Harvey's Garden

Amyotrophic lateral sclerosis

2 min read

A neurodegenerative disease with upper and lower motor neuron dysfunction. Pure motor neuron disease

Epidemiology

  • Mean age of onset is 65 years.

Etiology

Pathophysiology

  • Neurodegenerative disorder affecting both Upper Motor Neurons (UMN) and Lower Motor Neurons (LMN).
  • Most cases are sporadic (90-95%).
  • Familial cases (5-10%) often associated with superoxide dismutase 1 (SOD1) mutation (zinc-copper superoxide dismutase mutation).
  • Mechanism: Oxidative stress, glutamate excitotoxicity, and protein aggregation lead to neuronal death.
  • Degeneration of:
    • Anterior horn cells of spinal cord (LMN signs).
    • Corticospinal tract (UMN signs).
    • Motor nuclei of brainstem (CN V, IX, X, XII).
  • Focal Onset:
    • The degenerative process in ALS does not begin in all motor neurons simultaneously. It starts in a specific, focal group of motor neurons
  • Pattern of Spread (Prion-like Propagation):
    • The leading hypothesis is that the pathogenic proteins (e.g., misfolded TDP-43) propagate from sick neurons to healthy, synaptically connected neurons.

Clinical features

General disease characteristics

Early symptoms

  • Symptoms are highly variable and potentially non-specific (e.g., subtle vocal changes or difficulties grasping objects)
  • Asymmetric limb weakness, often beginning with weakness in the hands and feet
  • Bulbar symptoms such as dysarthria, dysphagia, and tongue atrophy (20% of cases at disease onset)
  • Pseudobulbar palsy with pseudobulbar affect may develop.
  • Fasciculations, cramps, and muscle stiffness
  • Weight loss
  • Split hand sign: a wasting pattern in which the muscles of the thenar eminence atrophy due to degeneration of the lateral portion of the anterior horn of the spinal cord

Late symptoms

  • Cognitive impairment (approx. 15% of ALS patients meet the criteria for frontotemporal dementia)
  • Autonomic symptoms (e.g., constipation, bladder dysfunction) may develop; the mechanism of development is unclear.
  • Life-threatening symptoms
    • Respiratory failure due to paralysis of respiratory muscles
    • Dysphagia due to bulbar weakness or pseudobulbar palsy

Diagnosis

  • Electromyography
    • Denervation: fibrillations, positive sharp waves, and large amplitudes
    • Fasciculations

Differential Diagnosis

  • Myasthenia gravis
    • Weakness improves with acetylcholinesterase inhibitors
    • No UMN or LMN signs

Treatment

  • Riluzole
    • A sodium-channel blocker that inhibits glutamate release in the CNS and decreases glutamate excitotoxicity
    • Prolongs survival and slows functional decline in patients with ALS (on average, for 3 months)
  • Edaravone
    • A free radical scavenger
    • Has been shown to slow functional decline in some patients with ALS

Graph View

Backlinks