Motor Neurone Disease
Stephen Hawking and the popular 'ice bucket challenge' have thrust this rare disease, annual incidence of 2/100,000, into the spotlight. It is characterised by progressive muscular weakness and eventual death, usually as a result of aspiration or respiratory failure.
The upper motor neurone axons (originating in the precentral gyrus) travel in the corticospinal and corticobulbar tracts to the brainstem and anterior horn of the spinal cord. Here they synapse directly with the lower motor neurones which innervate muscle fibres.
Autopsies of those with amyotrophic lateral sclerosis (ALS), the commonest form of MND, have shown atrophy of the precentral gyrus and the anterior horn cells. There have been no valid autopsy reports of other forms of MND.
Male:female - 2:1.
Average onset 5th-6th decade.
~10% of cases are familial.
|Onset||Symptoms||Signs||Form of MND|
|Commonly focal upper (then
lower) limb onset.
Weakness, stiffness and
cramping of hand.
Difficulty climbing stairs.
Fatigue when walking.
|Mixed UMN and LMN signs.||ALS|
|Mixed UMN (pseudobulbar)
and LMN (bulbar) signs:
|Progressive pseudobulbar and bulbar
|Small muscles of hands and
|Limb weakness.||LMN signs only (atrophy,
|Progressive muscular atrophy.|
|Slowly progressive tetraparesis
and pseudobulbar palsy.
|Lower limb weakness.
|UMN signs only (leg flexor weakness,
hypertonia, hyper-reflexia, upgoing
|Primary lateral sclerosis.|
There is no gold standard investigation. The Revised El Escorial Criteria is used to diagnose ALS. This criteria states that patients must have evidence of progressive UMN and LMN degenerative signs in the absence of electrophysiological or neuropathological evidence of other disease processes that may explain these signs.
The patient will be referred to neurology and it may take several months for a diagnosis to be made due to the severity of the prognosis. The average patient lives for 3 years.
The investigations are focused upon ruling out differential diagnoses. The following investigations may be useful:
- Electromyography - fibrillations (spontaneous action potentials produced as muscle fibres lose contact with innervating axon) and fasciculations (spontaneous depolarisation of a LMN causing synchronous muscle contractions)
- Blood tests - exclude Vitamin B12/folate deficiency, HIV, Lyme disease and other rare conditions.
- Muscle biopsy - exclude myopathies.
A multi-disciplinary approach to support the patient and their carers.
Riluzole (neuroprotective agent) is the only disease-modifying drug, increasing life expectancy by 2–4 months.
Symptomatic relief - analgesics, anti-cholinergics (reduce drooling), anti-spasticity agents and anti-depressants.
At later stages, enteral feeding.
NICE recommend the use of non-invasive ventilation as it significantly increases survival.
Refer to palliative care team.
The medial survival is 2–4 years.
The brainstem nuclei (cranial nerves III, IV and VI) and the sacral spinal cord are spared until late in ALS so patients have preserved eye movements, micturition and faecal continence.
90% of patients die in their sleep due to respiratory failure.