Motor Neurone Disease

Question 1

What is motor neurone disease?

Answer 1

Progressive disorder characterised by neuronal loss at all levels of the motor system from the cortex to the brainstem and anterior horn cells of the spinal cord.

Physical signs therefore include both upper and lower motor neurone signs.

Question 2

What different forms of motor neurone disease are there?

Answer 2

• Amyotrophic lateral sclerosis: Most common. Mixed UMN and LMN signs
• Progressive muscular atrophy: Predominantly LMN signs. Better prognosis than ALS. Rare
• Primary lateral sclerosis: Predominant UMN signs.
• Progressive bulbar palsy: Predominant bulbar involvement (pseudo- or bulbar palsy). Rare

Question 3

What is the pathophysiology of MND?

Answer 3

Exact mechanism unclear. Two potential mechanisms exist:

• The excitotoxicity theory e.g. glutamate reaches supra-physiological concentrations. Riluzole, a glutamate release inhibitor, shows some efficacy thus supporting this hypothesis
• The free-radical hypothesis: SOD-1 gene identified in familal MND backs this up, however anti-oxidants have so far shown no efficacy.

Question 4

What do you know about the genetics of MND?

Answer 4

• Most cases sporadic
• 5-10% of cases are familial, mostly with AD inheritance
• The most common mutation identified is SOD1 (encodes copper-zinc superoxide dismutase), found in 2% of patients and 20% of familial cases.

Question 5

What other conditions result in UMN and LMN symptoms?

Answer 5

Syringomyelia (LMN in arms, UMN in legs. Associated with cape-like loss of sensation and Horner’s syndrome)

Cervical myelopathy- look for sensory signs (not seen in MND). Lacks bulbar signs seen in MND.

MAST:

MND

Ataxia (Friedrich’s)

SCDC: B12 deficiency

Taboparesis

Question 6

What other conditions cause fasciculations?

Answer 6

Physiological- after exercise in healthy adults

Electrolyte disturbances (hypokalaemia, hypomagnesaemia)

Syringomyelia

Hereditary motor and sensory neuropathy

Drugs e.g. lithium, salbutamol

Question 7

How would you investigate a patient with suspected MND?

Answer 7

No diagnostic test- diagnosis of exclusion

• MRI brain/cord: exclude structural cause e.g. brainstem lesions, cervical cord compression
• EMG: Fasciculations
• LP: Exclude inflammatory causes

Question 8

What is the diagnostic criteria for ALS?

Answer 8

Revised El Escorial Criteria

Question 9

What is the management of MND?

Answer 9

MDT approach: neurologist, physio, OT, dietician, specialist nurse, GP, family

Respect patient autonomy and choice

Symptom control and QOL

• Conservative:
  
  • Discussions of end-of-life decisions e.g. DNAR, advanced directive
  • Early involvement palliative care
• Medical:
  
  • Supportive:
    
    • Drooling: amitriptyline
    • Dysphagia: NG or PEG feed
    • Resp failure: NIV
    • Pain: WHO ladder
    • Spasticity: baclofen, botulinum
  • Specific: Riluzole- disease modifying treatment. Does not improve symptoms or prevent death. Antiglutamatergic, prolongs life by approx 3 months mainly by delaying need for respiratory support.

Question 10

What is the prognosis of MND?

Answer 10

Most die within 3 years of onset

Main COD is respiratory failure from diaphragmatic weakness

Better prognosis for PMA and PLS

Question 11

What features suggest a poorer prognosis?

Answer 11

• Older age at presentation
• Female sex
• Bulbar onset

Question 12

What is the mean age of onset of MND?

Answer 12

60yo