What is multifocal motor neuropathy?

Multifocal Motor Neuropathy (MMN)

Multifocal motor neuropathy is a rare, acquired immune-mediated neuropathy characterized by chronic or stepwise progressive asymmetric limb weakness without sensory loss, distinguished by persistent multifocal partial motor conduction blocks on electrodiagnostic testing. 1, 2

Clinical Presentation

MMN presents with distinctive motor-only features that differentiate it from other neuropathies:

• Progressive asymmetric weakness affecting limbs in a patchy, multifocal distribution without any sensory abnormalities 3, 1, 2
• Upper extremities are more commonly affected than lower extremities, with distal muscles showing greater weakness than proximal muscles 1, 2
• Muscle wasting and atrophy develop in affected regions over time 4
• Reflexes are reduced asymmetrically in weak limbs 4
• Disease onset is typically in adulthood (ages 28-58 years in most series), though rare childhood cases have been reported 3, 4
• Progression is slow, occurring over 5-18 years in most patients 4

Diagnostic Features

The diagnosis of MMN requires specific electrophysiological and serological findings:

Electrodiagnostic Hallmarks

• Persistent multifocal partial motor conduction blocks are the pathognomonic finding—these represent focal areas where motor nerve conduction is blocked or severely slowed 1, 5, 2
• Sensory nerve conduction studies remain completely normal, which is critical for distinguishing MMN from chronic inflammatory demyelinating polyneuropathy (CIDP) 2
• Conduction blocks can be difficult to detect and require careful technique 2

Serological Markers

• High-titer anti-GM1 IgM antibodies are present in approximately 50-80% of patients 4, 1, 5
• Anti-GM2 antibodies may also be present in some cases 3
• These antibodies may cause changes in nodal and perinodal nerve structures that compromise conduction 2

Differential Diagnosis

MMN must be distinguished from several conditions with overlapping features:

• Amyotrophic lateral sclerosis (ALS) and other motor neuron diseases—critical to differentiate as prognosis and treatment differ completely 2
• Chronic inflammatory demyelinating polyneuropathy (CIDP) with asymmetric onset—distinguished by sensory involvement in CIDP 1, 2
• Lewis-Sumner syndrome (MADSAM neuropathy)—a multifocal acquired demyelinating sensory and motor neuropathy that includes sensory deficits 1

Treatment

High-dose intravenous immunoglobulin (IVIg) is the established first-line treatment for MMN, with corticosteroids and plasma exchange being largely ineffective. 1, 5, 2

IVIg Therapy

• Dosing: 1.6-2.4 g/kg given intravenously over 3-5 days 4
• Response timeline: Strength improves in 3-10 days, peaks at 2 weeks, and lasts an average of 2 months 4
• All patients in initial trials showed improvement, ranging from dramatic to mild functional gains 4
• Motor conduction blocks are reduced (at least partially) in most patients following treatment 4
• Repeated courses produce similar improvements, making this effective for long-term maintenance 4

Treatment Limitations and Alternatives

• Long-term IVIg maintenance does not prevent slowly progressive axonal degeneration that occurs over years 2
• Cyclophosphamide is effective in some patients but carries substantial adverse effects 2
• Corticosteroids and plasmapheresis are ineffective and should not be used 4, 1, 5
• Rituximab efficacy is not established in MMN 2

Prognosis

• Prognosis appears determined by initial response to IVIg treatment—patients who respond well initially tend to maintain benefit with continued therapy 3
• Partial responders may plateau after initial improvement, with symptoms stabilizing at a level better than baseline but not returning to normal 3
• Progressive axonal degeneration occurs slowly despite treatment, representing an ongoing challenge in long-term management 2