Acoustic and Perceptual Markers of Dysarthria in Amyotrophic Lateral Sclerosis (ALS)

Study Overview
=================
Brief Summary
-----------------
This study proposes to identify acoustic and perceptual markers related to upper motor neuron (UMN) degeneration and lower motor neuron (LMN) degeneration in the dysarthria of patients with amyotrophic lateral sclerosis (ALS) which involves the degeneration of both systems. ALS patients will be gathered in clinical groups according to electromyogram (EMG) and clinical signs observed in the bulbar site. UMN signs are defined as jaw clonus, gag reflex and pseudobulbar features (lability). LMN signs are defined as lingual atrophy and fasciculations. The dysarthria will be compared to dysarthria of patients involving an exclusive UMN system degeneration (in primitive lateral sclerosis) and an exclusive LMN system degeneration (Kennedy's disease). Patients will be compared to the controls who permitted to establish the standards of the MonPaGe tool. MonPaGe is a computerized tool based on a multidimensional and quantified assessment of voice and speech, by a set of targeted acoustic and perceptual criteria.

Detailed Description
-----------------
ALS is a motor neuron disease characterized by a progressive degeneration of motor neurons in the brain, brainstem, and spinal cord. Degeneration of the upper and lower motor neurons (UMN and LMN) leads to spasticity, impaired reflexes, muscle fatigue, muscle weakness and atrophy. PLS is a motor neuron disease involving exclusively the UMN system and Kennedy's disease is a genetic condition involving the LMN system. Those three different motor neuron diseases can lead to a dysarthria. Affected individuals with ALS vary significantly in the locus of disease onset, presentation at diagnosis and rate of progression. Regardless of the site of onset, most patients with ALS will experience bulbar motor deterioration that will lead to a dysarthria. According to Darley's classification of dysarthrias, dysarthria in ALS is grossly described as mixed (both spastic, due the UMN deterioration, and flaccid, due to the LMN deterioration). However, at the onset of bulbar signs, when the dysarthria is still mild, dysarthric profiles and bulbar clinical signs can vary within individuals. Perceptual and acoustic features of dysarthria in ALS have been studied but they have not been studied in dysarthric patients with PLS and KD. This study was motivated by the need to better understand the dysarthria in ALS and it's management in speech therapy. The goals of this study is to question the impact of the degeneration of the UMN system versus the LMN system on the speech motor system and see if the investigators can identify acoustic and perceptual markers related to UMN degeneration on one side and LMN degeneration on the other side. The investigators will compare acoustic and perceptual features between the recorded speech of different clinical groups. Clinical groups will be made according to clinical signs and EMG. The clinical signs for UMN involvement in the bulbar region are: gag reflex, jaw clonus, pseudobulbar features (lability). The clinical signs for LMN involvement are: lingual atrophy and fasciculation. The population will be composed by groups of ALS-LMN patients, ALS-UMN patients , PLS patients and KD patients and a control group already recruited by the LPP (Laboratoire de Phonétique et de Phonologie) team (CNRS...) which permitted to establish the standards of the MonPaGe tool that the investigators will use to analyse patients recorded speech. This tool is based on a multidimensional and quantified assessment of voice and speech, by a set of targeted acoustic and perceptual criteria.

Official Title
-----------------
Identification of Acoustic and Perceptual Markers of Lower and Upper Motor Neuron Signs in Dysarthria of Patients With Amyotrophic Lateral Sclerosis : a Comparison With Primitive Lateral Sclerosis, Kennedy's Disease and Controls

Conditions
-----------------
Amyotrophic Lateral Sclerosis, Primary Lateral Sclerosis, Kennedy's Disease

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Major patients diagnosed at the centre référent des maladies du motoneurone with ALS, PLS or KD, French motherhood language Mild to moderate severity of dysarthria according to the Perceptual Score of the BECD Without respiratory troubles according to the neurologist Without dementia. Exclusion Criteria: None

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Amyotrophic lateral sclerosis (ALS) patients<br> | |
| Primitive Lateral Sclerosis (PLS) patients<br> | |
| Kennedy's disease (KD) patients<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in each patterns of dysarthria | Patterns of dysarthria will be determined with post hoc unsupervised machine learning method (cluster analysis) from following measurements: Intelligibility: number of words recognized (score 0 to 15) Maximum phonation time (TMP), (milliseconds), Phonation: mean and standard deviation of fundamental frequency (Hz); jitter (%), shimmer (%);Signal to Noise Ratio (dB) Intensity modulation capacities (score 0 to 4), Articulation of consonants and vowels : global error score (score 0 to 53); qualitative profile of error; acoustic range variation (Hz), Coarticulation (Hz), Score of prosody, Verbal Diadococinesis : accuracy (score 0 to 4) ; control (score 0 to 4) and flow rate (syllables/sec), Speech flow rate (syllables/sec). | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional scale with the Norris score | The functional capacities of the bulbar site will be evaluated by the speech therapist with the Norris score.This examination will permit to identify UMN and LMN signs | 1 day | 
| Functional scale with the ALS functional rating scale-R (ALS FRS-R) | The functional capacities of the bulbar site will be evaluated by the speech therapist with the ALS functional rating scale-R (ALS FRS-R). This examination will permit to identify UMN and LMN signs | 1 day | 
| Severity of the dysarthria | A severity score of the dysarthria will be calculated with the Perceptual Score of the Batterie d'Evaluation Clinique de la Dysarthrie (BECD) | 1 day | 
| Clinical examination | Classical speech therapy clinical examination | 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acoustic and perceptual markers, Dysarthria, Amyotrophic lateral sclerosis, Primitive lateral sclerosis, Kennedy's disease