The levels of evidence (class I-IV) supporting the recommendations and ratings of recommendations (A-C, Good Practice Point [GPP]) are defined at the end of the "Major Recommendations" field.
Diagnostic Criteria (Good Practice Points)
- Clinical: the two core criteria and all exclusion criteria should be met (see Table 1, below)
- Electrodiagnostic: definite or probable conduction block (CB) in at least two nerves (see Table 2, below)
- Supportive: anti-GM1 antibody testing, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examination, and treatment response (see Table 3, below)
- Categories: definite and probable multifocal motor neuropathy (MMN) (see Table 4, below)
| Table 1. Clinical Criteria for Multifocal Motor Neuropathy (MMN) |
Core criteria (both must be present)
- Slowly progressive or stepwise progressive, asymmetric limb weakness, or motor involvement having a motor nerve distribution in at least two nerves, for more than 1 month*
- No objective sensory abnormalities except for minor vibration sense abnormalities in the lower limbs
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Supportive clinical criteria
- Predominant upper limb involvement**
- Decreased or absent tendon reflexes in the affected limb***
- Absence of cranial nerve involvement^
- Cramps and fasciculations in the affected limb
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Exclusion criteria
- 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
- Laboratory: cerebrospinal fluid protein >1g/L
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*Usually more than 6 months.
**At onset, predominant lower limb involvement accounts for nearly 10% of the cases.
***Slightly increased tendon reflexes, in particular in the affected arm, have been reported and do not exclude the diagnosis of MMN provided criterion 7 is met.
^12th nerve palsy has been reported.
| Table 2. Electrophysiological Criteria for Conduction Block (CB)* (Good Practice Points) |
- Definite motor CB*
Negative compound muscle action potential (CMAP) area reduction on proximal versus distal stimulation of at least 50% whatever the nerve segment length (median, ulnar, and peroneal). Negative CMAP amplitude on stimulation of the distal part of the segment with motor CB must be >20% of the lower limit of normal and >1mV (baseline negative peak) and an increase of proximal negative peak CMAP duration must be <30%.
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- Probable motor CB*
Negative CMAP area reduction of at least 30% over a long segment of an upper limb nerve with an increase of proximal negative peak CMAP duration <30%, or
Negative CMAP area reduction of at least 50% (same as definite) with an increase of proximal negative peak CMAP duration >30%
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- Normal sensory nerve conduction in upper limb segments with CB and normal sensory nerve action potential (SNAP) amplitudes (see exclusion criteria)
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*Evidence for CB must be found at sites distinct from common entrapment or compression syndromes.
| Table 3. Supportive Criteria |
- Elevated immunoglobulin M anti-ganglioside GM1antibodies (level A recommendation)
- Magnetic resonance imaging showing gadolinium enhancement and/or hypertrophy of the brachial plexuses (good practice point)
- Clinical improvement following intravenous immunoglobulin treatment (good practice point)
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| Table 4. Diagnostic Categories |
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Definite MMN
Clinical criteria 1, 2, and 7 to 11 and electrophysiological criteria 1 and 3 in one nerve
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Probable MMN
Clinical criteria 1, 2, and 7 to 11 and electrophysiological criteria 2 and 3 in two nerves
Clinical criteria 1, 2, and 7 to 11and electrophysiological criteria 2 and 3 in one nerve and at least one supportive criterion 1 to 3 (see Table 3 above)
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Diagnostic Tests (Good Practice Points)
- Clinical examination and electrodiagnostic tests should be considered in all patients.
- Anti-ganglioside GM1 antibody testing, MRI of the brachial plexus, and CSF examination should be considered in selected patients.
- Investigations to discover concomitant disease or exclude other possible causes should be considered, but the choice of tests will depend on the individual circumstances.
Treatment
- Intravenous immunoglobulin (IVIg) (2 g/kg given over 2 to 5 days) should be considered as the first line of treatment (level A recommendation) when disability is sufficiently severe to warrant treatment
- Corticosteroids are not recommended (good practice point)
- If an initial treatment with IVIg is effective, repeated IVIg treatment should be considered in selected patients (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the response (good practice point). Typical treatment regimen is 1 g/kg every 2 to 4 weeks or 2 g/kg every 1 to 2 months (good practice point)
- If IVIg is not (or not sufficiently) effective, then immunosuppressive treatment may be considered. Cyclophosphamide, cyclosporine, azathioprine, interferon-beta 1a (IFNb1a), or rituximab are possible agents (good practice point)
- Toxicity makes cyclophosphamide a less desirable option (good practice point).
Definitions:
Evidence Classification Scheme for a Diagnostic Measure
Class I: A prospective study in a broad spectrum of persons with the suspected condition, using a "gold standard" for case definition, where the test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class II: A prospective study of a narrow spectrum of persons with the suspected condition, or a well-designed retrospective study of a broad spectrum of persons with an established condition (by "gold standard") compared to a broad spectrum of controls, where test is applied in a blinded evaluation, and enabling the assessment of appropriate tests of diagnostic accuracy
Class III: Evidence provided by a retrospective study where either persons with the established condition or controls are of a narrow spectrum, and where test is applied in a blinded evaluation
Class IV: Any design where test is not applied in blinded evaluation OR evidence provided by expert opinion alone or in descriptive case series (without controls)
Evidence Classification Scheme for a Therapeutic Intervention
Class I: An adequately powered prospective, randomized, controlled clinical trial with masked outcome assessment in a representative population or an adequately powered systematic review of prospective randomized controlled clinical trials with masked outcome assessment in representative populations. The following are required:
- Randomization concealment
- Primary outcome(s) is/are clearly defined
- Exclusion/inclusion criteria are clearly defined
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences
Class II: Prospective matched-group cohort study in a representative population with masked outcome assessment that meets a–e above or a randomized, controlled trial in a representative population that lacks one criteria a–e
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion
Rating of Recommendations for a Diagnostic Measure
Level A rating (established as useful/predictive or not useful/predictive) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (established as probably useful/predictive or not useful/predictive) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (established as possibly useful/predictive or not useful/predictive) requires at least two convincing class III studies.
Rating of Recommendations for a Therapeutic Intervention
Level A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating (probably effective, ineffective, or harmful) requires at least one convincing class II study or overwhelming class III evidence.
Level C rating (possibly effective, ineffective, or harmful) requires at least two convincing class III studies.
Good Practice Point (GPP) When only class IV evidence was available but consensus could be reached, the Task Force offered advice as good practice points.
