Description

• Progressive, incurable disease of adults
• Neurodegenerative disease of the motor system at all levels
• Some patients have associated dementia
• Manifestations:
  • Muscle weakness
  • Wasting
  • Fasciculations
  • Babinski sign
  • Hyperreflexia
• Variants with predominately upper or lower motor neuron manifestations also occur
• Predilection for the motor system and sparing of other neurons
• May begin with bulbar symptoms of dysphagia and dysarthria
• Also known as “Lou Gehrig disease” after the famous baseball player who was affected
• Eventually leads to respiratory compromise secondary to weakness of diaphragm and other muscles of respiration
• 80% of cases begin between ages 40 and 70 yr
• Death (usually from respiratory paralysis) typically occurs within 3–5 yr of the diagnosis
• 50% die within 3 yr
• ∼10% ALS patients live 10 yr or more
• Males > females

Etiology

• Etiology of amyotrophic lateral sclerosis (ALS) is unknown
• ∼10% of affected patients have another affected family member
• Cigarette smoking and heavy metal exposure may be risk factors
• There is a disease cluster in the western Pacific
• Pathologically, there is loss of both upper and lower motor neuron cells

Signs and Symptoms

• Asymmetric limb weakness is the most common presentation of ALS (80%)
• May begin in either the arms (cervical onset) or the legs (lumbar onset):
  • Later all limbs are affected
• Bulbar ALS:
  • Usually presents with dysarthria or dysphagia
  • Second most common presentation
• Both lower motor neuron (weakness and wasting with fasciculation) and upper motor neuron signs (Babinski sign with hyperreflexia) occur
• Respiratory muscles and the vocal cords are affected late
• Muscle fasciculation is common, but may not be apparent to the patient
• Extraocular muscles, sphincters, cognition, and sensation are spared

• Most ED patients with ALS will present with an established diagnosis
• History should focus on clues regarding acute medical issues and functional decline
• When ALS is suspected due to a complaint of “weakness” consider this occurs with many illnesses including:
  • Pulmonary disease
  • Cardiac disease
  • Anemia
  • Endocrine disorders
  • Toxidromes
  • Diseases of muscles or joints
  • Spinal cord abnormalities
  • Depression
• Differentiate true weakness from: Shortness of breath, chest pain, joint pain, fatigue, poor exercise tolerance, etc.
• True weakness often leads to complaints of inability to perform specific tasks:
  • Bulbar palsy:
    • Facial weakness
    • Weakness and fasciculation of tongue
    • Dysarthria
  • Cervical onset ALS:
    • Difficulty with washing hair, using comb
    • Impaired pincer grip
  • Lumbar onset ALS:
    • Frequent trips secondary to foot drop
    • Difficulty walking up stairs

• A detailed and thorough neurologic exam is the key to diagnosis but is not typically performed in the ED
• Upper motor neuron disease causes slow uncoordinated movements and stiffness
• Lower motor neuron disease causes weakness accompanied by atrophy and muscle cramps are common
• Common findings:
  • Brisk reflexes
  • Fasciculations
  • Muscle wasting
• Exam should focus on excluding or confirming other conditions

Essential Workup

• Previously undiagnosed ALS:
  • Diagnosis of ALS is clinical and rarely made in the ED:
    • Recognition of the possibility of this disease is sufficient and mandates referral for workup
  • If ALS is suspected, forced vital capacity (FVC) should be performed
• Known ALS patient:
  • Patients with known disease and progressive symptoms:
    • Evaluate potentially treatable complications with lab and imaging studies
  • FVC is a sensitive indicator of respiratory muscle weakness:
    • FVC <50% of predicted is considered a sign of advanced disease
    • FVC <50% usually requires ventilatory support
    • Start with noninvasive positive pressure ventilation when possible
    • Compare with the patient's previous baseline
  • CXR may reveal aspiration or pneumonia or comorbid conditions such as CHF
  • Pulse oximetry and blood gas analysis aid in the diagnosis of respiratory failure
  • Electrolytes and other blood chemistry tests may reveal a treatable cause of increasing weakness

Diagnostic Tests and Interpretation

• In cases of undifferentiated weakness, consider CPK measurement along with blood chemistry:
  • Elevated CPK is associated with myopathy
• Electrolyte abnormalities such as hypokalemia, hypercalcemia, etc. may cause generalized weakness but this is typically in association with other signs and symptoms
• CBC, UA may be indicated to look for source of infection

• Check FVC
• Electromyography (EMG) may help confirm the diagnosis (not usually an ED test)

Differential Diagnosis

• Cervical cord compression:
  • Similar symptoms but usually acute onset with pain and sensory changes
  • Spinal MRI or myelography for diagnosis
• Thyrotoxicosis may mimic ALS:
  • Usually marked systemic symptoms
• Heavy metal poisoning (lead, mercury, arsenic)
• Syphilis and Lyme disease
• Lymphoma may have an associated lower motor neuron syndrome, which mimics ALS
• Bulbar ALS:
  • Esophageal cancer
  • Myasthenia gravis

Pre Hospital

• Many patients will have advanced directives:
  • Unless immediate intervention is essential, intubation should be avoided until directives have been ascertained
  • Noninvasive means of ventilatory support may be tried first

Initial Stabilization/Therapy

• Respiratory insufficiency or failure:
  • Ascertain any advanced directives
  • Noninvasive ventilatory support
  • Intubation as indicated
• Weaning off the ventilator is very difficult:
  • Average survival after institution of ventilation is 19 mo

Ed Treatment/Procedures

• Sedation and pain control as indicated:
  • Joint pain may respond to NSAIDs
• Insomnia from pressure pain (owing to immobility) may respond to diphenhydramine or amitriptyline
  • Insomnia may also be treated with benzodiazepines
• Aspiration or drooling may be treated with amitriptyline, atropine, or hyoscyamine (dries secretions)
• Muscle cramps may respond to baclofen or tizanidine
• Constipation is related to immobility and diet:
  • Treated with laxatives, stool softeners, and dietary changes

Medication

• Amitriptyline: 25–100 mg PO QHS
• Atropine: 0.4 mg PO q4–6h
• Baclofen: 10–25 mg PO TID
• Diphenhydramine: 25–50 mg PO nightly at bedtime
• Tizanidine 2–4 mg PO BID

Disposition

• Need for respiratory support
• Dehydration
• Unable to be cared for at home owing to progression of illness
• Complications (e.g., infection) or other diagnosis that requires admission

• Suspected ALS: Refer for outpatient evaluation if general condition permits and other serious conditions requiring admission are ruled out
• Complication of known ALS: Discharge if outpatient treatment available and stable respiratory status

Follow-Up Recommendations

If considering diagnosis of ALS, prompt follow-up with a neurologist should be arranged