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.