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Spotting MMN

Discover the key clinical features of MMN and why a timely diagnosis matters

DISEASE STATE EDUCATION

Spotting MMN

Discover the key clinical features of MMN and why a timely diagnosis matters

 

What is MMN?

MMN disease characteristics

Multifocal motor neuropathy (MMN) is a rare, chronic, autoimmune neuromuscular disease that is predominantly complement driven.1–3


MMN is associated with nerve thickening, and slow, progressive and disabling asymmetric limb weakness in the absence of sensory loss.4,5

Although patients with MMN generally have a normal life expectancy:6,7

of patients experience relatively severe disability, often affecting the arms

of patients report a mildly progressive disease course

MMN is thought to be an autoimmune disease driven by IgM autoantibodies that target GM1 and other gangliosides in motor neuron axons.3,8

The binding of anti-GM IgM may activate the classical complement pathway.9,10

Hallmark signs and symptoms of MMN

Hallmark signs and symptoms of MMN include slow, progressive, asymmetrical muscle weakness, low or absent tendon reflexes, increased weakness in cold temperatures, muscular atrophy, cramps, and fasciculations.6,7,11

Notably, MMN is not associated with objective sensory deficits, aside from minor vibration sense abnormalities in the lower limbs.7,12

Asymmetric muscle weakness

Slow, progressive, asymmetrical muscle weakness

Fasciculations (muscle contractions)

Fasciculations (muscle contractions)

Increased weakness in cold temperatures

Increased weakness in cold temperatures

Muscle atrophy

Muscle atrophy

The burden of MMN

Based on the findings of the first global MMN QoL survey (N=211), MMN restricts daily activities and impacts emotional well-being and overall QoL:13,a

56%

of respondents reported an impact on overall QoL

QoL
Asymmetric muscle weakness

62% reported impacts on activities of daily living and household chores

Asymmetric muscle weakness

75% reported exhaustion, 75% reported fatigue and 78% reported daytime drowsiness

Asymmetric muscle weakness

27% reported difficulty walking and 42% reported difficulty climbing stairs

Asymmetric muscle weakness

46% reported impacts on emotional well-being, including symptoms of depression, and 28% reported feelings of hopelessness

Asymmetric muscle weakness

53% reported muscle weakness and 20% reported cramping

Asymmetric muscle weakness

46% reported impacts on work activities

Asymmetric muscle weakness

55% reported impacts on social life and activities

Epidemiology of MMN

 MMN is a rare disease, with an estimated global prevalence of ≥0.6 cases per 100,000 persons (2010 estimate)6

1_BOX_2

MMN incidence is approximately 2.7 times higher in males than in females6

The mean age of onset is 40 years, although onset can range from 20 to 70 years6

Diagnostic delay in MMN

Patients with MMN are frequently misdiagnosed with other motor neuron diseases and diseases that can mimic MMN, such as ALS and CIDP.14,15

A cross-sectional, descriptive study of 88 Dutch patients found a median time of 5 years (range 0–36) from symptom onset to first IVIg treatment.16

A prompt diagnosis of MMN is critical, as disease severity has been shown to significantly correlate with the number of years untreated.7,16,17,b–d

 

Path to diagnosis

EFNS/PNS 2010 Clinical Diagnostic Criteria12

The EFNS/PNS 2010 guidelines define clinical, electrophysiological, and supportive criteria for an MMN diagnosis. They are based on existing evidence and the consensus of the Joint Task Force. 

 

The Joint Task Force agreed on good practice points to define the following MMN diagnostic criteria:12

Clinical criteria for MMN diagnosis include weakness without objective sensory loss
  • Slowly progressive or stepwise progressive, focal, asymmetricale limb weakness; that is, motor involvement in the motor nerve distribution of >2 nerves for >1 monthf
  • No objective sensory abnormalities except for minor vibration sense abnormalities in the lower limbs
  • Predominant upper limb involvement
  • Decreased/absent tendon reflexes in the affected limb
  • Absence of cranial nerve involvement
  • Cramps and fasciculations in the affected limb
  • Response in terms of disability or muscle strength to immunomodulatory treatment
  • Upper motor neuron signs
  • Marked bulbar involvement
  • Sensory impairment more marked than minor vibration loss in the lower limbs
  • Diffuse symmetric weakness during the initial weeks
The hallmark of MMN is the presence of multifocal CBg on electrophysiological testing outside of the usual sites of nerve compression

Definite or probable CB in ≥1 nerve is required for a diagnosis of MMN

  • Negative peak CMAP area reduction on proximal versus distal stimulation of ≥50% regardless of nerve segment length
  • Negative peak CMAP amplitude on stimulation of the distal segment with motor CB must be >20% of the lower limit of normal and >1 mV, and increase of proximal to distal negative peak CMAP duration must be ≤30%
  • Negative peak CMAP area reduction of ≥30% over a long segment of an upper limb nerve with an increase of proximal to distal negative peak CMAP duration ≤30%

OR

  • Negative peak CMAP area reduction of ≥50% with an increase of proximal to distal negative peak CMAP duration >30%

 

Upper limb segments with CB should have normal sensory nerve conduction

Supportive criteria for an MMN diagnosis include select laboratory tests and objective improvement following IVIg treatment
  • Elevated IgM anti-ganglioside GM1 antibodies
  • Increased signal intensity on T2-weighted imagingh associated with a diffuse nerve swelling of the brachial plexus
  • Increased CSF protein (<1 g/L)
  • Following IVIg treatment
Three defined diagnostic categories for MMN12

Based on the clinical, electrophysiological, and supportive criteria, the EFNS/PNS 2010 guidelines defined three levels of diagnostic certainty:12

Definite MMN
  • Meets core clinical criteria, exclusion criteria AND electrophysiological criteria for definite motor CB or normal sensory nerve conduction in upper limb segments with CB in one nerve

                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    

Probable MMN
  • Meets core clinical criteria, exclusion criteria AND electrophysiological criteria for probable motor CB and normal sensory nerve conduction in upper limb segments with CB in two nerves
  • Meets core clinical criteria, exclusion criteria AND electrophysiological criteria for probable motor CB and normal sensory nerve conduction in upper limb segments with CB in one nerve AND at least two supportive criteria
Possible MMN
  • Meets core clinical criteria, exclusion criteria AND normal sensory nerve conduction studies AND objective clinical improvement following IVIg treatment
  • Meets core clinical criteria 1 with clinical signs present in only one nerve, no objective sensory abnormalities, exclusion criteria AND electrophysiological criteria for definite or probable motor CB in one nerve

Achieving a differential diagnosis

According to the EFNS/PNS 2010 guidelines, MMN should be differentiated from other motor neuron diseases and diseases that can mimic MMN:1,12

Motor neuron diseases11,12

Hereditary neuropathy with liability to pressure palsies11,12

Guillain-Barré syndrome (acute motor axonal neuropathy variant)1

Entrapment neuropathies11,12

Spinal muscular atrophy1,11

Distal hereditary motor neuropathies1

Amyotrophic lateral sclerosis1,11

CIDP (particularly focal and pure motor variants)1,11,12

Lewis-Sumner syndrome1,12

Progressive muscular atrophy (lower motor neuron variant)1

MMN can be differentiated from other conditions based on imaging of the cervical spinal cord, electrophysiological tests, genetic testing, serology, and CSF analysis.1,12

In some cases, diagnosis may remain challenging, possibly necessitating serial assessment and trials of therapy.1,12

Footnotes:
aCompleted by 211 individuals with MMN in 2016, 53% women, 89% white, >70% located in the United States.13
bThe number (%) of male participants was 64 (73%) and the median (range) age of participants at symptom onset was 40 (22–66) years. Disease severity was measured using the ODSS and FSS scales.16
cHerraets et al. was a follow-up study to Cats et al.16 that examined a cross-sectional cohort of 142 Dutch patients with MMN. The number (%) of male participants was 46 (72%) for participants diagnosed before 2007 and 29 (81%) for participants diagnosed in or after 2007. The median (range) age at symptom onset was 40.3 (21.4–53.8) years for participants diagnosed before 2007 and 45.2 (30.1–67.2) years for participants diagnosed in or after 2007. Disease severity was measured using the ODSS, Self-Evaluation Scale, MMN-RODS, MRC Sum Score, and FSS scales.7
dVan Asseldonk et al examined 20 Dutch patients with MMN. The number (%) of male participants was 15 (75%) and the mean (SD) age at symptom onset was 34.4 (8.1) years. Disease severity was measured using the MRC Sum Score.17
eA difference of 1 MRC grade if strength is MRC >3 and 2 MRC grades if strength is MRC ≤3.12
fIf symptoms and signs are present only in the distribution of one nerve, only a possible diagnosis can be made.12
gA reduction in amplitude and area of the CMAP obtained by proximal versus distal stimulation of motor nerves in the absence of abnormal temporal dispersion.12
hMRI that depicts differences in T2 relaxation time between tissues.12

Abbreviations:
ALS=amyotrophic lateral sclerosis; CB=conduction block; CIDP=chronic inflammatory demyelinating polyradiculoneuropathy; CMAP=compound muscle action potential; CSF=cerebrospinal fluid; EFNS=European Federation of Neurological Societies; FSS=Fatigue Severity Scale; GM=monosialoganglioside; Ig=immunoglobulin; IVIg=intravenous immunoglobulin; MMN=multifocal motor neuropathy; MMN-RODS=Rasch-built Overall Disability Scale for multifocal motor neuropathy; MND=motor neuron disease; MRC=Medical Research Council; MRI, magnetic resonance imaging; mV=millivolts; ODSS=Overall Disability Severity Scale; PNS=Peripheral Nerve Society; QoL=quality of life; SD=standard deviation.

References:
1. Yeh WZ, et al. J Neurol Neurosurg Psychiatry. 2020;91(2):140–148. doi:10.1136/jnnp-2019-321532; 2. Deenen JC, et al. J Neuromuscul Dis. 2015;2(1):73–85; 3. Vlam L, et al. Neurol Neuroimmunol Neuroinflamm. 2015;2(4):e119. doi: 0.1212/NXI.0000000000000119; 4. Haakma W, et al. Eur Radiol. 2017;27(5):2216–2224. doi:10.1007/s00330-016-4575-0; 5. Léger JM, et al. Ther Adv Neurol Disord. 2015;8(3):109–122. doi:10.1177/1756285615575269; 6. Harschnitz O, et al. J Clin Immunol. 2014;34(suppl 1):S112–S119. doi:10.1007/s10875-014-0026-3; 7. Herraets I, et al. Neurology. 2020;95(14):e1979-e1987. doi:10.1212/WNL.0000000000010538; 8. Pascual-Goñi E, et al. Neurology. 2024;103:e209725. doi:10.1212/ WNL.0000000000210298; 9. Yuki N, et al. J Neurol Neurosurg Psychiatry. 2011;82(1):87–91. doi:10.1136/jnnp.2010.205856; 10. Budding K, et al. Eur J Neurol. 2025;32(1):e16541. doi:10.1111/ene.16541; 11. Allen JA, et al. Mayo Clin Proc Innov Qual Outcomes. 2024;8(1):74–81. doi:10.1016/j.mayocpiqo.2023.12.002; 12. Joint Task Force of the EFNS and the PNS. J Peripher Nerv Syst. 2010;15(4):295–301. doi:10.1111/j.1529-8027.2010.00290.x.; 13. Katz J, et al. First global multifocal motor neuropathy (MMN) quality of life (QOL) patient survey identifies needs in education and treatment. September 26, 2016. Available at: www.neuropathyaction.org/downloads/MMN_article%209-26-2016.pdf. (Accessed: March 2026); 14. Vlam L, et al. Nat Rev Neurol. 2011;8(1):48–58. doi:10.1038/nrneurol.2011.175; 15. Khandelwal N, et al. J Health Econ Outcomes Res. 2025;12(1):261-268. doi:10.36469/jheor.2025.140817; 16. Cats EA, et al. Neurology. 2010;75(9):818-825. doi:10.1212/WNL.0b013e3181f0738e; 17. van Asseldonk JTH, et al. J Neurol Neurosurg Psychiatry. 2006;77(6):743–747. doi:10.1136/jnnp.2005.064816

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