Amyotrophic lateral sclerosis Flashcards
what is the definition of ALS?
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, characterised by progressive muscle weakness that can start in limb, axial, bulbar, or respiratory muscles and then generalises relentlessly, causing progressive disability and ultimately death, usually from respiratory failure.
what is the epidemiology of ALS?
Mean age of onset is 57
More common in women under 70, same occurrence over 70
Higher incidence in white people
what is the aetiology of ALS?
Unknown, could be due to:
Glutamate toxicity - increased calcium entering neuronal cells causing dysfunction
Protein misfolding - foaming toxic oligomers
Oxidative stress - causing neuronal damage
Microglial activation - mutant SOD1 gene epressors may have altered protective mechanisms for nearby neurons
Mitochondrial dysfunction - mutant SOD1 in mitochondria causing damage through oxidative stress
Disrupted axonal transport - accumulation of neurofilament inclusions and slowing of transport
RNA metabolism - presence of TAR-DNA binding protein 43 pathology
what are the risk factors for ALS?
Genetic
Aged over 40
Military, athletic, cigarette, agricultural chemical exposure, lead exposure
what is the pathophysiology of ALS?
ALS is a neurodegenerative disorder, characterised by progressive loss of cortical (frontotemporal), bulbar (pons, medulla), and ventral cord motor neurons. After motor cell death, retrograde axonal degeneration follows, with subsequent denervation and reinnervation in corresponding muscles.
what are the key presentations of ALS?
Risk factors Upper extremity weakness Stiffness Poor coordination Spasic unsteady gait Painful muscle spasms Difficulties going up stairs Foot drop Stiffness and decreased balance Head drop Difficulties maintaining erect posture Muscle atrophy Increased lumbar lordosis Hyper-reflexias Dyspnoea Coughing or choking Strained slow speech Slurred nasal speech Limb onset (75%) Bulbar onset (20%) Respiratory onset (5%)
how is ALS diagnosed?
clinically, can use EMG (evidence of diffuse, ongoing, chronic denervation)
what are the differential diagnoses for ALS?
Cervical spondylitis
Multifocal motor neuropathy
Inclusion body myositis
how is ALS managed?
riluzole: 50 mg orally twice daily and end of life care, NIPPV or chronic invasive ventilation or palliative care for respiratory problems, carbocisteine: 2.25 g/day orally given in divided doses initially, reduce to 1.5 g/day as condition improves for difficulty expelling mucus, PEG tube or weight loss
how is ALS monitored?
Monitoring for respiratory decline (forced vital capacity) is recommended every 3 months. Monitoring for nutrition deficit (weight measurement) should be obtained at each clinic visit. In patients taking riluzole, monitoring for hepatotoxicity (liver function tests) and neutropenia (full blood count) should be done every month in the first 3 months and every 3 months afterwards.
what are the complications of ALS?
Resp failure, nutritional deficit, aspiration pneumonia
what is the prognosis of ALS?
ALS follows a progressive course without intervals of remissions, relapses, or stabilisation, causing progressive disability and ultimately death. The disease is highly variable between affected individuals in terms of clinical presentation and time course. Median survival is 3 to 5 years, but survival up to 10 years and even beyond (although rare at approximately 10% to 20%) has been reported.
