Amyotrophic Lateral Sclerosis (ALS) Differential Diagnoses

  • Author: Carmel Armon, MD, MSc, MHS; Chief Editor: Nicholas Lorenzo, MD   more...
 
Updated: Aug 26, 2011
 
 

Diagnostic Considerations

At times, the early presentation of several other neurological conditions may overlap that of amyotrophic lateral sclerosis (ALS). Appropriate evaluation (see Workup) 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 bulbar signs - Brainstem lesions including syrinx, mass, stroke, and demyelination forms or other degenerative diseases
  • Lower motor neuron bulbar signs - Cranial nerve palsies
  • Limb upper motor neuron signs - Cervical myelopathy, cord tumor, hereditary spastic paraparesis, transverse myelopathy, HIV-related myelopathy, syrinx
  • Limb lower motor neuron signs - Radiculopathy, plexopathy, neuropathy

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

If the presentation is rapid (hours, days or a few weeks), consider disorders such as myasthenia gravis and Guillain-Barré syndrome.

Other problems to consider include the following:

  • Acute viral infections involving motor neurons—polio, Coxsackie, and herpes zoster viruses
  • Brainstem syndromes
  • Cervical disk syndromes
  • Paraneoplastic neuropathy
  • Tay-Sachs/GM2 gangliosidosis disease (late onset)
  • Central nervous system tumors
  • Lead intoxication
  • Mercury poisoning
  • Motor neuropathies
  • Multifocal acquired demyelinating neuropathy
  • Monomelic Amyotrophy
  • Myopathies
  • Spinal cord AV malformation, monoclonal and disimmune gammopathies
  • Lymphoma
  • Vasculitis

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

Carmel Armon, MD, MSc, MHS  Professor of Neurology, Tufts University School of Medicine; Chief, Division of Neurology, Baystate Medical Center

Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, American Stroke Association, Massachusetts Medical Society, Movement Disorders Society, and Sigma Xi

Disclosure: Avanir Pharmaceuticals Consulting fee Consulting

Specialty Editor Board

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Neil A Busis, MD  Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside

Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD  Consulting Staff, Neurology Specialists and Consultants

Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, and American College of Physician Executives

Disclosure: Nothing to disclose.

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The 4 regions or levels of the body. Bulbar (muscles of the face, mouth, and throat); cervical (muscles of the back of the head and the neck, the shoulders and upper back, and the upper extremities); thoracic (muscles of the chest and abdomen and the middle portion of the spinal muscles); lumbosacral (muscles of the lower back, groin, and lower extremities).
Malignant biochemical transformation hypothesis. Risk factors operate up-stream to a putative malignant biochemical transformation, which causes the appearance of endogenous ALS-specific toxins. These putative toxins spread, behaving like a metastasizing biochemical malignancy, and cause the downstream biochemical, histologic and clinical consequences of ALS. (Adapted from Armon C. ALS: Clinical and Epidemiologic Clues to Pathogenesis. In: Neurobiology of ALS. Course Syllabus, 51st Annual Meeting. American Academy of Neurology, 1999.) The author has suggested that an acquired nucleic acid change (a somatic mutation) is the "malignant biochemical transformation" (Armon C. Acquired nucleic acid changes may trigger sporadic amyotrophic lateral sclerosis. Muscle Nerve. Sep 2005;32(3):373-7).
Muscle in nerve disease. Image courtesy of Dr. Friedlander, Associate Professor and Chair of Pathology at Kansas City University of Medicine and Biosciences.
Table 1. Familial Forms of ALS
GeneLocusProteinInheritance
ALS 121q22.1SOD1AD
ALS 22q33ALSINAR
ALS 318q21UnknownAD
ALS 49q34SETXAD
ALS 515q15UnknownAR
ALS 616q21UnknownAD
ALS 720ptel-p12UnknownAD
ALS 820q13.3VABPAD
ALS-FTD9q21-22UnknownAD
ALS-FTD9q21.3UnknownAD
ALS14q11.2AngiogeninAD
FTD 3CHMP2BAD
ALS 1TDP43AD
ALS2p13DynactinAD
AD –autosomal dominant; AR—autosomal recessive
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