Amyotrophic Lateral Sclerosis (ALS) for the American Board of Internal Medicine (ABIM) Exam

Amyotrophic Lateral Sclerosis (ALS) for the American Board of Internal Medicine (ABIM) Exam Clinical Presentation

• Early Symptoms: Asymmetric, progressive muscle weakness, often starting in the hands, feet, or bulbar region (dysarthria, dysphagia).
• Upper Motor Neuron (UMN) Signs: Hyperreflexia, spasticity, and positive Babinski sign.
• Lower Motor Neuron (LMN) Signs: Muscle wasting, fasciculations, flaccid paralysis.
• Bulbar Symptoms: Dysarthria, difficulty swallowing, and tongue fasciculations/atrophy.
• Respiratory Symptoms: Dyspnea, orthopnea, and hypoventilation due to diaphragmatic weakness.

Differential Diagnosis

• Cervical Myelopathy: Mimics ALS with UMN and LMN signs but is ruled out by imaging.
• Myasthenia Gravis (MG): Consider when dysphagia and weakness are prominent; distinguished by fluctuating weakness and positive acetylcholine receptor antibodies.
• Multiple Sclerosis (MS): Typically includes sensory symptoms and brain/spinal cord lesions on MRI, absent in ALS.

Diagnostic Approach

• Electromyography (EMG): Confirms widespread denervation in multiple regions (fibrillations, positive sharp waves).
• Nerve Conduction Studies (NCS): Normal sensory nerve conduction differentiates ALS from polyneuropathy.
• MRI of Brain and Spine: Used to exclude structural causes like tumors, spondylosis.
• Genetic Testing: In familial ALS, test for SOD1, C9orf72, TDP-43, or FUS mutations.

Management

• Disease-Modifying Therapies:
• Riluzole: Prolongs survival by slowing disease progression through glutamate inhibition.
• Edaravone: May slow functional decline in a subset of patients.
• Respiratory Support:
• Non-invasive Ventilation (BiPAP): Initiated when forced vital capacity (FVC) drops below 50% or in cases of sleep-disordered breathing.
• Tracheostomy/Mechanical Ventilation: Considered in advanced stages but involves quality-of-life discussions.
• Nutrition:
• Gastrostomy (PEG tube): Recommended for severe dysphagia to maintain nutrition and prevent aspiration.

Symptomatic Treatment

• Spasticity: Baclofen or tizanidine.
• Sialorrhea: Glycopyrrolate, atropine, or botulinum toxin injections.
• Muscle Cramps: Quinine sulfate or gabapentin.
• Respiratory Secretions: Anticholinergic agents or mechanical suctioning.
• Pain Management: NSAIDs, opioids for muscle pain or contractures.

Multidisciplinary Care

• ALS requires coordinated care involving neurologists, pulmonologists, physical therapists, speech therapists, and nutritionists.
• Physical Therapy: To prevent contractures and manage muscle stiffness.
• Speech Therapy: To assist with communication aids and swallowing difficulties.

End-of-Life Care and Ethical Considerations

• Advance Directives: Discuss early regarding ventilator support, gastrostomy, and resuscitation preferences.
• Palliative Care: Focus on managing symptoms like dyspnea, pain, and anxiety in the later stages of ALS.
• Hospice: Appropriate when life expectancy is under 6 months.

Prognosis

• Median survival is 3–5 years (3 years from diagnosis), with respiratory failure being the most common cause of death.
• Bulbar-onset ALS has a worse prognosis compared to limb-onset ALS.

For the ABIM exam, the emphasis is on clinical decision-making, especially in symptom management, end-of-life care, and the comprehensive approach to a patient with ALS.