Relationship Between ALS and MND
Motor neuron disease (MND) is an umbrella term for a group of neurodegenerative disorders affecting upper and/or lower motor neurons, while amyotrophic lateral sclerosis (ALS) is the most common specific type of MND, representing approximately 85% of all MND cases. 1
Terminology and Classification
MND serves as the broader diagnostic category, with ALS being the predominant subtype characterized by combined upper and lower motor neuron degeneration. 1 In the United Kingdom, the term "motor neuron disease" is often used interchangeably with ALS, though this is technically imprecise. 2
The MND Family Includes:
ALS (85% of cases): Degeneration of both upper motor neurons (in the motor cortex) and lower motor neurons (in the brainstem and spinal cord), producing hypertonicity, hyperreflexia, muscle weakness, atrophy, and fasciculations. 1, 3
Progressive Muscular Atrophy (PMA): Involves only lower motor neuron degeneration, causing progressive muscle weakness and atrophy without upper motor neuron signs (no hyperreflexia or spasticity). 1
Primary Lateral Sclerosis (PLS): Affects only upper motor neurons, resulting in spasticity and hyperreflexia without muscle atrophy or fasciculations. 1
Progressive Bulbar Palsy (PBP): A variant that primarily affects bulbar muscles first, causing dysarthria, dysphagia, and dysfunction of lower cranial nerves. 1
Pseudobulbar Palsy: Upper motor neuron dysfunction affecting the bulbar region, characterized by emotional lability, dysarthria, and dysphagia. 1
Key Distinguishing Features
Clinical Presentation Differences:
ALS presents with mixed signs: Both hypertonicity/hyperreflexia (upper motor neuron) AND muscle fasciculations/weakness/atrophy (lower motor neuron) occurring simultaneously. 1, 3
Other MND subtypes show isolated patterns: PMA shows only lower motor neuron signs, while PLS shows only upper motor neuron signs. 1
Sensory function remains intact across all MND variants, distinguishing them from peripheral neuropathies or spinal cord disorders. 3
Diagnostic Implications:
EMG findings differ: ALS demonstrates widespread denervation (fibrillation potentials, positive sharp waves) together with chronic reinnervation (large polyphasic motor units) across multiple body regions, confirming both upper and lower motor neuron involvement. 3, 4
The revised El Escorial criteria for ALS specifically require evidence of lower motor neuron signs, upper motor neuron signs, progressive spread, and absence of other disease processes. 1
Prognosis Variations
ALS carries a median survival of 3-4 years after symptom onset, with only 5-10% of patients surviving longer than 10 years. 5, 1, 3
Bulbar-onset ALS (25-35% of cases) has the shortest life expectancy, with approximately 80% developing dysarthria and dysphagia. 5, 4
Other MND variants may have different trajectories: PLS typically progresses more slowly than ALS, though some cases eventually evolve to show lower motor neuron involvement and are reclassified as ALS. 6
Clinical Pitfalls to Avoid
Do not assume all motor neuron presentations are ALS—the absence of combined upper and lower motor neuron signs should prompt consideration of alternative MND subtypes or mimics. 1 Approximately 90% of ALS cases are sporadic, while 10% are familial, often associated with mutations in genes such as C9orf72, SOD1, FUS, and TARDBP. 4, 7
Cervical spondylotic myelopathy is the most critical structural mimic because it can produce both upper and lower motor neuron signs and requires surgical decompression rather than ALS-directed therapy—MRI of the cervical spine without contrast is essential to exclude this. 4