Freezing of gait (FOG) is among the most debilitating symptoms of Parkinson disease and related disorders, often resulting in falls and a loss of independence. FOG has an episodic and heterogeneous nature that makes it difficult to measure and treat. The field currently lacks a consensus on how to precisely define this phenomenon. For this reason, the International Consortium for Freezing of Gait convened a group of experts to establish an updated ‘clinical’ definition of FOG for use in the clinical setting and a ‘technical’ definition for assessors to use when scoring FOG episodes from video recordings as an outcome in fundamental research and clinical trials. Guidelines on how to classify people with Parkinson disease into subgroups of those with or without FOG (non-FOG) are also provided. This position paper presents these new definitions and guidelines, offering a foundation for harmonizing the study and management of FOG. Freezing of gait (FOG) is among the most debilitating symptoms of Parkinson disease. This Consensus Statement from the International Consortium for Freezing of Gait presents new guidelines for the definition and assessment of FOG, with the aim of harmonizing the study and management of the condition.

Presynaptic inhibition (PSI) at the spinal cord level is crucial for coordinating postural preparation with step initiation. People with freezing of gait and Parkinson's disease (PD + FOG) show loss of PSI of the soleus muscle during step initiation that is associated with abnormal anticipatory postural adjustments (APA). Here, we hypothesize that increasing PSI of the soleus muscle during step initiation via wrist vibration in PD + FOG would decrease abnormally large APA. Fifteen PD + FOG performed self-initiated steps on a force platform without electrical stimulation and with test or conditioned Hoffman reflexes (H-reflex) to measure PSI of the soleus muscle under three conditions: OFF medication, OFF medication with vibration, and ON medication without vibration. Soleus H-reflexes were recorded during quiet stance (a control task) and when the amplitude of the APA under the same leg exceeded 10%-20% of the mean baseline mediolateral displacement. Vibration consisted of 200-300 Hz applied to the wrist when the ipsilateral leg during APA (same leg where H-reflexes were evoked) was on the ground. PD + FOG showed decreased PSI during APA in OFF and ON medication, but PSI was increased during vibration (p < 0.05). Increased PSI was associated with smaller APA during vibration (p < 0.05). Smaller APAs were associated with lower subjective freezing of gait severity (p < 0.05). These preliminary results show that wrist vibration decreases abnormal APA during step initiation by increasing ipsilateral PSI levels of the soleus muscle. Because PSI is modulated by cortical and brainstem areas related to FOG and APA, proprioceptive drive during vibration may reorganize these brain circuits.

Background The Mobility Rehab Auditory Feedback, a novel physical therapist-assisted system, uses verbal cues and a metronome as feedback during a single treadmill session, which may improve overground walking with and without a cognitive task in people with Parkinson’s disease (PD). Research question Is the Mobility Rehab Auditory Feedback system a safe and feasible intervention to improve gait in people with PD? Methods Twenty people with mild-to-moderate PD (age=69.8 years, disease duration=7.8 years), in the On-medication state, performed a 2-min overground walk before and after a 15-minute single treadmill session with the Mobility Rehab Auditory Feedback system. The system included an electronic tablet and five Opal sensors placed on both wrists and feet, and on the sternum. The system provides real-time verbal feedback on four gait metrics: arm swing range of motion, step duration, stride length, and elevation at mid-swing. Researchers selected one or two gait metrics (from the four) to focus on during the treadmill session. Results The upper and lower body gait metrics in both usual and dual-task overground walking showed significant improvements with small-to-large effect sizes following a single treadmill session with the Mobility Rehab Auditory Feedback system. Seventy percent of the participants perceived at least moderate improvement in their gait after the treadmill session. No adverse events were reported. Significance The effectiveness of a single treadmill session with the Mobility Rehab Auditory Feedback system demonstrates its safety and feasibility for retraining gait in people with mild-to-moderate PD.

Despite evidence of early neurodegeneration, postural instability is commonly associated with later stages of Parkinson’s disease (PD), mainly due to a lack of sensitive measures. Here, we aim to provide a sensitive, easily obtainable objective measure of postural instability for earlier clinical detection. We assessed postural sway in 40 newly diagnosed, untreated individuals with PD and 79 age-matched healthy controls while they stood quietly for 30 seconds with their eyes open and feet together. Body sway was recorded with a single accelerometer placed at the lumbar spine. We trained a convolutional neural network (CNN) to distinguish between the groups based on the frequency information of their sway signals. Our models reached an average accuracy, sensitivity, and specificity of 98.9%, 97.7%, and 98.9%, respectively. This suggests that characteristic frequency features of postural sway reflect subtle postural impairments in early PD, with great potential to translate into clinical applications.

People with Parkinson's disease and freezing of gait (PD+FOG) exhibit altered gait and turning compared to nonfreezing peers with PD (PD-FOG). However, less work has examined the effects of FOG status on daily-life mobility. Therefore, we compared daily-life gait and turning across PD+FOG and PD-FOG and related gait deficits to self-reported FOG severity and health-related quality of life (QOL). We collected daily-life mobility data over 7 days from 119 people with PD (PD+FOG = 47). Inertial sensors on the feet and lower back assessed 33 gait and balance outcomes. One-way ANCOVAs assessed the effect of FOG status on mobility. Five variables reflecting gait and turning quality were significantly worse in PD+FOG compared to PD-FOG after Holm correction: smaller turn angles, smaller foot pitch at initial contact, and increased variability of double-support time, stride length, and pitch at toe-off. Of these outcomes, two (turn angle & stride length variability) were significantly correlated with freezing severity, and 4 (turn angle, stride length variability, pitch at initial contact and pitch at toe-off variability) related to QOL. Turns per hour also related to QOL. In sum, PD+FOG exhibited worse daily-life gait quality (small turn angle and foot angle at heel strike and increased gait variability) and these outcomes were related to QOL and FOG severity. Daily-life gait quantity (number of turns, strides, and gait bouts per hour) was less affected by FOG. These results provide insight into daily-life mobility of PD+FOG, and support interventions aimed at quality of gait and turning for PD+FOG.

BACKGROUND:Mobility impairments are a hallmark of Parkinson's disease (PD). Telerehabilitation is becoming more common for people with PD; however, the validity and agreement of telerehabilitation's mobility measurements for people with PD are lacking. OBJECTIVES:We investigated the feasibility, safety, concurrent validity, agreement, and inter-rater reliability between remote and in-person home mobility assessments in people with PD. METHODS:Sixty-two people with mild-to-moderate PD were assessed ON medication on two different days. On the first day, Rater A conducted home-based in-person mobility assessments that included the Five-Time Sit-to-Stand (5TSTS), Timed-Up-and-Go Test (TUG), and 360-degree Rapid-Turns Test (360°RTT). On the second day, Rater B conducted the same home-based mobility assessments remotely (via videoconferencing). Feasibility and safety were monitored. The concurrent validity and agreement between the remote and in-person mobility assessments were analyzed using the Pearson correlation coefficient and the Bland-Altman analysis, respectively. Inter-rater reliability was analyzed using the intraclass correlation coefficient (ICC). RESULTS:Remote assessments were feasible and safe for all participants. Remote and in-person home mobility assessments, including 5TSTS (r = 0.95, P < 0.0001), TUG (r = 0.91, P < 0.0001), and 360°RTT for the dominant (r = 0.76, P < 0.0001) and non-dominant side (r = 0.77, P < 0.0001), were strongly and significantly correlated. Bland-Altman results showed relatively symmetrical distributions within the limits of agreement for all measurements. Inter-rater reliability was excellent (ICC ≥0.75) for all assessments. CONCLUSIONS:Home-based remote mobility assessments demonstrated feasibility, safety, validity, agreement, and excellent inter-rater reliability comparable to in-person assessments. Home-based, remote mobility assessments are comparable to in-person home mobility assessments in mild-to-moderate PD and can be implemented into telerehabilitation.

BACKGROUND:Clinical trials in spinocerebellar ataxia are currently limited by the large sample sizes required by available clinical endpoints. We aimed to devise a digital composite measure of standing and walking balance using wearable inertial sensors that would require smaller sample sizes. The new score is called the Score of Integrated Balance in Ataxia (SIBA). METHODS:In this study, we developed the SIBA based on a retrospective sample of adults (aged 18-75 years) with spinocerebellar ataxia types 1, 2, 3, or 6, recruited during clinical visits at five sites (four in the USA and one in Cuba) between June 23, 2017, and Aug 21, 2024. Participants were included if they had genetic confirmation of spinocerebellar ataxia, and were able to provide consent, walk 10 m independently without an assistive device, and stand unassisted for 30 s. A cohort of age-specific and sex-matched healthy controls were recruited from family members of the patients. To validate the SIBA, an independent sample of individuals with the same types of ataxias were recruited along with age-matched and sex-matched healthy controls from five centres in the USA (NCT04268147) between June 1, 2019, and April 30, 2024. We performed balance and gait assessments using six wearable sensors (Opal inertial measurement units, APDM Precision Motion, Clario, Portland, OR, USA) on the dorsum of each foot and hand, on the sternum, and on the lower lumbar (trunk) vertebral segments. We used the data from this assessment to develop a composite score from walking at a natural pace for 2 min and standing with feet together and apart for 30 s. We used a multiple criteria decision analysis to weight the relative importance of criteria to guide development of the score. The criteria represented the ability to distinguish groups with known differences, construct validity, reliability, progression, meaningfulness, and concurrent validity. The final composite score integrated two dynamic balance variables from gait (variability of toe-out and double-support time proportion of the gait cycle) and two static balance variables from stance (sway angle root mean square with normal stance width and sway acceleration root mean square with feet together). We compared the SIBA to the Scale for the Assessment and Rating of Ataxia (SARA) for reliability, the ability to distinguish between groups with known differences, construct validity, convergent validity, and the ability to track disease progression. FINDINGS:We included 258 individuals (131 females and 127 males) with spinocerebellar ataxia types 1, 2, 3, or 6 (40 premanifest and 218 ataxic) and 100 healthy controls (45 females and 55 males) in the development study; and 53 individuals (27 females and 26 males) with spinocerebellar ataxia types 1, 2, 3, or 6 and 24 healthy controls (14 females and 10 males) in the validation study. The SIBA showed concurrent validity with the SARA (r=0·736). The SIBA was also reliable (test-retest reliability; intraclass correlation coefficient=0·970), could distinguish between participants and healthy controls (area under the receiver operating characteristic curve [AUROC]=0·956), and related to fall risk (AUROC=0·760) in a validation cohort of ambulatory participants with spinocerebellar ataxia, independent from the larger, score-development cohort. Progression of ataxia over 1 year had an effect size five times larger than the SARA score (0·59 vs 0·11). Based on these estimates, clinical trials using the SIBA would require 88% fewer participants than SARA (171 vs 1491) to detect a 50% reduction in the rate of 1-year progression. INTERPRETATION:SIBA is a suitable digital measure of static and dynamic balance for the most common spinocerebellar ataxias in clinical trials. It may permit clinical trials to be completed more rapidly and with fewer participants. Future trials on responsiveness of the SIBA to interventions are needed in larger cohorts. FUNDING:Biogen, Clario, Pfizer, and the Alexander von Humboldt Foundation.

Introduction:Cognitive impairment is common in people with Parkinson's disease (PD). Mobility is also impaired in people with PD and functional mobility often requires cognitive dual-tasking to navigate complex environments in daily life. We hypothesized that visuospatial and executive cognitive dysfunction in people with PD will be associated with digital measures of mobility in daily life. Since freezing of gait (FoG) is associated with both cognitive dysfunction and mobility impairments, we also examined the influence of FoG on the cognition-mobility relationship. Here, we investigated, for the first time, the association between cognition and daily-life mobility in PD and the influence of FoG status. Methods:60 individuals with mild-to-moderate PD (17 with FoG and 43 without FoG) wore 3 inertial sensors (lumbar and feet) for a week of passive monitoring of mobility. Digital visuospatial (Line Orientation task) and executive tasks (Set-Shifting and Flanker task) were assessed in the ON medication state. Results:Visuospatial function was significantly associated with gait speed (r = -0.46, p = 0.008) and stride length (r = -0.40, p = 0.022). Set Shifting was significantly associated with stance time (r = -0.35, p = 0.046), double support time (r = -0.35, p = 0.046), and the variability of step duration during turning (r = 0.44, p = 0.016). The Flanker test was not associated with any gait variables. FoG status was less important than disease duration or age in the cognitive-mobility associations. Conclusions:Specific types of cognition were related to specific gait variables in daily life. People with PD with worse visuospatial functions had worse gait pace. In contrast, participants with worse executive function (set-switching) had worse dynamic postural control during gait. FoG status showed minimal influence on these associations.

This narrative review examines the utility of gait digital biomarkers in Parkinson’s disease (PD) research and clinical trials across four contexts: disease susceptibility/risk, disease progression, response to exercise, and fall prediction. The review of the literature to date suggests that upper body characteristics of gait (e.g., arm swing, trunk motion) may indicate susceptibility/risk of PD, while pace aspects (e.g., gait speed, stride length) are informative for tracking disease progression, exercise response, and fall likelihood. Dynamic stability aspects (e.g., trunk regularity, double-support time) worsen with disease progression but can improve with exercise. Gait variability emerges as a sensitive biomarker across all 4 contexts but with low specificity. The lack of standardized gait testing protocols and the lack of a minimum set of quantified digital gait biomarkers limit data harmonization across studies. Future studies, using a commonly agreed upon protocol, could be used to demonstrate the utility of specific gait biomarkers for clinical practice.

Background:Recent findings suggest that a single gait assessment in a clinic may not reflect everyday mobility. Objective:We compared gait measures that best differentiated individuals with spinocerebellar ataxia (SCA) from age-matched healthy controls (HC) during a supervised gait test in the clinic vs. a week of unsupervised gait during daily life. Methods:Twenty-six individuals with SCA types 1, 2, 3, and 6, and 13 (HC) wore three Opal inertial sensors (on both feet and lower back) during a 2-minute walk in the clinic and for seven days in daily life. Seventeen gait measures were analyzed to investigate the group differences using Mann-Whitney U-tests and area under the curve (AUC). Results:Ten gait measures were significantly worse in SCA than HC for the clinic test (p < 0.003), but only 3 were worse in daily life (p < 0.003). Only a few gait measures consistently discriminated groups in both environments. Specifically, variability in Swing Time and Double Support Time had AUCs of 0.99 (p < 0.0001) and 0.96 (p < 0.0001) in the clinic, and 0.84 (p < 0.0003) and 0.80 (p < 0.002) in daily life, respectively. Clinical gait measures showed stronger correlations with clinical outcomes (ie, SARA and FARS-ADL; r = 0.50-0.77) than between daily life gait measures (r = 0.31-0.49). Gait activity in daily life was not statistically significant between the SCA and HC groups (p > 0.06). Conclusions:Digital gait measures discriminate SCA in both environments. In-clinic measures are more sensitive, while daily life measures provide ecological validity, highlighting a trade-off and offering complementary insights.

OBJECTIVE:People with neurological conditions (PwNC) frequently fall, mainly due to balance impairments. Among the scales assessing balance, the Balance Evaluation System Test (BESTest) is one of the most comprehensive in evaluating all components of postural control. This study aimed to systematically review and summarize the measurement properties of the BESTest in PwNC. METHODS:Embase, MEDLINE, ScienceDirect, Scopus, and PEDro were searched up to December 2023. Studies assessing at least 1 BESTest measurement property in PwNC were included. Methodological quality of studies was assessed with the COSMIN Risk of Bias checklist. Overall rating and level of evidence for each property were given according to COSMIN criteria. Where possible, meta-analysis was performed. RESULTS:Thirty-six studies (1749 PwNC) were included. The BESTest demonstrated a high quality of evidence supporting good reliability (intraclass correlation coefficients = 0.96-0.98 for total score, and 0.70-0.98 for subsections), internal consistency, and measurement error. High quality levels of responsiveness, and content and construct validity were also found. However, evidence for structural validity was insufficient to be sure the BESTest actually tests several, or 1, balance constructs. Criterion validity cannot be evaluated. While translated into different languages, cross-cultural validity has never been assessed in PwNC. Evidence to support use of the BESTest for specific neurological conditions is limited to Parkinson disease and stroke, due to the small sample sizes and number of studies in other populations. CONCLUSION:This systematic review provided high quality evidence supporting the reliability, content and construct validity, and responsiveness of the BESTest to intervention, being able to detect balance changes and to differentiate heterogeneous PwNC based on fall history, falling risk, and physical performance. However, low-quality evidence was found when considering each neurological condition alone. To comprehensively understand the BESTest measurement properties, future studies are needed with larger samples for each neurological condition, especially assessing cross-cultural and structural validity. IMPACT:Assessing balance is crucial for fall risk prevention. The BESTest has been demonstrated to be a reliable, responsive, and valid scale usable in clinical setting for assessing balance in PwNC. LAY SUMMARY:Assessing balance is crucial for fall risk prevention. The BESTest has been demonstrated to be a reliable, responsive, and valid scale usable in clinical setting for assessing balance in PwNC.

Traditional clinical assessments in Parkinson's disease (PD) trials are limited by subjectivity and inter-rater variability. Digital health technologies (DHT) offer an objective continuous assessment of motor symptoms and are increasingly used in clinical research. This review evaluated the role of DHTs as outcome tools in pharmacological trials for PD. A systematic search of MEDLINE and Embase was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, covering studies up to August 31, 2025. Eligible studies included randomized controlled trials, open-label or crossover designs, and observational studies using DHTs to assess motor outcome variables in PD. Studies focusing only on technology development or with fewer than 10 participants were excluded. Data extracted included study design, DHT type, assessment setting, and motor parameters measured. Study quality was appraised using an eight-criterion tool, and level of evidence was rated using the Oxford Centre for Evidence-Based Medicine framework. A total of 42 studies were included, covering 26 distinct DHTs. These comprised 11 wearable sensors and 15 nonwearable systems such as motion capture platforms and force-sensing assessments. DHTs were used to measure bradykinesia, tremor, gait, balance, and nocturnal motor symptoms in both supervised and unsupervised settings. Fifteen studies were rated as high quality, 14 moderate, and 13 low. Among currently available tools, only Opal reached the threshold of Level 1a evidence. Other validated tools included the Parkinson's Kinetigraph, Actiwatch, and Roche PD Mobile Application (Level 1b). DHTs offer valuable tools for objective assessment in PD trials, though broader adoption requires greater standardization and regulatory alignment. © 2025 International Parkinson and Movement Disorder Society.

ImportanceFall risk and cognitive impairment are prevalent and burdensome in Parkinson disease (PD), requiring efficacious, well-tolerated treatment.ObjectiveTo evaluate the safety and efficacy of TAK-071, a muscarinic acetylcholine M1 positive allosteric modulator, in participants with PD, increased fall risk, and cognitive impairment.Design, Setting, and ParticipantsThis phase 2 randomized double-blind placebo-controlled crossover clinical trial was conducted from October 21, 2020, to February 27, 2023, at 19 sites in the US. Participants included patients aged 40 to 85 years with a diagnosis of PD, with at least 1 fall in the prior 12 months, with a Montreal Cognitive Assessment score of 11 to 26, and receiving stable antiparkinsonian medications and no acetylcholinesterase inhibitors.InterventionOne-to-one randomization to once-daily oral TAK-071 or placebo for 6 weeks, followed by washout and 6 weeks of crossover treatment.Main Outcomes and MeasuresThe primary end point was change from baseline in gait variability (stride time variability [STV]) during a 2-minute walk test with or without cognitive load. The secondary efficacy end point was change from baseline in a cognitive composite score consisting of tests of attention, executive function, and memory.ResultsAmong the 54 participants included in the analysis, 45 (83%) were male, mean (SD) age was 69.7 (6.9) years, and median Montreal Cognitive Assessment score was 24 (range, 17-26). After 6 weeks of treatment, the primary outcome was negative: the change from baseline in STV did not differ between participants receiving TAK-071 or placebo, with cognitive load (geometric mean ratio, 1.15; 95% CI, 0.94-1.41; P = .16) or without cognitive load (geometric mean ratio, 1.02; 95% CI, 0.88-1.18; P = .78). TAK-071 improved the secondary efficacy outcome (cognitive composite score) vs placebo. The least squares mean difference of the change from baseline was 0.22 (95% CI, 0.05-0.38; P = .01). Treatment-emergent adverse events occurred in 18 of 49 participants (37%) while receiving placebo and in 19 of 53 (36%) while receiving TAK-071. Four participants (8%) receiving TAK-071 had adverse events resulting in withdrawal of study drug; 4 had gastrointestinal tract adverse events.Conclusions and RelevanceIn this study, in participants with PD, risk for falls, and cognitive impairment, TAK-071 was well-tolerated. The treatment did not improve the primary outcome of gait variability, but did improve cognition compared with placebo. Larger and longer studies in more diverse populations are needed to better understand the safety and efficacy of TAK-071 in broader populations.Trial RegistrationClinicalTrials.gov Identifier: NCT04334317

IMPORTANCE:There is unclear evidence on when to initiate physical therapy after mild traumatic brain injury (mTBI) in a non-athlete, adult population. OBJECTIVE:The objective of this study was to investigate physical therapy timing after mTBI through changes in patient-reported and clinically-assessed tools and objective and mechanism measurements of sensorimotor balance control. DESIGN:This study was an investigator-blinded randomized control trial (NCT03479541). SETTING:The study took place at an academic research center. PARTICIPANTS:Two hundred and three participants were randomized to earlier physical therapy (n = 82) or to later physical therapy (n = 121). INTERVENTION:After enrollment, the earlier physical therapy group started rehabilitation within 1 week and the later group started rehabilitation after a 6-week wait period. All participants received similar rehabilitation; 6-week program administered and progressed by licensed physical therapists. MAIN OUTCOMES AND MEASURES:The primary outcome was the Dizziness Handicap Inventory (DHI). Secondary outcomes included common patient-reported/clinical assessments of mTBI and objective/mechanism measurements of balance, including novel measures of central sensorimotor integration. Differences between and within the groups on outcomes were examined with linear mixed-effect models, t tests, and effect sizes. RESULTS:While both groups significantly improved and reached similar levels on patient-reported outcomes (DHI and secondary outcomes), the earlier physical therapy group had significantly larger and faster rates of improvement compared to later physical therapy. There were differential effects of physical therapy timing on the objective/mechanism-measured outcomes. Specifically, there were significant improvements in sensorimotor time delay for the earlier physical therapy group and no change in the later group. Further, the later group worsened in the motor activation components for balance control while there was no change in the early group. CONCLUSION AND RELEVANCE:Earlier physical therapy after mTBI can improve symptoms at a faster rate relative to later physical therapy. Earlier physical therapy also showed improvements in sensorimotor aspects of balance control, not seen in the later group. There may be an important window to address central sensorimotor deficits after mTBI.

INTRODUCTION:Freezing of gait (FoG) is a debilitating motor symptom in Parkinson's disease (PD), often occurring during step initiation due to impaired anticipatory postural adjustments (APAs). Previous studies show inconsistent findings regarding APA alterations in people with PD with FoG (PwPD + FoG) and without FoG (PwPD-FoG). This study aimed to investigate APA characteristics using a force platform to assess postural control deficits associated with FoG. METHODS:We analyzed baseline data from 130 PwPD (70 with FoG) and 41 healthy controls. A force platform during self-initiated stepping measured APA duration, amplitude, and step amplitude. All participants with PD were tested in the ON medication. One-way ANOVA and ANCOVA (controlling for UPDRS-III and medication) were conducted to compare groups. RESULTS:APA duration was significantly shorter in Healthy compared to PwPD + FoG and PwPD-FoG, with no difference between PD groups. Step amplitude was significantly lower in PwPD + FoG compared to Healthy and PwPD-FoG, but this difference was insignificant after covariate. APA mediolateral amplitude followed PD + FoG < PD-FoG < Healthy; ANCOVA confirmed lower values in PwPD + FoG compared to PwPD-FoG. APA anteroposterior amplitude was also reduced in PwPD + FoG relative to PwPD-FoG and Healthy, with ANCOVA confirming significantly lower values in PwPD + FoG versus PwPD-FoG. NFOG-Q scores were negatively correlated with mediolateral and anteroposterior APA amplitudes. CONCLUSION:FoG in PD is associated with reduced APA amplitude (mediolateral and anteroposterior), suggesting postural control deficits persist despite dopaminergic medication. These findings highlight the importance of interventions targeting APA improvements to mitigate gait initiation failures in PwPD + FoG.

BackgroundSpinocerebellar ataxia (SCA) is a degenerative cerebellar disease, causing progressive impairment of gait and balance in adults. To identify the ideal subjects for disease-modifying therapies it is critical to identify biomarkers for the earliest stages of SCA.ObjectiveWe investigated whether prefrontal cortex activity is increased during walking in in early SCA or in pre-manifest SCA compared to healthy control subjects.MethodsSixteen participants with genetically determined SCA and 15 age-matched healthy controls participated in the study. The SARA was administered by a movement disorders specialist before the gait assessment. An 8-channel, mobile, fNIRS, with 2 reference channels, was used to record changes in oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin within the PFC. Participants walked for 2-minutes at a comfortable pace while wearing wireless, inertial sensors to derive gait characteristics.ResultsOf the 16 individuals with SCA, 9 were classified as pre-manifest (SARA < 3) and 7 as early SCA (SARA < 10). PFC activity (HbO2) while walking was greater than controls of similar age in people with SCA. Increased PFC activity was also present even in the pre-manifest stage of SCA. Increase in PFC activity was related to worse gait (double-support time and toe-out angle).ConclusionsPFC activity is increased in pre-manifest SCA, even when clinical scores are normal in the pre-manifest stage of the disease, and may serve as a biomarker that precedes onset of clinical disease. Increased PFC activity is consistent less automatic, cortical control of gait to compensate for impaired automatic, cerebellar control, even in early stages of ataxia.

BACKGROUND:Clinical outcomes assessments (COAs) in spinocerebellar ataxia (SCA) need to be standardized, ataxia-specific, sensitive to change, clinically relevant, and meaningful to patients. OBJECTIVES:To evaluate the longitudinal 1- and 2-year performances of different patient reported outcomes, including the Patient Reported Outcome Measure of Ataxia (PROM-Ataxia), and clinician reported outcomes, including FARS and SARA, in those with early manifest symptoms of SCA 1, 2, 3, and 6. METHODS:We studied 53 patients with early stage SCA1-3 and SCA6 from The Instrumented Data Exchange for Ataxia Study and 24 age-matched healthy controls. Participants were seen every 6 months for 2 years. Mixed models were used to estimate change over 12- and 24-months of follow-up. Changes on the FARS-FS and PGI-C were used as anchors to estimate meaningful changes. RESULTS:Among persons with SCA, mean age was 48.7 years and mean SARA score was 9.3. Few measures showed statistically significant changes at 12 months. At 24-months, the FARS-ADL, PROM-Ataxia total, PROM-Ataxia physical, and PROM-Ataxia ADL scores showed the strongest associations of change. CONCLUSIONS:Patient reported or derived outcome measures, such as FARS-ADL and ADL sub domain of the PROM-Ataxia, can capture longitudinal change in patients' symptom experience over a 2-year period and its impact on daily activities, even in those with early disease. More work is needed to identify outcomes that reliably capture change earlier.

BACKGROUND:Gait automaticity, the ability of the brain to control locomotion with minimal use of executive-attentional resources, is altered in people with Parkinson's disease (PD). Recently, we showed that step-synchronized tactile cueing improved gait regularity and freezing of gait in PD; however, it is not known if this cueing mode also improves gait automaticity. Thus, this study investigates the effects of step-synchronized tactile cueing (versus fixed cueing) on gait automaticity in the laboratory and during daily life. METHODS:This is a pilot, randomized, double-blinded study where sixty participants with PD will be randomized into one of two, cueing interventions: 1) personalized, step-synchronized tactile cueing and 2) tactile cueing at fixed intervals. Both cueing interventions use vibrotactile stimulation of wrist bands. During a laboratory study visit, we will measure cortical activity with a wireless, portable functional near-infrared spectroscopy system (fNIRS) during walking tasks. Gait will be assessed using inertial sensors placed on the limbs and trunk. In addition, in daily life, participants will use the same cueing mode at home. The primary outcomes include prefrontal & primary sensory cortex activity. Secondary outcomes are gait stride time, gait local dynamic stability, turn duration and trunk jerk during turning as metrics of gait automaticity in the laboratory. Daily life gait and turning are exploratory measures. DISCUSSION:This project will advance the understanding of brain mechanisms associated with walking automaticity during tactile cueing and provide the basis for innovative, personalized cueing to rehabilitate gait automaticity in people with PD. TRIAL REGISTRATION:ClinicalTrials.gov NCT05818189.