What are the differential diagnoses for acute flaccid paralysis in a patient who recently had a sore throat and fever?

Differential Diagnosis for Acute Flaccid Paralysis After Throat Pain and Fever

In a patient presenting with acute flaccid paralysis following throat pain and fever, the primary differential diagnoses are Guillain-Barré syndrome (most common), diphtheria-associated polyneuropathy, acute flaccid myelitis from enterovirus infection, and less commonly botulism or acute transverse myelitis. 1, 2

Most Likely Diagnoses Given the Clinical Context

Guillain-Barré Syndrome (GBS)

• GBS is the most common cause of acute flaccid paralysis and frequently follows upper respiratory or gastrointestinal infections 2
• Presents with ascending bilateral symmetric weakness progressing from legs to arms to cranial nerves 1, 2
• Characterized by areflexia or hyporeflexia in affected limbs 1, 2
• Distal paresthesias or sensory loss are typical 1, 2
• Typically reaches maximum disability within 2 weeks 1
• Maximum disability within 24 hours or after 4 weeks makes GBS less likely 1, 3

Diphtheria-Associated Polyneuropathy

• Can cause polyradiculoneuritis following pharyngeal infection 2
• Should be strongly considered when throat pain precedes paralysis 2
• Presents similarly to GBS with flaccid weakness 2

Acute Flaccid Myelitis (AFM)

• Predominantly affects previously healthy children with prodromal fever or respiratory symptoms 4
• Caused by nonpolio enteroviruses, particularly enterovirus D68 and A71 2, 5, 4
• Characterized by acute flaccid paralysis with spinal cord gray matter abnormalities on MRI 4
• Clinical manifestations described as "polio-like" due to anterior horn cell injury 4
• Enterovirus can be detected in stool samples weeks after primary infection when CSF testing is negative 5

Less Common but Critical Diagnoses

Botulism

• Presents with descending flaccid paralysis starting with cranial nerves, then trunk, then extremities 1, 2
• Preserved or normal reflexes distinguish botulism from GBS 1, 2
• No sensory involvement 1, 2
• Patients remain alert and oriented despite appearing intoxicated from ptosis and dysarthria 1, 3
• Altered mental status excludes botulism 1
• Frequently misdiagnosed as myasthenia gravis, stroke, or psychiatric disorders 1, 2

Infectious Causes

• Lyme borreliosis can cause polyradiculoneuritis 2
• CMV polyradiculomyelopathy in HIV patients causes GBS-like syndrome with urinary retention and CSF neutrophilic pleocytosis 2
• Rabies in endemic areas can cause flaccid paralysis 2
• Polio in regions where not eradicated (sub-Saharan Africa, Pakistan) 2
• Acute transverse myelitis from infectious causes 2

Brainstem and CNS Pathology

• Brainstem or meningoencephalitis can present with flaccid weakness 6, 2
• Brainstem stroke or vasculitis 2
• Arbovirus testing and rabies testing should be performed when acute flaccid paralysis is present 6

Critical Distinguishing Physical Examination Features

Pattern of Weakness Progression

• Ascending pattern (legs → arms → cranial nerves) indicates GBS 1, 2
• Descending pattern (cranial nerves → trunk → extremities) indicates botulism until proven otherwise 1, 2

Reflex Examination

• Areflexia or hyporeflexia strongly suggests GBS, though reflexes can be normal initially 1, 2
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis 1, 2

Sensory Examination

• Distal paresthesias or sensory loss typical in GBS 1, 2
• Sensory deficits absent in botulism 1, 2
• No sensory symptoms suggests botulism, myasthenia gravis, or pure motor disorders 2

Mental Status

• Alert and oriented mental status characteristic of botulism 1, 3, 2
• Altered consciousness suggests encephalitis, stroke, or metabolic encephalopathy rather than peripheral causes 2

Additional Differential Considerations

Metabolic and Toxic Causes

• Hypokalemia, hypophosphatemia, hypermagnesemia 2
• Thyrotoxic hypokalemic periodic paralysis (more common in certain geographic regions) 1, 2
• Organophosphate poisoning, heavy metal toxicity (lead, thallium, arsenic) 2

Neuromuscular Junction Disorders

• Myasthenia gravis presents with preserved reflexes and fatigable weakness 1
• Lambert-Eaton myasthenic syndrome 2

Spinal Cord Pathology

• Spinal cord compression or cauda equina syndrome 2
• Urgent imaging of spine needed when spinal cord involvement suspected 7

Critical Diagnostic Pitfalls to Avoid

• Do not dismiss GBS based on normal initial electrodiagnostic studies—changes may not appear until 10-14 days after symptom onset 1, 3, 2
• Do not wait for CSF protein elevation before initiating treatment 1, 3, 2
• Albuminocytologic dissociation supports GBS but is not required for diagnosis 1
• Botulism frequently misdiagnosed, with 34% presenting with only 1-2 cranial nerve palsies initially 1, 3, 2
• Asymmetric presentation does not exclude GBS, particularly the pharyngeal-cervical-brachial variant 1
• Facial paralysis in botulism can mask respiratory distress by producing placid expression and preventing nasal flaring 1, 3, 2