Ocular motor disorders in children and adults with mTBI: a scoping review protocol.

INTRODUCTION: Ocular motor function is susceptible to neurological injury because it requires a large portion of brain circuitry including every lobe of the brain, brainstem, thalamus, basal ganglia, cerebellum, cranial nerves and visual tracts. While reports of a high frequency of ocular motor dysfunctions after mild traumatic brain injury (mTBI) span multidisciplinary journals, there is no scoping review of the signs, diagnostic assessments and criteria, and appropriate management of ocular motor disorders post-mTBI. Post-mTBI ocular motor dysfunction has been reported to respond to active treatment. The objective of this scoping review is to map the available evidence on the diagnostic assessment and treatment modalities currently used in the management of mTBI-related ocular motor disorders in children and adults. This scoping review also aims to identify gaps in the current literature and provide suggestions for future research. METHODS AND ANALYSIS: This review will include populations with reported concussion and/or mTBI without restrictions on age, race, sex or time since injury. The review will evaluate the reported symptoms related to ocular motor dysfunction, types of assessments and diagnostic criteria used, reported treatments, and the level of evidence supporting the reported treatments. This review will exclude literature on brain injury of non-traumatic aetiology and moderate/severe traumatic brain injury. Ocular motor dysfunction after mTBI appears in journals across multiple disciplines. Thus, multiple databases will be evaluated including Pubmed, Embase, PEDro, OVID, Clinical Key, Google Scholar and REHABDATA. Literature will be searched from inception to present day. Evidence sources will include experimental study designs including randomised controlled trials, non-randomised controlled trials and interrupted time-series. Additionally, analytical observational studies including prospective and retrospective cohort studies, case series, cross-sectional studies and clinical practice guidelines will be considered for inclusion. Data will be extracted on clinical presentation, frequency, assessment, diagnostic criteria management strategies and outcomes of concussion and mTBI-related ocular motor disorders. ETHICS AND DISSEMINATION: This scoping review will use data from existing publications and does not require ethical approval by an institutional review board. Results will be disseminated through publication in a peer-reviewed scientific journal and presented at relevant conferences and as part of future workshops with professionals involved with diagnosis and management of patients with mTBI.

Psychogenic non-epileptic seizures and functional motor disorders in developmental age: A comparison of clinical and psychopathological features.

BACKGROUND: Psychogenic Non-Epileptic Seizures (PNES) and Functional Motor Disorders (FMDs) commonly represent the main clinical manifestations of Functional Neurological Disorders (FNDs). Despite their high prevalence in pediatric neurological services, literature on this topic is still spare for this population. The present study aimed to deepen the clinical knowledge of a pediatric FNDs sample through a demographic and clinical characterization of the most recurrent clinical patterns during the pediatric age. Moreover, a comparison of neuropsychological and psychopathological profiles of PNES and FMD patients was carried out to identify specific vulnerabilities and therapeutic targets linked with these different clinical manifestations. MATERIALS AND METHODS: A total of 43 FNDs patients (age range 7-17 years old) were retrospectively included in our study, enrolled in two subgroups: 20 with FMDs and 23 with PNES diagnosis. They were inpatients and outpatients referred over a period of 5 years and a standardized neurological, neuropsychological (WISC-IV/WAIS-IV), and psychiatric (CDI-2, MASC-2, ADES, DIS-Q, PID-5) evaluation was assessed. RESULTS: In PNES patients the most common clinical phenotypes were functional tonic-clonic (52%) and atonic (32%) manifestations while in the FMDs group were gait alterations (60%), functional myoclonus (35%), and tremor (35%). A higher frequency of cognitive impairment was reported in PNES patients with higher anxiety-depressive symptom rates than FMDs patients. CONCLUSIONS: Notably, specific neurocognitive and psychopathological profiles were described in PNES and FMDs, highlighting higher cognitive and psychiatric vulnerabilities in PNES, suggesting as well different strategy for therapeutic approaches.

Neurofilament light chain: a promising diagnostic biomarker for functional motor disorders.

OBJECTIVE: Functional motor disorders (FMDs) are disabling neurological conditions characterized by abnormal movements which are inconsistent and incongruent with recognized neurological diseases. Aim of this study is to investigate whether FMDs are related to structural axonal damage. METHODS: Consecutive patients with a definite diagnosis of FMD with no other neurological/psychiatric comorbidities (pure FMDs) and age-matched healthy controls (HCs) were recruited in a tertiary center and demographic/clinical data were collected. Serum neurofilament light chain (NfL) assessment was performed with ultrasensitive paramagnetic bead-based enzyme-linked immunosorbent assay. RESULTS: 34 patients with FMDs and 34 HCs were included. NfL levels were similar (p = 0.135) in FMDs (median 8.3 pg/mL, range 2-33.7) and HCs (median 6.1 pg/mL, range 2.7-15.6). The area under curve (0.606, 95% CI 0.468-0.743) confirmed that NfL concentration was not different in the two groups. NfL values were similar in patients with paroxysmal vs persistent disease course (p = 0.301), and isolated vs combined symptoms (p = 0.537). NfL levels were associated with age (p < 0.0001), but not with disease duration (p = 0.425), number of CNS acting drugs (p = 0.850), or clinical features (p = 0.983). DISCUSSION: Our preliminary data show that NfL levels are similar in patients with FMDs and HCs, indicating the lack of neuroaxonal damage. These results have relevant pathogenic and clinical implications and suggest that serum NfL may be a promising diagnostic biomarker, potentially useful to differentiate functional vs structural neurological disorders.

'Low-normal' motor skills in infants at high risk for poor developmental outcomes: A prevalence and prognostic study.

AIM: To investigate the prevalence and prognostic value of 'low-normal' motor skills in infants at high-risk for poor developmental outcomes. METHOD: Infants born extremely low-birthweight and extremely preterm discharged from neonatal intensive care between 2015 and 2018 completed the Alberta Infant Motor Scale (AIMS), Neuro-Sensory Motor Developmental Assessment (NSMDA) at corrected age 4, 8, and 12 months, and Griffiths Mental Development Scale at corrected age 12 months. RESULTS: Participating infants (n = 191) with a mean gestational age (95% confidence interval [CI]) of 26.80 weeks (26.60, 27.1) and mean birthweight (95% CI) of 869 grams (843, 895) included 45 (23.80%) infants small for gestational age. AIMS rated 50.32%, 35.37%, and 14.86% of infants within the 'low-normal' motor skills range (1-2 SD below the mean for age) at 4, 8, and 12 months respectively. Of the infants within the AIMS 'low-normal' skills range, 55.70%, 88.46%, and 59.10% were classified as having impairment by NSMDA at 4, 8, and 12 months respectively. Griffiths assessment at 12 months identified only 7.33% of infants with 'low-normal' skills and 3.33% with motor disability. Minimal motor impairment rating on the NSMDA at 4 or 8 months significantly predicted general development at 12 months. INTERPRETATION: High-risk infants with 'low-normal' motor skills may warrant referral to early intervention as associated impairment represents increased risk for poorer general development outcomes. WHAT THIS PAPER ADDS: High prevalence of 'low-normal' motor skill exists in high-risk infants. Clinical motor assessment validly identifies infants with motor impairment. Minimal motor impairment in high-risk infants is prognostic of general development. High-risk infants with 'low-normal' motor skills may warrant early intervention. Griffiths Scales of Child Development, Third Edition assessment at 12-months age may under-identify motor difficulties.

Triggers in functional motor disorder: a clinical feature distinct from precipitating factors.

BACKGROUND AND OBJECTIVE: People with functional motor disorder (FMD) report triggers-sensory or motor-induced stimuli that exacerbate or initiate paroxysmal occurrences of their movement disorder. These are a distinct phenomenon from precipitating factors occurring at the initial onset of the disorder. We aimed to assess triggers in FMD and understand their relevance to paroxysmal variability often seen in FMD. METHODS: We enrolled consecutive outpatients with a definite diagnosis of FMD. Each patient underwent a detailed clinical evaluation also including the presence of trigger factors and video-recordings both during neurological examination and physiotherapy treatment. Patients were classified as having "triggers" (T-FMD) or "not having triggers" (NoT-FMD) as well as "paroxysmal" compared to "persistent with paroxysmal variability". RESULTS: The study sample was 100 patients (82% female) with FMD; the mean age at onset was 41 years. Triggers were observed in 88% of patients and in 65 of these the FMD was pure paroxysmal. The most common triggers were movement or physical exercise, followed by emotional, visual, touch, and auditory stimuli; 39 (44%) were isolated and 49 (56%) were combined triggers. Among the T-FMD patients, FMD were paroxysmal in 74% (n = 65) and persistent with paroxysmal variability in 26% (n = 23). The T-FMD patients were younger (p = 0.016) and had a gait disorder (p = 0.035) more frequently than the NoT-FMD patients. DISCUSSION: Triggers are frequent in FMD and may have diverse overlapping clinical presentations. In this sample, FMD was most often paroxysmal, suggesting the value of noting triggers as clinical clues in the diagnosis and rehabilitation of FMD.

Better detection of reduced motor functioning in brain tumor survivors based on objective motor assessments: an incentive for improved standardized follow-up.

Long-term sequelae are well-known in childhood brain tumor survivors, but motor functioning remains poorly described. This cross-sectional study aimed to assess objective motor functioning, patient-specific risk factors, and parental perceptions. Fifty-two childhood brain tumor patients (pilocytic astrocytoma, medulloblastoma, and other types) who were at least 6 months out of treatment were evaluated. Mean age at testing was 11.7 years. Objective motor functioning was assessed with the Movement Assessment Battery for Children (MABC-2-NL) and/or Bruininks-Oseretsky test of motor proficiency (BOT-2). Functional walking capacity was assessed with the 6-min walk test (6MWT). Parent-reported motor functioning was addressed using the ABILHAND-Kids, ABILOCO-Kids questionnaires, and a standardized anamnesis. Patients showed impaired motor functioning in all domains (p < 0.001). Regarding risk factors, younger age at diagnosis (< 5 year) was significantly associated with lower scores on body coordination (p = 0.006). Adjuvant treatment resulted in lower scores for fine manual control of the BOT-2 (p = 0.024) and balance of MABC-2-NL (p = 0.036). Finally, questionnaires revealed an underestimation of motor problems as perceived by the parents. In conclusion, many children who are in follow-up for a brain tumor show impaired motor functioning on multiple aspects, with younger age at diagnosis and adjuvant treatment as specific risk factors. Based on the questionnaires and anamnesis, motor problems appear to be underestimated by the parents.  Conclusion: These findings point to the need for timely prospective screening of motor functioning. Based on a screening assessment, adequate rehabilitation programs can be applied in childhood brain tumor survivors, aiming to reduce the adverse impact on their daily lives, both for functional activities and cardiovascular fitness. What is Known: • A pediatric brain tumor and its treatment are associated with potential long-term motor sequelae. • Test assessments could enable us to objectify motor functioning of these patients. What is New: • Pediatric brain tumors survivors show lower motor performance compared to the norm, which is often underestimated by parents. • Younger age at diagnosis and adjuvant treatment could be specific risk factors.

A feasibility randomized controlled trial of a NICU rehabilitation program for very low birth weight infants.

Motor disability is common in children born preterm. Interventions focusing on environmental enrichment and emotional connection can positively impact outcomes. The NICU-based rehabilitation (NeoRehab) program consists of evidence-based interventions provided by a parent in addition to usual care. The program combines positive sensory experiences (vocal soothing, scent exchange, comforting touch, skin-to-skin care) as well as motor training (massage and physical therapy) in a gestational age (GA) appropriate fashion. To investigate the acceptability, feasibility and fidelity of the NeoRehab program in very low birthweight (VLBW) infants. All interventions were provided by parents in addition to usual care. Infants (≤ 32 weeks' GA and/or ≤ 1500 g birthweight) were enrolled in a randomized controlled trial comparing NeoRehab to usual care (03/2019-10/2020). The a priori dosing goal was for interventions to be performed 5 days/week. The primary outcomes were the acceptability, feasibility and fidelity of the NeoRehab program. 36 participants were randomized to the intervention group and 34 allocated to usual care. The recruitment rate was 71% and retention rate 98%. None of the interventions met the 5 days per week pre-established goal. 97% of participants documented performing a combination of interventions at least 3 times per week. The NeoRehab program was well received and acceptable to parents of VLBW infants. Programs that place a high demand on parents (5 days per week) are not feasible and goals of intervention at least 3 times per week appear to be feasible in the context of the United States. Parent-provided motor interventions were most challenging to parents and alternative strategies should be considered in future studies. Further studies are needed to evaluate the relationship between intervention dosing on long term motor outcomes.

Growth in infants, children and adolescents with unilateral and bilateral cerebral palsy.

To compare growth patterns during infancy, childhood and adolescence in children with unilateral and bilateral cerebral palsy (CP) phenotype and to assess the association with gross motor impairment, dysphagia and gestational age. We retrospectively studied 389 children with CP from a single center population in Munich, Germany. 1536 measurements of height and weight were tabulated and z-scored from 6 to 180 months of age. Generalized linear mixed model were used to examine the association between growth, GMFCS, dysphagia and gestational age by CP phenotype. Children with unilateral CP tend to grow similarly to their typically developed peers. In the main effect model, bilateral CP phenotype was significantly associated with decreased mean z-scores for height (ß [95% CI] - 0.953 [- 1.145, - 0.761], p < 0.001), weight (- 0.999 [- 1.176, - 0.807], p < 0.001) and BMI (ß [95% CI] - 0.437 [- 0.799, - 0.075]), compared with unilateral CP phenotype. This association remained significant in the interaction models. The height-for-age z-scores, weight-for-age decreased z-scores and BMI-for-age z-scores of children with bilateral CP and GMFCS III-V or dysphagia decreased more significantly than those of children with unilateral CP. Preterm birth was not significantly associated with decreased growth in height, weight and BMI. Reduced growth in children with bilateral CP was strongly associated with moderate to severe impairment in gross motor function (GMFCS III-V) and dysphagia.

Subthalamic dynamic neural states correlate with motor symptoms in Parkinson's Disease.

OBJECTIVE: This study aims to discriminate the dynamic synchronization states from the subthalamic local field potentials and investigate their correlations with the motor symptoms in Parkinson's Disease (PD). METHODS: The resting-state local field potentials of 10 patients with PD were recorded from the subthalamic nucleus. The dynamic neural states of multiple oscillations were discriminated and analyzed. The Spearman correlation was used to investigate the correlations between occurrence rate or duration of dynamic neural states and the severity of motor symptoms. RESULTS: The proportion of long low-beta and theta synchronized state was significantly correlated with the general motor symptom and tremor, respectively. The duration of combined low/high-beta state was significantly correlated with rigidity, and the duration of combined alpha/high-beta state was significantly correlated with bradykinesia. CONCLUSIONS: This study provides evidence that motor symptoms are associated with the neural states coded with multiple oscillations in PD. SIGNIFICANCE: This study may advance the understanding of the neurophysiological mechanisms of the motor symptoms and provide potential biomarkers for closed-loop deep brain stimulation in PD.

Comprehensive genetic analysis confers high diagnostic yield in 16 Japanese patients with corpus callosum anomalies.

Corpus callosum anomalies (CCA) is a common congenital brain anomaly with various etiologies. Although one of the most important etiologies is genetic factors, the genetic background of CCA is heterogenous and diverse types of variants are likely to be causative. In this study, we analyzed 16 Japanese patients with corpus callosum anomalies to delineate clinical features and the genetic background of CCAs. We observed the common phenotypes accompanied by CCAs: intellectual disability (100%), motor developmental delay (93.8%), seizures (60%), and facial dysmorphisms (50%). Brain magnetic resonance imaging showed colpocephaly (enlarged posterior horn of the lateral ventricles, 84.6%) and enlarged supracerebellar cistern (41.7%). Whole exome sequencing revealed genetic alterations in 9 of the 16 patients (56.3%), including 8 de novo alterations (2 copy number variants and variants in ARID1B, CDK8, HIVEP2, and TCF4) and a recessive variant of TBCK. De novo ARID1B variants were identified in three unrelated individuals, suggesting that ARID1B variants are major genetic causes of CCAs. A de novo TCF4 variant and somatic mosaic deletion at 18q21.31-qter encompassing TCF4 suggest an association of TCF4 abnormalities with CCAs. This study, which analyzes CCA patients usung whole exome sequencing, demonstrates that comprehensive genetic analysis would be useful for investigating various causal variants of CCAs.

Automated movement recognition to predict motor impairment in high-risk infants: a systematic review of diagnostic test accuracy and meta-analysis.

AIM: To assess the sensitivity and specificity of automated movement recognition in predicting motor impairment in high-risk infants. METHOD: We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Scopus databases and identified additional studies from the references of relevant studies. We included studies that evaluated automated movement recognition in high-risk infants to predict motor impairment, including cerebral palsy (CP) and non-CP motor impairments. Two authors independently assessed studies for inclusion, extracted data, and assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies-2. Meta-analyses were performed using hierarchical summary receiver operating characteristic models. RESULTS: Of 6536 articles, 13 articles assessing 59 movement variables in 1248 infants under 5 months corrected age were included. Of these, 143 infants had CP. The overall sensitivity and specificity for motor impairment were 0.73 (95% confidence interval [CI] 0.68-0.77) and 0.70 (95% CI 0.65-0.75) respectively. Comparatively, clinical General Movements Assessment (GMA) was found to have sensitivity and specificity of 98% (95% CI 74-100) and 91% (95% CI 83-93) respectively. Sensor-based technologies had higher specificity (0.88, 95% CI 0.80-0.93). INTERPRETATION: Automated movement recognition technology remains inferior to clinical GMA. The strength of this study is its meta-analysis to summarize performance, although generalizability of these results is limited by study heterogeneity.

Cognitive and Motor Outcome in Patients with Early-Detected Central Congenital Hypothyroidism Compared with Siblings.

CONTEXT: Early treatment of primary congenital hypothyroidism (CH) prevents irreversible brain damage. Contrary to primary CH, outcome studies on central CH are scarce. Most patients with central CH have multiple pituitary hormone deficiencies (MPHD); these patients are also at risk for neonatal hypoglycemia. OBJECTIVE: To assess cognitive and motor outcome in patients with early-treated central CH detected by the Dutch neonatal screening. METHODS: In this cross-sectional study, primary outcome full-scale intelligence quotient (FSIQ) was measured in patients with MPHD and patients with isolated central CH born between January 1, 1995, and January 1, 2015, with siblings as controls. Secondary outcomes were intelligence test subscales and motor function. Linear mixed models were used to compare both patient groups and siblings, followed by post hoc tests in case of significant differences. RESULTS: Eighty-seven patients (52 MPHD; 35 isolated central CH) and 52 siblings were included. Estimated marginal means for FSIQ were 90.7 (95% CI 86.4-95.0) in patients with MPHD and 98.2 (95% CI 93.0-103.5) in patients with isolated central CH. While patients with MPHD scored lower FSIQs than siblings (mean difference -7.9 points, 95% CI -13.4 to -2.5; P = .002), patients with isolated central CH did not. Processing speed was lower in both patient groups than in siblings (mean differences -10.5 and -10.3 points). Motor difficulties occurred significantly more often in patients (33%) versus siblings (5%; P = .004). CONCLUSION: In early-treated central CH, FSIQ is comparable with siblings in patients with isolated central CH, while patients with MPHD have a significantly lower FSIQ. This may be explained by disease-specific consequences of MPHD, such as neonatal hypoglycemia and more severe hypothyroidism.

Are early measured resting-state EEG parameters predictive for upper limb motor impairment six months poststroke?

OBJECTIVES: Investigate whether resting-state EEG parameters recorded early poststroke can predict upper extremity motor impairment reflected by the Fugl-Meyer motor score (FM-UE) after six months, and whether they have prognostic value in addition to FM-UE at baseline. METHODS: Quantitative EEG parameters delta/alpha ratio (DAR), brain symmetry index (BSI) and directional BSI (BSIdir) were derived from 62-channel resting-state EEG recordings in 39 adults within three weeks after a first-ever ischemic hemispheric stroke. FM-UE scores were acquired within three weeks (FM-UEbaseline) and at 26 weeks poststroke (FM-UEw26). Linear regression analyses were performed using a forward selection procedure to predict FM-UEw26. RESULTS: BSI calculated over the theta band (BSItheta) (ß = -0.40; p = 0.013) was the strongest EEG-based predictor regarding FM-UEw26. BSItheta (ß = -0.27; p = 0.006) remained a significant predictor when added to a regression model including FM-UEbaseline, increasing explained variance from 61.5% to 68.1%. CONCLUSION: Higher BSItheta values, reflecting more power asymmetry over the hemispheres, predict more upper limb motor impairment six months after stroke. Moreover, BSItheta shows additive prognostic value regarding FM-UEw26 next to FM-UEbaseline scores, and thereby contains unique information regarding upper extremity motor recovery. SIGNIFICANCE: To our knowledge, we are the first to show that resting-state EEG parameters can serve as prognostic biomarkers of stroke recovery, in addition to FM-UEbaseline scores.

Handwritten Geometrical Patterns in the Evaluation of Motor Symptoms in Psychotic Disorders.

The analysis of handwriting has been used in several contexts. For example, handwriting has shown to be of value in the study of motor symptoms in neurological and mental disorders. In the present work, the geometric analysis of handwriting patterns is proposed as a tool to evaluate motor symptoms in psychotic disorders. Specifically, we have employed the lacunarity, a measure of the heterogeneity of a spatial structure. Forty-two patients with a psychotic disorder and 35 matched healthy controls participated in the study. Participants were asked to copy some patterns with a pen on a white paper. The results showed that lacunarity was significantly higher in handwritten patterns from patients than from controls. In addition, we found higher values of lacunarity in handwritten patterns from patients with severe motor symptoms in comparison with patients with mild or absent motor symptoms. Lacunarity of handwritten patterns was significantly correlated with clinical scores of rigidity. In conclusion we argue that the heterogeneity of handwritten patterns could be used as a simple and objective measure of motor symptoms.

Earlier Acupuncture Enhancing Long-Term Effects on Motor Dysfunction in Acute Ischemic Stroke: Retrospective Cohort Study.

Stroke is the leading fatal disease in China. This retrospective study aimed to explore the optimal acupuncture intervention time for long-term efficacy on motor dysfunction in patients suffering from acute ischemic stroke through 1-year of follow-up. Three hundred and nine patients collected at Longhua Hospital from January 2016 to December 2017 were classified into 3 groups based on the acupuncture intervention time, including groups A (within 2 days), B (within 3-7 days) and C (within 8-14 days). All patients had received standard treatment combined with acupuncture therapy. Specifically, acupuncture was performed at the acupoints including LI4 (Hegu), ST40 (Fenglong), DU20 (Baihui), and motor area of the scalp, followed by 2 electroacupuncture protocols based on different muscle tensions once a day for 5 days consecutively. The time-effect relationship was assessed using both the Fugl-Meyer Assessment (FMA) and the modified Barthel index (MBI) on the 90th day and 1st year, respectively. Meanwhile, the modified Rankin scale (mRS), high-sensitivity C-reactive protein (hs-CRP), and fibrinogen (FIB) were also measured during the 1-year follow-up. The favorable outcome rate was 74.4%. One-way univariate analysis of variance (ANOVA) revealed significant differences in FMA and MBI on the 90th day among the 3 groups ([Formula: see text] < 0.05), while no significant differences were observed in FMA, MBI or mRS at the 1st year between groups A and B. The levels of hs-CRP and FIB ([Formula: see text] < 0.05) were markedly reduced. Binary logistic regression analysis suggested that patients with atrial fibrillation (AF) (odds ratio (OR): 3.156), chronic kidney disease (CKD) (OR: 2.563), diabetes mellitus (DM) (OR: 2.174) or stroke history (OR: 1.883) were more inclined to recover poorly from nerve function deficit ([Formula: see text] < 0.05). Earlier acupuncture intervention may have a better long-term effect on motor dysfunction and inflammation during the 1-year follow-up. Moreover, acupuncture within 2 days is probably the optimal treatment time for early recovery on the 90th day.

Real-Life Gait Performance as a Digital Biomarker for Motor Fluctuations: The Parkinson@Home Validation Study.

BACKGROUND: Wearable sensors have been used successfully to characterize bradykinetic gait in patients with Parkinson disease (PD), but most studies to date have been conducted in highly controlled laboratory environments. OBJECTIVE: This paper aims to assess whether sensor-based analysis of real-life gait can be used to objectively and remotely monitor motor fluctuations in PD. METHODS: The Parkinson@Home validation study provides a new reference data set for the development of digital biomarkers to monitor persons with PD in daily life. Specifically, a group of 25 patients with PD with motor fluctuations and 25 age-matched controls performed unscripted daily activities in and around their homes for at least one hour while being recorded on video. Patients with PD did this twice: once after overnight withdrawal of dopaminergic medication and again 1 hour after medication intake. Participants wore sensors on both wrists and ankles, on the lower back, and in the front pants pocket, capturing movement and contextual data. Gait segments of 25 seconds were extracted from accelerometer signals based on manual video annotations. The power spectral density of each segment and device was estimated using Welch's method, from which the total power in the 0.5- to 10-Hz band, width of the dominant frequency, and cadence were derived. The ability to discriminate between before and after medication intake and between patients with PD and controls was evaluated using leave-one-subject-out nested cross-validation. RESULTS: From 18 patients with PD (11 men; median age 65 years) and 24 controls (13 men; median age 68 years), ≥10 gait segments were available. Using logistic LASSO (least absolute shrinkage and selection operator) regression, we classified whether the unscripted gait segments occurred before or after medication intake, with mean area under the receiver operator curves (AUCs) varying between 0.70 (ankle of least affected side, 95% CI 0.60-0.81) and 0.82 (ankle of most affected side, 95% CI 0.72-0.92) across sensor locations. Combining all sensor locations did not significantly improve classification (AUC 0.84, 95% CI 0.75-0.93). Of all signal properties, the total power in the 0.5- to 10-Hz band was most responsive to dopaminergic medication. Discriminating between patients with PD and controls was generally more difficult (AUC of all sensor locations combined: 0.76, 95% CI 0.62-0.90). The video recordings revealed that the positioning of the hands during real-life gait had a substantial impact on the power spectral density of both the wrist and pants pocket sensor. CONCLUSIONS: We present a new video-referenced data set that includes unscripted activities in and around the participants' homes. Using this data set, we show the feasibility of using sensor-based analysis of real-life gait to monitor motor fluctuations with a single sensor location. Future work may assess the value of contextual sensors to control for real-world confounders.

Technology-aided assessment of functionally relevant sensorimotor impairments in arm and hand of post-stroke individuals.

BACKGROUND: Assessing arm and hand sensorimotor impairments that are functionally relevant is essential to optimize the impact of neurorehabilitation interventions. Technology-aided assessments should provide a sensitive and objective characterization of upper limb impairments, but often provide arm weight support and neglect the importance of the hand, thereby questioning their functional relevance. The Virtual Peg Insertion Test (VPIT) addresses these limitations by quantifying arm and hand movements as well as grip forces during a goal-directed manipulation task requiring active lifting of the upper limb against gravity. The aim of this work was to evaluate the ability of the VPIT metrics to characterize arm and hand sensorimotor impairments that are relevant for performing functional tasks. METHODS: Arm and hand sensorimotor impairments were systematically characterized in 30 chronic stroke patients using conventional clinical scales and the VPIT. For the latter, ten previously established kinematic and kinetic core metrics were extracted. The validity and robustness of these metrics was investigated by analyzing their clinimetric properties (test-retest reliability, measurement error, learning effects, concurrent validity). RESULTS: Twenty-three of the participants, the ones with mild to moderate sensorimotor impairments and without strong cognitive deficits, were able to successfully complete the VPIT protocol (duration 16.6 min). The VPIT metrics detected impairments in arm and hand in 90.0% of the participants, and were sensitive to increased muscle tone and pathological joint coupling. Most importantly, significant moderate to high correlations between conventional scales of activity limitations and the VPIT metrics were found, thereby indicating their functional relevance when grasping and transporting objects, and when performing dexterous finger manipulations. Lastly, the robustness of three out of the ten VPIT core metrics in post-stroke individuals was confirmed. CONCLUSIONS: This work provides evidence that technology-aided assessments requiring goal-directed manipulations without arm weight support can provide an objective, robust, and clinically feasible way to assess functionally relevant sensorimotor impairments in arm and hand in chronic post-stroke individuals with mild to moderate deficits. This allows for a better identification of impairments with high functional relevance and can contribute to optimizing the functional benefits of neurorehabilitation interventions.

An Instrumented Assessment of a Rhythmic Finger Task among Children with Motor Coordination Difficulties.

BACKGROUND: Coordination is crucial for motor function, yet objective clinical evaluations are limited. We therefore developed and tested the reliability and validity of a low-cost sensorized evaluation of a rhythmic finger task. METHODS: Children with coordination difficulties (n = 24) and typically developing children (n = 24) aged from 5 to 7 years performed the Sensorized Finger Sequencing Test (SFST), a finger sequencing test that records the correct sequence, total time, and the standard deviation (SD) of touch time. Additionally, motor performance tests and parents' reports were applied in order to test the reliability and validity of the SFST. RESULTS: The study group had significantly greater thumb-finger test scores-total time in the dominant hand (p = 0.035) and the SD of the touch time in both dominant (p = 0.036) and non-dominant (p = 0.032) hands. Motor performance tests were not correlated with the SFST. Test-retest reliability in 10 healthy children was found for the SD of touch time in the dominant hand (r = 0.87, p = 0.003). CONCLUSIONS: The SFST was successful in assessing the movement pattern variability reported in children with motor difficulties. This exploratory study indicates that the low-cost SFST could be utilized as an objective measure for the assessment of proprioception components, which currently are overlooked by standardized motor performance assessments.

Therapy of Parkinson's Disease Subtypes.

Early descriptions of subtypes of Parkinson's disease (PD) are dominated by the approach of predetermined groups. Experts defined, from clinical observation, groups based on clinical or demographic features that appeared to divide PD into clinically distinct subsets. Common bases on which to define subtypes have been motor phenotype (tremor dominant vs akinetic-rigid or postural instability gait disorder types), age, nonmotor dominant symptoms, and genetic forms. Recently, data-driven approaches have been used to define PD subtypes, taking an unbiased statistical approach to the identification of PD subgroups. The vast majority of data-driven subtyping has been done based on clinical features. Biomarker-based subtyping is an emerging but still quite undeveloped field. Not all of the subtyping methods have established therapeutic implications. This may not be surprising given that they were born largely from clinical observations of phenotype and not in observations regarding treatment response or biological hypotheses. The next frontier for subtypes research as it applies to personalized medicine in PD is the development of genotype-specific therapies. Therapies for GBA-PD and LRRK2-PD are already under development. This review discusses each of the major subtyping systems/methods in terms of its applicability to therapy in PD, and the opportunities and challenges designing clinical trials to develop the evidence base for personalized medicine based on subtypes.