Definition
Progressive degeneration of upper and lower motor neurones in the cortex, brainstem and spinal cord. Amyotrophic lateral sclerosis is the commonest form.
Epidemiology
- Incidence about 2 per 100,000 per year
- Peak onset between 50 and 70 years, with a slight male excess
- Familial disease in about 10%, with C9orf72 and SOD1 mutations
Classification
- Amyotrophic lateral sclerosis, with mixed upper and lower motor neurone signs
- Progressive muscular atrophy, lower motor neurone only
- Primary lateral sclerosis, upper motor neurone only
- Progressive bulbar palsy
- Revised El Escorial criteria grade diagnostic certainty
Clinical Features
- Painless asymmetric weakness, often starting in one hand or foot
- Wasting and fasciculation with brisk reflexes in the same limb
- No sensory loss, with sphincters spared
- Split hand sign, with thenar and first dorsal interosseous wasting sparing the hypothenar muscles
- Foot drop that mimics L5 radiculopathy or common peroneal palsy
- Dysarthria, dysphagia and tongue fasciculation in bulbar onset
Investigations
- EMG shows denervation in several body regions
- Nerve conduction studies exclude multifocal motor neuropathy with conduction block
- MRI cervical spine excludes compressive myelopathy
- Creatine kinase may be mildly raised
Differential Diagnosis
- Cervical myelopathy, the commonest mimic
- Radiculopathy
- Cubital tunnel syndrome with isolated hand wasting
- Multifocal motor neuropathy, which responds to immunoglobulin
- Inclusion body myositis
- Kennedy disease
Management
- Multidisciplinary care. Improves survival and quality of life
- Riluzole. Modest survival gain of a few months
- Non invasive ventilation. Improves survival in respiratory failure
- Orthoses. Ankle foot orthosis for foot drop and wrist splints for hand weakness
- Avoid unnecessary decompression. Spinal surgery does not alter the disease course
Prognosis
- Median survival 2 to 4 years from symptom onset
- Respiratory failure is the usual cause of death
References
- Hardiman O, Al-Chalabi A, Chio A, Corr EM, Logroscino G, Robberecht W, Shaw PJ, Simmons Z, van den Berg LH. Amyotrophic lateral sclerosis. Nat Rev Dis Primers. 2017, 3, 17071. PubMed
- Brooks BR, Miller RG, Swash M, Munsat TL. El Escorial revisited. Revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000, 1(5), 293-9. PubMed
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 19 October 2026.