Electrophysiological features of the peripheral neuropathy in patients with pathologic biallelic RFC1 repeat expansions

• Published in: Muscle & nerve Vol. 70; no. 5; pp. 1046 - 1052
• Main Authors: Calezis, Claudia, Bonello‐Palot, Nathalie, Verschueren, Annie, Azulay, Jean‐Philippe, Fortanier, Etienne, Grapperon, Aude‐Marie, Kouton, Ludivine, Gallard, Julien, Salort‐Campana, Emmanuelle, Attarian, Shahram, Delmont, Emilien
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2024; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Aged, 80 and over; Amplitudes; Ataxia; Autonomic nervous system; autonomic testing; Bilateral Vestibulopathy - genetics; Bilateral Vestibulopathy - physiopathology; Blink reflex; Blinking - physiology; Brain stem; CANVAS; Cerebellar ataxia; Cerebellar Ataxia - genetics; Cerebellar Ataxia - physiopathology; Cerebellum; Cranial nerves; DNA Repeat Expansion - genetics; Electrochemistry; Electrodiagnosis; Female; H-Reflex - genetics; H-Reflex - physiology; Heart rate; Heart Rate - genetics; Heart Rate - physiology; Humans; H‐reflex; Male; Middle Aged; Nerve conduction; Nerves; Neural Conduction - physiology; Peripheral Nervous System Diseases - diagnosis; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - physiopathology; Peripheral neuropathy; Polyneuropathy; Reflexes; Replication Protein C - genetics; RFC1 expansions; sensory neuronopathy; Sensory neurons; Skin; Sympathetic nervous system; Vestibular system; blink reflex; autonomic testing; H‐reflex; CANVAS; RFC1 expansions; sensory neuronopathy
• ISSN: 0148-639X; 1097-4598; 1097-4598
• DOI: 10.1002/mus.28257

Introduction/Aims Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is caused by RFC1 expansions. Sensory neuronopathy, polyneuropathy, and involvement of motor, autonomic, and cranial nerves have all been described with RFC1 expansions. We aimed to describe the electrodiagnostic features of patients with RFC1 expansions through multimodal electrophysiological investigations. Methods Thirty‐five patients, with a median age of 70 years, and pathologic biallelic repeat expansions in the RFC1 gene, were tested for motor and sensory nerve conduction, flexor carpi radialis (FCR) and soleus H‐reflexes, blink reflex, electrochemical skin conductance, sympathetic skin response (SSR), and heart rate variability with deep breathing (HRV). Results Only 16 patients (46%) exhibited the full clinical CANVAS spectrum. Distal motor amplitudes were normal in 30 patients and reduced in the legs of five patients. Distal sensory amplitudes were bilaterally reduced in a non‐length dependent manner in 30 patients. Conduction velocities were normal. Soleus H‐reflexes were abnormal in 19/20 patients of whom seven had preserved Achilles reflexes. FCR H‐reflexes were absent or decreased in amplitude in 13/14 patients. Blink reflex was abnormal in 4/19 patients: R1 latencies for two patients and R2 latencies for two others. Fourteen out of 31 patients (45%) had abnormal results in at least one autonomic nervous system test, either for ESC (12/31), SSR (5/14), or HRV (6/19). Discussion Less than half of the patients with RFC1 expansions exhibited the full clinical CANVAS spectrum, but nearly all exhibited typical sensory neuronopathy and abnormal H‐reflexes. Involvement of small nerve fibers and brainstem neurons was less common.