What are the clinical features of amyotrophic lateral sclerosis?

Clinical Features of Amyotrophic Lateral Sclerosis

ALS is characterized by the simultaneous degeneration of both upper and lower motor neurons, producing a distinctive combination of hyperreflexia and spasticity alongside muscle weakness, atrophy, and fasciculations, with relentless progression leading to respiratory failure within 3-5 years of symptom onset. 1, 2

Core Motor Neuron Signs

Upper Motor Neuron Features

• Hyperreflexia (exaggerated deep tendon reflexes) is a hallmark finding on neurological examination 1, 3
• Spasticity (increased muscle tone with velocity-dependent resistance to passive movement) develops as corticospinal tract degeneration progresses 1, 4
• Pathological reflexes including Babinski sign and Hoffmann sign indicate pyramidal tract involvement 3, 5
• Pseudobulbar affect (involuntary emotional expression disorder) occurs in a subset of patients and responds to dextromethorphan/quinidine 4

Lower Motor Neuron Features

• Muscle fasciculations (visible spontaneous muscle twitching) are characteristic and often precede weakness 1, 2
• Progressive muscle weakness begins focally and spreads contiguously to adjacent body regions 2, 3
• Muscle atrophy (wasting) develops as anterior horn cells degenerate 6, 5
• Hyporeflexia or areflexia may occur in severely atrophied muscles despite upper motor neuron disease 5, 7

Clinical Presentation Patterns

Limb-Onset (Spinal) ALS (65-75% of cases)

• Asymmetric limb weakness is the initial manifestation, typically starting in one arm or leg 8, 2
• Distal weakness (hand or foot) is more common than proximal weakness at onset 8, 7
• Focal muscle atrophy in the affected limb becomes evident within months 8, 5
• Contiguous spread to adjacent body regions occurs over 6-12 months 2, 3

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

• Dysarthria (slurred speech) develops in approximately 80% of bulbar-onset patients as the initial symptom 6, 8
• Dysphagia (difficulty swallowing) occurs in 80% of bulbar-onset cases, often presenting with choking episodes 6, 8
• Sialorrhea (drooling) results from impaired swallowing of saliva rather than increased production 1, 2
• Nasal regurgitation occurs due to soft palate weakness 1, 8
• Tongue atrophy and fasciculations are visible on examination 6

Disease Progression Characteristics

Temporal Pattern

• Relentless progression without remissions or fluctuations distinguishes ALS from other conditions 1, 9
• Focal onset with contiguous spread through adjacent spinal segments or cranial nerve nuclei is the typical pattern 2, 3
• Respiratory muscle involvement eventually occurs in all patients, typically 18-36 months after symptom onset 1, 4
• Extraocular muscles and sphincters are characteristically spared until very late stages 5, 4

Respiratory Features

• Dyspnea on exertion progresses to dyspnea at rest as diaphragm weakness advances 4, 1
• Orthopnea (difficulty breathing when lying flat) indicates significant diaphragm weakness 4
• Morning headaches and daytime somnolence suggest nocturnal hypoventilation 4
• Respiratory failure is the most common cause of death, occurring at a median of 3-5 years from symptom onset 1, 2

Extra-Motor Manifestations

Cognitive and Behavioral Changes (40-50% of patients)

• Executive dysfunction (impaired planning, organization, and decision-making) is the most common cognitive deficit 1, 2
• Behavioral disinhibition and apathy occur in the frontotemporal dementia spectrum 2, 3
• Language impairment including word-finding difficulty and reduced verbal fluency develops in some patients 2, 4
• Frank frontotemporal dementia meeting diagnostic criteria occurs in 10-15% of ALS patients 2, 5
• Cognitive impairment reduces compliance with non-invasive ventilation and affects treatment decision-making 1

Nutritional and Metabolic Features

• Progressive weight loss occurs in most patients due to dysphagia, hypermetabolism, and muscle wasting 6, 1
• Malnutrition at diagnosis increases mortality risk more than four-fold 1
• Each 5% body weight loss is associated with a 34% increase in mortality risk 1

Critical Diagnostic Pitfalls

• Absence of sensory symptoms or signs is expected; sensory involvement should prompt consideration of alternative diagnoses 3, 5
• Pain is not a primary feature of ALS; severe pain at onset suggests radiculopathy or other conditions 9, 3
• Waxing and waning symptoms are incompatible with ALS, which is relentlessly progressive 9
• Acute onset (symptoms developing in less than 24 hours) excludes ALS and suggests stroke or other acute processes 8
• Isolated fasciculations without weakness or atrophy for more than 12-24 months make ALS extremely unlikely 9

Prognosis and Survival

• Median survival is 3-5 years from symptom onset in typical progressive ALS 1, 8, 2
• Only 5-10% of patients survive longer than 10 years 1, 8
• Bulbar-onset disease generally has worse prognosis than limb-onset disease 8, 7
• Younger age at onset and longer diagnostic delay are associated with longer survival 7
• Presence of cognitive impairment worsens prognosis and reduces survival 1, 2