Table 1

Clinical features of LMN syndromes

		Typical pattern of weakness
		Symmetry	Proximal/distal	Limb predominance	Bulbar involvement	Disease progression	Investigation findings
SMA		Symmetrical	Proximal>distal	LL>UL	Yes	Slowly progressive	Homozygous deletion exon 7 SMN1 gene (94%); small percentage compound heterozygous for SMN1 deletion and an intragenic mutation of SMN1
SBMA		Symmetrical or asymmetrical	Proximal>distal	LL>UL	Yes	Slowly progressive	X-linked trinucleotide CAG expansion (>39 repeats) androgen receptor gene
dHMN		Symmetrical	Distal	LL>UL; exception dHMN V: UL predominance	Rare; laryngeal involvement in dHMN VII	Slowly progressive	Mutations in HSPB1, HSPB8, BSCL2, GARS, DCTN1, TRP4, SETX
Immune	GBS	Symmetrical	Distal>proximal	UL and LL	May occur	Acute: weakness usually progresses over hours-days	Anti-GM1 IgG antibody and anti-GD1a IgG antibody in AMAN variant
	MMN	Asymmetrical	Distal>proximal	UL	No	Slowly progressive	Anti-GM1 IgM in 30–80%
	CIDP (motor)	Symmetrical or asymmetrical	Proximal and distal	UL and LL	No	Relapsing-remitting	Anti-GM1 IgM often negative
MND (LMN variants)	Sporadic	Asymmetrical	Distal>proximal	Variable	May occur ∼10%	Median survival 3–4 years	Anti-GM1 IgM antibodies may be present but typically low titre Features of cortical hyperexcitability on TMS
	Flail arm	Symmetrical	Proximal>distal	UL	Not at onset; may develop later in disease course	Median survival ∼5 years
	Flail leg	Asymmetrical	Distal>proximal	LL	Not at onset; may develop later in disease course	Median survival ∼6 years
	Genetic	Asymmetrical	Variable	Variable	Variable	Variable; rapid and slowly progressive forms described	Mutations in SOD1, FUS, VAPB, and CHMP2B
MMA		Asymmetrical	Distal>proximal	UL involvement more frequent than LL	No	Insidious onset, slow progression, followed by stabilisation	MR findings: lower cervical cord atrophy, asymmetric cord flattening, and/or anterior displacement of the dorsal dura on neck flexion
Segmental LMN disease		Asymmetrical	Distal or proximal	UL	No	Insidious onset, slow progression up to 20 years	MRI may reveal ‘snake eyes’ appearance
Polio	Acute poliomyelitis	Asymmetrical	Proximal>distal	LL>UL	5–35% of patients	Acute: weakness usually progresses over hours-days	PCR poliovirus from CSF
Polio	Postpolio syndrome	Asymmetrical	Variable	Variable	Variable	Slowly progressive; fatigue and pain common	Changes 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.