Neurologic manifestations associated with cryoglobulinemia: A single center experience

Abstract

Introduction: Limited information is available describing the spectrum of neurological complications of cryoglobulinemia.

Methods: Single center retrospective review of patients with neurologic symptoms and elevated serum cryoglobulins, with their potential association being classified as definite, possible, or unlikely using defined criteria.

Results: Among 492 patients, 131 (87 classified as definite and 44 as possible) had neurologic symptoms associated with cryoglobulinemia. Common comorbidities included hepatitis C (N = 43), monoclonal gammopathy of undetermined significance (N = 20), Sjogren's syndrome (N = 17), membranoproliferative glomerulonephritis (N = 17), and systemic lupus erythematosus (N = 10). Features supporting an association between cryoglobulinemia and neurological symptoms were the presence of purpura (p < .001), positive rheumatoid factor (p = .001) and low C4 (p = .002). Common peripheral neurological diagnoses were symmetric polyneuropathy (N = 84), small fiber neuropathy (N = 25), and mononeuritis multiplex (N = 16). Central neurological manifestations were infrequent and included seizures (N = 3), posterior reversible encephalopathy syndrome (N = 2), intracerebral hemorrhage (N = 1), vasculitis (N = 1), rapidly progressive dementia (N = 1), lymphoma (N = 1), and myelitis/meningitis (N = 1). Treatments utilized included corticosteroids (N = 74), rituximab (N = 42), cyclophosphamide (N = 27), methotrexate, azathioprine, or mycophenolate mofetil (N = 28), anti-viral therapy (N = 20), plasmapheresis (N = 16), and intravenous immunoglobulin (N = 20). Neurologic symptoms associated with cryoglobulinemia remained stable or improved in 86% of patients.

Conclusion: This study describes a wide spectrum of patients with neurologic symptoms attributed to cryoglobulinemia and provides a framework to approach this challenging diagnosis.

Keywords: Central nervous system; Cryoglobulinemia; Immunotherapy; Mononeuritis multiplex; Peripheral nervous system; Peripheral neuropathy.