Clinical Features of Motor Neurone Disease (Amyotrophic Lateral Sclerosis)
Core Presentation
Motor neurone disease, particularly ALS, presents with a characteristic combination of upper motor neuron signs (hypertonicity, hyperreflexia, extensor plantar responses) and lower motor neuron signs (muscle fasciculations, weakness, atrophy, hyporeflexia) affecting bulbar, limb, and respiratory musculature in a progressive pattern. 1, 2
Upper Motor Neuron Features
- Spasticity with increased muscle tone and velocity-dependent resistance to passive movement 2
- Hyperreflexia manifesting as brisk or exaggerated deep tendon reflexes 3, 2
- Extensor plantar response (Babinski sign) indicating corticospinal tract involvement 2
- Clonus showing rhythmic muscle contractions in response to sudden, maintained stretch 2
Lower Motor Neuron Features
- Fasciculations are the most characteristic sign of lower motor neuron damage, appearing as spontaneous visible muscle twitches that originate from the motor neuron or distally along the axon 2
- Progressive muscle weakness and atrophy developing due to denervation 2, 4
- Hypotonia resulting from interruption of normal neural input 2
- Hyporeflexia or areflexia with diminished or absent deep tendon reflexes 2
- Flaccid paralysis characterized by decreased muscle tone with weakness 2
Pattern of Disease Progression
- Focal onset with weakness typically starting in the legs and progressing to the arms and cranial muscles, though onset can be asymmetrical or begin in different regions 1, 5
- Relentless progression with spread within a region or to other regions over time 1
- Patients typically reach maximum disability within 2 weeks of symptom onset; if progression occurs within 24 hours or after 4 weeks, alternative diagnoses should be considered 3
Bulbar Involvement
- Dysarthria (speech difficulties) affecting approximately 80% of patients with bulbar-onset ALS 6
- Dysphagia (swallowing difficulties) present in approximately 80% of bulbar-onset cases 6
- Difficulties with functions controlled by lower cranial nerves including tongue weakness and impaired palatal movement 6
- Emotional lability may occur with pseudobulbar palsy (upper motor neuron bulbar dysfunction) 1
Respiratory Manifestations
- Progressive respiratory compromise due to respiratory muscle weakness 4, 7
- Respiratory failure is the most common cause of death in ALS 6
- Median survival of 3-4 years after symptom onset, though 5-10% of patients survive longer than 10 years 3, 6
Associated Features
- Dysautonomia including blood pressure or heart rate instability, pupillary dysfunction, and bowel or bladder dysfunction 3
- Pain is frequently reported and can be muscular, radicular, or neuropathic in character 3
- Fatigue and sleep disorders are common complications 4
- Extra-motor manifestations occur in up to 50% of cases, including behavioral changes, executive dysfunction, and language problems; 10-15% meet criteria for frontotemporal dementia 5
Clinical Variants
- Pure motor variant with weakness without sensory signs 3, 1
- Progressive bulbar palsy with primary involvement of bulbar muscles first 1
- Progressive muscular atrophy involving only lower motor neurons without upper motor neuron signs 1
- Primary lateral sclerosis with pure upper motor neuron involvement 8
- Pharyngeal-cervical-brachial weakness limited to upper limbs 3
- Paraparetic variant with weakness limited to lower limbs 3
Critical Diagnostic Pitfalls
- Reflexes may be normal or even exaggerated in some patients with atypical ALS, particularly those with pure motor variant and AMAN subtype on electrophysiology 3
- Sensory symptoms should prompt reconsideration of pure motor neuron disease, as sensory pathways are not typically involved 2
- Young children (<6 years) can present atypically with poorly localized pain, refusal to bear weight, irritability, meningism, or unsteady gait rather than classic weakness 3