Amyotrophic Lateral Sclerosis (ALS) for the American Board of Psychiatry & Neurology (ABPN) Exam

Amyotrophic Lateral Sclerosis (ALS) for the American Board of Psychiatry & Neurology (ABPN) Exam focuses on neurophysiological, diagnostic, and comprehensive management. Pathophysiology

• Motor Neuron Degeneration: Progressive degeneration of both upper motor neurons (UMNs) in the motor cortex and lower motor neurons (LMNs) in the brainstem and spinal cord.
• SOD1 and C9orf72 mutations: Associated with familial ALS. Other genes like TDP-43 and FUS are also implicated in pathogenesis.
• Mechanisms of Disease: Glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, and protein misfolding play key roles in neurodegeneration.

Clinical Presentation

• UMN Signs: Hyperreflexia, spasticity, and a positive Babinski sign.
• LMN Signs: Fasciculations, muscle atrophy, and flaccid paralysis.
• Bulbar Symptoms: Dysarthria, dysphagia, and tongue fasciculations, leading to difficulty speaking and swallowing.
• Respiratory Symptoms: Weakness of the diaphragm and accessory muscles, leading to dyspnea, hypoventilation, and respiratory failure.
• Cognitive and Behavioral Changes: In some patients, frontotemporal dementia (FTD) may coexist with ALS, manifesting as executive dysfunction or personality changes.

Diagnostic Approach

• Clinical Diagnosis: Based on the presence of both UMN and LMN signs in at least three regions (bulbar, cervical, thoracic, lumbar).
• El Escorial Criteria: Used for diagnosis, which requires evidence of degeneration in both UMN and LMN with the exclusion of other diseases.
• Electromyography (EMG): Shows widespread denervation and reinnervation (fibrillations, fasciculations, positive sharp waves) consistent with LMN damage.
• Nerve Conduction Studies (NCS): Demonstrates normal sensory function, helping to distinguish ALS from peripheral neuropathy.
• MRI of Brain and Spine: To exclude structural lesions (e.g., cervical myelopathy, tumors) that can mimic ALS.
• Pulmonary Function Testing (PFT): To assess respiratory muscle function and predict the need for non-invasive ventilation.

Differential Diagnosis

• Primary Lateral Sclerosis (PLS): Involves only UMNs, presenting with spasticity and hyperreflexia without LMN signs.
• Progressive Muscular Atrophy (PMA): Involves only LMNs, with progressive weakness and atrophy but no UMN involvement.
• Multifocal Motor Neuropathy (MMN): Pure LMN disorder with asymmetric weakness, but distinguishable by positive anti-GM1 antibodies and response to IVIG.
• Myasthenia Gravis (MG): Characterized by fluctuating weakness and positive acetylcholine receptor antibodies.

See Motor Neuron Diseases for a review of PLS, PMA, and MMN. Genetic Considerations

• Familial ALS: Accounts for about 10% of cases; genetic testing for mutations in SOD1, C9orf72, TARDBP, and FUS is important in familial cases.
• Sporadic ALS: The majority of ALS cases are sporadic with no clear genetic cause.

Management

• Disease-Modifying Treatments:
• Riluzole: Reduces glutamate-mediated excitotoxicity, prolonging survival by a few months.
• Edaravone: An antioxidant that may slow progression in certain ALS patients.
• Symptomatic Management:
• Spasticity: Baclofen, tizanidine.
• Sialorrhea: Glycopyrrolate, atropine, or botulinum toxin injections.
• Muscle Cramps: Gabapentin or quinine sulfate.
• Pain: NSAIDs, opioids for managing painful contractures and spasticity.
• Respiratory Support: Non-invasive ventilation (BiPAP) when FVC drops below 50% or when nocturnal hypoventilation develops.
• Nutrition: PEG (percutaneous endoscopic gastrostomy) for patients with severe dysphagia.

Cognitive and Behavioral Symptoms

• Frontotemporal Dementia (FTD): Present in 10–15% of ALS patients. Screening for cognitive impairment is important.
• Psychiatric Symptoms: Depression and anxiety are common and should be addressed with SSRIs or counseling.

End-of-Life Care

• Advance Care Planning: Early discussions about life-sustaining treatments such as mechanical ventilation and PEG feeding.
• Palliative Care: Symptom management in advanced stages of ALS, focusing on pain, dyspnea, and emotional distress.
• Hospice Care: Considered when life expectancy is less than 6 months, focusing on quality of life and comfort.

Prognosis

• Median survival is 3–5 years (3 years from time of diagnosis), with respiratory failure being the leading cause of death.
• Bulbar-onset ALS tends to have a shorter survival compared to limb-onset ALS.

For the ABPN exam, focus on understanding the neurophysiological basis of ALS, diagnostic criteria, differential diagnosis, and the management of both motor and cognitive symptoms, including palliative care options.