What is the treatment for nodal and paranodal syndromes?

Treatment of Nodal and Paranodal Syndromes

Rituximab is the preferred treatment for nodal and paranodal antibody-associated neuropathies, with reported functional improvement in approximately 75% of patients, while conventional immunotherapies like corticosteroids and IVIG show poor response rates. 1, 2

Initial Treatment Approach

First-Line Therapy

• Rituximab should be initiated as the primary immunotherapy for patients with confirmed nodal/paranodal antibodies (anti-NF155, anti-NF186, anti-Caspr1, anti-CNTN1) 1, 2
• Rituximab demonstrated effectiveness in 6/8 (75%) of antibody-positive patients, compared to only 3/7 (42.9%) for corticosteroids and 1/7 (14.3%) for IVIG 2
• These patients respond poorly to conventional immunomodulatory therapies typically used for Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy 1

Alternative Immunosuppression

• If rituximab is unavailable or contraindicated, consider high-dose pulse methylprednisolone (500-1000 mg IV daily for 3-5 days) followed by oral prednisone taper, though response rates are significantly lower than rituximab 3, 2
• Transition to oral prednisone at 0.5-1 mg/kg/day (maximum 60 mg/day) after pulse therapy, with gradual taper over 3-6 months 3

Apheresis Considerations

Plasma Exchange and Immunoadsorption

• Plasma exchange (PLEx) and immunoadsorption (IA) show limited efficacy in nodal/paranodal antibody-positive patients 4
• In a cohort of 41 patients with nodal/paranodal antibodies, none of the 20 patients treated with PLEx and 4 treated with IA were judged to have good responses by treating clinicians 4
• Sequential serology suggests prolonged suppression of antibody levels with frequent apheresis cycles or adjuvant therapies may be required for effectiveness 4
• Apheresis should not be used as monotherapy but may be considered as adjunctive treatment with rituximab in severe cases 4

Antibody-Specific Clinical Features

Anti-NF155 Patients

• Younger age at onset (mean 19.6 ± 9.0 years) compared to anti-Caspr1 patients (55.3 ± 11.9 years) 2
• More severe nerve damage with longer distal motor latencies in ulnar and tibial nerves 2
• Predominantly IgG4 subtype antibodies 5

Anti-NF186/NF140 Patients

• Severe phenotype with conduction block or decreased distal motor amplitude 5
• Subacute onset with sensory ataxia in most cases 5
• May present with nephrotic syndrome or IgG4-related systemic disease 5
• Can have IgG3 antibodies that activate complement, requiring more aggressive treatment 5

Anti-Caspr1 Patients

• Typical CIDP clinical features with cranial nerve involvement (5/11 patients) and autonomic disturbances (3/11 patients) 2
• Less severe electrophysiological abnormalities compared to anti-NF155 patients 2

Monitoring and Treatment Duration

Response Assessment

• Monitor for clinical remission with serial neurological examinations rather than repeated electromyography/nerve conduction studies 6
• Clinical remission should be associated with autoantibody depletion and recovery of conduction block and distal motor amplitude 5
• Functional status improvement typically occurs within 3-6 months of rituximab initiation 2

Treatment Duration

• Continue rituximab until clinical remission and antibody depletion are achieved, typically requiring multiple cycles 5
• For patients achieving remission with immunosuppression, consider maintenance therapy for at least 12-18 months 7
• More prolonged treatment may be necessary in patients with persistent antibody positivity 4

Common Pitfalls

• Avoid using standard CIDP treatment protocols (IVIG, corticosteroids alone) as first-line therapy in confirmed nodal/paranodal antibody-positive patients, as response rates are poor 1, 2
• Do not rely on plasma exchange or immunoadsorption as monotherapy, as these modalities show minimal benefit in this patient population 4
• Recognize that these are pathologically distinct diseases requiring targeted B-cell depletion rather than general immunosuppression 1
• Test for specific nodal/paranodal antibodies (NF155, NF186, Caspr1, CNTN1) using cell-based assays to guide treatment decisions 2
• Monitor for systemic IgG4-related disease in patients with anti-NF186/NF140 antibodies, as they may require additional immunosuppression 5