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

Differentiating ALS from Guillain-Barré Syndrome

The key distinction is temporal progression: GBS develops over days to 2 weeks with ascending bilateral weakness and absent reflexes, while ALS progresses insidiously over months to years with mixed upper and lower motor neuron signs and preserved reflexes.

Critical Distinguishing Features

Onset and Progression Pattern

• GBS presents acutely or subacutely, with maximum disability typically reached within 2 weeks, though the diagnostic window extends to 4 weeks 1, 2
• ALS develops insidiously over months, with average diagnostic delays of 10-16 months from symptom onset due to its heterogeneous presentation 3
• If nadir is reached in less than 24 hours, this should cast doubt on GBS diagnosis 2
• ALS patients survive on average 3-5 years from symptom onset, while GBS has a triphasic course with 60-80% walking independently by 6 months 3, 2

Pattern of Weakness

• GBS shows rapidly progressive bilateral ascending weakness, typically starting in the legs and progressing to arms and cranial muscles 1, 4
• ALS presents with asymmetric weakness that can begin in limbs or bulbar regions, without the characteristic ascending pattern 3
• GBS weakness is symmetric and bilateral from onset 1
• ALS often begins focally in one limb or bulbar region before spreading 3

Reflex Examination (Most Reliable Clinical Discriminator)

• GBS demonstrates decreased or absent reflexes in most patients at presentation and almost all at nadir 1, 4
• ALS shows hyperreflexia due to upper motor neuron involvement, often with pathological reflexes like Babinski sign 3
• This reflex pattern is the single most reliable bedside distinguishing feature between these conditions

Motor Neuron Involvement Pattern

• GBS affects both motor neurons but spares upper motor neuron signs (no spasticity, no Babinski) 1
• ALS demonstrates both upper and lower motor neuron degeneration, causing mixed findings: spasticity, hyperreflexia, fasciculations, and muscle wasting 3
• Stiffness as a presenting symptom suggests upper motor neuron involvement, which occurs in ALS but not GBS 5

Muscle Wasting Timeline

• GBS rarely shows limb wasting (only 2% of patients) 5
• ALS invariably develops muscle wasting (100% of patients during disease course) 5
• Absence of wasting within 3 years of onset strongly suggests against ALS 5

Sensory Involvement

• GBS commonly presents with distal paresthesias or sensory loss preceding or accompanying weakness 1, 4
• ALS is purely motor without sensory symptoms or signs 3
• Pain (muscular, radicular, or neuropathic) is frequently reported in GBS but not characteristic of ALS 1, 4

Preceding Illness

• GBS is preceded by infection in approximately two-thirds of patients within 6 weeks of symptom onset, including Campylobacter jejuni, cytomegalovirus, hepatitis E, Mycoplasma pneumoniae, Epstein-Barr virus, or Zika virus 1, 4
• ALS has no consistent infectious trigger, though about 10% of cases are related to genetic variants 3

Diagnostic Testing Patterns

Cerebrospinal Fluid Analysis

• GBS shows albumino-cytological dissociation (elevated protein with normal cell count), though protein may be normal early in disease 1
• ALS does not require CSF analysis for diagnosis, as it is based on clinical signs and exclusion of other causes 3

Electrodiagnostic Studies

• GBS reveals sensorimotor polyradiculoneuropathy or polyneuropathy with demyelinating or axonal features 1
• ALS shows denervation with fasciculations and fibrillations in multiple regions, indicating lower motor neuron loss 3
• GBS can be classified into AIDP, AMAN, or AMSAN subtypes, though one-third remain equivocal 6

MRI Findings

• GBS may show nerve root enhancement on gadolinium-enhanced MRI, a sensitive but nonspecific finding 6, 1
• ALS does not show nerve root enhancement; MRI is used primarily to exclude spinal cord pathology 3
• MRI in GBS is most useful for excluding differential diagnoses like brainstem stroke, spinal cord inflammation, or leptomeningeal malignancy 6, 1

Disease Course and Prognosis

• GBS follows a monophasic triphasic pattern (progressive, plateau, recovery phases) with mortality of 3-10% despite treatment 4, 7
• ALS is relentlessly progressive with no recovery phase and nearly 100% mortality, averaging 3-5 years survival 3
• GBS recovery can continue for more than 3 years after onset 4
• Treatment-related fluctuations occur in only 2-5% of GBS patients 4

Common Pitfalls to Avoid

• Do not rely solely on weakness pattern; examine reflexes carefully as this is the most discriminating feature
• Do not dismiss GBS if protein is normal on early CSF analysis; it may take time to develop albumino-cytological dissociation 1
• Do not diagnose ALS without excluding GBS and other treatable mimics through electrodiagnostic studies 3
• Be aware that approximately 20% of GBS patients develop respiratory failure, which can occur rapidly 2
• Remember that GBS is treatable with intravenous immunoglobulin or plasma exchange within 2-4 weeks of onset, making timely differentiation critical 2