What is the differential diagnosis for flaccid quadriparesis?

Differential Diagnosis for Flaccid Quadriparesis

The differential diagnosis for flaccid quadriparesis is primarily determined by the pattern and direction of weakness progression, with ascending symmetric weakness indicating Guillain-Barré syndrome, descending paralysis suggesting botulism, and the presence or absence of reflexes and sensory findings further narrowing the diagnosis. 1, 2

Primary Diagnostic Categories

Peripheral Nerve Disorders

• Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid quadriparesis, characterized by ascending bilateral symmetric weakness progressing from legs to arms to cranial nerves, with areflexia or hyporeflexia in affected limbs 1, 3, 4
• GBS subtypes include acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor-sensory axonal neuropathy (AMSAN) 5
• Chronic inflammatory demyelinating polyneuropathy (CIDP) with acute onset can mimic GBS 5
• Diphtheria-associated polyneuropathy and Lyme borreliosis can cause polyradiculoneuritis 5

Neuromuscular Junction Disorders

• Botulism presents with descending flaccid paralysis starting with cranial nerves, then trunk, then extremities, with preserved or normal reflexes and no sensory involvement 1, 2
• Myasthenia gravis demonstrates jaw-closing weakness in 88.8% of cases, distinguishing it from other causes 3
• Lambert-Eaton myasthenic syndrome should be considered in the differential 5

Muscle Disorders

• Polymyositis/dermatomyositis shows jaw-opening weakness in 71.4% of cases 3
• Hypokalemic periodic paralysis (including thyrotoxic variant) presents with jaw-opening weakness in 83.3% of cases and is more common in low-income settings 5, 3
• Acute rhabdomyolysis and drug-induced toxic myopathy (from colchicine, chloroquine, emetine, or statins) 5
• Critical illness polyneuropathy or myopathy 5

Spinal Cord Pathology

• Acute transverse myelitis from infectious causes (HIV, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, syphilis, tuberculosis) 5
• Acute flaccid myelitis associated with enteroviruses (D68, A71), arthropod-borne viruses (Zika, chikungunya, West Nile), rabies, or polio 5
• CMV polyradiculomyelopathy in HIV patients causes Guillain-Barré-like syndrome with urinary retention, progressive bilateral leg weakness, flaccid paraplegia, and CSF neutrophilic pleocytosis 5
• Spinal cord compression or cauda equina syndrome 5

Metabolic and Toxic Causes

• Electrolyte disorders: hypokalaemia (most common), hypophosphataemia, hypermagnesaemia 5
• Vitamin deficiencies: B1 (beriberi, Wernicke encephalopathy), B12 (subacute combined degeneration), vitamin E 5
• Organophosphate poisoning (common in low-resource settings) 5
• Heavy metal toxicity: lead, thallium, arsenic 5
• Porphyria 5

Infectious Causes

• Tetanus (Clostridium tetani) and botulism (C. botulinum) 5
• Polio in regions where it has not been eradicated (sub-Saharan Africa, Pakistan) 5
• Rabies in endemic areas 5
• Brainstem or meningoencephalitis 5

Other Considerations

• Brainstem stroke or vasculitis 5
• Leptomeningeal metastases or neurolymphomatosis 5
• Mitochondrial disease 5
• Functional or conversion disorder 5

Critical Distinguishing Features

Pattern of Weakness Progression

• Ascending pattern (legs → arms → cranial nerves): GBS is most likely 1, 6, 7
• Descending pattern (cranial nerves → trunk → extremities): botulism until proven otherwise 1, 2
• Reaching maximum disability within 24 hours or after 4 weeks: makes GBS less likely 2

Reflex Examination

• Areflexia or hyporeflexia: strongly suggests GBS, though reflexes can be normal initially 1, 2
• Normal or preserved reflexes: indicates botulism or myasthenia gravis 1
• GBS patients very rarely have jaw muscle weakness (only 4.1%), which helps distinguish from other causes 3

Sensory Involvement

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

Mental Status

• Alert and oriented: characteristic of botulism despite appearing intoxicated from ptosis and dysarthria 2
• Altered consciousness: suggests encephalitis, stroke, or metabolic encephalopathy rather than peripheral causes 5

Geographic and Demographic Variations

More Common in Low-Income Settings

• Organophosphate intoxication, botulism, rabies, polio, and tetanus occur more frequently in low- and middle-income countries 5
• Hypokalaemic thyrotoxic periodic paralysis is more common in certain geographic regions 5
• Infections with HIV, HTLV-1, and arthropod-borne viruses (Zika, chikungunya, West Nile) are frequently reported in several low-income countries 5

Pediatric Considerations

• The differential diagnosis in children differs from adults due to atypical or non-specific features such as meningism or poorly localized pain 5, 6
• Vascular causes, vitamin deficiencies, drug-induced myopathy, and CIDP occur less frequently in children 5
• Acute severe pain syndrome may present as pseudo-encephalopathy in younger children with GBS 7

Common Pitfalls to Avoid

• Do not dismiss GBS based on normal initial electrodiagnostic studies, as changes may not appear until 10-14 days after symptom onset 1
• Do not wait for CSF protein elevation before initiating treatment for suspected GBS 2
• Botulism is frequently misdiagnosed as myasthenia gravis, stroke, or psychiatric disorders, with 34% presenting with only 1-2 cranial nerve palsies initially 2
• Facial paralysis in botulism can mask respiratory distress by producing a placid expression and preventing nasal flaring 2