Is anterior horn cell disease mainly caused by motor neuron disease?

Anterior Horn Cell Disease and Motor Neuron Disease

Anterior horn cell disease is primarily caused by motor neuron diseases, with amyotrophic lateral sclerosis (ALS) representing approximately 85% of all motor neuron disease cases. 1, 2

Classification and Pathophysiology

• Anterior horn cell disorders affect the cell bodies of lower motor neurons located in the anterior horn of the spinal cord, representing central nervous system disorders with peripheral manifestations 1
• Motor neuron diseases involve progressive degeneration of motor neurons, resulting in atrophy of skeletal muscles including respiratory muscles 3
• ALS, the most common motor neuron disease, involves degeneration of both upper and lower motor neurons in the brain and spinal cord along the corticospinal tracts 3

Types of Anterior Horn Cell Disorders

• The primary anterior horn cell disorders include:
  • Amyotrophic lateral sclerosis (ALS) - most common, representing 85% of motor neuron disease cases 3
  • Spinal muscular atrophy (SMA) types I to III in children 4
  • Progressive muscular atrophy (PMA) 4
  • Primary lateral sclerosis (PLS) 4
  • Progressive bulbar palsy (PBP) 4
  • Kennedy's disease 4
  • Poliomyelitis 1
  • Some manifestations of Pompe disease 1

Diagnostic Approach

• Electrodiagnostic studies are crucial for diagnosing anterior horn cell disorders 1, 4:

  • Motor nerve conduction studies may be normal or reveal low compound muscle action potential (CMAP) amplitudes with relatively normal conduction velocities 4
  • Sensory nerve conduction studies are typically normal (except in Kennedy's disease) 4
  • Needle electromyography (EMG) is essential and typically shows:
    • Abnormal spontaneous activity including fibrillation potentials and positive sharp waves 4
    • Fasciculation potentials and complex repetitive discharges 4
    • Abnormal motor unit morphology with polyphasic motor units and large amplitude/duration motor unit action potentials 4
    • Reduced recruitment with abnormally rapidly firing motor units 4

• Perform needle EMG in initial evaluation to determine presence of denervation as evidence of anterior horn cell involvement 5

• Perform nerve conduction studies at initial evaluation 5

Imaging in Anterior Horn Cell Disorders

• MRI of the head without IV contrast is recommended as the initial imaging modality for suspected motor neuron disease 6
• Common MRI findings include:
  • Abnormal T2/STIR signal in the anterior horns ("snake eyes" appearance) in the spine 6
  • Abnormal T2/FLAIR signal in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 1

Clinical Monitoring and Management

• Motor and functional assessments are recommended at 3-6 month intervals for children under five years, and annually in older children and adults 5, 6
• Regular assessment of musculoskeletal impairments, functional deficits, and disability levels is recommended for clinical monitoring 6
• For ALS specifically, riluzole (50 mg twice daily) has been shown to extend survival time to tracheostomy or death by approximately 60-90 days compared to placebo 7
• The American Academy of Medical Genetics and Genomics recommends submaximal, functional, and aerobic exercise for progressive muscle diseases, while avoiding excessive resistive and eccentric exercise 6

Distinguishing Features from Other Neurological Disorders

• Anterior horn cell disorders differ from peripheral neuropathies:

  • Peripheral neuropathies involve pathology of peripheral nerves outside the spinal cord 1
  • Peripheral neuropathies typically present with both sensory and motor symptoms, often in a length-dependent pattern 1
  • Anterior horn cell disorders primarily affect motor function with preserved sensory function 1

• Anterior horn cell disorders differ from muscular dystrophies:

  • Muscular dystrophies are genetic diseases characterized by progressive weakness due to primary muscle pathology 3
  • Muscular dystrophies typically lack the upper motor neuron signs (hyperreflexia, spasticity) seen in ALS 3
  • Muscular dystrophies often have onset in childhood or adolescence (though some forms can present in adulthood) 3

Prognosis

• ALS has a mean survival of 3-5 years after symptom onset, with only 5-10% living longer than 10 years 3
• Other motor neuron diseases have variable progression rates, but most are progressive degenerative diseases 4