Medicine chapters
Motor neurone disease (amyotrophic lateral sclerosis)
Motor neurone disease is a progressive degeneration of upper and lower motor neurones that causes wasting, fasciculation and spasticity with no sensory loss; riluzole and supportive care are the treatment.
- Motor neurone disease (MND/ALS) destroys upper and lower motor neurones in the cortex, brainstem and spinal cord, giving wasting and fasciculation alongside brisk reflexes and extensor plantars.
- Sensation, eye movements and sphincters are spared, which separates it from most mimics.
- Diagnosis is clinical with EMG support; riluzole (glutamate release inhibitor) adds a few months; NIV and gastrostomy support survival, which is usually under 3–5 years.
On this page
Overview
Motor neurone disease (MND), called amyotrophic lateral sclerosis (ALS) in many countries, is a relentless degeneration of motor neurones in the motor cortex, brainstem motor nuclei and anterior horns of the spinal cord. It causes weakness with a mixture of upper and lower motor neurone signs and no sensory loss.
It is uncommon (about 2 per 100 000 a year), presents mostly between 50 and 75, and is slightly commoner in men below 70. Death, usually from respiratory failure or aspiration, follows within a few years.
Pathogenesis
- Usually sporadic, cause unknown.
- Glutamate excitotoxicity and oxidative damage are implicated (the basis for riluzole).
- Hallmark: ubiquitinated inclusions of TDP-43 (and FUS) in motor neurones.
- Familial in 5–10%: mutations in SOD1 (superoxide dismutase, an antioxidant enzyme), TDP-43, FUS, and a hexanucleotide repeat expansion in C9orf72 on chromosome 9 (the commonest familial cause, linked with MND-frontotemporal dementia overlap).
- About 5% develop frontotemporal dementia and up to 40% have milder frontal (executive) impairment.
Clinical features
Upper and lower motor neurone signs together
| Lower motor neurone (anterior horn, brainstem nuclei) | Upper motor neurone (corticospinal, corticobulbar) |
|---|---|
| Weakness and wasting | Weakness |
| Fasciculation (visible twitching) | Spasticity |
| Cramps | Brisk reflexes, clonus |
| Reduced tone | Extensor plantars, brisk jaw jerk |
A brisk reflex in a wasted, fasciculating limb is the classic MND sign. Few other diseases give UMN and LMN signs in the same segment without sensory loss.
Fasciculations arise because surviving axons sprout to take over denervated muscle fibres, forming large motor units that fire spontaneously.
What is spared
- Sensation (no numbness or pain from the disease itself).
- Eye movements (until very late).
- Bladder and bowel sphincters (usually).
- Cerebellar function.
Sensory symptoms or sphincter disturbance early on point away from MND, towards cervical myelopathy, B12 deficiency or a cord lesion.
Clinical patterns
| Type | Neurones affected | Features |
|---|---|---|
| Amyotrophic lateral sclerosis (commonest) | UMN + LMN | Asymmetric limb weakness and wasting (often one hand: "split hand"), fasciculation, brisk reflexes; spreads to other limbs and trunk |
| Progressive bulbar palsy (about 20% at onset) | Lower cranial nuclei ± their UMN | Dysarthria, dysphagia, nasal regurgitation, choking; wasted, fasciculating tongue |
| Progressive muscular atrophy | LMN only | Wasting, weakness, fasciculation spreading from one limb |
| Primary lateral sclerosis (rare, 1–2%) | UMN only | Slow spastic tetraparesis and pseudobulbar palsy; best prognosis |
These patterns usually merge as the disease advances.
Bulbar versus pseudobulbar palsy
| Feature | Bulbar (LMN) | Pseudobulbar (UMN) |
|---|---|---|
| Tongue | Wasted, fasciculating, flaccid | Small, stiff, slow, no fasciculation |
| Jaw jerk | Normal or absent | Brisk |
| Speech | Nasal, slurred | Slow, strained ("hot potato") |
| Emotion | Normal | Emotional lability (inappropriate laughing or crying) |
| Causes | MND, Guillain-Barré, myasthenia, syringobulbia | MND, bilateral strokes, multiple sclerosis |
MND is notable because it can cause both together (mixed bulbar palsy).
"MND: Motor Not Daily-sensation": everything motor, nothing sensory, eyes and sphincters spared.
Investigations
There is no single diagnostic test; the diagnosis is clinical and the work-up excludes mimics.
- EMG: widespread denervation (fibrillation and fasciculation potentials, large motor units), including in clinically normal muscles.
- Nerve conduction: sensory conduction normal; no conduction block (which would suggest multifocal motor neuropathy).
- MRI of the brain and cervical spine: to exclude compression (cervical spondylotic myelopathy) and other structural causes.
- Bloods: CK (may be mildly raised), B12, thyroid function, calcium, serum protein electrophoresis; anti-GM1 antibodies if multifocal motor neuropathy is suspected.
- Respiratory function: forced vital capacity to monitor and time ventilation.
EMG showing widespread denervation with normal sensory nerve conduction is the key supportive test; MRI of the cervical spine excludes the commonest mimic.
Mimics to exclude
| Mimic | Distinguishing feature |
|---|---|
| Cervical spondylotic myelopathy/radiculopathy | Neck pain, sensory signs, sphincter change; MRI shows compression |
| Multifocal motor neuropathy | Pure LMN, conduction block, anti-GM1; responds to IVIG (treatable) |
| Vitamin B12 deficiency | Sensory loss (vibration, proprioception), absent ankle jerks |
| Myasthenia gravis (bulbar) | Fatigable weakness, ptosis, eye muscles involved; no wasting |
| Kennedy disease (X-linked bulbospinal atrophy) | Men, gynaecomastia, sensory neuropathy |
| Thyrotoxicosis, lead poisoning, post-polio syndrome | History and tests |
Management
No treatment stops the disease. Care is multidisciplinary and palliative from early on.
- Riluzole: inhibits presynaptic glutamate release (sodium channel blocker); slows progression slightly and prolongs survival by about 3–4 months. Monitor liver enzymes and blood count.
- Breathing: non-invasive ventilation for respiratory muscle weakness improves survival and quality of life.
- Nutrition: gastrostomy (PEG or radiologically inserted) when swallowing is unsafe or weight falls; best done before respiratory function is too poor.
- Symptoms: drooling (anticholinergics such as hyoscine or amitriptyline), cramps, spasticity (baclofen), emotional lability, pain, depression.
- Communication aids, physiotherapy, occupational therapy, speech and language therapy.
- Advance care planning and palliative care; opioids and benzodiazepines for breathlessness and distress at the end of life.
Riluzole works by reducing glutamate release; it is the standard disease-modifying drug but adds only a few months.
Prognosis
- Relentlessly progressive. Survival beyond 3 years is unusual; a few live for a decade or more.
- Bulbar onset and older age carry a worse prognosis; primary lateral sclerosis and pure LMN forms are slower.
The name explains the signs: "amyotrophic" means muscle wasting from anterior horn cell loss (LMN), and "lateral sclerosis" means scarring of the lateral corticospinal tracts (UMN). Neither part involves sensory pathways.
Expect: a vignette of wasting and fasciculation with brisk reflexes and extensor plantars and normal sensation (MND); which functions are spared (sensation, eye movements, sphincters); the investigation that supports it (EMG showing denervation); riluzole and how it works (reduces glutamate release); the four clinical patterns, especially progressive bulbar palsy with a fasciculating tongue; bulbar versus pseudobulbar palsy; mimics such as cervical myelopathy and multifocal motor neuropathy with conduction block; cause of death (respiratory failure).
Quick revision
- MND = UMN + LMN degeneration; no sensory loss; eyes and sphincters spared.
- Classic sign: brisk reflexes in wasted, fasciculating muscles; extensor plantars.
- Types: ALS (commonest), progressive bulbar palsy, progressive muscular atrophy (LMN only), primary lateral sclerosis (UMN only).
- Pathology: TDP-43 inclusions; familial 5–10% (SOD1, C9orf72 with FTD overlap).
- EMG shows denervation; sensory nerve conduction normal; MRI spine to exclude myelopathy.
- Riluzole (anti-glutamate) adds a few months; NIV and gastrostomy support survival.
- Death from respiratory failure or aspiration, usually within 3–5 years.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Does motor neurone disease cause numbness?
No. Sensory pathways are spared, so prominent sensory loss suggests a different diagnosis such as cervical myelopathy or B12 deficiency.
How does riluzole work in MND?
It reduces the release of glutamate from nerve endings, lessening excitotoxic damage; it slows progression only slightly, by a few months.
What is the commonest cause of death in MND?
Respiratory failure from weakness of the breathing muscles, often with aspiration pneumonia from bulbar weakness.
Why is multifocal motor neuropathy important to exclude?
It can look like lower motor neurone MND but shows conduction block on nerve studies and responds to intravenous immunoglobulin, so it is treatable.