What are the differences between Guillain-Barre Syndrome (GBS) and Amyotrophic Lateral Sclerosis (ALS)?

Guillain-Barré Syndrome vs. Amyotrophic Lateral Sclerosis: Key Distinguishing Features

Guillain-Barré syndrome (GBS) is an acute, monophasic, immune-mediated peripheral nerve disorder with potential for significant recovery, while ALS is a chronic, progressive, degenerative disease of motor neurons with no recovery and invariably fatal outcome.

Disease Course and Timing

GBS progresses rapidly over days to 2 weeks (maximum 4 weeks), reaches a plateau, then recovers, whereas ALS progresses relentlessly over months to years without remission.

• GBS reaches maximum disability within 2 weeks in most patients, with 60-80% able to walk independently by 6 months 1
• The disease follows a predictable triphasic pattern: progressive phase, plateau phase, and recovery phase 2
• GBS is fundamentally monophasic, though 2-5% experience relapses 1, 3
• Clinical improvement in GBS is most extensive in the first year and can continue for >5 years 1
• ALS, by contrast, shows continuous motor neuron degeneration without plateau or recovery phases

Anatomical Location of Pathology

GBS affects the peripheral nervous system (nerve roots and peripheral nerves), while ALS affects both upper and lower motor neurons in the central nervous system (brain and spinal cord).

• GBS is a polyradiculoneuropathy with damage to peripheral nerves and nerve roots 1, 4
• Electrophysiological studies in GBS demonstrate peripheral nerve dysfunction, distinguishing between demyelinating (AIDP) and axonal (AMAN/AMSAN) subtypes 1
• ALS involves degeneration of motor neurons in the motor cortex, brainstem, and anterior horn cells of the spinal cord

Sensory Involvement

GBS typically includes sensory symptoms and signs, whereas ALS is purely a motor neuron disease without sensory involvement.

• Distal paresthesias or sensory loss commonly precede or accompany weakness in GBS 1, 3
• Sensory abnormalities are characteristic features of classic GBS presentation 5
• ALS patients maintain normal sensation throughout the disease course, which is a critical distinguishing feature

Reflex Pattern

Reflexes are decreased or absent in GBS, while ALS characteristically shows hyperreflexia due to upper motor neuron involvement.

• Reflexes are decreased or absent in most GBS patients at presentation and almost all at nadir 1, 3
• The areflexia in GBS results from peripheral nerve damage 1
• ALS typically demonstrates brisk reflexes, often with pathological reflexes (Babinski sign) due to upper motor neuron degeneration

Etiology and Pathophysiology

GBS is an immune-mediated disorder typically triggered by preceding infection, while ALS is a neurodegenerative disease without clear immune or infectious triggers.

• Approximately two-thirds of GBS patients report infection symptoms in the 6 weeks preceding onset 1, 3
• Six pathogens are temporally associated with GBS: Campylobacter jejuni, Cytomegalovirus, Hepatitis E virus, Mycoplasma pneumoniae, Epstein-Barr virus, and Zika virus 3
• GBS involves aberrant immune response with complement activation, macrophage infiltration, and edema in peripheral nerves 1, 3
• ALS pathophysiology involves protein aggregation, oxidative stress, and excitotoxicity without primary immune mechanisms

Treatment Response

GBS responds to immunomodulatory therapy with potential for complete recovery, while ALS has no disease-modifying treatment and is universally fatal.

• Intravenous immunoglobulin (0.4 g/kg daily for 5 days) or plasma exchange are equally effective treatments for GBS 1, 4
• Treatment should be initiated within 2-4 weeks of symptom onset in GBS patients unable to walk unaided 2, 4
• No immunotherapy is effective in ALS, and treatment is purely supportive (riluzole and edaravone provide only modest benefit)

Prognosis and Mortality

GBS mortality is 3-10% with most patients recovering functional independence, while ALS is invariably fatal within 2-5 years of diagnosis.

• Despite requiring mechanical ventilation in 20% of cases, 60-80% of GBS patients walk independently at 6 months 1, 3
• GBS mortality remains 3-10% even with optimal care, primarily due to autonomic dysfunction 1, 3
• ALS has 100% mortality, typically from respiratory failure within 2-5 years of symptom onset

Common Pitfalls in Differentiation

The most critical error is mistaking early GBS for ALS or vice versa, which has profound treatment and prognostic implications.

• If progression continues beyond 8 weeks from onset, consider acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) rather than GBS, which occurs in approximately 5% of cases initially diagnosed as GBS 4
• Nadir reached in less than 24 hours should cast doubt on GBS diagnosis 2
• The presence of upper motor neuron signs (hyperreflexia, Babinski sign) argues strongly against GBS and toward ALS
• Absence of sensory symptoms strongly suggests ALS rather than typical GBS
• CSF examination showing elevated protein with normal cell count supports GBS diagnosis 1