Management of Amyotrophic Lateral Sclerosis (ALS)
Pathogenesis and Epidemiology
ALS is a relentlessly progressive neurodegenerative disease characterized by degeneration of both upper and lower motor neurons in the brain and spinal cord, leading to progressive muscle weakness, paralysis, and typically death within 3-5 years of symptom onset. 1
Pathophysiological Mechanisms
The disease involves progressive degeneration of both upper motor neurons and lower motor neurons along the corticospinal tracts, representing the most common motor neuron disease at approximately 85% of all motor neuron disease cases 1
The etiology is multifactorial, involving increased oxidative stress, glutamate toxicity, mitochondrial dysfunction, inflammation, and apoptosis 1
The primary pathological process is progressive axonal degeneration and death of motor neurons themselves and their axons, not a demyelinating disease 1
Approximately 90% of ALS cases are sporadic without a known genetic mutation 2
Epidemiology and Prognosis
Mean survival is 3-5 years after symptom onset, with only 5-10% of patients living longer than 10 years 1
Bulbar-onset ALS has significantly worse outcomes compared to spinal-onset, with median survival of 28 months versus 44 months for spinal-onset patients with dysphagia 2
Respiratory failure due to respiratory muscle weakness is the most common cause of death 1
Aspiration pneumonia occurs in 11.4-13% of bulbar ALS cases and represents a leading cause of mortality 2
Clinical Presentation and Progression
Motor Neuron Signs
Classical ALS presents with mixed upper and lower motor neuron signs: upper motor neuron signs include hypertonicity and hyperreflexia, while lower motor neuron signs include muscle fasciculations, weakness, and atrophy 1
Approximately 80% of patients with bulbar-onset ALS develop dysarthria and dysphagia 1
Cognitive Impairment
- Up to 40% of patients with ALS have evidence of cognitive impairment, which may affect treatment decisions and compliance 1
Disease-Modifying Pharmacotherapy
Three FDA-approved disease-modifying treatments are currently available: riluzole, edaravone, and sodium phenylbutyrate/taurursodiol, all offering modest effects on disease progression. 3, 4
Riluzole
Riluzole is FDA-approved for the treatment of ALS and was the first drug approved in 1995, offering only modest survival benefit 5, 6
This neuroprotective agent targets glutamatergic mechanisms 6
Edaravone
Edaravone injection is FDA-approved for the treatment of ALS, administered as 60 mg intravenous infusion over 60 minutes 7
The dosing schedule consists of an initial treatment cycle with daily dosing for 14 days followed by a 14-day drug-free period, then subsequent treatment cycles with daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods 7
Edaravone has been shown to slow down the loss of physical function in ALS patients by 33% compared to placebo 8
As a potent free radical scavenger, it prevents oxidative stress from inducing motor neuron death and inhibits nitration of tyrosine residues in the cerebrospinal fluid 8
Contraindication: Patients with a history of hypersensitivity to edaravone or any inactive ingredients should not receive this medication 7
Critical warning: Edaravone injection contains sodium bisulfite, which may cause allergic-type reactions, including anaphylactic symptoms and asthmatic episodes in susceptible people 7
Sodium Phenylbutyrate/Taurursodiol
- This combination therapy has shown significant slowing of disease progression and prolonged survival 6
Multidisciplinary Care Framework
Multidisciplinary care is essential for improving survival and quality of life, and should include neurology, pulmonology, gastroenterology, speech-language pathology, nutrition, physical therapy, occupational therapy, social work, and palliative care from the time of diagnosis. 2
- There is considerable evidence that multidisciplinary care improves both survival and quality of life in ALS 1
Respiratory Management
Initiate non-invasive ventilation (NIV) when forced vital capacity (FVC) falls below 80% of normal with symptoms, FVC <50% predicted, or evidence of sleep-disordered breathing. 2
Use bilevel positive airway pressure (BPAP) with backup respiratory rate for patients with bulbar impairment 2
Respiratory assist device (RAD) placement should occur before FVC falls below 50% of predicted 2
Nutritional Management
Assessment and Monitoring
Conduct nutritional status assessment (BMI, weight loss) every 3 months to detect early malnutrition 2
All patients with suspected bulbar dysfunction require swallow screening before initiating oral intake; those with positive screening require videofluoroscopy swallowing study (VFSS) 2
Dysphagia Management
For dysphagia, adapt food texture to facilitate swallowing, implement chin-tuck postural maneuvers, and use thicker liquids and semisolid foods with high water content instead of thin liquids. 2
Modification of food texture (soft, semisolid or semiliquid states) is often required to compensate for a poor oral preparation phase and ease oral and pharyngeal transport while avoiding episodes of choking 9
The chin-tuck posture proved to be useful in the majority of cases, offering a valuable protection mechanism for the airways by opening the valleculae and preventing penetration into the larynx 9
Head rotation is indicated in the case of hypertonicity, incomplete release or premature UES closure 9
Hyperextended head posture is indicated in the absence of lingual pump only if safe transit is ensured 9
In cases of penetration without aspiration into the laryngeal inlet (23% of patients), throat clearing every three to four swallowing acts can prevent possible postswallowing inhalation 9
Important caveat: Both the oral as well as the pharyngeal stage of swallowing may be compromised in 97% of ALS patients, and aspiration can be present in 22% of patients even without clinical aspiration signs or subjective complaints 9
Nutritional Supplementation
Patients who experience appreciable levels of fatigue should be advised to eat their food as several small meals a day, with dietetic counseling focusing on meal enrichment by use of high-calorie foods 9
Nutritional supplementation is recommended for ALS patients who do not cover their nutritional requirements with an enriched diet, though there is insufficient data to affirm that oral nutritional supplementation can improve survival 9
In case of constipation caused by abdominal weakness, dietary fiber can be added to the diet 9
Enteral Nutrition
Percutaneous endoscopic gastrostomy (PEG) placement should occur before respiratory function significantly deteriorates, ideally when FVC remains >50% of predicted 2
Enteral nutrition (tube feeding) is preferred over parenteral nutrition for ALS patients requiring nutritional therapy 10
Parenteral nutrition should only be considered in acute settings when enteral nutrition is contraindicated or not feasible 10
Home parenteral nutrition is generally not indicated in ALS patients due to high complication rates (3.11 per 1000 catheter days) 10
Management of Sialorrhea
- Anti-muscarinic therapy or botulinum toxin A can be used to manage sialorrhea, though no evidence has been found to link the treatment of saliva problems with the improvement of dysphagia 9
Physical Activity
Low to moderate physical activity should be advised as long as it doesn't worsen the patient's condition, as some evidence suggests that endurance and resistance exercises may slow disease progression and improve functionality and quality of life 10
Avoid excessive physical exertion that could lead to fatigue and worsen symptoms 10
Palliative Care Integration
A palliative care approach must be adopted from the time of diagnosis, not reserved for end-stage disease, with early referral to palliative services essential because speech and communication become severely limited in later stages. 2, 1
Initiate end-of-life discussions at specific trigger points: presence of patient distress, evolution of disease, or expressed desire of the patient to discuss these issues 2
Advance care planning should be initiated early, including discussions about advance directives, ventilatory support, feeding tubes, and end-of-life care 1
Critical pitfall: Late referral to palliative services is common and negatively impacts quality of life; however, access to assistive equipment might sometimes be limited once the patient formally receives palliative care, highlighting the need for early integration of palliative care into larger multidisciplinary care 1
Implement structured caregiver support including counseling, support groups, and crisis management systems, as behavioral deficits in ALS have significant negative impact on caregivers' quality of life 1
Symptomatic Management
- Symptomatic treatments address common symptoms including anxiety, depression, emotional lability (pseudobulbar affect), fasciculations, fatigue, insomnia, muscle cramps or spasms, musculoskeletal pain due to immobility, neuropathic type pain, excessive salivation (sialorrhea), spasticity, constipation, and urinary urgency 4