Motor Neurone Disease (MND)

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management

Definition

Motor neurone disease (MND) is a progressive neurodegenerative disorder characterised by the selective loss of motor neurones in the brain and spinal cord, leading to muscle weakness, wasting, and respiratory failure.

Aetiology

The exact cause of MND is unknown, but it is believed to involve a combination of genetic and environmental factors.

1. Genetic Factors:

  • Approximately 5–10% of cases are familial.
  • Mutations in the C9orf72, SOD1, TARDBP, and FUS genes are implicated.

2. Environmental Factors:

  • Exposure to toxins (e.g., heavy metals, pesticides).
  • Head trauma.
  • Smoking.
  • Military service (some studies suggest increased risk).

Pathophysiology

  • Progressive degeneration of upper motor neurones (UMNs) in the motor cortex and lower motor neurones (LMNs) in the brainstem and spinal cord.
  • Loss of UMNs leads to spasticity, while loss of LMNs results in muscle atrophy and weakness.
  • Glutamate excitotoxicity and oxidative stress are thought to play a role in neuronal death.

Risk factors

  • Age (most cases occur in people over 50 years).
  • Male sex (MND is slightly more common in men).
  • Family history of MND or other neurodegenerative diseases.
  • Smoking (linked to increased risk).

Signs and symptoms

MND presents with a combination of upper and lower motor neurone signs, depending on the subtype.

Common Features:

  • Progressive muscle weakness and wasting.
  • Dysarthria (slurred speech).
  • Dysphagia (difficulty swallowing).
  • Respiratory muscle weakness leading to breathlessness.
  • No significant sensory loss (distinguishes from other neurological conditions).

Subtypes of MND:

Amyotrophic Lateral Sclerosis (ALS) (Most Common):
  • Both UMN and LMN signs.
  • Weakness typically begins in one limb and spreads.
Progressive Bulbar Palsy (PBP):
  • Early involvement of speech and swallowing muscles.
  • Poor prognosis due to aspiration risk.
Primary Lateral Sclerosis (PLS):
  • Predominantly UMN signs (spasticity, hyperreflexia).
  • Less muscle wasting compared to ALS.
Progressive Muscular Atrophy (PMA):
  • Predominantly LMN signs (flaccidity, fasciculations).
  • Slower progression than ALS.

Investigations

  • Clinical assessment: diagnosis is largely clinical, supported by investigations.
  • Electromyography (EMG): confirms LMN involvement, showing fibrillations and fasciculations.
  • Nerve conduction studies: helps exclude other neuromuscular disorders.
  • MRI brain and spine: excludes mimics (e.g., cervical myelopathy, stroke).
  • Blood tests:
    • Creatine kinase (CK) may be mildly elevated.
    • Excludes other conditions (e.g., thyroid dysfunction, vitamin B12 deficiency).

Management (specialist only)

1. Pharmacological Treatment:

  • Riluzole: slows disease progression by reducing glutamate excitotoxicity.

2. Symptom Management:

For Spasticity:
  • Baclofen or tizanidine.
For Drooling (Sialorrhoea):
  • Glycopyrronium bromide or botulinum toxin injections.
For Dysphagia:
  • Speech and language therapy (SLT) input.
  • Consider percutaneous endoscopic gastrostomy (PEG) if swallowing deteriorates.
For Respiratory Support:
  • Non invasive ventilation (NIV) improves survival and quality of life.

3. Multidisciplinary Support:

  • Neurology input for disease monitoring.
  • Physiotherapy for mobility and contracture prevention.
  • Occupational therapy for adaptive aids.
  • Palliative care for symptom management and end-of-life planning.
NeurologymypanotesMotor Neurone Disease (MND)