Motor Neurone Disease

Question 1

What is motor neurone disease?

Answer 1

Age related condition with selective irreversible loss of a specific group of neurones.

Late onset and relentless progression

ALS linked with amyotrophy (muscle wasting) and lateral sclerosis

Question 2

What is the aeitology of MND?

Answer 2

No clear understanding or aetiology but likely linked with complex interaction between genetically determined predisposition and environmental triggers

95% sporadic
5% inherited (AD) mendelian inheritance - most common 9p chromosome C9ORF72 mutation
other mutations: SOD1, TLS/FUS, ANG, TDP43
Sometimes there is incomplete penetrance and therefore sporadic disease may have genetic link

Question 3

Describe the disease phenotype with C9ORF72

Answer 3

Manifest behavioural variant of FTD

It has incomplete penetrance of up to 80%

Question 4

Do we get protein aggregates in MND?

Answer 4

possibly TDP42-opathies found in 95% of MND cases

Question 5

What are the clinical features of MND?

What is spared? which results in?

Where is onset?

Answer 5

Progressive degeneration of the motor system with mixed UMN and LMN signs with fasciculations

UMN:
increased tone decrease power and increased reflexes

LMN:
Decreased bulk, tone, power and reflexes

Sparing of intellect, sensation, sphincter function and eye movement

This results in progressive, painless paralysis and wasting

80% limb onset 20% bulbar onset (speech and swallowing problems)

Question 6

Describe the spectrum of clinical features of MND

Answer 6

UMN: Primary Lateral sclerosis (2%) (Slow progression, good prognosis)
Both: Amyotrophic lateral sclerosis (75%) and Progressive bulbar palsy (20%)
LMN: Progressive Muscular Atrophy (3%) (Slow progression, good prognosis)

Question 7

What are the predominant clinical features of the following:

• ALS
• PBP
• PMA
• PLS

Answer 7

ALS: mixed UMN and LMN degeneration. Presents with progressive weakness and wasting in any distribution. Retained weak reflex and wasted muscles. Fasciculations and muscle cramps prominent
* Foot drop, proximal Upper and lower limb weakness, flail arms

PBP: speech and swallowing difficulties progression to dysarthria over 6-24 months and dysphagia (1-3 years)
complicated by pneumonia, wt loss and anorexia

PMA: LMN degeneration

PLS: UMN degeneration dominated by weakness and spasticity

Question 8

How do we diagnose MND?

Answer 8

Based on clinical evaluation but usually a diagnosis of exclusion - bloods, scans, LP, IMG negative

Electrophysiology - abnormality of motor nerves
Electromyography - active denervation and re-innervation with compensatory motor unit remodelling
Nerve conduction studies - normal velocities but reduced compound motor action potential amplitudes

Question 9

Management of MND

1. Symptomatic relief
2. Disease modification

Answer 9

1. Sialorrhoea (drooling of saliva)
   Anticholinergics amitryptiline, salivary gland radiotherapym botox
2. Riluzole etc. all failed

Question 10

What are the dictators of prognosis?

Answer 10

Respiratory function: better FVC = better survival - treat with NIV but can prolong life and suffering

Age

Disease phenotype - PBP

Nutritional failure -dysphagia (difficult) /aphagia (inability) /anorexia

Quick diagnosis suggests rapidly progressive disease and hence a poor prognosis