At-home Treatment With Cortico-spinal tDCS for Amyotrophic Lateral Sclerosis

Difference in ALS Functional Rating Scale-Revised (ALSFRS-R) between groups at 16 weeks. The ALSFRS provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The ALSFRS includes ten questions that rate the patients level of functional impairment in performing one of ten common tasks. Each task is rated on a five-point scale from 0 (can't do) to 4 (normal ability). Individual item scores are summed to produce a reported score of between 40 (no impairment) and 0 (severe impairment).

Difference in the ALS Functional Rating Scale-Revised (ALSFRS-R) between groups at 32 weeks and 48 weeks. The ALSFRS provides a physician-generated estimate of the patient's degree of functional impairment, which can be evaluated serially to objectively assess any response to treatment or progression of disease. The ALSFRS includes ten questions that rate the patients level of functional impairment in performing one of ten common tasks. Each task is rated on a five-point scale from 0 (can't do) to 4 (normal ability). Individual item scores are summed to produce a reported score of between 40 (no impairment) and 0 (severe impairment).

Difference in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 score (ALSAQ-40) from baseline.The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ) is a patient self-report health status scale. The ALSAQ is specifically used to measure the subjective well-being of patients with amyotrophic lateral sclerosis. There are 40 items/questions with 5 discrete scales: physical mobility (10 items), activities of daily living and independence (10 items), eating and drinking (3 items), communication (7 items), emotional reactions (10 items). Patients are asked to think about the difficulties they may have experienced during the last two weeks (e.g. I have found it difficult to feed myself). Patients are asked to indicate the frequency of each event by selecting one of 5 options (Likert scale):

never/rarely/sometimes/often/always or cannot do at all. The total ranges from 0 (no impairment) to 160 (severe impairment).

Difference in the Caregiver Burden Inventory (CBI) score between groups from baseline.The CBI scale is 24- item scale designed to assess the experience of caregivers of older people. The multidimensional instrument assesses five domains of burden (time-dependence, developmental, physical, social, and emotional). Items are scored on a 4-point scale, ranging from "not at all descriptive" to "very descriptive". The scale ranges from 0 (no impairment) to 96 (severe impairment).

Difference in Quality of Life EQ-5D-5L Scale between groups from baseline.The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The scale ranges from 5 (no impairment) to 25 (severe impairment).

Muscle strength will be evaluated using a handheld dynamometer, a validated tool for objective measurement of isometric muscle force. Muscle groups typically involved in ALS will be assessed bilaterally using standardized testing positions. For each muscle group, participants will be instructed to perform a maximal voluntary isometric contraction against the dynamometer for approximately 3-5 seconds. Two trials will be performed per muscle, and the highest peak force (measured in Newtons) will be recorded. The sum of 10 muscles per side (20 overall) will be evaluated.

Difference in Plasma neurofilament levels between groups from baseline. Neurofilament light chain (NfL), a well-established biomarker of neuroaxonal injury, can be reliably quantified in plasma (pNfL) and has shown superior diagnostic accuracy in differentiating patients with amyotrophic lateral sclerosis (ALS) from those with ALS mimic syndromes. In addition, numerous studies have emphasized the prognostic value of both cerebrospinal (cNfL) and plasma (pNfL) NfL levels, reporting strong correlations with disease progression rate (DPR) and overall survival. Notably, early longitudinal investigations indicate that pNfL levels remain relatively stable over the disease course, underscoring their promise as biomarkers for monitoring therapeutic response.

Difference in Survival from the onset of symptoms between groups. Survival is defined as the time from the symptom onset to death from any cause. Patients who are alive at the time of the last follow-up are censored at the date of last contact.