Description

• Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease that affects approximately 1.5–3 per 100,000 people and 5000 new diagnoses per year
• Also known as “Lou Gehrig Disease” for the famous baseball player who contracted the illness.
• Causes incurable, progressive paralysis of upper and lower motor neurons
• Upper and lower motor neuron signs will either coexist at presentation, or develop over time
• Commonly begins with unilateral signs of lower motor neuron degeneration
• May begin with bulbar symptoms of dysphagia and dysarthria
• Eventually leads to respiratory compromise secondary to weakness of diaphragm and other muscles of respiration
• Some patients have associated dementia
• Manifestations:
  • Muscle weakness
  • Wasting
  • Fasciculations
  • Babinski sign
  • Hyperreflexia
• Variants with upper or lower motor neuron predominance exist
• 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% of patients die within 3 yr
• ∼10% of ALS patients live 10 yr or more
• Males > Females

Etiology

• Genetic and environmental factors have been implicated in causality; however, precise etiology is unknown.
• 5–10% of affected patients have another affected family member, affecting males and females equally as often
• 90–95% of cases are sporadic, affecting males more often than females
• Risk factors may include concussions, military jobs, cigarette smoke, heavy metal exposure, pesticides, cyanobacteria, and electromagnetic fields
• Cigarette smoking and heavy metal exposure may be risk factors

Signs And Symptoms

• Suspect ALS in a patient with progressive, unilateral ascending weakness
• Asymmetric limb weakness is the most common initial presenting symptom (70%)
• Bulbar symptoms of dysarthria or dysphagia as an initial presenting symptom account for approximately 25% of cases

Truncal involvement at onset accounts for approximately 5% of patients

• 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 usually affected later in the disease course
• Muscle fasciculations are common, but may not be apparent to the patient
• Extraocular muscles, sphincters, cognition, and sensation are spared

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 urgent evaluation and workup by neurology
  • If ALS is suspected, assessment of respiratory parameters including forced vital capacity (FVC) should be performed
  • Avoid hypercarbia to prevent triggering hypercapnic drive
  • Establish goals of care including code status early
• Known ALS patient:
  • Patients with known disease and progressive symptoms:
    • Evaluate potentially treatable complications with lab and imaging studies
    • Review code status and discuss palliative care options with progressive patients when appropriate
  • FVC is a sensitive indicator of respiratory muscle weakness:
    • Start with noninvasive positive pressure ventilation when possible before intubation
    • FVC <50% of predicted is considered a sign of advanced disease and usually requires ventilatory support
    • 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

Differential Diagnosis

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

Prehospital

Controversies:

• 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 q8h
• Diphenhydramine: 25–50 mg PO nightly at bedtime
• Tizanidine 2–4 mg PO q12h

Disposition

Follow-Up Recommendations

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