Is a mixed sensorimotor polyradiculoneuropathy with both axonal and demyelinating features amenable to treatment?

Is Mixed Sensorimotor Mixed Axonal and Demyelinating Polyradiculoneuropathy Amenable for Treatment?

Yes, mixed sensorimotor polyradiculoneuropathy with both axonal and demyelinating features is highly amenable to treatment, with 60-75% response rates to immunotherapy when the underlying cause is immune-mediated. 1

Diagnostic Clarification Required

The critical first step is determining whether this represents an acute or chronic process, as this fundamentally changes treatment approach:

• If progression occurred over days to 4 weeks, this suggests Guillain-Barré syndrome (GBS) or acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which requires immediate immunotherapy. 2
• If progression extends beyond 8 weeks, this indicates chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or a variant, which also responds well to immunotherapy but requires different dosing strategies. 2, 3
• Mixed axonal and demyelinating features on electrodiagnostic studies are compatible with both GBS and CIDP, and do not exclude either diagnosis—the temporal course is the key distinguishing factor. 2, 4

First-Line Treatment for Acute Presentation (GBS/AIDP)

If symptoms progressed rapidly (days to 4 weeks) and the patient cannot walk unaided:

• Administer intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 consecutive days (total dose 2 g/kg) as first-line therapy. 2, 5
• Alternatively, plasma exchange 200-250 mL/kg over 4-5 sessions provides equivalent efficacy. 2, 5
• Unlike idiopathic GBS, corticosteroids ARE recommended when GBS occurs in the context of immune checkpoint inhibitor therapy or other immune-mediated conditions, with methylprednisolone 2-4 mg/kg/day added to IVIg or plasma exchange. 1, 5
• Expected outcome: 80% of patients regain independent walking ability at 6 months, though recovery may continue for more than 3 years. 2, 5

First-Line Treatment for Chronic Presentation (CIDP)

If symptoms progressed over at least 8 weeks:

• Initiate pulse methylprednisolone 1g IV daily for 3-5 days for severe or progressing symptoms, followed by a taper over at least 4-6 weeks. 2
• Oral corticosteroids alone or with immunosuppressive therapy achieve 60-75% response rates in peripheral neuropathies. 1, 2
• Standard IVIG dosing is 2g/kg administered over 5 days as an alternative or adjunct to corticosteroids. 2
• For severe cases with acute inflammatory demyelinating polyneuropathy-type presentation, combine pulse corticosteroids PLUS IVIG. 2
• Plasma exchange is an established first-line option, particularly effective in severe cases. 2

Treatment Response Expectations and Monitoring

• Approximately 40% of patients do not improve in the first 4 weeks following treatment—this does not necessarily indicate treatment failure, as progression might have been worse without therapy. 2, 5
• Treatment-related fluctuations (TRFs) occur in 6-10% of patients, defined as disease progression within 2 months following initial treatment-induced improvement. 2, 5
• Repeat the full course of IVIG or plasma exchange for TRFs, as this indicates the treatment effect has worn off while inflammation persists. 2
• If progression continues after 8 weeks from onset or if the patient has three or more TRFs, reconsider the diagnosis as acute-onset CIDP—this occurs in approximately 5% of patients initially diagnosed with GBS. 5

Second-Line and Refractory Treatment

For patients with inadequate response to first-line therapy (approximately 25% of CIDP patients):

• Rituximab should be considered in consultation for patients with limited or no improvement after first-line therapy. 1, 2, 6
• Other immunosuppressants include methotrexate, azathioprine, or mycophenolate mofetil for maintenance therapy or when symptoms do not resolve after 4 weeks. 2, 6

Special Diagnostic Considerations

The mixed axonal and demyelinating pattern requires exclusion of specific treatable conditions:

• POEMS syndrome should be considered in patients with progressive polyneuropathies of mixed demyelinating and axon loss features, especially those not responding to standard CIDP treatment. 7
• Check serum vascular endothelial growth factor (VEGF) levels and perform targeted bone marrow biopsy if POEMS is suspected, as initial serum immunofixation and skeletal surveys may be normal. 7
• Chronic immune sensorimotor polyradiculopathy (CISMP) is a CIDP variant affecting both sensory and motor nerve roots without evidence of peripheral nerve demyelination—all reported patients demonstrated good responses to immunotherapies. 8
• Obtain metastatic bone surveys for osteosclerotic myeloma and serum electrophoresis with immunofixation for monoclonal gammopathies to exclude mimics of CIDP. 3

Critical Pitfalls to Avoid

• Do not delay treatment beyond 2 weeks in acute presentations, as this is associated with severe neurological deficit and poor outcomes. 1
• Do not perform plasmapheresis immediately after IVIG administration, as it removes the therapeutic immunoglobulin. 2
• Do not assume treatment failure if progression continues in the first 4 weeks—40% of patients do not improve initially but may still benefit from therapy. 2, 5
• Do not dismiss the diagnosis based on normal cerebrospinal fluid protein in the first week—albumino-cytological dissociation may develop later. 5
• Do not use corticosteroids alone for idiopathic GBS—they are not recommended and may be harmful. 5

Prognosis Summary

• For GBS: 80% regain independent walking ability at 6 months, with mortality of 3-10% primarily from cardiovascular and respiratory complications. 2, 5
• For CIDP: 60-75% response rate to first-line immunotherapy, with most patients requiring maintenance treatment for years. 1, 2, 9
• Recovery can continue for more than 3 years in both conditions, with improvement possible even more than 5 years after onset. 2, 5