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.

Movement disorders in cell surface antibody mediated autoimmune encephalitis: a meta-analysis.

Background: Autoimmune encephalitis (AE) is an increasingly recognized neuroinflammatory disease entity in which early detection and treatment leads to the best clinical outcomes. Movement disorders occur in AE but their characteristics are not well defined. Objectives: To identify the frequency, classification, and prognostic significance of movement disorders in AE. Methods: We conducted a systematic review and random-effects meta-analysis of movement disorders in cell surface antibody mediated AE. The frequency of any movement disorder as well as the classification of movement disorders in AE serotypes was determined. We looked at adults 18 years and older and included publications that described at least 10 cases. We used the following four electronic databases: Medline (Ovid), EMBASE (Ovid), APA Psychinfo, and Cochrane library. Results: A total of 1,192 titles and abstracts were reviewed. Thirty-seven studies were included in the final meta-analysis. At least one kind of movement disorder was present in 40% of the entire AE cohort, 53% with anti-NMDA receptor antibodies, 33% with anti-CASPR2 antibodies, 30% with anti-LGI1 antibodies and 13% with anti-GABA receptor antibodies. Dyskinesia was the commonest movement disorder in anti-NMDA antibody mediated AE and faciobrachial dystonic seizures were most frequent in anti-LGI1 antibody mediated AE. Patients with a movement disorder tended to have a higher mortality. The risk of bias in the included studies was mostly moderate or high. Conclusion: Movement disorders are common in AE and their identification, in conjunction with other clinical and paraclinical features, may facilitate earlier diagnosis. The prognostic implications of movement disorders in AE warrant further dedicated study. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023386920.

Computerized analysis of speech and voice for Parkinson's disease: A systematic review.

BACKGROUND AND OBJECTIVE: Speech impairment is an early symptom of Parkinson's disease (PD). This study has summarized the literature related to speech and voice in detecting PD and assessing its severity. METHODS: A systematic review of the literature from 2010 to 2021 to investigate analysis methods and signal features. The keywords "Automatic analysis" in conjunction with "PD speech" or "PD voice" were used, and the PubMed and ScienceDirect databases were searched. A total of 838 papers were found on the first run, of which 189 were selected. One hundred and forty-seven were found to be suitable for the review. The different datasets, recording protocols, signal analysis methods and features that were reported are listed. Values of the features that separate PD patients from healthy controls were tabulated. Finally, the barriers that limit the wide use of computerized speech analysis are discussed. RESULTS: Speech and voice may be valuable markers for PD. However, large differences between the datasets make it difficult to compare different studies. In addition, speech analytic methods that are not informed by physiological understanding may alienate clinicians. CONCLUSIONS: The potential usefulness of speech and voice for the detection and assessment of PD is confirmed by evidence from the classification and correlation results.

Parkinson's disease, dopaminergic drugs and the plant world.

A large proportion of drugs used for the treatment of neurological disorders relate to naturally occurring compounds, many of which are plant alkaloids. This is particularly true of Parkinson's disease (PD). The pharmacopoeia of PD has strong botanical origins, while major discoveries about the neurochemistry of the basal ganglia came from the study of phytochemicals. This article narrates the development of pharmacotherapy for PD in terms of historically important plant-derived substances-tropane and hamala alkaloids, reserpine, levodopa, apomorphine, and ergoline dopamine receptor agonists. Alkaloids are nitrogen-containing secondary metabolic products that tend to be biologically active. They appear to be involved in plants' adaptation to herbivorous animals, though their exact purpose and the ways in which they work are uncertain. A sizable group of alkaloids influence animal dopaminergic systems, highlighting a key biological relationship. While animals must acquire the energy that plants harness, plants need to engage with the animal attribute that they lack-movement-in order to maximize their reproductive fitness. Neuroactive flowering plant compounds have been interacting with vertebrate and invertebrate motor systems for 100 million years. A deep evolutionary connection helps to explain why the pharmacological treatment of PD is imprinted with the power of these mysterious botanical chemicals.

Geste Antagoniste Effects on Motor Performance in Dystonia-A Kinematic Study.

Background: The kinematic effects of gestes have not previously been studied. The mechanism(s) by which these sensory tricks modify dystonic movement is not well understood. Objectives: A kinematic investigation of the geste phenomenon in patients with dystonia. Methods: Twenty-three patients with dystonia associated with a geste were studied. Twenty-nine healthy controls also participated. Fifteen seconds of finger tapping was recorded by electromagnetic sensors, and the task was repeated with geste. Separable motor components were extracted using a custom-written MATLAB script. Performance with and without geste was compared using Wilcoxon signed ranks testing. Results: Speed and fluency of finger tapping is impaired in dystonia. When patients executed their geste, speed of movement (amplitude × frequency) increased (P < 0.0001), and halts decreased (P = 0.007). Conclusions: That gestes improve not only dystonic muscle contraction but also the efficiency of voluntary movement suggests a broad influence at the premotor control stage.

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.

The Thermodynamic Consequences of Parkinson's Disease.

Several lines of evidence point to a pervasive disturbance of energy balance in Parkinson's disease (PD). Weight loss, common and multifactorial, is the most observable sign of this. Bradykinesia may be best understood as an underinvestment of energy in voluntary movement. This accords with rodent experiments that emphasise the importance of dopamine in allocating motor energy expenditure. Oxygen consumption studies in PD suggest that, when activities are standardised for work performed, these inappropriate energy thrift settings are actually wasteful. That the dopaminergic deficit of PD creates a problem with energy efficiency highlights the role played by the basal ganglia, and by dopamine, in thermodynamic governance. This involves more than balancing energy, since living things maintain their internal order by controlling transformations of energy, resisting probabilistic trends to more random states. This review will also look at recent research in PD on the analysis of entropy-an information theory metric of predictability in a message-in recordings from the basal ganglia. Close relationships between energy and information converge around the concept of entropy. This is especially relevant to the motor system, which regulates energy exchange with the outside world through its flow of information. The malignant syndrome in PD, a counterpart of neuroleptic malignant syndrome, demonstrates how much thermodynamic disruption can result from breakdown of motor signalling in an extreme hypodopaminergic state. The macroenergetic disturbances of PD are consistent with a unifying hypothesis of dopamine's neurotransmitter actions-to adapt energy expenditure to prevailing economic circumstances.

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.

Detecting Effect of Levodopa in Parkinson's Disease Patients Using Sustained Phonemes.

BACKGROUND: Parkinson's disease (PD) is a multi-symptom neurodegenerative disease generally managed with medications, of which levodopa is the most effective. Determining the dosage of levodopa requires regular meetings where motor function can be observed. Speech impairment is an early symptom in PD and has been proposed for early detection and monitoring of the disease. However, findings from previous research on the effect of levodopa on speech have not shown a consistent picture. METHOD: This study has investigated the effect of medication on PD patients for three sustained phonemes; /a/, /o/, and /m/, which were recorded from 24 PD patients during medication off and on stages, and from 22 healthy participants. The differences were statistically investigated, and the features were classified using Support Vector Machine (SVM). RESULTS: The results show that medication has a significant effect on the change of time and amplitude perturbation (jitter and shimmer) and harmonics of /m/, which was the most sensitive individual phoneme to the levodopa response. /m/ and /o/ performed at a comparable level in discriminating PD-off from control recordings. However, SVM classifications based on the combined use of the three phonemes /a/, /o/, and /m/ showed the best classifications, both for medication effect and for separating PD from control voice. The SVM classification for PD-off versus PD-on achieved an AUC of 0.81. CONCLUSION: Studies of phonation by computerized voice analysis in PD should employ recordings of multiple phonemes. Our findings are potentially relevant in research to identify early parkinsonian dysarthria, and to tele-monitoring of the levodopa response in patients with established PD.

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.

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.

Raised visual contrast thresholds with intact attention and metacognition in functional motor disorder.

Functional motor disorders (FMDs) are distinguished by signs that lack congruence with recognised patterns of organic disease and show inconsistency over time. Their pathophysiology is poorly understood, but there is evidence that irregularities in perceptual and cognitive processing lie at the heart of these conditions. Here, we draw on a predictive coding account of functional neurological disorders to study perceptual decision-making in three groups: 20 patients with FMDs (14 with functional movements and 6 with functional weakness), 20 with phenotypically-matched organic motor disorders, and 20 age-matched healthy controls. We examine four cognitive domains with putative roles in FMD pathogenesis: attention, expectations, sensory processing (perceptual sensitivity), and metacognition (introspective evaluation of performance). We augmented a dual-task paradigm, manipulating the visual contrast required for target detection to examine these domains in one design. With sensory input (stimulus contrast) psychometrically adjusted to staircase target detection at a fixed level for all groups, the FMD group exhibited statistically equivalent attentional, expectational and metacognitive processing to healthy controls. However, we demonstrate Bayesian evidence and a frequentist trend that FMD patients require higher visual contrast than controls to maintain the same detection sensitivity (BF10 = 8.1, pholm = .066). This was statistically equivalent to the visual contrast required by the organic group, and unlikely to be accounted for by medication use or comorbid psychopathology. The organic group showed differences in processing of attention and expectations for target detection that were not observed in either healthy controls or the functional group. The distinctive behavioural profile of FMDs may arise from abnormalities in basic sensory processing, while higher attentional, expectational and metacognitive mechanisms remain intact. Conceptualising functional neurological disorders under a predictive coding account may consolidate and refine existing pathophysiological theories about them.

Movement disorders in psychiatric patients.

The observability of movement gives it advantages when trying to draw connections between brain and mind. Disturbed motor function pervades schizophrenia, though it is difficult now to subtract the effects of antipsychotic treatment. There is evidence from patients never exposed to these drugs that dyskinesia and even parkinsonism are to some degree innate to schizophrenia. Tardive dyskinesia and drug-induced parkinsonism are the most common movement disorders encountered in psychiatric practice. While D2 dopamine receptor blockade is a causative factor, both conditions defy straightforward neurochemical explanation. Balanced against the need to manage schizophrenic symptoms, neither prevention nor treatment is easy. Of all disorders classified as psychiatric, catatonia sits closest to organic neurology on the neuropsychiatric spectrum. Not only does it occur in the setting of unequivocally organic cerebral disease, but the alterations of consciousness it produces have 'organic' qualities even when the cause is psychiatric. No longer considered a subtype of schizophrenia, catatonia is defined by syndromic features based on motor phenomenology. Both severe depression and obsessive-compulsive disorder may be associated with 'soft' extrapyramidal signs that resemble parkinsonian bradykinesia. As functional neuroimaging studies suggest, movement and psychiatric disorders involve the same network connections between the basal ganglia and the cerebral cortex.

Health at the writing desk of John Ruskin: a study of handwriting and illness.

Though John Ruskin (1819-1900) is remembered principally for his work as a theorist, art critic and historian of visual culture, he wrote exhaustively about his health in his correspondence and diaries. Ruskin was prone to recurring depressive and hypochondriacal feelings in his youth and adulthood. In 1871, at the age of 52 years, he developed an illness with relapsing psychiatric and neurological features. He had a series of attacks of brain disturbance, and a deterioration of his mental faculties affected his writing for years before curtailing his career a decade before he died. Previous writers have suggested he had a psychiatric malady, perhaps schizophrenia or schizoaffective disorder. But the more obvious conclusion from a close medical reading of Ruskin's descriptions of his illness is he had some sort of 'organic' brain illness. This paper aims to give insight into the relationship between Ruskin's state of well-being and the features of his writing through a palaeographical study of his letters and diary entries. We examine the handwriting for physical traces of Ruskin's major brain illness, guided by the historical narrative of the illness. We also examine Ruskin's recording of his experiences for what they reveal about the failure of his health and its impact on his work. Ruskin's handwriting does not have clear-cut pathological features before around 1885, though suggestions of subtle writing deficits were present as early as 1876. After 1887, Ruskin's handwriting shows fixed pathological signs-tremor, disturbed letter formation and features that reflect a slow and laborious process of writing. These observations are more than could be explained by normal ageing, and suggest the presence of a neurological deficit affecting writing control. Our findings are consistent with conclusions that we drew from the historical record-that John Ruskin had an organic neurological disorder with cognitive, behavioural, psychiatric and motor effects.

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.

Propensity for seizure-related cortical laminar necrosis in hepatic encephalopathy.

•Hepatic encephalopathy may predispose to seizure-related cortical laminar necrosis.•Elevated ammonia levels potentially compound the excitotoxic effects of epilepsy.•Early identification and treatment of seizures in liver disease could be protective.

Cerebellar atrophy with Chiari malformation: An example of trans-synaptic degeneration?

A 23-year old man was found to have a Chiari Type 1 malformation and cerebellar atrophy. While this association has previously been described, the remote cerebellar atrophy is difficult to explain. We believe the answer lies with our finding of signal hyperintensity on MR imaging at the level of the inferior olives. This suggest hypertrophic olivary degeneration, caused by trans-synaptic degeneration following disruption to the Guillain-Mollaret triangle. Propagation of this process to the cerebellar Purkinje cells occurs in some cases. We describe a case in support of this hypothesis and review previously published evidence.