[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Motor neuron diseases

# Motor neuron diseases

- Lesion

Motor neuron diseases kill the nerve cells that move muscles; ALS takes both upper and lower motor neurons and causes progressive paralysis.

Updated Nov 12, 2026

## Key points

- ALS: mixed upper (spasticity, brisk reflexes, Babinski) and lower (weakness, atrophy, fasciculations) motor neuron signs; sensation, eye movements and sphincters spared.
- Pathology: loss of anterior horn cells, pale lateral corticospinal tracts, thin anterior roots, grouped atrophy in muscle; TDP-43 inclusions in most cases.
- Bunina bodies: small eosinophilic inclusions in surviving motor neurons.
- Kennedy disease: X-linked CAG expansion in the androgen receptor; slow lower motor neuron weakness, gynecomastia, testicular atrophy.
- Spinal muscular atrophy: SMN1 deletion, autosomal recessive; the floppy infant (type 1) to milder adult forms; SMN2 copies modify severity.

## What it is

Motor neuron diseases are degenerations of the neurons that control skeletal muscle. Amyotrophic lateral sclerosis destroys upper motor neurons in the motor cortex and lower motor neurons in the brainstem and anterior horns, sparing sensation, and is usually fatal within a few years from respiratory failure. Most cases are sporadic; familial ones involve C9orf72, SOD1, TARDBP or FUS. Kennedy disease is an X-linked polyglutamine disorder of lower motor neurons, and spinal muscular atrophy is a recessive disease of infancy and childhood caused by SMN1 loss.

## Step by step

- Genetic or sporadic triggers disturb RNA processing or protein handling (TDP-43, SOD1).
- Motor neurons, large and long, accumulate damage; glutamate toxicity and glia add injury.
- Upper motor neurons die and the lateral corticospinal tracts degenerate.
- Lower motor neurons die; muscles lose innervation, twitch and waste.
- Breathing muscles weaken, causing respiratory failure.

## Motor neuron diseases compared

| Disease | Neurons | Genetics | Clue |
| --- | --- | --- | --- |
| [ALS](https://durgical.com/en/conditions/amyotrophic-lateral-sclerosis/) | Upper and lower | Mostly sporadic; C9orf72, SOD1, TARDBP, FUS | TDP-43 inclusions; often with FTD |
| Kennedy disease | Lower (and dorsal root ganglia) | X-linked, CAG in androgen receptor | Gynecomastia, men only |
| [Spinal muscular atrophy](https://durgical.com/en/conditions/spinal-muscular-atrophy/) | Lower | Autosomal recessive, SMN1 loss | Infant hypotonia, tongue fasciculations |
| [Poliomyelitis (acquired)](https://durgical.com/en/conditions/poliomyelitis-and-acute-flaccid-paralysis/) | Lower | Viral | Asymmetric, acute |

## Clinical notes

- ALS often begins with asymmetric hand weakness or bulbar symptoms such as dysarthria and dysphagia.
- Gene-directed therapies have changed the outlook of spinal muscular atrophy.

## Memory aid

ALS takes the top and the bottom of the motor chain and leaves feeling, eyes and bladder alone.

## Test yourself

Think of the answer, then tap the question to see it.

## Which neurons are lost in ALS?

Both upper motor neurons in the motor cortex and lower motor neurons in the brainstem and spinal anterior horns.

## Which gene is deleted in spinal muscular atrophy?

SMN1 (survival motor neuron 1); the number of SMN2 copies modifies severity.

## What is the genetic cause of Kennedy disease?

An X-linked CAG repeat expansion in the androgen receptor gene.

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## Elsewhere in DurgiPedia

- [Upper versus lower motor neuron lesions](https://durgical.com/en/physiology/upper-versus-lower-motor-neuron-lesions/)
- [Motor cortex and the corticospinal tract](https://durgical.com/en/physiology/motor-cortex-and-the-corticospinal-tract/)
- [Upper vs lower motor neuron syndrome](https://durgical.com/en/clinical-exam/upper-vs-lower-motor-neuron-syndrome/)

## Connections

## Related 5

- [Neurodegeneration: the protein table](https://durgical.com/en/general-pathology/neurodegeneration-the-protein-table/)
- [Frontotemporal lobar degeneration](https://durgical.com/en/general-pathology/frontotemporal-lobar-degeneration/)
- [Poliomyelitis and rabies](https://durgical.com/en/general-pathology/poliomyelitis-and-rabies/)
- [Nonclassic inheritance: repeat expansions, mitochondrial genes, imprinting, mosaicism](https://durgical.com/en/general-pathology/nonclassic-inheritance-repeat-expansions-mitochondrial-genes-imprinting-mosaicis/)
- [Reading a muscle biopsy: neurogenic vs myopathic](https://durgical.com/en/general-pathology/reading-a-muscle-biopsy-neurogenic-vs-myopathic/)

## Related conditions 4

- [Amyotrophic lateral sclerosis](https://durgical.com/en/conditions/amyotrophic-lateral-sclerosis/)
- [Spinal muscular atrophy](https://durgical.com/en/conditions/spinal-muscular-atrophy/)
- [Frontotemporal dementia](https://durgical.com/en/conditions/frontotemporal-dementia/)
- [Poliomyelitis and acute flaccid paralysis](https://durgical.com/en/conditions/poliomyelitis-and-acute-flaccid-paralysis/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Amyotrophic lateral sclerosis: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/amyotrophic-lateral-sclerosis/) (MedlinePlus, US National Library of Medicine, 2026); [Spinal muscular atrophy: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy/) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/general-pathology/motor-neuron-diseases/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/motor-neuron-diseases/