Motor Neuron Disease

 

Motor neuron disease (MND)

• Background

  Pathophysiology

  • Loss of upper and lower motor neurons, affecting the motor cortex, cranial nerve nuclei, or anterior horn cells.
  • May be due to oxidative stress from excess glutamate, the excitatory neurotransmitter.
  • 90% sporadic, 10% familial.

  Epidemiology

  • 1/400 lifetime risk.
  • Male:Female ratio 3:2.
  • Mean onset 55-75 years old.

• Signs and symptoms

  Common symptoms:

  • Upper limb and spine: weak/clumsy grip, wrist drop, neck flexion weakness.
  • Lower limb: foot drop, unsteady spastic gait, balance problems, difficulty rising from chairs.
  • Respiratory and bulbar: slow/slurred speech, dysphagia, SOB, aspiration pneumonia, morning headache from CO2 retention.
  • Fronto-temporal dementia (10-20%).

  Mixed upper and lower motor neuron signs, usually asymmetrical:

  • UMN: ↑reflexes, ↑tone.
  • LMN: fasciculations, muscle atrophy.
  • ↓Power reflects both UMN and LMN pathology.

  Types

  Amyotrophic lateral sclerosis

  • 50% of all MND.
  • Affects motor cortex and anterior horn cells.
  • Upper and lower MN. Usually limb-onset, but can be bulbar or respiratory-onset.

  Progressive bulbar palsy

  • Upper and lower MN of cranial nerves 9-12, causing mixed bulbar and pseudobulbar palsy.

  Primary lateral sclerosis

  • Damage to Betz cells of Motor cortex.
  • Upper MN only: spastic paraparesis, pseudobulbar palsy. No dementia.

  Progressive muscular atrophy

  • Anterior horn cell damage.
  • Lower MN only: weakness and wasting, affecting distal muscles first such as the small muscles of hands and feet.

• Differential diagnosis

  Neck flexion weakness DDx:

  • Myasthenia gravis.
  • Guillain Barré syndrome.
  • Polymyositis

  Foot drop is more commonly from a peripheral cause, such as:

  • Peroneal nerve compression.
  • Sciatica

  Mixed upper/lower motor neuron signs DDx:

  • Cervical radiculomyelopathy.
  • Multifocal motor neuropathy.
  • B12 deficiency

  Distinguishing features of MND vs. other conditions:

  • No sensory or sphincter disturbance, unlike MS or polyneuropathy.
  • No eye movement problems, unlike myasthenia gravis.

• Investigations

  • Clinical diagnosis: upper and lower motor neuron signs without evidence of other cause. Can also be UMN or LMN alone if nothing else explains findings.
  • MRI and LP to exclude other causes.
  • EMG may detect subclinical denervation.
  • Respiratory testing at diagnosis and to monitor progression: pulse oximetry (± ABG if abnormal), vital capacity, and sniff nasal inspiratory pressure (SNIP) plus maximal inspiratory pressure (MIP). Consider sleep studies.

• Management

  MDT inc. neurologist, physio, OT, dietician, speech and language, psychology.

  Limb symptom relief:

  • Baclofen, dantrolene, diazepam, or gabapentin for spasticity.
  • Quinine for muscle cramps.
  • Analgesia for joint pain.

  Bulbar symptom relief:

  • Soft food, NG tube, or PEG for dysphagia.
  • Glycopyrrolate for drooling.

  Respiratory symptom relief:

  • NIV for respiratory failure or sleep apnoea (can also prolong life).
  • Opioids or benzodiazepines for SOB.

  Life-prolonging treatments:

  • Riluzole – an antiglutamatergic – adds 3 months of life.
  • NIV or invasive ventilation via tracheostomy.

• Prognosis

  • 3-5 year life expectancy. Death is usually from respiratory failure.
  • Worse prognosis: bulbar-onset, ↑age, ↓FVC.
  • Better prognosis: 30% survive >5 years, some much longer, especially if young and with limb-onset ALS or PMA.