What are the symptoms and treatment options for a patient with Amyotrophic Lateral Sclerosis (ALS)?

Symptoms and Treatment of Amyotrophic Lateral Sclerosis (ALS)

Clinical Presentation and Symptoms

ALS presents with progressive motor neuron degeneration causing muscle weakness, wasting, and spasticity, with two main onset patterns: bulbar (affecting speech and swallowing) or spinal/limb onset, where bulbar-onset carries significantly worse prognosis with median survival of 25-28 months versus 44 months for spinal-onset. 1

Motor Symptoms

• Progressive muscle weakness and atrophy affecting voluntary muscles throughout the body 2
• Spastic paralysis from upper motor neuron loss combined with flaccid weakness from lower motor neuron degeneration 2
• Fasciculations (muscle twitching) are characteristic 2
• The disease spares sensory, autonomic, and eye movement functions 2

Bulbar Symptoms

• Dysphagia (swallowing difficulty) progresses through 5 distinct stages, affecting food intake, increasing meal time, and causing fatigue 3
• Dysarthria (speech impairment) deteriorates over approximately 18 months from first bulbar symptom, with 60% of patients losing functional speech and requiring augmentative communication 4
• Sialorrhea (excessive drooling) due to impaired swallowing 1
• Nasal regurgitation 1

Respiratory Symptoms

• Progressive respiratory muscle weakness leading to respiratory failure, the primary cause of death within 3-5 years of symptom onset 5
• Decreased lung function is a common adverse effect 6

Other Symptoms

• Muscle cramps, pathological crying or laughter, spasms, and spasticity 7
• Severe pain of uncertain origin, frozen shoulder, and painful mouth ulcers can occur 8
• Weight loss and malnutrition develop in 0-21% at diagnosis and worsen progressively 1

Pharmacological Treatment

Riluzole 50 mg twice daily (taken at least 1 hour before or 2 hours after meals) is FDA-approved and remains the primary disease-modifying therapy, with modest effects on slowing disease progression. 6

Disease-Modifying Medications

• Riluzole has neuroprotective effects by modulating glutamate neurotransmission 2
• Monitor serum aminotransferases before and during treatment; discontinue if liver dysfunction develops 6
• Edaravone and sodium phenylbutyrate/taurursodiol are also approved in some countries for moderate effects on disease progression 5

Important Riluzole Precautions

• Contraindicated in patients with severe hypersensitivity reactions 6
• Not recommended with baseline liver enzymes greater than 5 times upper limit of normal 6
• Monitor for neutropenia; advise patients to report febrile illness 6
• Discontinue if interstitial lung disease develops 6
• Avoid coadministration with strong CYP1A2 inhibitors (increases adverse reactions) or inducers (decreases efficacy) 6

Symptomatic Medications

• Anticholinergics as first-line for sialorrhea, with botulinum toxin injections to salivary glands as second-line 1
• Medications for cramps, pathological crying/laughter, spasms, and spasticity 7
• Anticholinergics for excess respiratory mucus 7

Nutritional Management

Conduct nutritional assessment (BMI, weight loss) every 3 months, and place percutaneous endoscopic gastrostomy (PEG) before forced vital capacity (FVC) falls below 50% of predicted—never when FVC is below 30%. 1

Early Nutritional Interventions

• Videofluoroscopy should be performed at diagnosis to detect early dysphagia, even in asymptomatic patients with bulbar symptoms 3, 1
• Adapt food texture to facilitate swallowing: use soft, semisolid, or semiliquid consistency 3, 9
• Implement chin-tuck posture and other postural maneuvers to protect the airway 9
• Use thicker liquids and semisolid foods with high water content instead of thin liquids 3, 9
• Fractionate and enrich meals with energy; add oral nutritional supplementation if weight loss progresses 9

Advanced Nutritional Support

• Enteral nutrition via gastrostomy (preferably PEG) is recommended when oral intake becomes insufficient 3
• Enteral nutrition is strongly preferred over parenteral nutrition 9
• Parenteral nutrition should only be considered in acute settings when enteral nutrition is contraindicated, due to high complication rates (3.11 per 1000 catheter days) 9

Respiratory Management

Initiate non-invasive ventilation (NIV) when FVC falls below 80% with symptoms, FVC below 50% predicted, or evidence of sleep-disordered breathing on polysomnography. 1

Respiratory Monitoring

• Establish baseline pulmonary function with slow vital capacity (SVC) measurements 3
• Measure peak cough flow (PCF) to assess airway clearance ability 3
• Monitor regularly for respiratory decline 10

Ventilatory Support

• Use bilevel positive airway pressure (BPAP) with backup respiratory rate for better patient-ventilator synchrony, especially in patients with bulbar impairment 1
• Critical caveat: Compliance with NIV is adversely affected by cognitive impairment, requiring careful assessment before implementation 1
• Consider invasive ventilation via tracheostomy for patients who choose this option 7

Palliative Care Approach

Adopt a palliative care approach from the time of diagnosis with early referral to palliative services—not reserved for end-stage disease—because speech and communication become severely limited in later stages. 3, 1

Timing of Palliative Care

• Early referral establishes relationships with palliative staff before communication becomes impaired 3
• Initiate end-of-life discussions at specific trigger points: patient distress, disease evolution, or patient's expressed desire to discuss 1
• Currently, only 28-30% of ALS patients successfully access palliative services, representing a major gap in care 8

Advance Care Planning

• Discuss advance directives early while patient retains cognitive capacity to process information and appreciate consequences 8
• Address preferences for gastrostomy, non-invasive ventilation, and invasive ventilation 8
• Advance directives are believed useful in 78% of European centers, though only 30% of patients complete them 8

Multidisciplinary Care Structure

Multidisciplinary care improves both survival and quality of life in ALS and should include neurology, pulmonology, gastroenterology, speech-language pathology, nutrition, physical therapy, occupational therapy, social work, and palliative care. 1

Communication Support

• All patients with suspected bulbar dysfunction require swallow screening before initiating oral intake 1
• Introduce communication devices and strategies (sign language, communication boards, computer systems) before dysarthria severely impairs communication 7, 4
• Speech-language therapy interventions should be targeted timely based on communicative need 4

Physical Activity

• Advise low to moderate physical activity (endurance and resistance exercises) as long as it doesn't worsen the patient's condition, as some evidence suggests it may slow disease progression 9
• Avoid excessive physical exertion that could lead to fatigue 9

Equipment and Services

• Critical pitfall: Equipment and service delays can result in catastrophic safety risks; all requests for equipment and services should be considered urgent and handled expeditiously 1
• Provide special mobility equipment much earlier than for other muscle diseases, as ALS progression is much faster 7

Diagnostic Approach

Initial Evaluation

• MRI head without IV contrast is usually appropriate for initial imaging to exclude other conditions, with abnormal T2/FLAIR signal in corticospinal tracts being common 3
• Electromyography (EMG) is the most important diagnostic test, showing denervation and reinnervation patterns in multiple body regions 3

Prognostic Assessment

• Disease severity and progression rate are determined by the ALS Functional Rating Scale-Revised (ALSFRS-R) 10
• Monitor slow vital capacity (SVC), peak cough flow (PCF), and body mass index (BMI) to guide interventions 10
• Neurofilament light chain (NF-L) is being investigated as a prognostic biomarker 10

Special Considerations

Cognitive Impairment

• Patients with executive dysfunction are at higher risk of falls, choking episodes, and injuries, requiring comprehensive safety measures 1
• Cognitive impairment affects NIV compliance and requires careful assessment 1

Aspiration Risk

• Aspiration pneumonia occurs in 11.4-13% of bulbar ALS cases and represents a leading cause of mortality 1
• Patients with positive bedside swallow screening or high aspiration risk require videofluoroscopy swallowing study (VFSS) 1

Terminal Phase Management

• During the terminal phase, prioritize treatment of restlessness, anxiety, pain, and dyspnea 7
• Palliative symptom management forms part of terminal care 7