Multifocal motor neuropathy: a review of pathogenesis, diagnosis, and treatment

Figures & data

Table 1 Clinical criteria for the diagnosis of MMN⁸

Core (both criteria required)

1. Slowly progressive or stepwise progressive, focal, asymmetric limb weakness; that is, motor involvement in the motor nerve distribution of at least two nerves for more than 1 month. If symptoms and signs are present only in the distribution of one nerve, only a possible diagnosis can be made.

2. No objective sensory abnormalities except for minor vibration sense abnormalities in the lower limbs.

Supportive

3. Predominant upper limb involvement.

4. Decreased or absent tendon reflexes in the affected limb.

5. Absence of cranial nerve involvement.

6. Cramps and fasciculations in the affected limb.

7. Response in terms of disability or muscle strength to immunomodulatory therapy.

Exclusion criteria

8. Upper motor neuron signs.

9. Marked bulbar involvement.

10. Sensory impairment more marked than minor vibration loss in the lower limbs.

11. Diffuse symmetric weakness during the initial weeks.

Note: Copyright © 2010 Peripheral Nerve Society. Reproduced with permission from John Wiley & Sons, Inc. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. J Peripher Nerv Syst. 2010;15(4):295–301.

Abbreviation: MMN, multifocal motor neuropathy.

Table 2 Classic features of multifocal motor neuropathy and other neuromuscular disorders with similar clinical and electrodiagnostic features

Clinical features		Laboratory features	Electrodiagnostic	Treatment
Multifocal motor neuropathy
Asymmetric, distal > proximal, upper limb > lower limb weakness without sensory loss. Some patients with subjective sensory loss, pain, and fatigue		CSF protein usually normal 40%–50% of patients may have IgM ganglioside antibodies^Citation43	Multifocal demyelinating motor neuropathy with or without conduction block	IVIg, rituximab, and cyclophosphamide Does not respond to steroids or plasma exchange
Disorder	Overlapping features	Distinctive clinical features	Diagnostic features: laboratory and EDx	Treatment
Neuromuscular disorders with similar clinical and electrodiagnostic features
Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM)	Asymmetric, distal > proximal, upper limb > lower limb involvement	Prominent sensory loss	CSF protein usually elevated with no pleocytosis EDx: Multifocal demyelinating sensory and motor neuropathy with conduction block	Steroids, IVIg, and plasma exchange Others include: azathioprine, cyclosporine, cyclophosphamide, and methotrexate
Multifocal acquired motor axonopathy (MAMA)	Asymmetric, distal > proximal weakness without sensory loss		Normal CSF studies EDx: Multifocal axonal motor neuropathy in the distribution of individual nerves with no demyelination or conduction block (closely mimics motor neuron disease)	IVIg? Close observation for signs of motor neuron disease
Hereditary neuropathy with predisposition to pressure palsy (HNPP)	Asymmetric weakness in the distribution of multiple named nerves, typically at common entrapment sites	Sensory loss, may have family history (autosomal dominant)	Genetic testing for PMP22 deletion EDx: Focal neuropathies at common sites of entrapment (may have underlying demyelinating neuropathy and occasionally closely mimics CIDP)	Supportive, avoid positioning/postures that lead to compression of susceptible nerves
Motor neuron disease	Asymmetric weakness without sensory loss	May have upper motor neuron signs and cognitive involvement, usually more prominent muscle atrophy	Clinical criteria supported by EMG fndings EDx: active and chronic motor axon loss and fasciculations in multiple regions	Supportive

Abbreviations: CIDP, chronic inflammatory demyelinating neuropathy; CSF, cerebrospinal fluid; EDx, electrodiagnostic; EMG, electromyography; IgM, immunoglobulin M; IVIg, intravenous immunoglobulin.

Table 3 Electrophysiological criteria for conduction block⁸

Definite*

Negative peak CMAP area reduction on proximal versus distal stimulation of at least 50% regardless of nerve segment length (median, ulnar, and peroneal).

Negative peak CMAP amplitude on stimulation of the distal nerve segment >20% of the lower limit of normal and >1 mV.

Increase of proximal to distal negative peak CMAP duration of ≤30%.

Probable*

Negative peak CMAP area reduction of at least 30% over a long segment (eg, wrist to elbow or elbow to axilla) of an upper limb nerve with increase of proximal to distal negative peak CMAP duration of ≤30%.

Or negative peak CMAP area reduction of at least 50% with an increase of proximal to distal negative peak CMAP duration of >30%.

Notes:

* In MMN, sensory nerve conduction in the nerve segments with CB are normal. Copyright © 2010 Peripheral Nerve Society. Reproduced with permission from John Wiley & Sons, Inc. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. J Peripher Nerv Syst. 2010;15(4):295–301.

Abbreviations: CB, conduction block; CMAP, compound muscle action potential; MMN, multifocal motor neuropathy.

Table 4 Diagnostic criteria for definite or probable MMN⁸

Definite	Probable	or	Probable
Clinical
• All core criteria (1,2)	• All core criteria (1,2)		• All core criteria (1,2)
• All exclusion criteria (8–11)	• All exclusion criteria (8–11)		• All exclusion criteria (8–11)
Electrophysiologic
• Definite CB criteria, one nerve	• Probable CB criteria, two nerves		• Probable CB criteria, one nerve
• Normal SNAP conduction in motor nerve(s) with CB	• Normal SNAP conduction in motor nerve(s) with CB		• Normal SNAP conduction in motor nerve(s) with CB
Laboratory/supportive
• Supportive only (not necessary)	• Supportive only (not necessary)		Two of the following:
			• Elevated IgM antiganglioside GM1 antibodies
			• Increased CSF protein (<1 g/dL)
			• Increased T2-signal intensity on MRI of brachial plexus with diffuse nerve swelling
			• Objective clinical improvement following IVIg treatment

Note: Copyright © 2010 Peripheral Nerve Society. Reproduced with permission from John Wiley & Sons, Inc. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revision. J Peripher Nerv Syst. 2010;15(4):295–301.

Abbreviations: CB, conduction block; CSF, cerebrospinal fluid; IgM, immunoglobulin M; IVIg, intravenous immunoglobulin; MMN, multifocal motor neuropathy; MRI, magnetic resonance imaging; SNAP, sensory nerve action potential.

Table 5 Diagnostic criteria for possible MMN⁸

Possible	or	Possible
Clinical
• All core criteria (1,2)		• All core criteria (1,2), one nerve
• All exclusion criteria (8–11)		• All exclusion criteria (8–11)
Electrophysiological
• Normal SNAP conduction in motor nerve(s) with CB		• Definite or probable CB, one nerve
		• Normal SNAP conduction in motor nerve(s) with CB
Laboratory/supportive
• Objective clinical improvement following IVIg treatment		• Supportive only (not necessary)

Note: Copyright © 2010 Peripheral Nerve Society. Reproduced with permission from John Wiley & Sons, Inc. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society–first revision. J Peripher Nerv Syst. 2010;15(4):295–301.

Abbreviations: CB, conduction block; IVIg, intravenous immunoglobulin; MMN, multifocal motor neuropathy; SNAP, sensory nerve action potential.

Joint Task Force of theEFNSthePNSEuropean Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – first revisionJ Peripher Nerv Syst201015429530121199100

 PubMed Web of Science ®Google Scholar

Nobile-OrazioEGiannottaCMussetLMessinaPLégerJMSensitivity and predictive value of anti-GM1/galactocerebroside IgM antibodies in multifocal motor neuropathyJ Neurol Neurosurg Psychiatry Epub812013

 Web of Science ®Google Scholar