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.