The Aim of the Study is to Characterize Patients Exhibiting Muscular Atrophy and Weakness Who Require a Muscle Biopsy for Diagnosis (IBM vs Atypical MND), Through an Innovative Technique Which Enables the Evaluation of the Neuromuscular Junction Involvement in Each Condition

N/AActive Not RecruitingNCT07796776

IRCCS San Raffaele30 enrolled

Overview

The aim of the study is to characterize 30 patients exhibiting muscular atrophy and weakness who require a muscle biopsy for diagnosis (suspected inclusion body myopathy vs atypical motor neuron disease), through an innovative technique (a muscle biopsy with Electrostimulation for Enhanced Neuromuscular Junction sampling), to evaluate the involvement of the neuromuscular junction in each disease and to better characterize shared and divergent patterns of TDP-43 pathology within the peripheral nervous system in both disorders.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Inclusion Body Myositis (IBM)Motor Neuron Disease, Amyotrophic Lateral Sclerosis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients exhibiting progressive muscle weakness and atrophy with a classic clinical IBM pattern or with an atypical clinical IBM pattern or with an atypical MND pattern * Able to understand and sign the informed consent * Treated according to standard of care clinical practice Exclusion Criteria: * Contraindications to needle EMG or skeletal muscle biopsy * Psychiatric diseases that may interfere with adherence to the follow-up protocol

Locations (1)

Outcomes

Primary Outcomes

Diagnostic sensitivity of an integrated clinical, neurophysiological, metabolic and histopathological model in the differential diagnosis between IBM and MND.

To achieve a diagnostic sensitivity of \>90% for the differential diagnosis between IBM and MND integrating clinical variables (site of onset, scales reflecting disease progression rate, muscle strength), neurophysiological indices (presence and degree of active denervation signs, presence of myopathic or neurogenic motor unit potentials), histopathological parameters (myopathic or neuropathic pattern of disease) and metabolic measures (hyper- vs hypo-metabolism) into a multivariable binary logistic regression model, using the final diagnosis confirmed during longitudinal follow-up as the reference standard.

Time frame: At the end of the follow-up period (24 months of follow-up)

Secondary Outcomes

To evaluate signs of muscle and neuromuscular junction (NMJ) involvement at neuropathological level in each disease

To investigate disease-specific histological signatures, comparing the pattern of fiber degeneration, the presence of inflammatory infiltrates, the presence of protein aggregation markers (such as pTDP-43) and their localization, the presence of mitochondrial changes (the percentage of age-exceeding number of COX-negative fibers) and the NMJ involvement by evaluating the presynaptic and postsynaptic integrity (quantified as the percentage of synaptophysin and Ach-R clustering, respectively) between IBM and MND (through Fisher's exact test or Mann-Whitney U test, as appropriate) and to evaluate the prognostic role of each histological parameter (through Kaplan-Meier followed by log-rank test and Cox proportional hazards regression).

Time frame: At the end of the follow-up period (24 months of follow-up)