Muscle activation strategies of people with early-stage Parkinson's during walking.

INTRODUCTION: Some people with Parkinson's disease (PD) frequently have an unsteady gait with shuffling, reduced strength, and increased rigidity. This study has investigated the difference in the neuromuscular strategies of people with early-stage PD, healthy older adults (HOA) and healthy young adult (HYA) during short-distance walking. METHOD: Surface electromyogram (sEMG) was recorded from tibialis anterior (TA) and medial gastrocnemius (MG) muscles along with the acceleration data from the lower leg from 72 subjects-24 people with early-stage PD, 24 HOA and 24 HYA during short-distance walking on a level surface using wearable sensors. RESULTS: There was a significant increase in the co-activation, a reduction in the TA modulation and an increase in the TA-MG lateral asymmetry among the people with PD during a level, straight-line walking. For people with PD, the gait impairment scale was low with an average postural instability and gait disturbance (PIGD) score = 5.29 out of a maximum score of 20. Investigating the single and double support phases of the gait revealed that while the muscle activity and co-activation index (CI) of controls modulated over the gait cycle, this was highly diminished for people with PD. The biggest difference between CI of controls and people with PD was during the double support phase of gait. DISCUSSION: The study has shown that people with early-stage PD have high asymmetry, reduced modulation, and higher co-activation. They have reduced muscle activity, ability to inhibit antagonist, and modulate their muscle activities. This has the potential for diagnosis and regular assessment of people with PD to detect gait impairments using wearable sensors.

Abnormal vocal cord movement treated with botulinum toxin in patients with asthma resistant to optimised management.

BACKGROUND AND OBJECTIVE: Abnormal vocal cord movement may coexist with asthma and cause additional upper/middle airway obstruction. The condition may be a form of muscular dystonia that could contribute to asthma resistant to optimised treatments. Botulinum toxin causes temporary paralysis of muscle and may be an effective local treatment that improves asthma control. METHODS: In an observational study, we evaluated the benefits of unilateral vocal cord injection with botulinum toxin in 11 patients (total 24 injections). Subjects had asthma resistant to optimised treatment and abnormal vocal cord movement. Responses after botulinum toxin treatment were assessed using asthma control test (ACT) scores, vocal cord narrowing quantified by computerised tomography (CT) of the larynx and spirometry. Side-effects were recorded. RESULTS: ACT scores improved overall (9.1 ± 2.4 before and 13.5 ± 4.5 after treatment; difference 4.4 ± 4.2; P < 0.001). There was also an improvement in airway size on CT larynx (time below lower limit of normal at baseline 39.4 ± 37.63% and improved to 17.6 ± 25.6% after injection; P = 0.032). Spirometry was not altered. One patient experienced an asthma exacerbation but overall side-effects were moderate, chiefly dysphonia and dysphagia. CONCLUSIONS: Although a placebo effect cannot be ruled out, local injection of botulinum toxin may be an effective treatment for intractable asthma associated with abnormal vocal cord movement. Further mechanistic studies and a double-blind randomised controlled trial of botulinum toxin treatment are merited.

NeuroDiag: Software for Automated Diagnosis of Parkinson's Disease Using Handwriting.

OBJECTIVE: A change in handwriting is an early sign of Parkinson's disease (PD). However, significant inter-person differences in handwriting make it difficult to identify pathological handwriting, especially in the early stages. This paper reports the testing of NeuroDiag, a software-based medical device, for the automated detection of PD using handwriting patterns. NeuroDiag is designed to direct the user to perform six drawing and writing tasks, and the recordings are then uploaded onto a server for analysis. Kinematic information and pen pressure of handwriting are extracted and used as baseline parameters. NeuroDiag was trained based on 26 PD patients in the early stage of the disease and 26 matching controls. METHODS: Twenty-three people with PD (PPD) in their early stage of the disease, 25 age-matched healthy controls (AMC), and 7 young healthy controls were recruited for this study. Under the supervision of a consultant neurologist or their nurse, the participants used NeuroDiag. The reports were generated in real-time and tabulated by an independent observer. RESULTS: The participants were able to use NeuroDiag without assistance. The handwriting data was successfully uploaded to the server where the report was automatically generated in real-time. There were significant differences in the writing speed between PPD and AMC (P<0.001). NeuroDiag showed 86.96% sensitivity and 76.92% specificity in differentiating PPD from those without PD. CONCLUSION: In this work, we tested the reliability of NeuroDiag in differentiating between PPD and AMC for real-time applications. The results show that NeuroDiag has the potential to be used to assist neurologists and for telehealth applications. Clinical and Translational Impact Statement - This pre-clinical study shows the feasibility of developing a community-wide screening program for Parkinson's disease using automated handwriting analysis software, NeuroDiag.

Wearable Accelerometer and Gyroscope Sensors for Estimating the Severity of Essential Tremor.

BACKGROUND: Several validated clinical scales measure the severity of essential tremor (ET). Their assessments are subjective and can depend on familiarity and training with scoring systems. METHOD: We propose a multi-modal sensing using a wearable inertial measurement unit for estimating scores on the Fahn-Tolosa-Marin tremor rating scale (FTM) and determine the classification accuracy within the tremor type. 17 ET participants and 18 healthy controls were recruited for the study. Two movement disorder neurologists who were blinded to prior clinical information viewed video recordings and scored the FTM. Participants drew a guided Archimedes spiral while wearing an inertial measurement unit placed at the mid-point between the lateral epicondyle of the humerus and the anatomical snuff box. Acceleration and gyroscope recordings were analyzed. The ratio of the power spectral density between frequency bands 0.5-4 Hz and 4-12 Hz, and the sum of power spectrum density over the entire spectrum of 2-74 Hz, for both accelerometer and gyroscope data, were computed. FTM was estimated using regression model and classification using SVM was validated using the leave-one-out method. RESULTS: Regression analysis showed a moderate to good correlation when individual features were used, while correlation was high ([Formula: see text] = 0.818) when suitable features of the gyro and accelerometer were combined. The accuracy for two-class classification of the combined features using SVM was 91.42% while for four-class it was 68.57%. CONCLUSION: Potential applications of this novel wearable sensing method using a wearable Inertial Measurement Unit (IMU) include monitoring of ET and clinical trials of new treatments for the disorder.

Wearable sensors during drawing tasks to measure the severity of essential tremor.

Commonly used methods to assess the severity of essential tremor (ET) are based on clinical observation and lack objectivity. This study proposes the use of wearable accelerometer sensors for the quantitative assessment of ET. Acceleration data was recorded by inertial measurement unit (IMU) sensors during sketching of Archimedes spirals in 17 ET participants and 18 healthy controls. IMUs were placed at three points (dorsum of hand, posterior forearm, posterior upper arm) of each participant's dominant arm. Movement disorder neurologists who were blinded to clinical information scored ET patients on the Fahn-Tolosa-Marin rating scale (FTM) and conducted phenotyping according to the recent Consensus Statement on the Classification of Tremors. The ratio of power spectral density of acceleration data in 4-12 Hz to 0.5-4 Hz bands and the total duration of the action were inputs to a support vector machine that was trained to classify the ET subtype. Regression analysis was performed to determine the relationship of acceleration and temporal data with the FTM scores. The results show that the sensor located on the forearm had the best classification and regression results, with accuracy of 85.71% for binary classification of ET versus control. There was a moderate to good correlation (r2 = 0.561) between FTM and a combination of power spectral density ratio and task time. However, the system could not accurately differentiate ET phenotypes according to the Consensus classification scheme. Potential applications of machine-based assessment of ET using wearable sensors include clinical trials and remote monitoring of patients.

A randomized, double-blind, placebo-controlled trial of levetiracetam for dyskinesia in Parkinson's disease.

BACKGROUND: This randomized double blind, placebo-controlled crossover study investigated the antidyskinetic effects of levetiracetam in Parkinson's disease. METHODS: Sixteen participants with levodopa-induced dyskinesia were enrolled. Hourly videotaped dyskinesia assessments scored by the Goetz method and hourly Unified Parkinson's Disease Rating Scale motor subscale scoring were conducted on 1 day at the end of each treatment period. RESULTS: Dyskinesia was slightly less on placebo (P = .26). Patient diary records also showed less dyskinesia on placebo (P = .10). Parkinsonism was a little worse on levetiracetam, at borderline statistical significance (P = .05). CONCLUSIONS: Levetiracetam was well tolerated at doses up to 2000 mg per day, but we did not detect any antidyskinetic properties.

Movement Disorders in Children.

CONTEXT: Movement disorders represent a common presentation in pediatrics and are often a source of clinical and diagnostic dilemmas. In this review, we provide an overview of common causes along with simplified clinical approach and management options for major movement disorders. SOURCES: This narrative review is based on contemporary evidence and personal experience. Medline was searched for recent advances, current understanding and consensus on classification, clinical features, diagnosis and treatment. RESULTS: Movement disorders are classified as hyperkinetic and hypokinetic disorders, the latter being rare in childhood. The hyperkinetic disorders include dystonia, chorea, athetosis, tics and tremor, stereotypies, myoclonus, startle syndromes and functional disorders. Some movement disorders can be benign and developmental. A large proportion of conditions are genetic in origin with a guarded prognosis. Some of the conditions may be post-infectious, immune-mediated or drug induced. Multiple types of movement disorders are present in many conditions. The age at onset, type and distribution of abnormal movements and presence of associated neurological and systemic features help in narrowing the differential diagnosis. The pharmacotherapy of movement disorders is complex and evolving. CONCLUSION: A synopsis of movement disorders presenting in pediatric age has been provided, incorporating the latest evidence. A simplified approach for clinical diagnosis has been developed for dystonia and chorea.

Computerised analysis of writing and drawing by essential tremor phenotype.

We investigated whether computerised analysis of writing and drawing could discriminate essential tremor (ET) phenotypes according to the 2018 Consensus Statement on the Classification of Tremors. The Consensus scheme emphasises soft additional findings, mainly motor, that do not suffice to diagnose another tremor syndrome. Ten men and nine women were classified by blinded assessors according to Consensus Axis 1 definitions of ET and ET plus. Blinded scoring of tremor severity and alternating limb movement was also conducted. Twenty healthy participants acted as controls. Four writing and three drawing tasks were performed on a Wacom Intuos Pro Large digital tablet with a pressure-sensor mounted ink pen. Sixty-seven computerised measurements were obtained, comprising static (dimensional and temporal), kinematic and pen pressure features. The mean age of ET participants was 67.2±13.0 years and mean tremor duration was 21.7±19.0 years. Six were classified as ET, five had one plus feature and eight had two plus features. The computerised analysis could predict the presence and number of ET plus features. Measures of acceleration and variation of pen pressure performed strongly to separate ET phenotypes (p<0.05). Plus features were associated with higher scores on the Fahn-Tolosa-Marin Tremor Rating Scale (p=0.001) and it appeared that ET groups were mainly being separated according to severity of tremor and by compensatory manoeuvres used by participants with more severe tremor. There were, in addition, a small number of negative kinematic correlations suggesting some slowness with ET plus. Abnormal repetitive limb movement was also correlated with tremor severity (R=0.57) by clinical grading. Critics of the Consensus Statement have drawn attention to weaknesses of the ET plus concept in relation to duration and severity of ET. This classification of ET may be too biased towards tremor severity to assist in distinguishing underlying biological differences by clinical measurement.

Differences in Levodopa Response for Progressive and Non-Progressive Micrographia in Parkinson's Disease.

Background: Micrographia, one element of the dysgraphia of Parkinson's disease (PD), may be classified according to the presence or absence of a decremental pattern. The decremental form, progressive micrographia, is an expression of the sequence effect seen generally in bradykinesia. Its responsiveness to levodopa has not been evaluated kinematically. Objectives: Aim of this study is to investigate the difference in levodopa response for progressive and non-progressive micrographia. Methods: Twenty-four PD patients and 24 age-matched repeatedly wrote the letter e on a computerized digital tablet. PD patients performed the task two times, in a defined off state and again after levodopa. Scripts were classified as progressive micrographia (PDPM) or non-progressive micrographia (PDNPM) depending on whether a 10% decrement was seen between the first and final characters of a line of lettering. Results: While levodopa produced a similar response on the MDS-UPDRS motor scale for the two groups, the effect on the two types of micrographia was different. While writing speed improved significantly in both groups after levodopa, the responses were over twofold greater for PDNPM. Moreover, the decremental features of PDPM-in size, speed, and pen-pressure-were largely unaltered by a levodopa dose. Conclusions: Progressive micrographia is less responsive to levodopa. Our findings agree with research showing that the sequence effect of bradykinesia is relatively resistant to medication. Yet we did not find a weaker overall levodopa motor benefit. Caution is needed in the interpretation of such micrographia measurements for estimating drug responses.

Differentiating between Parkinson's disease patients and controls using variability in muscle activation during walking.

Surface electromyography (sEMG) of the lower limb muscles has been proposed to evaluate motor dysfunctions in Parkinson's disease (PD) patients. Variability in the sEMG could be used as an indicator of poor muscle coordination, but previous studies have reported conflicting results. This study has examined the variability of muscle using the coefficients of variance of Tibialis anterior (TA) and Medial gastrocnemius (MG) lower limb muscles for 24 PD, 24 age matched controls (CO), and 24 young controls (YC), during different phases of the gait cycle. The gait intervals were measured using the inertial measurement unit (IMU). We observed a statistically significant difference between PD and control for the variability of lower limb muscle when comparing the sub-phases of the gait. It was also found that the difference was more pronounced for the TA muscle.

Estimation of Parkinson's disease severity from voice features of vowels and consonant.

This study has investigated the efficiency of voice features in estimating the motor Unified Parkinson's Disease Rating Scale (UPDRS) score in Parkinson's disease (PD) patients. A total of 26 PD patients (mean age = 72) and 22 control subjects (mean age = 66.91) were recruited for the study. The sustained phonation /a/, /u/ and /m/ were collected in both off-state and on-state of Levodopa medication. The average motor UPDRS for PD off-state patients was 27.31, on-state was 20.42 and that of controls was 2.63. Voice features were extracted from the phonation tasks and were reduced to the most relevant 6 features for each phonation task using the Least Absolute Shrinkage and Selection Operator (LASSO) feature ranking method. The correlation between the reduced features and motor UPDRS was tested using the Spearman correlation coefficient test. AdaBoost regression learner was trained and used for automatically estimating the motor UPDRS score using the voice features. The results show that the vocal features for /m/ performed best by estimating the motor UPDRS score for PD off-state with the mean absolute error (MAE) of 3.52 and 5.90 for PD on-state. This study shows that assessment of voice can be used for day to day remote monitoring of PD patients.

Which Gait Parameters and Walking Patterns Show the Significant Differences Between Parkinson's Disease and Healthy Participants?

This study investigated the difference in the gait of patients with Parkinson's disease (PD), age-matched controls and young controls during three walking patterns. Experiments were conducted with 24 PD, 24 age-matched controls and 24 young controls, and four gait intervals were measured using inertial measurement units (IMU). Group differences between the mean and variance of the gait parameters (stride interval, stance interval, swing interval and double support interval) for the three groups were calculated and statistical significance was tested. The results showed that the variance in each of the four gait parameters of PD patients was significantly higher compared with the controls, irrespective of the three walking patterns. This study showed that the variance of any of the gait interval parameters obtained using IMU during any of the walking patterns could be used to differentiate between the gait of PD and control people.

Complexity Measures of Voice Recordings as a Discriminative Tool for Parkinson's Disease.

In this paper, we have investigated the differences in the voices of Parkinson's disease (PD) and age-matched control (CO) subjects when uttering three phonemes using two complexity measures: fractal dimension (FD) and normalised mutual information (NMI). Three sustained phonetic voice recordings, /a/, /u/ and /m/, from 22 CO (mean age = 66.91) and 24 PD (mean age = 71.83) participants were analysed. FD was first computed for PD and CO voice recordings, followed by the computation of NMI between the test groups: PD-CO, PD-PD and CO-CO. Four features reported in the literature-normalised pitch period entropy (Norm. PPE), glottal-to-noise excitation ratio (GNE), detrended fluctuation analysis (DFA) and glottal closing quotient (ClQ)-were also computed for comparison with the proposed complexity measures. The statistical significance of the features was tested using a one-way ANOVA test. Support vector machine (SVM) with a linear kernel was used to classify the test groups, using a leave-one-out validation method. The results showed that PD voice recordings had lower FD compared to CO (p < 0.008). It was also observed that the average NMI between CO voice recordings was significantly lower compared with the CO-PD and PD-PD groups (p < 0.036) for the three phonetic sounds. The average NMI and FD demonstrated higher accuracy (>80%) in differentiating the test groups compared with other speech feature-based classifications. This study has demonstrated that the voices of PD patients has reduced FD, and NMI between voice recordings of PD-CO and PD-PD is higher compared with CO-CO. This suggests that the use of NMI obtained from the sample voice, when paired with known groups of CO and PD, can be used to identify PD voices. These findings could have applications for population screening.

Effect of levodopa on handwriting tasks of different complexity in Parkinson's disease: a kinematic study.

Levodopa treatment does improve Parkinson's disease (PD) dysgraphia, but previous research is not in agreement about which aspects are most responsive. This study investigated the effect of levodopa on the kinematics of writing. Twenty-four patients with PD of less than 10 years duration and 25 age-matched controls were recruited. A practically defined off state method was used to assess the levodopa motor response, measured on the Unified Parkinson's Disease Rating Scale Part III. The kinematic features for six handwriting tasks involving different levels of complexity were recorded from PD patients in off and on states and from the control group. Levodopa is effective for simple writing activities involving repetition of letters, denoting improved fine motor control. But the same benefit was not seen for copying a sentence and a written category fluency test, tasks that carry memory and cognitive loads. We also found significant differences in kinematic features between control participants and PD patients, for all tasks and in both on and off states. Serial testing of handwriting in patients known to be at risk for developing PD might prove to be an effective biomarker for cell loss in the substantia nigra and the associated dopamine deficiency. We recommend using a panel of writing tasks including sentence copying and memory dependence. Dual-task effects may make these activities more sensitive to early motor deficits, while their weaker levodopa responsiveness would cause them to be more stable indicators of motor progression once symptomatic treatment has been commenced.

A Kinematic Study of Progressive Micrographia in Parkinson's Disease.

Progressive micrographia is decrement in character size during writing and is commonly associated with Parkinson's disease (PD). This study has investigated the kinematic features of progressive micrographia during a repetitive writing task. Twenty-four PD patients with duration since diagnosis of <10 years and 24 age-matched controls wrote the letter "e" repeatedly. PD patients were studied in defined off states, with scoring of motor function on the Unified Parkinson's Disease Rating Scale Part III. A digital tablet captured x-y coordinates and ink-pen pressure. Customized software recorded the data and offline analysis derived the kinematic features of pen-tip movement. The average size of the first and the last five letters were compared, with progressive micrographia defined as >10% decrement in letter stroke length. The relationships between dimensional and kinematic features for the control subjects and for PD patients with and without progressive micrographia were studied. Differences between the initial and last letter repetitions within each group were assessed by Wilcoxon signed-rank test, and the Kruskal-Wallis test was applied to compare the three groups. There are five main conclusions from our findings: (i) 66% of PD patients who participated in this study exhibited progressive micrographia; (ii) handwriting kinematic features for all PD patients was significantly lower than controls (p < 0.05); (iii) patients with progressive micrographia lose the normal augmentation of writing speed and acceleration in the x axis with left-to-right writing and show decrement of pen-tip pressure (p = 0.034); (iv) kinematic and pen-tip pressure profiles suggest that progressive micrographia in PD reflects poorly sustained net force; and (v) although progressive micrographia resembles the sequence effect of general bradykinesia, we did not find a significant correlation with overall motor disability, nor with the aggregate UPDRS-III bradykinesia scores for the dominant arm.

Efficacy of Guided Spiral Drawing in the Classification of Parkinson's Disease.

BACKGROUND: Change of handwriting can be an early marker for severity of Parkinson's disease but suffers from poor sensitivity and specificity due to inter-subject variations. AIM: This study has investigated the group-difference in the dynamic features during sketching of spiral between PD and control subjects with the aim of developing an accurate method for diagnosing PD patients. METHOD: Dynamic handwriting features were computed for 206 specimens collected from 62 Subjects (31 Parkinson's and 31 Controls). These were analyzed based on the severity of the disease to determine group-difference. Spearman rank correlation coefficient was computed to evaluate the strength of association for the different features. RESULTS: Maximum area under ROC curve (AUC) using the dynamic features during different writing and spiral sketching tasks were in the range of 0.67 to 0.79. However, when angular features ($\boldsymbol{\varphi }$ and ${\boldsymbol{p}_{\boldsymbol{n}}}$) and count of direction inversion during sketching of the spiral were used, AUC improved to 0.933. Spearman correlation coefficient was highest for ϕ and ${\boldsymbol{p}_{\boldsymbol{n}}}$. CONCLUSION: The angular features and count of direction inversion which can be obtained in real-time while sketching the Archimedean guided spiral on a digital tablet can be used for differentiating between Parkinson's and healthy cohort.

Neurological sequelae of intrauterine warfarin exposure.

Warfarin embryopathy is a well-defined manifestation of intrauterine warfarin exposure. The embryopathy phenotype as it relates to the nervous system is broad and poorly recognised. We describe an adult with neurological sequelae of fetal warfarin exposure. We review previous cases with neurological sequelae and discuss the pathogenetic mechanism in light of recent research.

Distinguishing Different Stages of Parkinson's Disease Using Composite Index of Speed and Pen-Pressure of Sketching a Spiral.

The speed and pen-pressure while sketching a spiral are lower among Parkinson's disease (PD) patients with higher severity of the disease. However, the correlation between these features and the severity level (SL) of PD has been reported to be 0.4. There is a need for identifying parameters with a stronger correlation for considering this for accurate diagnosis of the disease. This study has proposed the use of the Composite Index of Speed and Pen-pressure (CISP) of sketching as a feature for analyzing the severity of PD. A total of 28 control group (CG) and 27 PD patients (total 55 participants) were recruited and assessed for Unified Parkinson's Disease Rating Scale (UPDRS). They drew guided Archimedean spiral on an A3 sheet. Speed, pen-pressure, and CISP were computed and analyzed to obtain their correlation with severity of the disease. The correlation of speed, pen-pressure, and CISP with the severity of PD was -0.415, -0.584, and -0.641, respectively. Mann-Whitney U test confirmed that CISP was suitable to distinguish between PD and CG, while non-parametric k-sample Kruskal-Wallis test confirmed that it was significantly different for PD SL-1 and PD SL-3. This shows that CISP during spiral sketching may be used to differentiate between CG and PD and between PD SL-1 and PD SL-3 but not SL-2.

Epilepsy with focal cerebral calcification: role of magnetization transfer MR imaging.

BACKGROUND: Some patients with focal cerebral calcification (FCC) have no seizure or a benign course of epilepsy, whilst others with a similar lesion have uncontrolled epilepsy. AIMS: To look for perilesional hyperintensity, presumed to be indicative of gliosis, around FCC on magnetization transfer (MT) MRI and to correlate seizure outcome with its presence. SETTING AND DESIGN: Case control study. MATERIAL AND METHODS: Fifty-one patients with epilepsy and 30 controls with single calcified cerebral lesion on CT were studied. Clinical and treatment details were noted. EEG and T1, T2, MT and contrast enhanced MRI were done. STATISTICAL ANALYSIS USED: Student's t test. RESULTS: On MT MRI, perilesional gliosis was seen around the focal calcified lesion in 17 (33.3%) patients. None of the controls had perilesional gliosis. The mean monthly seizure frequency was significantly higher in the 17 patients having perilesional gliosis (2.63+1.15) as compared to the 34 patients without it (0.59+0.63; P= 0.0014). Perilesional gliosis was seen in 8 out of 11 (72.7%) patients who were on 2 AEDs and in all 5 (100%) patients who were on 3 or more AEDs. It was present only in 4 (11.4%) out of 35 patients who were on one AED. CONCLUSION: Gliosis around a cerebral calcified lesion as seen on T1 weighted MT MRI indicates poor seizure control.