Motor neuron disease Flashcards
What is motor neuron disease?
Cluster of major degenerative diseases characterised by selective loss of neurons in motor cortex, cranial nerve nuclei and anterior horn cells
May have limb or bulbar onset
What are the 4 different presentations of motor neuron disease?
UMN pathology - primary lateral sclerosis
LMN pathology - primary muscular atrophy
Mixture - amyotrophic lateral sclerosis (most common) - worse prognosis if bulbar onset
Bulbar only - progressive bulbar palsy (CN IX - XII)
How common is MND?
Relatively uncommon
More common in men
Median age of onset 60
Often fatal in 2-4 years
What is the aetiology of MND?
Usually sporadic and of unknown cause (80%)
No established risk factors
5-10% cases familial
- Linked to mutation in free radical scavenging enzyme superoxide dismutase
- Also linked to TDP-42, C9LRF72, and FUS
- Autosomal dominant
What is the pathology of MND?
Degenerative condition affecting motor neurons - anterior horn cells
Relentless and unexplained destruction of UMN and anterior horn cells in brain and spinal cord causing both UMN and LMN dysfunction
No sensory loss of sphincter disturbance
Never affects eye movements
Causes reactive O2 species which damage DNA, lipids, and proteins
Most patients die within 3 years from resp failure as a result of bulbar palsy (impairment of CN 9,10,11,12) and pneumonia
What are the UMN signs?
Spastic dysarthria
Increased muscle tone
Hyper-reflexia
Muscle weakness
What are the LMN signs?
Flaccid dysarthria
Loss of muscle tone
Loss of reflexes
Muscle weakness
How does ALS present?
Loss of motor neurons in motor cortex and anterior horn cells
LMN and UMN signs
Split hand sign - thumb side of hand seems adrift due to excessive wasting around it - much less hypothenar wasting
Cramps common but non-specific
Wrist and foot drop
How does progressive muscular atrophy present?
LMN signs
Gradual spreading of signs to involve other adjacent spinal segments
Affects distal muscle groups before proximal
How does progressive bulbar palsy present?
LMN signs
Lower cranial nerves (9, 10, 11, 12) and nuclei initially only affected
Dysarthria, dysphagia, nasal regurgitation of fluids and choking - presenting symptoms
Lesions of tongue and muscles of talking, swallowing, flaccid, fasciculating tongue, jaw jerk normal/absent, speech quiet, horse, nasal
How does primary lateral sclerosis present?
UMN only
Least common
Loss of betz cells in motor cortex
No cognitive decline
When should you think of MND?
> 40 with stumbling spastic gait, foot drop +/- proximal myopathy, weak grip and shoulder abduction or aspiration pneumonia
What other symptoms could you get with MND?
Frontaltemporal dementia occurs in 25%
Regardless of body part that is first affected, weakness, atrophy spread to other parts of body with varying degree of UMN symptoms and eventually involve muscles of all 4 extremities and the trunk as well as bulbar muscles
Rectal and bladder sphincters and oculomotor muscles spared
No sensory symptoms
What are the differential diagnosis of MND?
MS or polyneuropathies - no sensory loss or sphincter disturbance
Myasthenia gravis - MND never affects eye movement
Diabetic amyotrophy
Guillain-Barre syndrome
Spinal cord tumours
Multi-focal motor neuropathy with conduction block
Radiculopathy
CIDP
Myopathy
How is MND diagnosed?
Clinical diagnosis based clinical findings
Brain/cord MRI - helps exclude inflammatory causes
LP - to exclude inflammatory causes
NCS + EMG - denervation of muscles due to degeneration of LMNs confirmed by EMG - supports diagnosis by aiming to exclude differentials
