pediatric dose: 10 mg/day of bioactivated GRA for 6 months

Evaluation of global brain atrophy through the measurement of total brain volume normalized for head size using high-field Magnetic Resonance Imaging (MRI). Higher values indicate better brain volume preservation, while a decrease over time indicates progression of brain atrophy.

Evaluation of regional atrophy focusing on the cerebral cortex. Measurement of cortical gray matter volume normalized for head size using high-field MRI. This parameter is used to quantify the loss of cortical tissue specifically.

FA is a DTI-derived metric that reflects the microstructural integrity of white matter. In Multiple Sclerosis, a reduction in FA values is a marker of axonal damage and demyelination, even in Normal Appearing White Matter (NAWM).The unit of measurement is the Ratio (Scale from 0 to 1, where 1 indicates maximum diffusion/directional integrity.

MD measures the average magnitude of water diffusion. An increase in MD values in MS patients indicates loss of structural barriers, typically due to neurodegeneration, inflammation, or loss of myelin. This parameter provides a global index of tissue destruction.

It assesses 30 non motor symptoms across 9 domains, with scores ranging from 0 (no symptoms) to 12 per group (severity x frequency), resulting in a total score of 0 to 360, indicating the extent of the non-motor symptom burden. Lower score indicate fewer symptoms; a negative change from baseline indicates improvement in symptoms. Mean scores vary with disease severity, reflecting increased problems with sleep disturbances, mood, cognition, gastrointestinal function, etc.

Depression severity is assessed using the 17-item Hamilton Rating Scale for Depression (HRSD). Based on the total score, participants will be classified into the following levels: no depression (0-7), mild depression (8-13), moderate depression (14-18), severe depression (19-22), and very severe depression (≥23). The Hamilton Anxiety Rating Scale (HAM-A) is a psychological questionnaire to evaluate the anxiety. The Hamilton Anxiety Rating Scale (HAM-A), which consists of 14 items, each rated on a 5-point scale. The total score, obtained by adding the individual items, ranges from 0 to 56. A score ≤17 indicates mild anxiety; 18-24 indicates mild to moderate anxiety; 25-30 indicates moderate to severe anxiety.

It is a patient-reported outcome measure consisting of 8 items that assesses health-related quality of life in Parkinson's disease. It includes one representative item for each domain of the original PDQ-39: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and physical discomfort. Participants rate their experiences in the previous month using a 5-point Likert scale (0 = never to 4 = always). The total score is converted into a Summary Index (SI) ranging from 0 to 100, with higher scores indicating poorer health-related quality of life.Summary Index scores were interpreted as follows: 0-20 indicating good quality of life with minimal disease impact, 21-40 mild impairment, 41-60 moderate impairment, 61-80 marked impairment, and 81-100 severe impairment of quality of life.

The PDSS-2 is a 15-item self-administered questionnaire used to evaluate sleep disturbances and nocturnal symptoms in patients with Parkinson's Disease. It covers various domains including motor symptoms at night, sleep quality, and daytime sleepiness. Each item is scored on a 5-point Likert scale from 0 (never) to 4 (very often). The total score ranges from 0 to 60. A total score ≥ 15-18 is often considered indicative of clinically significant sleep disturbance.

The EQ-5D-3L is a standardized instrument for measuring health-related quality of life. It consists of a questionnaire with 5 item: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. These responses are converted into a single index score (utility value) using a country-specific value set.

The CGI-I is a clinician-rated scale that assesses how much the patient's illness has improved or worsened relative to a baseline state.It is scored on a 7-point Likert scale: 1=very much improved since the initiation of treatment; 2=much improved; 3=minimally improved; 4=no change from baseline (the initiation of treatment); 5=minimally worse; 6= much worse; 7=very much worse since the initiation of treatment

The PGI-C is a self-reported scale reflecting the patient's belief about the efficacy of treatment and their overall change in health status since the start of the study. It uses a 7-point scale where: 1 = Very much improved; 2 = Much improved; 3 = Minimally improved; 4 = No change; 5 = Minimally worse; 6 = Much worse; 7 = Very much worse.

Evaluation of cerebral electrical activity using the Micromed Brain Quick System (System Plus Evolution software) with a 48-channel recording head. Recordings will follow the International 10-20 system (or reduced electrode sets for infants < 40 cm). The signal will be processed with a sampling frequency of 256 Hz, a high-pass filter of 1.6 Hz, a low-pass filter of 30 Hz, and a sensitivity of 100 μV/cm. Assessments will include wakefulness, sleep deprivation, and afternoon rest. For patients with severe neurological conditions, video-EEG and polygraphy will be associated. The analysis focuses on background activity evolution and paroxysmal abnormalities according to ILAE guidelines.Unit of Measure: Qualitative and Quantitative neurophysiological parameters (presence/absence of epileptiform activity and mean frequency in Hz.

Evaluation of the severity of dysphagia (swallowing impairment). The DOSS is a 7-point scale used to systematically rate functional longitudinal changes in swallowing. Scores range from 1 (Severe dysphagia: nothing by mouth) to 7 (Normal in all situations).

The Griffiths-3 Scale (Griffiths III) is a comprehensive developmental assessment for young children (birth to nearly 6 years) that measures mental and physical growth across five key domains: Foundations of Learning, Language & Communication, Eye & Hand Coordination, Personal-Social-Emotional, and Gross Motor.Unit of Measure: Developmental Quotient (DQ) score (Standardized score where the mean is 100 and the standard deviation is 15. Higher scores indicate more advanced development).

Evaluation of oro-pharyngeal and esophageal motility using the HRM ManoScan™ ESO System. The procedure uses a catheter (max diameter 2.75 mm to 4.2 mm, selected based on age/weight) and follows international standards (e.g., German Guidelines for neurogenic dysphagia). Key metrics include the characterization of esophageal function and the study of the esophagogastric junction motility.Unit of Measure: Composite Score and Manometric Parameters (including mmHg for pressures and Chicago Classification v4.0 metrics).

Evaluation of the metabolic profile in human biofluids (plasma and urine) using Liquid Chromatography-Mass Spectrometry (LC-MS). The analysis includes:

Exogenous Compound Tracking: Determination of the metabolic fate and bioavailability of the administered phytocompound (Glucoraphanin/Sulforaphane).

Targeted Plasma Metabolomics: Quantitative analysis of essential amino acids (Tryptophan, Tyrosine, Phenylalanine) and their catabolites.

Microbiota-Derived Metabolites: Assessment of Short-Chain Fatty Acids (SCFAs) and Medium-Chain Fatty Acids (MCFAs) in plasma as indicators of gut microbiota modulation.

Urinary Endogenous Metabolites: Evaluation of changes in the urinary metabolic fingerprint to identify biomarkers of response to treatment.

Evaluation of gene expression changes in response to the study treatment. RNA sequencing (RNA-seq) will be performed using Illumina platforms. The bioinformatics pipeline includes:Data Quality Control: FastQC for raw data assessment. Preprocessing: Trimmomatic for adapter trimming and quality filtering.Alignment: STAR aligner against the GRCh38 human reference genome.

Quantification: Transcript counting via the HTSeq-count package. Differential Expression: Identification of Differentially Expressed Genes (DEGs) using the DESeq2 library in R. Statistical analysis: To ensure robustness, false positives will be controlled using the Benjamini-Hochberg post-hoc procedure with a significance threshold (q-value) set at 0.05.