What is the differential diagnosis (Ddx) for Guillain-Barré Syndrome (GBS)?

Differential Diagnosis for Guillain-Barré Syndrome

When evaluating a patient with suspected GBS, systematically exclude central nervous system disorders, neuromuscular junction disorders, metabolic derangements, and toxic exposures, as these conditions can mimic the acute flaccid paralysis of GBS but require entirely different management approaches. 1

Key Clinical Features That Should Raise Suspicion for Alternative Diagnoses

Before considering the differential, recognize that certain findings cast significant doubt on a GBS diagnosis:

• Marked, persistent asymmetry of weakness should prompt consideration of alternative diagnoses 2, 1
• Increased CSF cell count (>50 × 10⁶/L mononuclear or polymorphonuclear cells) strongly suggests an infectious or inflammatory process other than GBS 1
• Descending flaccid paralysis (cranial nerves → trunk → extremities) indicates botulism until proven otherwise, not GBS 3
• Normal or preserved reflexes with flaccid paralysis suggests botulism or myasthenia gravis rather than GBS 3

Central Nervous System Disorders

Spinal cord and brainstem pathology must be excluded early, as these conditions may present with similar weakness patterns but require urgent imaging and distinct treatments:

• Acute transverse myelitis from sarcoidosis, Sjögren syndrome, or infectious causes 1
• Acute flaccid myelitis due to arthropod-borne viruses or other viruses 1
• Neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disorder 1
• Spinal cord compression from tumor or structural lesions 1
• Brainstem stroke 1
• Brainstem inflammation or infection from sarcoidosis, Sjögren syndrome, neuromyelitis optica, or MOG antibody-associated disorder 1
• Subacute combined degeneration from vitamin B12 deficiency 1
• Wernicke encephalopathy from vitamin B1 deficiency 1

Peripheral Nervous System Disorders

Infectious and inflammatory polyradiculoneuropathies can closely mimic GBS but may require pathogen-specific therapy:

• Polyradiculoneuritis from HIV, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, diphtheria, or Lyme borreliosis 1
• Chronic inflammatory demyelinating polyneuropathy (CIDP), particularly acute-onset CIDP, should be considered if progression continues after 8 weeks from onset, which occurs in approximately 5% of patients initially diagnosed with GBS 4
• Diabetic neuropathy and drug-induced diabetic neuropathy 1
• Critical illness polyneuropathy 1

Distinguishing GBS from CIDP

The temporal pattern of disease progression is the critical distinguishing feature:

• GBS progresses rapidly over days to 4 weeks with areflexia, typically reaching maximum disability within 2 weeks 5, 3
• CIDP progresses over at least 8 weeks with areflexia 5
• Deterioration after 8 weeks from onset or three or more deteriorations suggests CIDP rather than GBS 5

Neuromuscular Junction Disorders

These conditions can present with acute weakness but typically have distinct patterns of fatigability and preserved reflexes:

• Myasthenia gravis 1
• Lambert-Eaton myasthenic syndrome 1
• Botulism (Clostridium botulinum) - characterized by descending paralysis 1, 3
• Tetanus (Clostridium tetani) 1

Muscle Disorders

Primary muscle pathology should be considered, particularly when creatine kinase is markedly elevated:

• 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

Electrolyte abnormalities can cause acute flaccid paralysis and are rapidly reversible with appropriate correction:

• Hypokalaemia or hypokalaemic thyrotoxic periodic paralysis 1
• Hypophosphataemia 1
• Hypomagnesaemia 1
• Hypermagnesaemia 1
• Hyperthyroidism and hypothyroidism 1
• Porphyria 1
• Copper deficiency 1

Malignancy

Neoplastic infiltration of nerve roots or meninges can mimic GBS:

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

Toxic Exposures

Environmental and occupational toxins must be considered based on exposure history:

• Organophosphate poisoning 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

Central nervous system infections can present with weakness and altered mental status:

• Meningitis and/or meningoencephalitis 1
• Rabies 1
• Polio 1

Other Conditions

• Conversion or functional disorder should be considered when objective findings are inconsistent with the clinical presentation 1
• Cauda equina syndrome 1
• Vasculitis 1

Diagnostic Approach to Narrow the Differential

Laboratory testing should be guided by the differential diagnosis in individual patients:

• Complete blood counts and blood tests for glucose, electrolytes, kidney function, and liver enzymes to exclude infections or metabolic/electrolyte dysfunctions 2
• CSF examination showing albumino-cytological dissociation (elevated protein with normal cell count) supports GBS, while elevated cell count (>50 × 10⁶/L) suggests alternative diagnoses 2, 1
• Electrodiagnostic studies demonstrating peripheral nerve dysfunction help differentiate GBS subtypes and exclude other neuropathies 2, 3
• Anti-GQ1b antibody testing should be considered when Miller Fisher syndrome is suspected, as it is found in up to 90% of MFS patients 2
• MRI or ultrasound imaging should be considered in atypical cases to exclude structural lesions 4