Defining new digital biomarkers (dBMKs) allowing a comprehensive assessment and monitoring of neurological Wilson's disease (NWD) to bridge the existing practice gaps.

BACKGROUND AND PURPOSE:Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD. METHODS:A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores. RESULTS:Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported. CONCLUSIONS:STN or GPi DBS are ineffective on dystonia related to WD.

Les locuteurs dysarthriques atteints de maladie de Parkinson idiopathique (Dys-MPI) peuvent présenter un trouble de la fluence de la parole (TFacq) (Juste et al., 2018). Celui-ci partage des signes avec les troubles de la fluence de la parole neurodéveloppementaux (bégaiements, bredouillements) (TFdev) (Hartelius, 2014). Des similarités neurophysiologiques, telles des modifications de l'activité dopaminergique des noyaux gris centraux et de leurs réseaux cortico-sous-corticaux, sont également relevées chez les locuteurs TFdev et ceux avec MPI (Chang et al., 2020 ; Shahed et Jankovic, 2001). Ces éléments évoqueraient un lien éventuel entre les TFdev et l'apparition d'une MPI à l'âge adulte. Cette étude de cas-témoin, prospective et rétrospective, vise (i) à déterminer la proportion de TFdev chez les Dys-MPI par rapport aux locuteurs contrôles neurotypiques, (ii) à étudier l'impact des facteurs : âge du diagnostic de la MPI, type du premier symptôme dysarthrique et proportion de TFacq, sur la présence de TFdev chez les Dys-MPI. Cent un Dys-MPI et 124 locuteurs contrôles neurotypiques, ont répondu à un questionnaire sur leur parole actuelle et celle dans l'enfance. Trois juges ont réalisé une analyse perceptive d'enregistrements de parole continue des Dys-MPI, en période « on », avec la grille perceptive de la BECD (Auzou et Rolland-Monnoury, 2019). Les Dys-MPI ont présenté un taux de TFdev plus important (15 %) que les locuteurs contrôles (6 %). Le délai d'apparition du premier symptôme de dysarthrie est plus court chez les Dys-MPI avec TFdev (2,93 ans) que chez ceux sans TFdev (5,82 ans). Nos résultats viennent confirmer et compléter l'enquête d'Hartelius (2014) retrouvant une proportion notable de sujets parkinsoniens avec TFdev, mais non comparés à des locuteurs contrôles. Nos données restent toutefois à nuancer en raison du diagnostic rétrospectif de TFdev établi à partir d'un questionnaire.

Background Vocoid epenthesis within consonant clusters has been claimed to contribute to the diagnosis of apraxia of speech. In clinical practice, the clinicians often doubt about the correct production of clusters as the C-C transition may be minimally disrupted.Aims To demonstrate the value of acoustic analysis in clinical practice as a reliable complement to perceptive judgment.Methods & Procedures We compared the acoustic signature and the perceptive detection of vocoid epentheses in unvoiced consonant clusters within pseudo-words produced by 40 participants presenting different subtypes of motor speech disorders (including apraxia of speech (AoS) and dysarthria) and matched neurotypical controls.Outcomes & Results The results indicate that vocoid epenthesis was acoustically visible in 3 out of 10 participants with AoS, and in one out of 30 participants with dysarthria. One-quarter of these vocoid epentheses was not detected via auditory perception by expert listeners (speech and language therapists) who also made false detections.Conclusions The current results indicate that vocoid epenthesis is not systematic at least in mild AoS. Moreover, an important proportion is misdetected by ear, even by expert clinicians, meaning that visualisation of the acoustic signal can be of precious help.

Purpose: The clinical diagnosis of motor speech disorders (MSDs) is mainly based on perceptual approaches. However, studies on perceptual classification of MSDs often indicate low classification accuracy. The aim of this study was to determine in a forced-choice dichotomous decision-making task (a) how accuracy of speech-language pathologists (SLPs) in perceptually classifying apraxia of speech (AoS) and dysarthria is impacted by speech task, severity of MSD, and listener's expertise and (b) which perceptual features they use to classify. Method: Speech samples from 29 neurotypical speakers, 14 with hypokinetic dysarthria associated with Parkinson's disease (HD), 10 with poststroke AoS, and six with mixed dysarthria associated with amyotrophic lateral sclerosis (MD-FlSp [combining flaccid and spastic dysarthria]), were classified by 20 expert SLPs and 20 student SLPs. Speech samples were elicited in spontaneous speech, text reading, oral diadochokinetic (DDK) tasks, and a sample concatenating text reading and DDK. For each recorded speech sample, SLPs answered three dichotomic questions following a diagnostic approach, (a) neurotypical versus pathological speaker, (b) AoS versus dysarthria, and (c) MD-FlSp versus HD, and a multiple-choice question on the features their decision was based on. Results: Overall classification accuracy was 72% with good interrater reliability, varying with SLP expertise, speech task, and MSD severity. Correct classification of speech samples was higher for speakers with dysarthria than for AoS and higher for HD than for MD-FlSp. Samples elicited with continuous speech reached the best classification rates. An average number of three perceptual features were used for correct classifications, and their type and combination differed between the three MSDs. Conclusions: The auditory-perceptual classification of MSDs in a diagnostic approach reaches substantial performance only in expert SLPs with continuous speech samples, albeit with lower accuracy for AoS. Specific training associated with objective classification tools seems necessary to improve recognition of neurotypical speech and distinction between AoS and dysarthria.

There is a general agreement that speaking requires attention at least for conceptual and lexical processes of utterance production. However, conflicting results have been obtained with dual-task paradigms using either repetition tasks or more generally tasks involving limited loading of lexical selection. This study aimed to investigate whether post-lexical processes recruit attentional resources. We used a new dual-task paradigm in a set of experiments where a continuous verbal production task involved either high or low demand on lexical selection processes. Experiment 1 evaluates lexical and post-lexical processes with a semantic verbal fluency task, whereas Experiments 2 and 3 focus on post-lexical processes with a non-propositional speech task. In each experiment, two types of non-verbal secondary tasks were used: processing speed (simple manual reaction times) or inhibition (Go/No-go). In Experiment 1, a dual-task cost was observed on the semantic verbal fluency task and each non-verbal task. In Experiment 2, a dual-task cost appeared on the non-verbal tasks but not on the speech task. The same paradigm was used with older adults (Experiment 3), as increased effort in post-lexical processes has been associated with ageing. For older adults, a dual-task cost was also observed on the non-propositional verbal task when speech was produced with the inhibition non-verbal task. The results suggest an attentional cost on post-lexical processes and strategic effects in the resolution of the dual-task.

To respond to the need of objective screening tools for motor speech disorders (MSD), we present the screening version of a speech assessment protocol (MonPaGe-2.0.s), which is based on semi-automated acoustic and perceptual measures on several speech dimensions in French. We validate the screening tool by testing its sensitivity and specificity and comparing its outcome with external standard assessment tools. The data from 80 patients diagnosed with different types of mild to moderate MSD and 62 healthy test controls were assessed against the normative data obtained on 404 neurotypical speakers, with Deviance Scores computed on seven speech dimensions (voice, speech rate, articulation, prosody, pneumophonatory control, diadochokinetic rate, intelligibility) based on acoustic and perceptual measures. A cut-off of the MonPaGe total deviance score (TotDevS) >2 allowed MSD to be diagnosed with specificity of 95% and an overall sensitivity of 83.8% on all patients pulled, reaching 91% when very mildly impaired patients were excluded. A strong correlation was found between the MonPaGe TotDevS and an external composite perceptual score of MSD provided by six experts. The MonPaGe screening protocol has proven its sensitivity and specificity for diagnosing presence and severity of MSD. Further implementations are needed to complement the characterization of impaired dimensions in order to distinguish subtypes of MSD.

Automatic techniques in the context of motor speech disorders (MSDs) are typically two-class techniques aiming to discriminate between dysarthria and neurotypical speech or between dysarthria and apraxia of speech (AoS). Further, although such techniques are proposed to support the perceptual assessment of clinicians, the automatic and perceptual classification accuracy has never been compared. In this paper, we investigate a three-class automatic technique and a set of handcrafted features for the discrimination of dysarthria, AoS and neurotypical speech. Instead of following the commonly used One-versus-One or One-versus-Rest approaches for multi-class classification, a hierarchical approach is proposed. Further, a perceptual study is conducted where speech and language pathologists are asked to listen to recordings of dysarthria, AoS, and neurotypical speech and decide which class the recordings belong to. The proposed automatic technique is evaluated on the same recordings and the automatic and perceptual classification performance are compared. The presented results show that the hierarchical classification approach yields a higher classification accuracy than baseline One-versus-One and One-versus-Rest approaches. Further, the presented results show that the automatic approach yields a higher classification accuracy than the perceptual assessment of speech and language pathologists, demonstrating the potential advantages of integrating automatic tools in clinical practice.

To assist clinicians in the differential diagnosis and treatment of motor speech disorders, it is imperative to establish objective tools which can reliably characterize different subtypes of disorders such as apraxia of speech (AoS) and dysarthria. Objective tools in the context of speech disorders typically rely on thousands of acoustic features, which raises the risk of difficulties in the interpretation of the underlying mechanisms, overadaptation to training data, and weak generalization capabilities to test data. Seeking to use a small number of acoustic features and motivated by the clinical-perceptual signs used for the differential diagnosis of AoS and dysarthria, we propose to characterize differences between AoS and dysarthria using only six handcrafted acoustic features, with three features reflecting segmental distortions, two features reflecting loudness and hypernasality, and one feature reflecting syllabification. These three different sets of features are used to separately train three classifiers. At test time, the decisions of the three classifiers are combined through a simple majority voting scheme. Preliminary results show that the proposed approach achieves a discrimination accuracy of 90%, outperforming using state-of-the-art features such as openSMILE which yield a discrimination accuracy of 65%.

V-to-V anticipatory coarticulation is frequently taken as an indicator of the anticipated planning of an up-coming vowel, and thus the manifestation of a process where context-dependent speech targets or coordinated gestures are planned together before execution (e.g. [1], [2], [3]). In this study, V-to-V anticipatory coarticulation in French is compared in 4 groups of patients presenting different Motor Speech Disorders-Apraxia of Speech (AoS) and 3 types of dysarthrias associated with Amyotrophic Lateral Sclerosis (D-ALS), Parkinson (D-Pk) and Wilson (D-Wl) diseases-with the aim of getting further insights into the understanding of the control of coarticulation in speech (as in [4], [5], [6]). It is hypothesized that perturbed coarticulatory patterns may arise as a consequence of disruption in the planning and sequencing of speech targets into cohesive speech units, as expected in AoS where speech is often described as 'syllabified' or 'segmentalized'. However, it can also derive from deficits in the motor programming or execution of speech whose consequences are slower movements, restricted displacement and/or perturbed coordination between gestures, as can be encountered in dysarthria. So far, inconsistent results have been found in the literature regarding coarticulatory patterns in different MSD (see [5] & [6]). Moreover, AoS patients are more often compared to patients with aphasia than to patients with dysarthria. More data is thus needed to understand whether deficits linked to distinct cerebral disorders do impact coarticulation, and how they can shed light on the levels and units over which coarticulation is planned.

Speaking while doing another task is frequent in everyday life. While the effect of speaking on performing another task has been often studied, little is known on the effect of dual-task on speech, or on the bidirectional interference of one task on the other. Here, we investigate dual-task effects on both speech rate and on performances in non-verbal attentional tasks with a bidirectional approach. Task properties are varied for the type of speech task: counting vs. sentence production, the type of non-verbal tasks in terms of attentional demand (go vs. go-nogo), and mode of presentation of the stimuli. Speech rate is found to decrease under dual-task conditions only in the counting task, and with most of the concurrent non-verbal tasks. Processing of the non-verbal tasks is also modified when speaking, but the direction of the effect depends on the type of speech tasks and of non-verbal tasks.

Wilson disease (WD) is a rare genetic disorder characterized by copper overload in the liver and the brain. Neurological presentations are mainly related to the accumulation of copper in the basal ganglia, the brainstem, and the cerebellum. Dysarthria is a frequent symptom, with dystonic, spastic, or parkinsonian components and is usually resistant to medical or voice rehabilitation therapies. Here, we report the case of a patient with WD diagnosed at the age of 12, who presented a severe and constant dysarthria from dystonic origin which was unresponsive to benzodiazepines and anticholinergic drugs. When she was 25-year-old, she tried zolpidem at bedtime for sleeping difficulties and reported a paradoxical effect of this drug on her voice. To confirm the effect of zolpidem on her dystonic dysarthria, we realized a full evaluation of her dysarthria at baseline without zolpidem and after 4 days of treatment by 10 mg twice a day. Lexical access was evaluated by the semantic fluency; dysarthria by the Intelligibility Score, the spontaneous speech and reading rates, the maximum phonation time on the sustained vowel [ a] and by a perceptive evaluation. Two hours after the intake of zolpidem, improvement of all the parameters tested, with the exception of the maximum phonation time, was observed. Semantic fluency increased by 59%, the spontaneous speech rate by 88% and the reading rate by 76%. General dystonia remained unchanged and the tolerance of zolpidem was satisfactory. Since then, the patient takes zolpidem 5 mg five times a day, and 4 years later shows persistent improvement in oral communication and a good drug tolerance. In this single-case study, we showed that regular daytime intake of zolpidem could have a persisting effect on a complex dystonic dysarthria that was resistant to usual medical treatments.

MonPaGe est un outil d’évaluation de la parole couvrant différents aspects de la production de la parole (voix, mobilité et précision articulatoire, prosodie, fluence, processus phonologiques, intelligibilité, etc.) et différents facteurs pouvant affecter cette production (complexité et longueur des séquences, types de son, position prosodique, contexte phonétique, parole continue ou isolée, etc.). Le temps de passation est adapté à la pratique clinique (15 minutes environ). L’analyse permet l’extraction semi-automatique d’indices perceptifs et acoustiques de la parole de patients adultes atteints de troubles moteurs de la parole. Ce protocole répond à un besoin criant d’outils normés et validés pour la langue française (Jan, 2007). Les batteries tels que la BECD (Auzou et Rolland-Monnoury, 2006) permettent une évaluation perceptivo-motrice de la dysarthrie (Darley et al., 1969), mais n’en offre pas une analyse acoustique directe. Le logiciel Vocalab 4 (Sicard E., et al., 2013 ; Sicard A. et Sicard E., 2014) et les applications du constructeur anglo-saxon KayPentax® (ADSV, MDVP) restent uniquement dédiés à l’analyse de la voix. Notre groupe de réflexion, composé d’orthophonistes, de phonéticiens et de psycholinguistes, a élaboré un protocole d’évaluation comprenant des modules couvrant divers aspects de la parole : productions de [a] tenus, diadococinésies verbales, syllabes, pseudo-mots, phrases avec modulations prosodiques et lecture d’un texte. Le protocole est entièrement informatisé, tant au niveau de la passation des modules successifs (incluant l’enregistrement des productions du patient) que de la procédure d’évaluation, c’est-à-dire de la cotation qualitative (perceptifs ou visuels sur représentations spectrographiques) et quantitative (mesures acoustiques) de caractères déviants dans la parole. L’informatisation permet une meilleure standardisation des conditions de passation, des critères d’évaluation et du pré-traitement des données recueillies. Cette présentation décrira le protocole et fera un point sur l’avancée de sa validation et normalisation auprès de différentes populations (sains et pathologiques).

Hypersialorrhea, corresponding to excessive salivation is a symptom frequently reported in Wilson's disease, especially in its neurological form. The prevalence of this frequent complaint has not been often evaluated. During a 7-month period, 87 consecutive Wilson's disease patients answered to the simple question "do you have the sensation of excess saliva in your mouth?" to evaluate the frequency of this symptom. A sub-sample of 10 consecutive Wilson's disease patients with drooling was recruited to undergo quantitative and qualitative measures to evaluate the mechanism of hypersialorrhea. Excessive drooling or excess saliva was found in 46 % of patients followed at the French Reference Centre. Ninety-eight percent of them presented neurological symptoms and drooling was found in only one patient without neurological symptoms. Our study showed that patients with a complaint of excessive saliva produced significantly higher quantities of saliva at rest than controls. Endoscopic examination was abnormal in six patients. A significant decrease of swallowing frequency, longer swallow latencies, and poor swallowing capacities may partly explain the salivary stasis. Oropharyngeal sensitivity disorders were present in 50 % of our patients. The decrease of the swallowing frequency observed in all patients could be related to cognitive and behavioral abnormalities with initiation difficulties objectified by longer latencies triggered by all the ingested volumes. This study confirmed the hypothesis of a multifactorial origin of hypersialorrhea in patients who have been diagnosed in Wilson's disease. It was essential to evaluate drooling with a multidisciplinary consultation to better identify the underlying mechanisms and to implement strategies for speech therapy and therapeutic adaptation.

Les patients atteints de la maladie de Wilson(MW) peuvent présenter une dysarthrie touchant l'intelligibilité de la parole. Une dysphagie, de présentation variable, lui est souvent associée, nécessitant ainsi des adaptations. Au vu de ces difficultés, nous avons eu pour objectifs de concevoir et de mettre en place des outils cliniques orthophoniques visant à faciliter la communication et offrir un support personnalisable concernant la déglutition. Une enquête menée auprès des soignants et une évaluation des besoins des patients ont permis d'élaborer un outil de communication augmentatif et alternatif (CAA) sous la forme d'une planche de communication. Elle comporte un alphabet et des pictogrammes regroupés par domaine. Pour améliorer la prise en charge de la dysphagie, un livret de déglutition personnalisable et annotable a été créé. Il rassemble une partie informative et des recommandations établies à partir des études portant sur la dysphagie wilsonienne. L'outil de CAA, distribué par les centres de référence et de compétences MW, a été remis aux patients dysarthriques sévèrement inintelligibles, à leur entourage et leurs intervenants médicaux et non-médicaux. Suite au bilan orthophonique et/ou phoniatrique, le livret de déglutition, annoté de conseils personnalisés, est fourni au patient dysphagique. Il est également destiné aux aidants et autres soignants. La mise en place de ces outils s'est accompagnée de transmissions ciblées sur la communication et la déglutition. Ces outils, déjà proposés à une vingtaine de patients et à leur entourage, s'avèrent facilement maniables et transportables et s'adaptent à la variabilité des dysphagies et des dysarthries. La communication avec le patient est facilitée et les troubles relatifs à la déglutition mieux compris par l'entourage et les soignants. Ces supports contribuent à améliorer le suivi et la qualité de vie des patients wilsoniens dysarthriques et dysphagiques dans leurs différents environnements. Des actions de formation du personnel soignant sont envisagées.