What are the potential diagnoses for a 60-year-old patient with sudden onset of severe neurological symptoms, including quadriparesis, ptosis, dysarthria, and dysphagia?

Differential Diagnosis for Sudden-Onset Severe Neurological Symptoms at Age 60

The most critical diagnosis to consider in a 60-year-old with sudden onset of quadriparesis, ptosis, dysarthria, and dysphagia is brainstem or cerebellar stroke, which requires immediate neuroimaging and stroke protocol activation. 1

Immediate Life-Threatening Considerations

Posterior Circulation Stroke

• Brainstem and cerebellar strokes are dangerous causes of vertigo and bulbar symptoms that can present with dysarthria, dysmetria, dysphagia, or sensory/motor loss. 1
• The sudden onset at age 60 is highly characteristic of vascular etiology, particularly posterior circulation involvement. 1
• Physical examination typically discloses neurologic findings relating to the posterior circulation including dysarthria, dysmetria, and dysphagia. 1
• Immediate brain imaging (preferably MRI) is essential to identify cerebellar or brainstem lesions and determine eligibility for acute stroke interventions. 1

Myasthenia Gravis or Myasthenic Crisis

• Myasthenia gravis can present with sudden-onset fatigable muscle weakness, ptosis, double vision, dysphagia, dysarthria, facial muscle weakness, and respiratory insufficiency. 1
• While typically gradual, MG can present acutely, particularly as myasthenic crisis, and has been reported with sudden onset even mimicking stroke in patients around age 60. 2, 3
• The combination of ptosis, dysarthria, dysphagia, and quadriparesis is classic for generalized MG. 1, 4
• Edrophonium testing, anti-acetylcholine receptor antibodies, and electromyography are diagnostic. 2, 5
• Critical pitfall: Respiratory muscle involvement can be life-threatening and requires immediate recognition. 1

Secondary Diagnostic Considerations

Botulism

• Botulism presents with cranial nerve dysfunction including ptosis, diplopia, dysarthria, dysphonia, and dysphagia, followed by descending paralysis. 1
• The sudden onset and bulbar symptoms with descending weakness match the clinical pattern. 1
• Unlike stroke, symptoms are typically symmetric and progress in a descending pattern. 1

Guillain-Barré Syndrome (or Miller Fisher Variant)

• Guillain-Barré can present with ascending progressive muscle weakness, facial weakness, and difficulty swallowing, though Miller Fisher variant specifically presents with ataxia, areflexia, and ophthalmoplegia. 1
• The sudden onset and age are compatible, though ascending pattern is more typical than the quadriparesis presentation. 1

Immune Checkpoint Inhibitor-Related Neurologic Toxicity

• If the patient has cancer history and recent immunotherapy exposure, neurologic irAEs can present as myasthenia gravis, myasthenic syndrome, or Guillain-Barré-like syndrome with median onset at 4 weeks (range 1-68 weeks). 1
• Presenting symptoms may include fatigable muscle weakness, ptosis, double vision, dysphagia, dysarthria, and facial weakness. 1

Mitochondrial Myopathy (Progressive External Ophthalmoplegia)

• PEO can rarely present with acute onset dysphagia, quadriparesis, ptosis, and respiratory insufficiency, mimicking myasthenic crisis. 3
• C10orf2 (PEO1) gene mutations should be considered when myasthenia testing is negative. 3

Critical Diagnostic Algorithm

Step 1: Immediate Assessment

• Activate stroke protocol if presentation is within therapeutic window for intervention. 1
• Assess airway and respiratory function given dysphagia and potential for aspiration or respiratory muscle weakness. 1, 5
• Check for fluctuating symptoms (suggests MG) versus sudden fixed deficit (suggests stroke). 1

Step 2: Emergent Neuroimaging

• MRI brain with focus on posterior fossa is the preferred modality to identify brainstem/cerebellar stroke, mass lesions, or demyelinating disease. 1
• CT head if MRI unavailable or contraindicated. 1

Step 3: Targeted Laboratory and Electrophysiologic Testing

• Anti-acetylcholine receptor antibodies, muscle enzymes, thyroid function. 5
• Electromyography/nerve conduction studies if myasthenia or neuropathy suspected. 2, 5
• Consider lumbar puncture if Guillain-Barré suspected (elevated protein with normal cell count). 1

Step 4: Specialized Testing Based on Initial Results

• If imaging negative and MG suspected: edrophonium test, repetitive nerve stimulation. 2
• If concern for botulism: stool culture, serum toxin assay, food history. 1
• If immunotherapy history: coordinate with oncology for irAE management. 1

Common Pitfalls to Avoid

• Do not assume stroke is excluded based on normal CT alone—MRI is far more sensitive for posterior fossa lesions. 1
• Do not overlook respiratory compromise—both myasthenic crisis and botulism can cause respiratory failure requiring intubation. 1
• Do not dismiss MG based on negative edrophonium test alone—seronegative MG exists and requires antibody testing and EMG. 2
• Do not delay dysphagia assessment—aspiration pneumonia is a major cause of morbidity and mortality in neurogenic dysphagia. 5