Motor Neurone Disease

Question 1

Notes on pathophysiology of ALS

Answer 1

• Hardening of lateral parts of spinal cord -> lateral sclerosis (corticospinal tracts)
• A/W SOD 1 mutation, chromosome 21. Glutamate toxicity mediated via redox system. Discovery of this has not led to new treatment options - SOD1 not A/W with TGP 43 inclusions in the brain and spinal cord - pathological signature of MND
• Current line of thinking -> MND begins focally in cerebral motor cortex, anterograde excitotoxicity spreading to lower motor neurone via anterior horn cell -> wasting and weakness

Question 2

Features of MND

Answer 2

• Most often begin focally - focal weakness affecting one arm or leg
• Sensory symptoms uncommon at presentation, fasciculations rare at presentation but common during course of illness
• Some presentations don’t appear to have a UMN component - classically the flail arm/man in barrel presentation - if you put a barrel over their head they can’t lift up their arms

**Split hand syndrome
- **Abductor pollicus brevis/first dorsal interossei more severely involved than abductor digiti minimi (muscles required for pincer grip more strongly represented in the brain)

**Cognitive and behavioural symptoms
**- 50% have cognitive impairment - executive dysfunction, language, memory recall, social cognition
80% behavioural impairment - apathy, disinhibition
15% ALS/FTD diagnosis - prognosis poorer, shorter survival, stronger predictor of carer burden than motor impairment

Question 3

Notes on diagnosis of motor nuerone disease

Answer 3

• Most undergo structural imaging of brain and spinal cord to exclude other process e.g. vascular, stroke
• Can possibly see signal change in corticospinal tracts on MRI Head
• **Spinal cord
• **- Sometimes uncertainty whether herniated disc may be contributing to symptoms of weakness over MND - patients that undergo surgical intervention ?accelerate progression of ALS
• **Nerve conduction studies and electromyography
• **Degenerated motor unit - some sprouting from motor unit (collateral) to reinervate denervated muscle fibres
• Large motor unit typical of MND
• Other evidence of denervation = fibrillations, ositive sharp waves and fasciculation potentials

Question 4

Diagnostic criteria for ALS

Answer 4

Question 5

Notes on epidemiology of sporadic MND

Answer 5

• Often affects patients with no comorbidities and otherwise well
• Normal or low BMI (rarely obese)
• Fitness oriented, athletic
• Reduced coronary artery disease in family history

Question 6

Treatment options for motor neurone disease

Answer 6

1. MDT - increases survival, hydrotherapy improves quality of life
2. Symptomatic - spasticity (baclofen, botox), sialorrhoea (botox, amitriptyline), weight loss/dysphagia - PEG tubes,
3. Respiratory support
   - NIV improves survival, quality of life, less fatigue
   - Start when symptomatic with decline in respiratory function
   - Inspiratory mucle training e.g. breathing in and out against a spring improves patient outcomes

**Medical therapies
- Riluzole
**- Reduces glutamate release and the uptake back into the motor neurone
-Improves survival by approx. 6 months
- Trials - well tolerated, earlier commencement is better (particularly for bulbar disease)
- **Edaravone
- **Free radical scavenger - recently approved by FDA
- For younger patients, early disease - slows progression