Amyotrophic Lateral Sclerosis

This article provides a comprehensive overview of Amyotrophic Lateral Sclerosis (ALS), a degenerative motor neuron disease characterized by symptoms like hyperreflexia, spasticity, and limb weakness. It emphasizes the need for a multidisciplinary management approach involving various healthcare professionals. The article details treatments like riluzole, edaravone, and investigational therapies, along with their dosages and side effects. It also discusses experimental therapies, symptom management strategies for respiratory issues, dysphagia, muscle spasms, fatigue, and pseudobulbar affect, and underscores the importance of palliative and hospice care.

Amyotrophic Lateral Sclerosis Overview

ALS is a degenerative motor neuron disease with both upper and lower motor neuron symptoms and signs. The upper motor neuron features include hyperreflexia and spasticity, while the lower motor neuron signs include atrophy and fasciculation. Asymmetric limb weakness is the most common presentation of the disease. ALS causes impairment affecting limbs, bulbar, axial and respiratory muscles (life threatening). Also, patients may have cognitive impairment related to frontotemporal dementia (FTD). The median survival of ALS is three to five years.

Multidisciplinary Management Approach

Multidisciplinary approach for management is required. It includes neurologists, physical therapists, occupational therapists, speech therapists, respiratory therapists, dieticians and social workers. Treatment includes disease modifying agents, investigational therapy and symptom management.

Disease-Modifying Treatments

Disease modifying treatment could slow down the progression of the disease. They include riluzole (50 mg twice daily), edaravone (60 mg is by intravenous infusion over 60 minutes. Treatment is started with daily infusion for 14 days, followed by 14 days off treatment. Subsequent treatment cycles involve daily edaravone 60 mg infusions on 10 days within a 14- day period, followed by 14 days off treatment). The most common adverse effects of riluzole are asthenia, dizziness, gastrointestinal disorders, and elevations in liver enzyme activities. Liver function tests are indicated monthly for the first three months of riluzole treatment and every three months thereafter. Edaravone could cause injection site contusion, gait disturbance and/ or headache.

Experimental Therapies

New experimental therapies for ALS include Antisense oligonucleotide therapy and ravulizumab (long acting C5 complement inhibitor) are still under investigation.

Symptom Management Strategies

Symptom management is directed to respiratory symptoms, dysphagia, muscle spasm, fatigue, and/ or pseudobulbar affect. Patients with ALS should have serial assessment of respiratory function with forced vital capacity (FVC) every three months starting at the time of diagnosis. A decrease to <25-30% of predicted is associated with significant risk of respiratory failure or sudden death. Noninvasive positive pressure ventilation (NPPV) is the standard of care for patients with respiratory insufficiency. Invasive mechanical ventilation might be considered and has to be discussed carefully with attention to the full burdens and benefits to the patient. Additionally, discussions with patients should include the option to stop the ventilation at any time Dysphagia increases the risk for insufficient caloric intake and worsening of fatigue. Initial management of dysphagia includes modification of food and fluid consistency. In addition, nutritional supplementation using PEG may be helpful for stabilising weight loss. Muscle spasms can cause severe pain and discomfort. Nonpharmacological measures include stretching and massage . Also, mexiletine 150 mg daily, levetiracetam (500 mg daily) could help. Fatigue is very common in ALS. Modafinil 100 mg daily could be beneficial. Other treatment options for fatigue include glucocorticoids (a two- week trial of dexamethasone 8 mg daily) and megasterol acetate (400 - 800 mg daily). Pseudobulbar affect (emotional liability) which result from bilateral corticobulbar tract degeneration. Treatment options for pseudobulbar affect include the combination of dextromethorphan/ quinidine (20 mg/ 10mg at a starting dose of one capsule daily for seven days, then increase to one capsule twice daily). Also, amitriptyline 10- 25 mg at bedtime, fluvoxamine 100 mg daily could benefit.

Palliative Care and End-of-Life Considerations

Finally, palliative care is required in the course of the disease and referral to hospice care is advised in the terminal phase of ALS. A discussion of advance directives should be initiated early in the disease.

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