What is the differential diagnosis for a patient presenting with acute flaccid paralysis?

Differential Diagnosis of Acute Flaccid Paralysis

Primary Diagnostic Categories

The differential diagnosis of acute flaccid paralysis is broad and includes life-threatening conditions requiring immediate recognition, with Guillain-Barré syndrome and botulism being the most critical to distinguish early. 1, 2

Peripheral Nerve Disorders

• Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis, presenting with ascending bilateral symmetric weakness progressing from legs to arms to cranial nerves, with areflexia or hyporeflexia in affected limbs 1, 2
• GBS subtypes include acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor-sensory axonal neuropathy (AMSAN) 1
• Chronic inflammatory demyelinating polyneuropathy (CIDP) with acute onset can mimic GBS but progresses over more than 8 weeks 1, 3
• Diphtheria-associated polyneuropathy and Lyme borreliosis can cause polyradiculoneuritis 1
• Critical illness polyneuropathy or myopathy occurs in critically ill patients 1

Neuromuscular Junction Disorders

• Botulism presents with descending flaccid paralysis starting with cranial nerves (drooping eyelids, weakened jaw clench), then trunk, then extremities, with preserved or normal reflexes and no sensory involvement 4, 1
• Lambert-Eaton myasthenic syndrome should be considered in the differential 1
• Myasthenia gravis can present with fluctuating weakness and cranial nerve involvement 4

Spinal Cord Disorders

• Acute flaccid myelitis (AFM) associated with enteroviruses (D68, A71), arthropod-borne viruses (Zika, chikungunya, West Nile), rabies, or polio presents with acute onset asymmetric weakness and areflexia 1, 5, 6
• West Nile virus infection causes poliomyelitis-like syndrome with asymmetric weakness, areflexia, and involvement of spinal anterior horn cells 7
• Acute transverse myelitis from infectious causes can cause flaccid paralysis 1
• CMV polyradiculomyelopathy in HIV patients causes Guillain-Barré-like syndrome with urinary retention, progressive bilateral leg weakness, flaccid paraplegia, and CSF neutrophilic pleocytosis 1
• Spinal cord compression or cauda equina syndrome can cause flaccid weakness 1

Muscle Disorders

• Hypokalemic periodic paralysis (including thyrotoxic variant) presents with jaw-opening weakness and is more common in low-income settings 1, 8
• Acute rhabdomyolysis and drug-induced toxic myopathy from colchicine, chloroquine, emetine, or statins can cause flaccid paralysis 1

Metabolic and Toxic Causes

• Electrolyte disorders including hypokalaemia, hypophosphataemia, and hypermagnesaemia can cause weakness 1, 8
• Organophosphate poisoning causes cholinergic crisis with flaccid paralysis 1
• Heavy metal toxicity (lead, thallium, arsenic) and porphyria are potential causes 1, 8
• Neuroparalytic snake envenomation is a common cause in endemic areas, accounting for over 50% of cases in some regions 8

Central Nervous System Disorders

• Brainstem stroke or vasculitis can cause flaccid weakness 1
• Brainstem or meningoencephalitis can present with flaccid paralysis 1
• Leptomeningeal metastases or neurolymphomatosis can cause neurological symptoms 1

Nutritional Deficiencies

• Vitamin B1 deficiency (beriberi, Wernicke encephalopathy), B12 deficiency (subacute combined degeneration), and vitamin E deficiency can cause neurological symptoms 1

Other Considerations

• Polio in regions where it has not been eradicated (sub-Saharan Africa, Pakistan) remains a consideration 1
• Rabies in endemic areas can cause flaccid paralysis 1
• Tetanus (Clostridium tetani) can cause rigidity but may present atypically 1
• Mitochondrial disease can cause weakness 1
• Functional or conversion disorder can mimic organic paralysis 1

Critical Distinguishing Features for Immediate Triage

Pattern of Weakness Progression

• Ascending pattern (legs → arms → cranial nerves) strongly suggests Guillain-Barré syndrome 1, 2, 3
• Descending pattern (cranial nerves → trunk → extremities) indicates botulism until proven otherwise 4, 1, 2
• Asymmetric presentation suggests acute flaccid myelitis, West Nile virus infection, or stroke 5, 6, 7

Reflex Examination

• Areflexia or hyporeflexia strongly suggests Guillain-Barré syndrome, though reflexes can be normal initially 1, 2, 3
• Normal or preserved reflexes with flaccid paralysis indicates botulism, myasthenia gravis, or periodic paralysis 1, 2, 3

Sensory Examination

• Distal paresthesias or sensory loss is typical in Guillain-Barré syndrome but absent in botulism 1
• No sensory symptoms suggests botulism, myasthenia gravis, acute flaccid myelitis, or pure motor disorders 1, 6

Mental Status

• Alert and oriented is characteristic of botulism despite appearing intoxicated from ptosis and dysarthria 4, 1
• Altered consciousness suggests encephalitis, stroke, or metabolic encephalopathy rather than peripheral causes 1

Cranial Nerve Involvement

• Symmetric cranial neuropathies (drooping eyelids, weakened jaw clench, dilated pupils) suggest botulism 4
• Facial weakness can occur in both Guillain-Barré syndrome and botulism, but in botulism it can mask respiratory distress by producing a placid expression and preventing nasal flaring 4, 1, 3

Autonomic Dysfunction

• Cardiac arrhythmias and blood pressure instability indicate autonomic dysfunction in Guillain-Barré syndrome and are life-threatening 2
• Dry mouth, dry eyes, urinary retention, constipation or ileus suggest botulism 4

Common Diagnostic Pitfalls to Avoid

• Do not dismiss Guillain-Barré syndrome based on normal initial electrodiagnostic studies, as changes may not appear until 10-14 days after symptom onset 1, 2, 3
• Do not wait for CSF protein elevation before initiating treatment for suspected Guillain-Barré syndrome 2, 3
• Botulism is frequently misdiagnosed as myasthenia gravis, stroke, or psychiatric disorders, with 34% presenting with only 1-2 cranial nerve palsies initially 4, 1, 3
• Facial paralysis in botulism can mask respiratory distress by producing a placid expression and preventing nasal flaring 4, 1, 3
• Asymmetric presentation does not exclude Guillain-Barré syndrome, particularly the pharyngeal-cervical-brachial variant 3
• Do not assume Bell's palsy for isolated facial weakness without excluding other causes through history and physical examination 4

Geographic and Epidemiologic Considerations

• Organophosphate intoxication, botulism, rabies, polio, and tetanus occur more frequently in low- and middle-income countries 1
• Neuroparalytic snake envenomation is a leading cause in endemic regions, accounting for over 50% of acute flaccid paralysis cases in some areas 8
• Hypokalemic thyrotoxic periodic paralysis is more common in certain geographic regions 1
• Infections with HIV, HTLV-1, and arthropod-borne viruses (Zika, chikungunya, West Nile) are frequently reported in low-income countries 1
• Japanese encephalitis can present with acute flaccid paralysis with clinical and pathological features similar to poliomyelitis 4
• Acute flaccid myelitis shows seasonal peaks every 2 years in the United States since 2012, linked to enterovirus D68 outbreaks 6

Immediate Life-Threatening Assessment Priorities

Approximately 20% of Guillain-Barré syndrome patients develop respiratory failure requiring mechanical ventilation, which can occur without obvious dyspnea, emphasizing the need for rapid assessment. 2

• Check vital capacity and negative inspiratory force immediately, as respiratory compromise can develop rapidly and requires intubation before crisis 2
• Monitor for cardiac arrhythmias and blood pressure instability indicating autonomic dysfunction 2
• Assess for bulbar weakness (dysphagia, dysarthria) predicting aspiration risk and respiratory compromise 4, 2
• Institute frequent serial monitoring of respiratory and bulbar function, as serial measurements are more helpful than single measurements 4
• Focus respiratory examination on respiratory rate, lung auscultation, work of breathing including accessory muscle use, nasal flaring, and paradoxical breathing 4
• Consider respiratory status in context of neurologic status because paralysis can alter signs typically associated with respiratory distress 4