What are the clinical manifestations of Amyotrophic Lateral Sclerosis (ALS)?

Clinical Manifestations of Amyotrophic Lateral Sclerosis

ALS is a progressive neurodegenerative disorder characterized by combined upper and lower motor neuron dysfunction, presenting with progressive muscle weakness, atrophy, fasciculations, and hyperreflexia, while crucially preserving sphincter control, sensory function, intellectual abilities, and skin integrity. 1, 2

Two Primary Presentation Patterns

ALS manifests in two distinct clinical forms that determine prognosis and symptom trajectory:

Bulbar-Onset ALS (25-35% of patients)

• Dysarthria and dysphagia develop in almost 80% of bulbar-onset patients, representing the hallmark features of this presentation 1
• Speech difficulties and swallowing problems are the initial symptoms, often appearing before limb weakness 2
• Median survival is significantly shorter at 25-28 months from symptom onset, compared to 44 months for spinal-onset patients with dysphagia 3
• Older age at onset further worsens prognosis in this subtype 1

Limb-Onset ALS (65-75% of patients)

• Muscle weakness is the primary symptom, typically beginning focally in one limb and spreading to other regions 1, 4
• Patients initially present with problems in dexterity or gait resulting from progressive weakness 2
• The disease begins focally but spreads relentlessly throughout the motor system 4

Core Motor Manifestations

Lower Motor Neuron Signs

• Progressive muscle weakness and atrophy affecting skeletal muscles including respiratory muscles 1, 5
• Fasciculations (visible muscle twitching) are characteristic 2
• Muscle wasting becomes increasingly severe over months to years 2

Upper Motor Neuron Signs

• Increased reflexes (hyperreflexia) despite muscle weakness 2
• Spasticity requiring medication management 6
• Pathological reflexes indicating corticospinal tract involvement 7

Bulbar Dysfunction Manifestations

Up to 30% of ALS patients present with swallowing impairment at diagnosis, and practically all patients develop dysphagia as disease progresses 1

Swallowing Abnormalities Progress Through Distinct Phases:

• Delayed bolus transport from oral cavity to pharynx is the most frequent videofluoroscopic finding 1
• Decreased pharyngeal contraction and low tongue driving forces 1
• Oral residue affects all patients regardless of bulbar symptom presence 1
• Pharyngeal residue develops universally in ALS patients 1
• Silent aspiration can occur, detectable only by instrumental evaluation 1

Associated Bulbar Features:

• Sialorrhea (excessive drooling) caused by difficulty swallowing saliva with accompanying aspiration risk 6
• Nasal regurgitation 3
• Difficulty with chewing and oral preparation of food 1
• Prolonged meal times leading to muscular fatigue 1

Respiratory Manifestations

Respiratory failure is the primary cause of death in ALS, with most patients dying of respiratory complications within 3-5 years of diagnosis 5, 2

• Progressive weakness of respiratory muscles including diaphragm and intercostals 1, 5
• Difficulty coughing up thick, sticky mucus 6
• Excess mucus accumulation in respiratory tract 6
• Aspiration pneumonia occurs in 11.4-13% of bulbar ALS cases and represents a leading cause of mortality 3
• Symptoms of hypoventilation include morning headaches, daytime sleepiness, and disturbed sleep 8

Nutritional and Metabolic Manifestations

Weight loss and malnutrition develop in 0-21% of patients at diagnosis and worsen progressively, with weight loss >5% doubling the risk of death 1, 3

Contributing Factors:

• Muscular fatigue during eating requiring prolonged meal times 1
• Anorexia attributed to psychosocial distress, depression, and polypharmacy 1
• Paradoxically increased energy requirements due to increased work of breathing, lung infections, and other metabolic factors 1
• Constipation from weakness of abdominal and pelvic muscles, limiting fluid and fiber intake 1

Extra-Motor Manifestations

In up to 50% of cases, extra-motor manifestations occur including behavioral changes, executive dysfunction, and language problems 7

• Cognitive dysfunction affects 20-50% of cases, mainly frontotemporal dementia 1
• In 10-15% of patients, cognitive problems are severe enough to meet clinical criteria for frontotemporal dementia 7
• Behavioral changes and executive dysfunction 7
• Emotional lability with pathological crying or laughter requiring medication 6

Preserved Functions (Critical Diagnostic Features)

Sphincter control, sensory function, intellectual abilities (in 50-80% of cases), and skin integrity remain preserved throughout the disease course 2

• Bladder and bowel control maintained 2
• No sensory loss or paresthesias 2
• Eye movements typically spared 7

Disease Progression Pattern

The disease begins focally in the central nervous system and spreads relentlessly, with patients becoming completely disabled over months to years 2, 4

• Mean survival is 3-5 years from symptom onset, with only 5-10% living longer than 10 years 1
• Eventual respiratory failure and malnutrition with dehydration are the primary causes of death 1
• Patients require ventilatory support and gastrostomy as disease advances 2
• Up to 95% of patients in the United States choose not to undergo tracheostomy 5

Additional Symptomatic Manifestations

• Cramps requiring medication management 6
• Spasms and spasticity treatable with medication 6
• Progressive loss of mobility requiring adaptive equipment much earlier than other muscle diseases due to rapid progression 6
• Communication difficulties as dysarthria progresses, eventually requiring adaptive strategies from sign language to advanced computer systems 6