Amyotrophic Lateral Sclerosis Differential Diagnoses

Updated: Aug 18, 2023
  • Author: Carmel Armon, MD, MSc, MHS; Chief Editor: Nicholas Lorenzo, MD, CPE, MHCM, FAAPL  more...
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Diagnostic Considerations

At times, the early presentation of several other neurologic conditions may overlap that of amyotrophic lateral sclerosis (ALS). Appropriate evaluation can exclude these alternatives and confirm the diagnosis of ALS. Fully expressed ALS usually cannot be mistaken for any other disorder.

For patients with a new focal presentation, the differential diagnoses by region include the following:

  • Upper motor neuron (UMN) bulbar signs: Brainstem lesions including syrinx, mass, stroke, and demyelinating forms of other degenerative diseases

  • Lower motor neuron (LMN) bulbar signs: Cranial nerve palsies

  • Limb UMN signs: Cervical myelopathy, cord tumor, hereditary spastic paraparesis, transverse myelopathy, HIV-related myelopathy, syrinx

  • Limb LMN signs: Radiculopathy, plexopathy, neuropathy

Differential diagnoses for patients with more advanced disease most commonly include the following:

If the onset is rapid (over hours, days or a few weeks), consider disorders such as myasthenia gravis, Guillain-Barré syndrome, acute motor axonal neuropathy, West Nile virus, and botulism.

Other problems to consider, as appropriate, include the following:

  • Acute viral infections involving motor neurons: Coxsackie, West Nile, and herpes zoster viruses; polio

  • Brainstem syndromes

  • Cervical disk syndromes

  • Paraneoplastic neuropathy

  • Tay-Sachs/GM2 gangliosidosis disease (late onset)

  • Central nervous system tumors

  • Lead intoxication

  • Mercury poisoning

  • Copper deficiency myelopathy

  • Motor neuropathies

  • Multifocal acquired demyelinating neuropathy

  • Monomelic amyotrophy

  • Myopathies

  • Spinal cord arteriovenous malformation

  • Monoclonal gammopathies

  • Lymphoma

  • Vasculitis

Differential Diagnoses