Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurones.

• Incidence is 2 per 100,000, with onset at 55 to 65 years, male predominance 1.5:1.

• 10% familial: C9orf72 repeat expansion (commonest), SOD1, TARDBP, FUS. Frontotemporal dementia in up to 50% (cognitive or behavioural change).

• Median survival is 2 to 4 years from onset, with death from respiratory failure.

• Forms: limb onset (70%), bulbar onset (25%), respiratory onset.

• Asymmetric limb weakness, wasting, fasciculations, cramps (lower motor neurone); spasticity, hyperreflexia, Babinski sign (upper motor neurone).

• Bulbar: dysarthria, dysphagia, tongue fasciculation, sialorrhoea, pseudobulbar affect.

• Respiratory: orthopnoea, morning headache, dyspnoea.

• Sensory examination and eye movements and sphincters are preserved.

• Clinical diagnosis (Gold Coast criteria): progressive upper and lower motor neurone signs in one or more regions, supported by EMG (active denervation and chronic reinnervation in multiple regions).

• MRI brain and spine to exclude cervical myelopathy, structural lesions; nerve conduction studies to exclude multifocal motor neuropathy with conduction block.

• Blood: CK, TSH, B12, anti-GM1, paraprotein, HIV, Lyme, heavy metals as indicated. Neurofilament light chain supportive.

• Genetic testing (C9orf72, SOD1, TARDBP, FUS) in familial cases and offered to all.

• Baseline forced vital capacity, sniff nasal pressure, swallowing assessment, ALSFRS-R scale.

• Riluzole 50 mg twice daily (extends survival by 2 to 3 months); monitor liver tests.

• Edaravone 60 mg IV daily for 10 days then 10 of 14 days monthly, or oral 105 mg daily.

• Tofersen 100 mg intrathecal (28 mg loading doses) for SOD1 mutation.

• Multidisciplinary clinic care improves survival: nutrition (gastrostomy at weight loss over 10% or FVC above 50%), non invasive ventilation (FVC under 50% or symptomatic hypoventilation), cough assist.

• Symptoms: sialorrhoea (glycopyrronium 1 mg three times daily, botulinum toxin to salivary glands), cramps (baclofen, quinine alternatives), spasticity (baclofen 5 to 20 mg), pseudobulbar affect (dextromethorphan/quinidine 20/10 mg twice daily).

• Communication aids early, occupational therapy, wheelchair and orthoses.

• Advance care planning and palliative care (morphine 2.5 mg for dyspnoea, midazolam).