Motor neurone disease

Question 1

Define

Answer 1

• A progressive neurodegenerative disorder of cortical, brainstem and spinal motor neurons (lower and upper motor neurons)

Question 2

What are the 4 subtypes?

Answer 2

o Amyotrophic Lateral Sclerosis (ALS)
• AKA Lou Gehrig’s disease
• Combined generation of upper AND lower motor neurones resulting a mix of LMN and UMN signs

o Progressive Muscular Atrophy Variant
• Only LMN signs
• Better prognosis

o	Progressive Bulbar (LMN) and pseudobulbar (UMN) Palsy Variant
•	Dysarthria 
•	Dysphagia 
•	Wasted fasciculating tongue 
•	Brisk jaw jerk reflex 

o	Primary Lateral Sclerosis Variant
•	UMN pattern of weakness 
•	Rare
•	Progressive tetraparesis (all 4 limbs are paralysed)
•	Brisk reflexes 
•	Extensor plantar responses 
•	NO LMN signs

No involvement of the sensory system or the motor nerves to the eyes or sphincters.

Question 3

Explain the aetiology/risk factors

Answer 3

• UNKNOWN
• Free radical damage and glutamate excitotoxicity have been implicated
• Pathology
o Progressive motor neurone degeneration and death
o Gliosis replacing lost neurones
• Associations
o Frontotemporal lobar dementia

Question 4

Epidemiology

Answer 4

• RARE
• Incidence: 2/100,000
• Mean age of onset: 55 yrs
• more common in men
• 5-10% have a family history with autosomal dominant inheritance e.g. mutations in SOD-1 (free radical scavenging enzyme)

Question 5

What are the presenting symptoms?

Answer 5

• Weakness of limbs
• Speech disturbance (slurring or reduction in volume)
• Swallowing disturbance (e.g. choking on food)
• Behavioural changes (e.g. disinhibition, emotional lability)

Question 6

What are the signs?

Answer 6

•	Combination of UMN and LMN signs 
•	LMN Features
o	Muscle wasting 
o	Fasciculations  
o	Flaccid weakness 
o	Hyporeflexia
•	UMN Features
o	Spastic weakness 
o	Babinski's sign
o	Hyperreflexia
•	Sensory examination - should be NORMAL (differentiates from cervical cord lesion)

Question 7

What are the appropriate investigations?

Answer 7

CLINICAL diagnosis
• Bloods
o Mild elevation in CK
o ESR
o Anti-GM1 ganglioside antibodies
• Electromyography (EMG) – shows muscle denervation
• Nerve conduction studies - often normal
• MRI - exclude cord compression and brainstem lesions
• Spirometry - assess respiratory muscle weakness