amyotrophic%20lateral%20sclerosis
AMYOTROPHIC LATERAL SCLEROSIS
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with undetermined etiology that primarily involves the motor neurons in the cerebral cortex, brainstem and spinal cord.
There is no cure and the mean duration of survival is 2-5 years without tracheostomy and ventilator support.
Clinical hallmarks of ALS are: presence of upper & lower motor neuron features involving the brainstem and spinal cord and progressive limb weakness, respiratory insufficiency, spasticity, hyperreflexia, and bulbar symptoms such as dysarthria and dysphagia.

Introduction

  • Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease of the motor system
  • Also known as motor neuron disease or Lou Gehrig’s disease
  • It is a progressive neurodegenerative disorder that primarily involves the motor neurons in the cerebral cortex, brainstem and spinal cord
  • Some cases of ALS are sporadic but can be found familial
  • Mean age of onset is 43-52 years old in familial and 58-63 years old in sporadic cases
  • A 1.5:1 male to female ratio, increasing age and hereditary disposition being the main risk factors
  • Cognitive dysfunction occurs in 30-50% 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)

Signs and Symptoms

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 amyotrophic lateral sclerosis (ALS) include:

  • Limb-onset amyotrophic lateral sclerosis: Combination of  upper motor neuron and lower motor neuron 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 upper motor neuron involvement
  • Progressive muscular atrophy with pure lower motor neuron involvement

Signs and symptoms:

  • Upper motor neuron dysfunction leads to muscle weakness, spasticity and brisk deep tendon reflexes (DTR)
  • Lower motor neuron 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
    • It does not correlate 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
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