Amyotrophic Lateral Sclerosis Signs and Symptoms

Cập nhật: 30 August 2022
Được đánh giá bởi

Giới thiệu

  • Most common neurodegenerative disease of the motor system
  • ALS is classified as a type of motor neuron disease and is colloquially referred to as Lou Gehrig’s disease
  • It is a progressive neurodegenerative disorder that primarily involves the motor neurons in the cerebral cortex, brainstem and spinal cord
  • Most cases of ALS are sporadic (90-95%) but can also be familial (5-10%)

Dịch tễ học

  • Incidence is 0.6-3.8 per 100000 person-years while prevalence is 2.7-8.4 per 100000 persons
  • Risk of developing ALS increases with age
    • Mean age of onset
      • Sporadic: 58-63 years old
      • Familial: 43-52 years old
  • A 1.2-2:1 male to female ratio, increasing age and hereditary disposition being the main risk factors
  • Cognitive dysfunction occurs in 20-50% of cases, and 5-15% develop dementia usually of frontotemporal type
  • There is no cure and the mean duration of survival is 2-5 years without tracheostomy and ventilator support
  • Survival is dependent on several factors (eg clinical presentation, rate of disease progression, early onset of respiratory failure and nutritional status)

Sinh lý bệnh

  • Motor neuron degeneration and death with glial cells replacing lost neurons
  • Disappearance of cortical motor cells leads to retrograde axonal loss and gliosis in the corticospinal tract
  • The spinal cord atrophies, the ventral roots become thin, and large myelinated fibers in motor nerves decrease in number
  • Affected muscles show denervation atrophy and evidence of reinnervation
  • ALS w/ frontotemporal dementia (ALS-FTD) may include a loss of frontal or temporal cortical neurons
  • There is loss of nonmotor neurons with axons contributing to the descending fronto-ponto-cerebellar tract and reduced density of myelinated sensory fibers
  • Intracellular inclusions in degenerating neurons and glia are often reported in neuropathologic studies

Yếu tố nguy cơ

  • Advanced age
  • Family history
  • Cigarette smoking
  • Genetic susceptibility
    • Common Asian variants: SOD1, FUS, C9ORF7, TARDBP
  • Environmental toxin exposure
  • Military service

Clinical Presentation

Clinical Hallmarks of Amyotrophic Lateral Sclerosis (ALS)

  • Presence of upper motor neuron (UMN) and lower motor neuron (LMN) features involving the brainstem and spinal cord
  • Progressive limb weakness, respiratory insufficiency, spasticity, hyperreflexia, and bulbar symptoms such as dysarthria and dysphagia

Main Presentations of ALS

  • Limb-onset amyotrophic lateral sclerosis: Combination of UMN and LMN signs in the limbs
  • Bulbar-onset amyotrophic lateral sclerosis: Speech and swallowing difficulties with limb features developing later in the course of disease
  • Primary lateral sclerosis with pure UMN involvement
  • Progressive muscular atrophy with pure LMN involvement

Signs and Symptoms

  • UMN dysfunction leads to muscle weakness, spasticity and brisk deep tendon reflexes (DTR)
  • LMN dysfunction leads to muscle fasciculations, wasting and weakness
  • Both upper and lower limb involvements are present at diagnosis in about 30-40% of patients
    • Weakness of the lower extremities may first be noted as frequent tripping, stumbling, or awkwardness when walking or running
    • Upper limb weakness may first be noticed as difficulty in buttoning clothes, picking up small objects or turning keys
    • As symptoms worsen, muscle atrophy becomes apparent and spasticity complicates gait and dexterity
    • Patients may experience muscle pain/cramps due to clonus and hyperreflexia
    • Immobility from weakness and spasticity results in painful joint complications
  • Bulbar symptoms are present initially in 19-25% of patients
    • Dysarthria and dysphagia are the most common bulbar symptoms in amyotrophic lateral sclerosis and can reduce patient’s life expectancy and quality of life
    • Bulbar upper motor neuron dysfunction present as spastic dysarthria characterized by slow, labored and distorted speech with nasal quality; pathologically brisk gag and jaw reflexes may also be noted
    • Bulbar lower motor neuron dysfunction lead to tongue wasting, weakness, fasciculations, flaccid dysarthria and dysphagia
  • Extraocular muscles, bladder and bowel control, sensory function, visual disturbances, basal ganglia and skin integrity may remain unaffected
  • Irrespective of the presence or absence of bulbar motor signs, emotional lability occurs in at least half of patients
    • There is conflicting data regarding its correlation with cognitive impairment
    • Prominent pseudobulbar features (eg pathological weeping, laughing or yawning) can be socially disabling
  • A frontotemporal syndrome occurs in up to half of patients with amyotrophic lateral sclerosis and is associated with a poorer prognosis
    • Symptoms of cognitive dysfunction may appear before or after the onset of motor symptoms

Course and Progression

  • Amyotrophic lateral sclerosis is relentlessly progressive
    • 50% die within 30 months of symptom onset
    • 20% survive 5-10 years after symptom onset
  • Factors that reduce survival are older age of onset, early respiratory dysfunction and bulbar-onset disease
  • Independent predictors of prolonged survival include limb-onset disease, younger age at presentation, and shorter diagnostic delay
  • Weakness progresses to disability and eventual need for ventilatory assistance
    • Death is usually caused by respiratory failure