How does Amyotrophic Lateral Sclerosis (ALS) typically present?

Clinical Presentation of Amyotrophic Lateral Sclerosis (ALS)

ALS typically presents with progressive, asymmetric muscle weakness starting either in the limbs (65-75% of cases) or bulbar muscles affecting speech and swallowing (25-35% of cases), accompanied by both upper motor neuron signs (hyperreflexia, spasticity) and lower motor neuron signs (fasciculations, atrophy). 1

Two Main Presentation Patterns

Limb-Onset (Spinal) ALS - Most Common Form

• Represents 65-75% of all ALS cases and manifests with initial symptoms in the extremities 1
• Progressive muscle weakness begins focally in arms or legs, typically asymmetrically 1, 2
• Patients notice problems with dexterity (difficulty with buttons, writing) or gait disturbances (tripping, foot drop) 3
• Spinal motor neuron injury leads to peripheral muscle weakness and atrophy in the affected limbs 1
• Disease spreads from the initial site to involve other body regions over months to years 2

Bulbar-Onset ALS - Less Common but Distinctive

• Accounts for 25-35% of cases with initial symptoms affecting speech and swallowing 1
• Approximately 80% of bulbar-onset patients develop dysarthria (slurred speech) and dysphagia (difficulty swallowing) as primary manifestations 1, 4
• Patients may present with nasal regurgitation from soft palate weakness 4
• Sialorrhea (drooling) occurs due to impaired swallowing of saliva rather than increased production 4

Characteristic Motor Neuron Signs - The Diagnostic Hallmark

Upper Motor Neuron Signs (Brain and Corticospinal Tract)

• Hyperreflexia (exaggerated deep tendon reflexes) 4, 5
• Spasticity and increased muscle tone 6, 5
• Pathologic reflexes may be present 4

Lower Motor Neuron Signs (Spinal Cord and Brainstem)

• Muscle fasciculations (visible twitching under the skin) 4, 3, 5
• Progressive muscle atrophy and wasting 6, 3
• Weakness that worsens over time 1, 2
• The combination of both upper AND lower motor neuron signs in the same body region distinguishes ALS from other neuromuscular disorders 7, 4

Disease Progression Pattern

• Onset is focal but disease spreads contiguously to adjacent body regions over time 2
• Progression is relentless and continuous without remissions 4
• Patients typically reach severe disability requiring assistive devices within months to years 2
• Mean time from symptom onset to diagnosis is approximately 12 months, representing a critical delay 8
• Respiratory muscle involvement is inevitable and typically limits survival to 3-5 years after symptom onset 1, 4, 5

Extra-Motor Manifestations - Increasingly Recognized

• Cognitive dysfunction occurs in 20-50% of ALS cases, mainly frontotemporal dementia patterns 1
• Up to 40-50% of patients have behavioral changes, executive dysfunction, and language problems 1, 4
• 10-15% meet full criteria for frontotemporal dementia (FTD) 2
• Sphincter control, sensory function, and skin integrity are characteristically preserved throughout the disease course 3
• Eye movements typically remain intact until very late stages 3

Important Clinical Pitfalls to Recognize

Atypical Presentations That Delay Diagnosis

• Weakness can be asymmetric or predominantly proximal/distal rather than the classic pattern 9
• Severe diffuse pain may precede weakness, mimicking other conditions 9
• Young children may present with nonspecific features like refusal to bear weight or irritability 9
• In pure motor variants with AMAN subtype, reflexes may be normal or even exaggerated rather than diminished, contradicting the typical pattern 9

Red Flags for Alternative Diagnoses

• Symptom onset in less than 24 hours suggests stroke or other acute process 9
• Progression to maximum disability after more than 4 weeks should prompt consideration of other diagnoses 9
• Prominent sensory symptoms or sensory loss on examination argues against ALS 3
• Loss of sphincter control early in disease course suggests alternative diagnosis 3

Timeline and Natural History

• Disease typically progresses over months to years, not days to weeks 3, 2
• Respiratory failure from respiratory muscle weakness is the most common cause of death 1, 5
• Only 5-10% of patients survive longer than 10 years from symptom onset 1, 4
• The neurodegenerative process begins long before clinical symptoms appear, with approximately 20% motor neuron loss already present at symptom onset 8

Epidemiologic Context

• Annual incidence is 1-2 cases per 100,000 people 1, 3
• Most commonly diagnosed in middle age, with higher prevalence in men 3
• Approximately 85-90% of cases are sporadic without known genetic mutation or family history 1, 7
• 10-15% have familial ALS with autosomal dominant inheritance pattern 2