Unmet Needs and Challenges in Diagnosis and Treatment of Multifocal Motor Neuropathy

Multifocal Motor Neuropathy (MMN) is often mistaken for other motor neuron diseases, such as Amyotrophic Lateral Sclerosis (ALS). At the 2024 Peripheral Nerve Society (PNS) annual meeting in Montreal, Canada, Richard Lewis, Professor of Neurology at Cedars-Sinai, Los Angeles, CA, USA, and Katie Beadon, Assistant Clinical Professor at the University of British Columbia, Canada, highlighted the complexities and unmet needs of MMN diagnosis and treatment in an Argenx-sponsored symposium.

MMN is a rare neurological disorder characterized by progressive, asymmetric muscle weakness without significant sensory loss. Dr. Lewis addressed vital questions: What mechanisms underlie its pathogenesis? How can it be accurately diagnosed and distinguished from other motor neuron diseases? The diagnosis of MMN remains a significant challenge, with many patients initially misdiagnosed with ALS. Disease severity correlates significantly with the number of years untreated, underscoring the urgency of early and accurate diagnosis. Dr. Beadon expressed how this is frustrating to clinicians as well, 'This is frustrating to us as a clinician to treat these patients because the more you go untreated, the more likely you are to have irreversible deficits in disability." Dr. Lewis presented a cross-sectional study showing a median time of five years from symptom onset to the first Intravenous immunoglobulin (IVIG) treatment, underscoring the critical need for prompt diagnosis. He emphasized, "Five years is a long time; we need to do better than that."  Dr. Beadon discussed the guidelines of the European Federation of Neurological Societies (EFNS)/PNS for managing MMN. The EFNS/PNS 2010 guidelines define the clinical, electrophysiological, and supportive criteria for MMN diagnosis. Clinical criteria for MMN diagnosis include weakness without objective sensory loss.

Understanding the immunopathogenesis of MMN may inform treatment approaches. MMN pathogenesis involves humoral and cellular immunity and the complement system, which has three pathways—classical, lectin, and alternative—leading to immune responses such as opsonization, macrophage clearance, membrane attack complex formation, and cell lysis. The complement system has become a target for new drug development, with several drugs now available that inhibit different parts of this system. IVIG is considered the first-line treatment for MMN. Its efficacy is well-supported by several randomized controlled trials. This treatment approach has significantly improved muscle strength and reduced disease progression, providing a critical option for patients with MMN. Dr. Beadon presented a case study of a 40-year-old patient with MMN. The patient was initially treated with IVIG and later required an increased dose. Despite initial improvement, he eventually experienced progressive symptoms and had to retire from his profession as a welder. Interestingly, transitioning from intravenous to subcutaneous immunoglobulins improved his quality of life. Dr. Lewis added, "Picking up on improvement due to treatment is important, and it is important that patients are informed to watch for improvement."

The speakers concluded by emphasizing the need to explore new therapeutic targets and the potential for advancements in treatment options for MMN.