This is a single-session, case-control study that incorporates digital tools for assessing speech and motor function in motor neuron disease. Patients with motor neuron disease (including amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and progressive muscular atrophy (PMA)) and age-matched healthy controls will be enrolled. Subjects will complete a speech and handwriting assessment during the study visit on a tablet computer (BioSensics LLC, Newton, MA). We will explore whether these digital biomarkers are sensitive to functional disease severity as reported by the ALS Functional Rating Scale - Revised (ALFRS-R) [1]. We will also compare assessment data between the patient and control groups.

ALS is a progressive neuromuscular disease that causes weakness and inevitably affecting multiple motor processes within the body. To assess changes in functional mobility, clinicians and clinical investigators often rely on the ALS Functional Rating Scale - Revised (ALSFRS-R), a standardized 12-item questionnaire that has been in use for decades. Although thoroughly validated, this scale has received criticism for providing a coarse reflection of a patient's disease, scaling non-linearly within and across functional domains, and without the sensitivity to reflect day-to-day variability or small but meaningful changes.

This study includes collection of digital speech and fine motor control assessment data at a single study visit. Features extracted from this data will be compared with standard clinical disease outcome measures and also the features derived from control participant data. We will use these comparisons to explore the use of these digital assessments in capturing the range of functional changes that occur in ALS and the related motor neuron diseases of PLS and PMA that are regularly treated in the ALS clinic.

Inclusion Criteria:

1. [Patient Group Only] Diagnosis of definite, probable, probable laboratory-supported, or possible ALS by revised El Escorial research criteria [Brooks2000], primary lateral sclerosis (PLS), or progressive muscular atrophy (PMA).

2. [Patient Group Only] at least minimal speech or handwriting ability

   1. ALSFRS-R speech score of 2 ("intelligible speech with repeating") or greater, OR
   2. ALSFRS-R handwriting score of 2 ("not all words are legible") or greater.

3. [Control Group Only] Possess no neurological or orthopedic problems that affects their speech or handwriting AND age-matched to the existing patient cohort.

4. 18 years of age or older;

5. Fluent in written and spoken English.

Exclusion Criteria:

1. Currently or previously enrolled in STUDY00013892 (NCT05271435)
2. Neurological or orthopedic problems (independent of their inclusionary diagnosis for the patient group) that affects their speech or handwriting
3. Pregnant or nursing woman
4. Prisoner or institutionalized individuals
5. Have any clinically relevant medical history of other disease or diseases that, in the opinion of the research team, exclude the subject from participation (including severe cognitive dysfunction).

Patients with motor neuron disease and age- and sex-matched, neurologically-healthy controls.

Study data without identifiers may be shared with other researchers at reasonable request of the PI

Data will become available upon publication