Amyotrophic lateral sclerosis (in short)
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by
progressive muscular paralysis reflecting degeneration of motor neurones in the primary
motor cortex, corticospinal tracts, brainstem and spinal cord.
- Incidence (average
1.89 per 100,000/year) and prevalence (average 5.2 per100,000) are relatively uniform
in Western countries, although foci of higher frequency occur in the Western Pacific.
- The mean age of onset for sporadic ALS is about 60 years.
- Overall, there is a slight
male prevalence (M:F ratio~1.5:1).
- Approximately two thirds of patients with typical
ALS have a spinal form of the disease (limb onset) and present with symptoms related
to focal muscle weakness and wasting, where the symptoms may start either distally
or proximally in the upper and lower limbs.
- Gradually, spasticity may develop in the
weakened atrophic limbs, affecting manual dexterity and gait.
- Patients with bulbar
onset ALS usually present with dysarthria and dysphagia for solid or liquids, and
limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the
vast majority of cases will occur within 1–2 years.
- Paralysis is progressive and leads
to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5
years for limb onset ALS cases.
- Most ALS cases are sporadic but 5–10% of cases are
familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases.
- The diagnosis is based on clinical history,
examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease)
by appropriate investigations.
- The pathological hallmarks comprise loss of motor neurones
with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and
TDP-43 immunoreactive inclusions in degenerating lower motor neurones.
- Signs of upper
motor neurone and lower motor neurone damage not explained by any other disease process
are suggestive of ALS.
- The management of ALS is supportive, palliative, and multidisciplinary.
Non-invasive ventilation prolongs survival and improves quality of life.
- Riluzole (Rilutek, Riluzole Zentiva)
is the only drug that has been shown to extend survival.