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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 conditions

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 fasiculations.
  • 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 fasiculations.
  • MRI showed mild parietal volume loss near the vertex and marked susceptibility along the motor cortex that extended anteriorly into the paracentral lobule.

Treatment

  • Multidisciplinary approach:
    • Neurologist
    • Respiratory physician
    • Speech and language therapist
    • Physiotherapist
    • Occupational therapist
    • Palliative care team
  • Pharmacological interventions:
    • Riluzole: Glutamate antagonist, prolongs survival by 2-3 months
    • Edaravone: Antioxidant, approved for use in some countries
  • Symptomatic management:
    • Baclofen or botulinum toxin for spasticity
    • Anticholinergics for sialorrhoea
    • Non-invasive ventilation for respiratory insufficiency
  • Nutritional support:
    • Percutaneous endoscopic gastrostomy (PEG) feeding when dysphagia progresses
  • Emerging therapies:
    • Gene therapy approaches (e.g., antisense oligonucleotides for SOD1 mutations)
    • Stem cell therapies (under investigation)

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