Quo vadis motor neuron disease?

Table 1 Possible differential diagnoses and diagnostic clues to discriminate from motor neuron disease[23]

Alternative diagnosis	Diagnostic clue
Cervical (myelo) neuropathy	Cervicalgia, osteopaenia/osteoporosis, abnormal cervical MRI
Benign fasciculations	Absence of weakness, limited distribution, young age
Nutritional (B12 or Cu deficiency)	Usually have sensory impairment
Motor predominant CIDP	Relapsing-remitting course, evidence of demyelination on NCS, IVIG-responsive
Multifocal motor neuropathy with conduction block	Weakness with little wasting, distal and slowly progressive, absent bulbar involvement, conduction block on NCS
Autoimmune and paraneoplastic	e.g., stiff person’s syndrome: GAD, amphiphysin, gephyrin antibodies, EMG differences
HIV, HTLV1	HIV: History, sensory neuropathy, opportunistic infections
Parsonage-Turner syndrome (or brachial neuritis)	Preceded by pain, preceding vaccination/viral illness, process arrests and followed by recovery, usually upper limb
Inclusion body myositis	Distribution - forearm and quadriceps, raised CK, muscle biopsy
Hirayama’s disease	Upper limb, young males from Asia, unilateral, may arrest after a few years
Radiation-induced motor neuropathies	History and distribution of radiotherapy
Kennedy’s disease	Family history (X-linked), gynecomastia
Spinal muscular atrophy	Only affects lower MNs
Primary progressive multiple sclerosis	MRI and/or cerebrospinal fluid (oligoclonal bands)
Adrenoleucodystrophy	Family history (X-linked), adult onset, slowly progressive, usually have sensory ataxia and sphincteric involvement
Hexosaminidase A deficiency	Family history, dystonia, ataxia, psychosis
Poliomyelitis or post-polio syndrome	Clinical history and NCS/EMG
Hereditary spastic paraparesis	Family history and genetic testing

Cu: Copper; CIDP: Chronic inflammatory demyelinating polyneuropathy; NCS: Nerve conduction studies; IVIG: Intravenous immunoglobulin; GAD: Glutamic acid decarboxylase; EMG: Electromyography; HIV: Human immunodeficiency virus; HTLV: Human T-cell lymphotropic virus; MRI: Magnetic resonance imaging; CK: Creatinine kinase.

Table 2 Motor neuron disease subtypes, discriminating features and possible differential diagnoses

MND subtype	Clinical features	Possible differential diagnoses
ALS	Affect both upper MNs and lower MNs	Cervical myeloneuropathy
	Onset 50 or 60 s	HIV
	Median survival 3 to 5 yr
PLS	Only affect upper MNs 3 yr from onset	Cervical myelopathy
	Onset 50 s	Nutritional (B12 or Cu deficiency)
	Profound spasticity	Primary progressive multiple sclerosis
	Progressive quadriparesis	Hereditary spastic paraparesis
	Late cranial nerve involvement	Stiff person syndrome
	Rarely bulbar onset	Tropical spastic paraparesis (HTLV1)
	Slow progression	Adrenomyeloneuropathy
	Median survival 5 to 10 yr	Hexosaminidase A deficiency
		Corticobasal degeneration
PMA	Only affect upper MNs 3 yr from onset	Benign fasciculations
	Focal asymmetric distal weakness, followed by proximal involvement	Post-polio syndrome
	Late bullar/respiratory involvement	Adult onset spinal muscular atrophy
	Earlier onset than ALS	Inclusion body myositis
	Raised CK (< 10 × normal)
	Median survival 3 to 5 yr

HIV: Human immunodeficiency virus; Cu: Copper; CK: Creatinine kinase; ALS: Amyotrophic lateral sclerosis; PLS: Primary lateral sclerosis; HTLV: Human T-cell lymphotropic virus; PMA: Progressive muscular atrophy.