The project aims to perform both conventional nerve-conduction studies and axonal-excitability assessments using the TRONDF protocol in patients with selected forms of Charcot-Marie-Tooth disease, with comparison to individuals affected by dysimmune, acquired neuropathies, specifically chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-MAG-neuropathy. The study further includes the analysis of nerve fibers obtained from skin biopsy in patients with CMT, as well as ultrasound evaluation of nerves (from the wrist to the axilla) and of intrinsic hand muscles. Axonal-excitability techniques involve the delivery of two electrical stimuli to the nerve under investigation; both stimuli vary in intensity, whereas only the first, known as the conditioning stimulus, varies in duration. Changes in response amplitude are then measured as these stimulation parameters are systematically adjusted. Some preliminary studies have already suggested the effectiveness of this method in distinguishing CMT1A from certain forms of acquired demyelinating disease, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and CIDP. Despite the promising results, only a limited number of studies have so far been conducted in humans and mice, and no comprehensive and systematic study has yet been carried out describing the changes in axonal excitability in the various CMT subtypes, either in humans or in mouse models.
The subject is ≥ 18 years old.
A genetically confirmed diagnosis of one of the several CMT subtypes (i.e., CMT1A, CMT1B, CMTX1, CMT2I/J, CMT4B, CMT4D and CMT4J) OR
A clinical diagnosis of either Chronic Inflammatory Demyelinating Polyneuropathy or anti-MAG polyneuropathy
Known neuropathy from another cause (e.g., diabetes, chronic renal insufficiency, medications, alcohol), including previous carpal tunnel syndrome surgery.
History of exposure to chemotherapeutic agents (e.g., bortezomib, vincristine, cisplatin, taxol, vedotin/auromycin-conjugated antibodies), or other medications (e.g., disulfuram, thalidomide, voriconizole, chronic colchicine use) that can cause neuropathy, active alcohol abuse.
History of cancer, other than skin cancer, within 5 years prior to enrollment.
Pregnancy or nursing.
* A minimum of 30 patients with a genetically confirmed diagnosis of CMT * At least 15 patients diagnosed with either Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or anti-myelin associated glycoprotein (MAG) polyneuropathy as a disease control group.
Other
Prospective
Not listed
Strength-Duration Time Constant
Strength-duration time constant (SDTC, ms) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Recovery Cycle of Nerve Excitability Parameters
Recovery cycle of nerve excitability parameters measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy), including superexcitability and late subexcitability (% threshold change)
Threshold Electrotonus
Threshold Electrotonus (TE, % threshold change at specified time intervals) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Current-Threshold (I/V) Relationship
Current-threshold (I/V) relationship parameters (e.g., slope of threshold change versus polarizing current) measured using threshold tracking nerve excitability testing in participants with genetically defined Charcot-Marie-Tooth disease subtypes and acquired immune-mediated neuropathies (CIDP and anti-MAG neuropathy).
Peripheral nerve cross-sectional area by ultrasound
Cross-sectional area (CSA, mm²) of the median and ulnar nerves measured by ultrasound from the wrist to the axilla in participants with Charcot-Marie-Tooth disease, CIDP, and anti-MAG neuropathy.
Muscle thickness by ultrasound
Muscle thickness (mm) of the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles measured by ultrasound in participants with Charcot-Marie-Tooth disease, CIDP, and anti-MAG neuropathy.
Muscle echogenicity by ultrasound (Heckmatt scale)
Muscle echogenicity graded using the Heckmatt scale (grades 1-4) in the abductor pollicis brevis, abductor digiti minimi, and first dorsal interosseous muscles. Heckmatt scale grading: Grade 1: normal Grade 2: increased muscle echogenicity with preserved architecture and normal bone reflection Grade 3: increased echogenicity with partial loss of architecture and reduced bone reflection Grade 4: markedly increased echogenicity with complete loss of architecture and absent bone reflection
Correlation of ultrasound parameters with clinical and electrophysiological measures
Correlation between ultrasound parameters (nerve CSA, muscle thickness, and Heckmatt grade) and clinical severity measured by CMTNS/CMTES and axonal excitability parameters.
Axonal excitability strength-duration time constant in mouse models
Strength-duration time constant (SDTC, ms) measured using threshold tracking nerve excitability testing in TM/TM mice carrying the MPZ T124M mutation, C3-PMP22 transgenic mice, and wild-type control mice.
Recovery Cycle of excitability parameters in mouse models
Recovery Cycle of excitability parameters, including relative refractory period (ms), superexcitability (% threshold change), and late subexcitability (% threshold change), measured in TM/TM mice, C3-PMP22 transgenic mice, and wild-type control mice.
Threshold Electrotonus in mouse models
Threshold Electrotonus (TE, % threshold change at specified time intervals) measured in TM/TM mice, C3-PMP22 transgenic mice, and wild-type control mice.
Current-threshold (I/V) relationship in mouse models
Current-threshold (I/V) relationship parameters (e.g., slope of threshold change versus polarizing current) measured in TM/TM mice, C3-PMP22 transgenic mice, and wild-type control mice.
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