TD group. The inferior region of STN exhibited fast HFOs (fHFOs) (260-450 Hz), which have a significantly higher center frequency in the PIGD group. The cross-frequency coupling between fHFOs and beta band in the inferior region of STN was significantly stronger in the PIGD group. Our results indicate that the spatiospectral dynamics of STN-LFPs can be used as an objective method to distinguish these two motor subtypes of PD. These observations might lead to the development of sensing and stimulation strategies targeting the subterritories of STN for the personalization of deep-brain stimulation (DBS).

Proprioception: the missing link in the pathogenesis of tinnitus?

OBJECTIVES: The object of this study was to relate cervical spine pathology to the occurrence of tinnitus and of cervical pain. DESIGN: A retrospective analysis of 124 patients with tinnitus as main complaint and 300 patients with cervical pain as main complaint who visited our clinic in a two-year period. RESULTS: In patients with tinnitus as main complaint, 64% of the patients have also cervical pain, and in patients with cervical pain as main complaint, 44% of the patients have tinnitus. Both groups of patients have in common a high prevalence of postural instability and dizziness, degeneration of the intervertebral disc between the fifth and seventh cervical vertebrae, and a large anterior spur in front of the fifth cervical vertebrae. Patients with cervical pain as main complaint have more degeneration of the intervertebral disc between the third and fourth cervical vertebrae, a larger anterior spur in front of the third cervical vertebrae and more loss of cervical lordosis. CONCLUSIONS: Postural instability is an important discriminant factor in patients with cervical pain and in patients with tinnitus as main complaint. In patients with cervical pain postural instability was associated with the occurrence of tinnitus. In patients with tinnitus, there is evidence for two profiles of somatic tinnitus, discriminated by the occurrence of postural instability and low-frequency hearing loss. It seems that the combination of tinnitus and postural instability begins as a cervical pain syndrome and that the tinnitus aggravates in time, possibly by the occurrence of hearing loss, internal diseases, or surgery of the lower limb.

Psychosocial research in the diabetic foot: Are we making progress?

BACKGROUND/METHODS: This review summarizes recent advances regarding the role of psychological factors in people with a diabetic foot ulcer (DFU). It describes the detrimental effects of diabeticfoot complications and in particular, Charcot Neuroarthropathy (CN), on health status and quality of life (QoL) and emphasizes the importance of utilizing DFU-specific assessment tools. RESULTS: Diabetic neuropathy (DN)-related postural instability is key in generating depression in high DFU risk patients and in predicting offloading non-adherence those with active DFUs. Patients' views of their own DFU risk are largely inconsistent with biomedical models, resulting in a lack of preventive foot self-care. Furthermore, DFUs are a source of specific emotional responses, with fear of amputation predominant. While fear of amputation is associated with better preventive foot self-care, it appears to be linked to DFU non-healing, though mechanisms are yet to be elucidated. Until now, systemically released stress hormones were recognized as the only biological mechanism through which psychological stress influences healing. Recently, the skin has been found to be an extra-adrenal site for glucocorticoid synthesis with local, tissue-specific cortisol implicated in DFU non-healing. CONCLUSIONS: These observations could potentially lead to future targets for therapeutic and psychological interventions.

Pedunculopontine Nucleus Microstructure Predicts Postural and Gait Symptoms in Parkinson's Disease.

BACKGROUND: There is an urgent need to identify individuals at risk of postural instability and gait difficulties, and the resulting propensity for falls, in Parkinson's disease. OBJECTIVES: Given known relationships between posture and gait and degeneration of the cholinergic pedunculopontine nucleus, we investigated whether metrics of pedunculopontine nucleus microstructural integrity hold independent utility for predicting future postural instability and gait difficulties and whether they could be combined with other candidate biomarkers to improve prognostication of these symptoms. METHODS: We used stereotactic mapping of the pedunculopontine nucleus and diffusion tensor imaging to extract baseline pedunculopontine nucleus diffusivity metrics in 147 participants with Parkinson's disease and 65 controls enrolled in the Parkinson's Progression Markers Initiative. We also recorded known candidate markers of posture and gait changes: loss of caudate dopamine and CSF ß-amyloid 1-42 levels at baseline; as well as longitudinal progression motor symptoms over 72-months. RESULTS: Survival analyses revealed that reduced dopamine in the caudate and increased axial diffusivity in the pedunculopontine nucleus incurred independent risk of postural instability and gait difficulties. Binary logistic regression and receiver operating characteristics analysis in 117 participants with complete follow-up data at 60 months revealed that only pedunculopontine nucleus microstructure provided more accurate discriminative ability for predicting future postural instability and gait difficulties than clinical and demographic variables alone. CONCLUSION: Dopaminergic and cholinergic loss incur independent risk for future postural instability and gait difficulties, and pedunculopontine nucleus microstructure can be used to prognosticate these symptoms from early Parkinson's disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.