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Motor Neurone Disease (MND)

Summary

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  • Progressive neurodegenerative disorder affecting upper and lower motor neurons
  • Characterised by muscle weakness, atrophy, and eventual paralysis
  • Diagnosis based on clinical presentation, electromyography, and exclusion of other conditions1

Pathophysiology

  • Degeneration of motor neurons in the brain, brainstem, and spinal cord
  • Exact cause unknown, but involves:
    • Oxidative stress
    • Mitochondrial dysfunction
    • Protein aggregation (e.g., TDP-43)
    • Glutamate excitotoxicity
  • Genetic factors implicated in some cases (e.g., C9orf72, SOD1 mutations)

Demographics

  • Incidence: 1-2 per 100,000 person-years
  • Prevalence: 4-6 per 100,000 population
  • Mean age of onset: 55-65 years
  • Male to female ratio: 1.5:1
  • 5-10% of cases are familial

Diagnosis

  • Clinical features:
    • Progressive muscle weakness and atrophy
    • Fasciculations
    • Spasticity
    • Dysarthria and dysphagia
    • Respiratory insufficiency
  • Diagnostic criteria:
    • El Escorial criteria
    • Awaji criteria (includes electrophysiological findings)
  • Investigations:
    • Electromyography (EMG) and nerve conduction studies
    • Blood tests to exclude mimics
    • Genetic testing in familial cases

Imaging

  • Conventional MRI:
    • Often normal in early stages
    • May show cortical atrophy and hyperintensity of corticospinal tracts on T2-weighted images
  • Advanced MRI techniques:
    • Diffusion tensor imaging (DTI): Reduced fractional anisotropy in corticospinal tracts
    • Functional MRI: Altered activation patterns in motor and extra-motor regions
    • Magnetic resonance spectroscopy: Reduced N-acetylaspartate (NAA) in motor cortex
  • PET imaging:
    • FDG-PET: Hypometabolism in frontal and temporal regions
    • PET with radioligands for neuroinflammation (e.g., [11C]-PK11195)

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  • 70-year-old patient presented with left-sided weakness and spasticity, and executive dysfunction.
  • Excessive susceptibility artefact in the motor cortex (motor band sign) was most apparent around the right hand motor knob.
  • There was no significant volume loss or corticospinal tract hyperintensity.

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  • A 45-year-old patient had a rapidly progressive tetraparesis over 6 months with upper motor signs and tongue fasciculations.
  • MRI showed subtle hyperintensity within the corticospinal tracts and excessive susceptibility artefact in the motor cortex.

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  • 65-year-old patient presented with twitching arms and legs, muscle weakness and frequent falls.
  • MRI showed marked hyperintensity within the corticospinal tracts and excessive susceptibility artefact in the motor cortex, representing the motor band sign.

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  • 60-year-old patient presenting with brisk reflexes, lower limb weakness and tongue fasciculations.
  • MRI showed mild parietal volume loss near the vertex and marked susceptibility along the motor cortex that extended anteriorly into the paracentral lobule.

Treatment

  • Riluzole modestly prolongs survival; care is largely supportive and multidisciplinary
  • Imaging clues are the "motor band sign" (motor cortex SWI hypointensity) and corticospinal tract T2 hyperintensity

Differential diagnosis

Differential Diagnosis Differentiating Feature
Wallerian degeneration Corticospinal tract T2 hyperintensity in the context of a prior stroke or injury; follows expected degeneration pathway
Primary lateral sclerosis Similar bilateral corticospinal tract T2 hyperintensity and motor band sign; no lower motor neuron involvement
Cervical myelopathy Structural cord compression with degenerative changes on MRI; T2 hyperintensity at the level of compression
Multiple sclerosis Periventricular and juxtacortical demyelinating plaques; Dawson fingers; short spinal cord lesions
Hepatic encephalopathy T1 hyperintensity in globus pallidus; corticospinal tract changes; no motor band sign

  1. Dharmadasa et al. Motor neurone disease. 2018. Handbook of clinical neurology - Open in new tab. ↩