Table 1

Clinical features of LMN syndromes

 Typical pattern of weakness
SymmetryProximal/distalLimb predominanceBulbar involvementDisease progressionInvestigation findings
SMASymmetricalProximal>distalLL>ULYesSlowly progressiveHomozygous deletion exon 7 SMN1 gene (94%); small percentage compound heterozygous for SMN1 deletion and an intragenic mutation of SMN1
SBMASymmetrical or asymmetricalProximal>distalLL>ULYesSlowly progressiveX-linked trinucleotide CAG expansion (>39 repeats) androgen receptor gene
dHMNSymmetricalDistalLL>UL; exception dHMN V: UL predominanceRare; laryngeal involvement in dHMN VIISlowly progressiveMutations in HSPB1, HSPB8, BSCL2, GARS, DCTN1, TRP4, SETX
ImmuneGBSSymmetricalDistal>proximalUL and LLMay occurAcute: weakness usually progresses over hours-daysAnti-GM1 IgG antibody and anti-GD1a IgG antibody in AMAN variant
MMNAsymmetricalDistal>proximalULNoSlowly progressiveAnti-GM1 IgM in 30–80%
CIDP (motor)Symmetrical or asymmetricalProximal and distalUL and LLNoRelapsing-remittingAnti-GM1 IgM often negative
MND (LMN variants)SporadicAsymmetricalDistal>proximalVariableMay occur ∼10%Median survival 3–4 yearsAnti-GM1 IgM antibodies may be present but typically low titre Features of cortical hyperexcitability on TMS
Flail armSymmetricalProximal>distalULNot at onset; may develop later in disease courseMedian survival ∼5 years
Flail legAsymmetricalDistal>proximalLLNot at onset; may develop later in disease courseMedian survival ∼6 years
GeneticAsymmetricalVariableVariableVariableVariable; rapid and slowly progressive forms describedMutations in SOD1, FUS, VAPB, and CHMP2B
MMAAsymmetricalDistal>proximalUL involvement more frequent than LLNoInsidious onset, slow progression, followed by stabilisationMR findings: lower cervical cord atrophy, asymmetric cord flattening, and/or anterior displacement of the dorsal dura on neck flexion
Segmental LMN diseaseAsymmetricalDistal or proximalULNoInsidious onset, slow progression up to 20 yearsMRI may reveal ‘snake eyes’ appearance
PolioAcute poliomyelitisAsymmetricalProximal>distalLL>UL5–35% of patientsAcute: weakness usually progresses over hours-daysPCR poliovirus from CSF
Postpolio syndromeAsymmetricalVariableVariableVariableSlowly progressive; fatigue and pain commonChanges of chronic denervation with reinnervation on needle electromyography
  • AMAN, acute motor axonal neuropathy; CHMP2B, chromatin-modifying protein 2b; CIDP, chronic inflammatory demyelinating polyneuropathy; CSF, cerebrospinal fluid; dHMN, distal hereditary motor neuropathy; FUS, fused in sarcoma; GBS, Guillain-Barré syndrome; LL, lower limb; LMN, lower motor neuron; MMA, monomelic amyotrophy; MMN, multifocal motor neuropathy; MND, motor neuron disease; SBMA, spinobulbar muscular atrophy; SMA, spinal muscular atrophy; SOD1, superoxide dismutase type 1; TMS, transcranial magnetic stimulation; UL, upper limb; VAPB, vesicle-associated membrane protein/synaptobrevin-associated membrane protein B.