- •Cryoglobulinemia is associated with infectious, hematological and connective tissue disorders.
- •Peripheral nervous system disorders are commoner than central in cryoglobulinemia.
- •Symmetrical and asymmetrical polyneuropathies occur frequently in cryoglobulinemia.
- •High cryoglobulin level is more likely associated with neurological symptoms.
- •Immunosuppressive therapy improves neurological outcome in cryoglobulinemia.
Limited information is available describing the spectrum of neurological complications of cryoglobulinemia.
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.
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.
This study describes a wide spectrum of patients with neurologic symptoms attributed to cryoglobulinemia and provides a framework to approach this challenging diagnosis.
Abbreviations:MC (mixed cryoglobulinemia), HCV (hepatitis C virus), SFN (small fiber neuropathy), CNS (central nervous system), PNS (peripheral nervous system), SLE (systemic lupus erythematosus), OR (odds ratio), RF (rheumatoid factor), EDX (electrodiagnostic), PRES (posterior reversible encephalopathy syndrome), CI (confidence interval), IVIG (intravenous immunoglobulin), MRC (medical research council), IVMP (intravenous methylprednisolone), CK (creatine kinase)
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Published online: January 25, 2019
Accepted: January 24, 2019
Received in revised form: January 17, 2019
Received: July 22, 2018
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