Neurological manifestations in patients with VEXAS syndrome

Area of Science:

• Neurology
• Rheumatology
• Genetics

Background:

• VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a recently identified autoinflammatory disorder.
• It is caused by somatic mutations in the UBA1 gene, leading to systemic inflammation.
• Neurological manifestations of VEXAS syndrome are not well-characterized.

Purpose of the Study:

• To determine the prevalence of neurological involvement in VEXAS syndrome.
• To describe the clinical spectrum of neurological manifestations.
• To evaluate the treatment outcomes for neurological complications.

Main Methods:

• Retrospective multicenter study using data from the French VEXAS Registry (Nov 2020-Mar 2023).
• Inclusion of additional cases identified via a national call for observations.
• Multidisciplinary review of patients with confirmed UBA1 somatic mutations and neurological symptoms.

Main Results:

• 17 out of 291 (6%) patients in the registry had neurological involvement; 13 additional cases were identified.
• 30 patients had neurological manifestations: 21 (70%) with peripheral nervous system (PNS) and 9 (30%) with central nervous system (CNS) involvement.
• PNS manifestations included polyneuropathy and cranial nerve involvement. CNS manifestations included encephalopathy, cerebral infarcts, and PRES. Treatments included steroids (68% improvement) and steroid-sparing agents (90%), with a 30% mortality rate.

Conclusions:

• Neurological manifestations occur in a significant proportion of VEXAS syndrome patients.
• These manifestations are diverse, affecting both the central and peripheral nervous systems.
• Early diagnosis and treatment are crucial for managing VEXAS syndrome's neurological complications.