What are the differential diagnoses for Guillain-Barré Syndrome (GBS)?

Differential Diagnoses for Guillain-Barré Syndrome

The differential diagnosis of GBS is broad and must be systematically categorized by anatomical location in the nervous system, with CNS disorders (particularly spinal cord and brainstem pathology), metabolic/electrolyte disturbances, and neuromuscular junction disorders being the most critical to exclude. 1

Central Nervous System Disorders

Spinal Cord Pathology

• Acute transverse myelitis from sarcoidosis, Sjögren syndrome, or infectious causes (HIV, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, syphilis, tuberculosis, diphtheria) 1
• Acute flaccid myelitis due to arthropod-borne viruses (Zika, chikungunya, West Nile virus) or other viruses (rabies, polio, enterovirus D68 or A71) 1
• Neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disorder 1
• Spinal cord compression from tumor or structural lesions 1
• Subacute combined degeneration from vitamin B12 deficiency 1

Brainstem Disorders

• Brainstem inflammation or infection from sarcoidosis, Sjögren syndrome, neuromyelitis optica, or myelin oligodendrocyte glycoprotein antibody-associated disorder 1
• Brainstem stroke 1
• Brainstem compression 1
• Wernicke encephalopathy from vitamin B1 deficiency 1

Peripheral Nervous System Disorders

Neuropathies

• Acute-onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) - consider if progression continues beyond 8 weeks from onset, occurring in approximately 5% of patients initially diagnosed with GBS 2
• Polyradiculoneuritis from HIV, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, diphtheria, or Lyme borreliosis 1
• Diabetic neuropathy and drug-induced diabetic neuropathy 1
• Critical illness polyneuropathy 1

Neuromuscular Junction Disorders

• Myasthenia gravis 1
• Lambert-Eaton myasthenic syndrome 1
• Botulism (Clostridium botulinum) 1
• Tetanus (Clostridium tetani) 1

Muscle Disorders

• Inflammatory myositis 1
• Acute rhabdomyolysis 1
• Drug-induced toxic myopathy from colchicine, chloroquine, emetine, or statins 1
• Myositis from influenza virus, HIV, HTLV-1, or enterovirus infection 1
• Mitochondrial disease 1

Metabolic and Electrolyte Disorders

• Hypokalaemia or hypokalaemic thyrotoxic periodic paralysis (particularly common in certain geographic regions) 1
• Hypophosphataemia 1
• Hypomagnesaemia 1
• Hypermagnesaemia 1
• Hyperthyroidism and hypothyroidism 1
• Porphyria 1
• Copper deficiency 1

Malignancy

• Leptomeningeal metastases 1
• Neurolymphomatosis 1
• Brainstem or spinal cord tumors 1

Toxic Exposures

• Organophosphate poisoning (particularly common in low- and middle-income countries) 1
• Heavy metal poisoning from lead, thallium, or arsenic 1
• Diethylene glycol, ethylene glycol, methyl alcohol (methanol), and N-hexane 1
• Ethyl alcohol (ethanol) or paraquat poisoning 1
• Snakebite envenomation 1

Infectious Diseases

• Meningitis and/or meningoencephalitis 1
• Rabies (more common in low- and middle-income countries) 1
• Polio (sporadic cases in certain regions) 1

Other Conditions

• Conversion or functional disorder 1
• Cauda equina syndrome 1
• Vasculitis 1

Key Clinical Features That Cast Doubt on GBS Diagnosis

These "red flags" should prompt consideration of alternative diagnoses:

• Increased CSF cell count (>50 × 10⁶/L mononuclear or polymorphonuclear cells) 1
• Marked, persistent asymmetry of weakness 1
• Bladder or bowel dysfunction at onset or persistent during disease course 1
• Fever at onset 1
• Sharp sensory level indicating spinal cord injury 1
• Hyperreflexia or clonus 1
• Extensor plantar responses 1
• Nadir <24 hours 1
• Continued progression >4 weeks after symptom onset 1
• Alteration of consciousness (except in Bickerstaff brainstem encephalitis) 1
• Severe respiratory dysfunction with limited limb weakness at onset 1

Geographic Considerations

The differential diagnosis varies by geographic region due to differences in infectious disease prevalence, nutritional deficiencies, and toxic exposures 1:

• More common in low- and middle-income countries: hypokalaemic thyrotoxic periodic paralysis, organophosphate intoxication, botulism, rabies, polio, tetanus, HIV-related conditions, HTLV-1 infections, and arbovirus infections (Zika, chikungunya, West Nile virus) 1
• Less common in low- and middle-income countries: sarcoidosis, Sjögren syndrome, Lambert-Eaton myasthenic syndrome, mitochondrial disease, Lyme borreliosis 1

Diagnostic Approach to Differentiate GBS from Mimics

• MRI imaging is not routine for GBS diagnosis but is essential for excluding brainstem infection, stroke, spinal cord inflammation, nerve root compression, or leptomeningeal malignancy 1
• CSF analysis showing elevated protein with normal cell count (albumino-cytological dissociation) supports GBS, though normal protein in the first week does not exclude it 1, 3
• Electrodiagnostic studies demonstrating motor or sensorimotor neuropathy support GBS, but normal early studies do not rule it out 1, 3
• Sural sparing pattern (normal sural SNAP with abnormal median/ulnar SNAPs) is characteristic of GBS, seen in 67% of patients under 60 years 3