Autoimmune Neuropathies - Neuropathic Disease

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Progressive extremity weakness, sensory symptoms

Laboratory Testing

  • Initial testing to rule out more common diseases
    • CBC
    • Sedimentation rate (ESR) and C-reactive protein (CRP)
    • Electrolytes to rule out obvious infectious cause or metabolic derangement
  • Cerebrospinal fluid testing – glucose, protein, cell count and culture
    • Protein – elevated in ~80%
    • WBC is usually normal
      • Typically <10 cells/mm3 – usually monocytes
      • Presence of >50 cells/mm3 with polymorphonuclear leukocyte predominance should prompt investigation of infectious etiologies
  • Other testing (based on individual presentation)
    • Diarrheal illness – C. jejuni testing
    • Recent upper respiratory infection – consider mycoplasma, EBV, CMV
    • Other tests to consider – HIV, hepatitis A (HAV) and B (HBV)
    • Ocular symptoms – acetylcholine receptor testing to rule out myasthenia gravis
  • Neuronal markers – consider if above testing is normal
    • Test choice depends on whether the presentation is
      • Sensory only – most common
      • Sensorimotor
      • Motor predominant
    • Test choice also depends on risk of underlying malignancy

Histology

  • Nerve biopsy

Imaging Studies

  • Perform MRI/CT if any question of structural lesion

Other Testing

  • Nerve conduction study – confirmatory of motor or sensory pattern
    • Conduction block, prolonged distal latencies, delayed F-waves, reduction in maximum motor conduction velocity

Differential Diagnosis

  • Antibody titers do not correlate with disease level activity in paraneoplastic syndromes
    • Do not use titers for monitoring treatment

Autoimmune neuropathies can be acute or chronic and can involve axonal degeneration and demyelination.

  • Autoimmune neuropathy classifications
  • Monoclonal gammopathy-associated neuropathy
  • Polyclonal inflammatory polyneuropathy
  • Guillain-Barré syndrome (GBS)
  • Chronic inflammatory demyelinating polyneuropathy
  • Multifocal motor neuropathy (MMN)
  • Paraneoplastic neuropathy

Classification

Pathophysiology

  • Antibodies against specific glycolipids or glycoproteins, such as anti-GM1 and anti-myelin associated glycoprotein, are associated with inflammatory and often demyelinating neuropathies
  • Multiple antibodies are associated with neuropathic disease
    • These antibodies interfere with processes of myelination, myelin maintenance or axon-Schwann cell interaction
  • Paraneoplastic antibodies are directed against intracellular antigens in the nucleus or cytoplasm of neurons
    • Main effect is cell-mediated damage to neurons and axons
    • No specific antibody has been shown to be sensitive enough for use as a diagnostic tool
    • Paraneoplastic neuronal markers frequently precede a diagnosis of cancer

Clinical Presentation

  • Non-paraneoplastic neuropathies
    • Most common presentation is GBS
    • Subtypes
      • Acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN), acute sensory neuropathy, Fisher syndrome
        • AIDP is the most frequent subtype of GBS in North America and Europe (associated with GM1, GM2, GD1a antibodies)
          • May cause acute sensory ataxia or acute pandysautonomia
        • AMAN and AMSAN are associated with the ganglioside antibodies (GM1, GM1b, GD1a)
        • Fisher variant of GBS is associated with GQ1b antibodies
          • Characterized by extraocular symptoms, ataxia, hyporeflexia and ophthalmoplegia
        • AMAN and Fisher variants are uncommon in children
    • Other GBS variants
      • Bickerstaff brainstem encephalitis
        • Usually a post-viral inflammatory illness with progressive ophthalmoplegia, ataxia and disturbance of consciousness (or hyperreflexia)
        • May overlap with Fisher syndrome and GBS
      • Chronic form of Guillain-Barré inflammatory demyelinating polyneuropathy
        • Shares features with GBS but has a much poorer prognosis for full recovery
    • Symptoms
      • Infection (eg, upper respiratory infection, gastroenteritis) during the 6 weeks prior to presentation in ~33% of patients
      • Acute limb paralysis, weakness (ascending and often asymmetric), numbness and other motor disturbances
      • Sensory symptoms are a minor feature
      • Axonal form – more rapid onset and more severe respiratory symptoms
      • AMAN – purely motor form
      • Fisher syndrome – includes ophthalmoplegia, optic neuritis, ptosis or lid retraction, ataxia, areflexia
  • Paraneoplastic polyneuropathies
  • Other autoimmune neuropathies – frequently present with slow-onset muscle weakness

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Sensory Neuropathy Antibody Panel with Reflex to Titer and Neuronal Immunoblot 2007965
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Immunoblot

Limitations

Some antibodies may be associated with more than one disease and/or cancer

Motor and Sensory Neuropathy Evaluation with Reflex to Titer and Neuronal Immunoblot 2007966
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Immunoblot

Limitations

Some antibodies may be associated with more than one disease and/or cancer

Motor and Sensory Neuropathy Evaluation with Immunofixation Electrophoresis and Reflex to Titer and Neuronal Immunoblot 2007967
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Qualitative Immunoblot/Quantitative Nephelometry/Quantitative Capillary Electrophoresis/Qualitative Immunofixation Electrophoresis

Limitations

Some antibodies may be associated with more than one disease and/or cancer

Motor Neuropathy Panel 0051225
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Quantitative Nephelometry/Quantitative Capillary Electrophoresis/Qualitative Immunofixation Electrophoresis

Limitations

Some antibodies may be associated with more than one disease and/or cancer

Myelin Associated Glycoprotein (MAG) Antibodies, IgM and Sulfate-3-Glucuronyl Paragloboside (SGPG) Antibodies, IgM 2004412
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Ganglioside (Asialo-GM1, GM1, GM2, GD1a, GD1b, and GQ1b) Antibodies 0051033
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Limitations

Role of isolated anti-GM2 antibodies unknown

Test by itself not diagnostic; should be used in conjunction with other clinical parameters to confirm disease

Amphiphysin Antibody, IgG 2008893
Method: Qualitative Immunoblot

Sulfate-3-Glucuronyl Paragloboside (SGPG) Antibody, IgM 0051284
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Myelin Associated Glycoprotein (MAG) Antibody, IgM 0051285
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Ganglioside (GM1) Antibodies, IgG and IgM 0050591
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Ganglioside (GM1, GD1b, and GQ1b) Antibodies, IgG and IgM 2004998
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Related Tests

Guidelines

England JD, Gronseth GS, Franklin G, Carter GT, Kinsella LJ, Cohen JA, Asbury AK, Szigeti K, Lupski JR, Latov N, Lewis RA, Low PA, Fisher MA, Herrmann DN, Howard JF, Lauria G, Miller RG, Polydefkis M, Sumner AJ, American Academy of Neurology. Practice Parameter: evaluation of distal symmetric polyneuropathy: role of autonomic testing, nerve biopsy, and skin biopsy (an evidence-based review). Report of the American Academy of Neurology, American Association of Neuromuscular and Electrodiagnosti Neurology. 2009; 72(2): 177-84. PubMed

General References

de Freitas MR G. Infectious neuropathy. Curr Opin Neurol. 2007; 20(5): 548-52. PubMed

Lunn MP T, Willison HJ. Diagnosis and treatment in inflammatory neuropathies. J Neurol Neurosurg Psychiatry. 2009; 80(3): 249-58. PubMed

Mauermann ML, Burns TM. The evaluation of chronic axonal polyneuropathies. Semin Neurol. 2008; 28(2): 133-51. PubMed

Meuth SG, Kleinschnitz C. Multifocal motor neuropathy: update on clinical characteristics, pathophysiological concepts and therapeutic options. Eur Neurol. 2010; 63(4): 193-204. PubMed

Rabie M, Nevo Y. Childhood acute and chronic immune-mediated polyradiculoneuropathies. Eur J Paediatr Neurol. 2009; 13(3): 209-18. PubMed

Ramchandren S, Lewis RA. Monoclonal gammopathy and neuropathy. Curr Opin Neurol. 2009; 22(5): 480-5. PubMed

Vallat J, Sommer C, Magy L. Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. Lancet Neurol. 2010; 9(4): 402-12. PubMed

van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008; 7(10): 939-50. PubMed

Vernino S, Wolfe GI. Antibody testing in peripheral neuropathies. Neurol Clin. 2007; 25(1): 29-46. PubMed

Vucic S, Kiernan MC, Cornblath DR. Guillain-Barré syndrome: an update. J Clin Neurosci. 2009; 16(6): 733-41. PubMed

Winer JB. Guillain-Barré syndrome. BMJ. 2008; 337: a671. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Jaskowski TD, Martins TB, Litwin CM, Hill HR. Immunoglobulin (Ig) M antibody against myelin associated glycoprotein (MAG): A comparison of methods. J Clin Lab Anal. 2004; 18(4): 247-50. PubMed

Medical Reviewers

Last Update: February 2016