Why IVIG and Plasmapheresis Take Time to Work in GBS
IVIG and plasmapheresis do not "cure" GBS instantly because they only remove circulating antibodies and inflammatory mediators during the acute inflammatory phase—they cannot reverse nerve damage that has already occurred, and clinical improvement depends on the natural timeline of axonal regeneration and remyelination, which takes weeks to months regardless of treatment. 1
The Fundamental Mechanism Explains the Delay
Both treatments provide acute immunomodulatory benefit only during the active inflammatory phase—they mechanically remove pathogenic antibodies (like anti-GM1, anti-GD1a antibodies from Campylobacter jejuni molecular mimicry) and inflammatory mediators, but the underlying autoimmune response can continue after treatment ends 1, 2
The treatment effect is not permanent—IVIG works through complement inactivation, neutralization of idiotypic antibodies, cytokine inhibition, and saturation of Fc receptors on macrophages, but these effects are temporary 2
Clinical improvement typically begins within days to weeks after treatment completion, not immediately during infusion, because nerve recovery must occur through biological processes that cannot be accelerated 1
The Natural Disease Timeline Determines Recovery Speed
GBS follows a monophasic course with three distinct phases: progression (reaching maximum disability within 2 weeks in most patients), plateau (lasting days to weeks or months), and recovery 1, 3
Treatment initiated within the first 2 weeks limits the extent of nerve damage but cannot prevent the plateau phase—the disease must run its natural course before recovery begins 1
About 40% of treated patients show no improvement in the first 4 weeks, which does not indicate treatment failure—progression might have been worse without therapy, but the plateau phase still occurs 4, 1
Recovery depends on axonal regeneration and remyelination, biological processes that take months to years—60-80% of patients walk independently at 6 months, with continued improvement possible for more than 5 years 4, 1, 5
Why the 2-Week Treatment Window Matters
Most GBS patients reach maximum disability within 2 weeks of onset, defining the critical treatment window when immunotherapy can modify disease course 1
Treatment after the plateau phase is unlikely to provide additional benefit because the inflammatory process has resolved and recovery depends entirely on nerve regeneration 1
Both IVIG (0.4 g/kg daily for 5 days) and plasmapheresis (200-250 ml plasma/kg over 5 sessions) demonstrate equivalent efficacy when initiated within 14 days of symptom onset 1
Treatment-Related Fluctuations Indicate Ongoing Inflammation
6-10% of patients experience treatment-related fluctuations (TRFs) within 2 months following initial improvement, indicating the treatment effect has worn off while the inflammatory phase remains active 4, 1
TRFs require repeat treatment with full-course IVIG or plasma exchange, though evidence supporting this practice is limited 4, 1
In ~5% of patients, repeated clinical relapses (three or more TRFs and/or deterioration ≥8 weeks after onset) suggest acute-onset CIDP rather than GBS, requiring diagnosis revision 1, 3
Common Pitfall: Confusing Treatment Effect with Natural Recovery
The monophasic nature of GBS means patients will eventually enter a recovery phase regardless of treatment—IVIG and plasmapheresis accelerate recovery and reduce severity during the acute inflammatory period, but cannot eliminate the natural disease timeline 1
Treatment does not prevent the need for mechanical ventilation in all cases—approximately 20% of GBS patients require ventilation within the first week regardless of treatment choice 1, 5
The "20/30/40 rule" for respiratory monitoring remains critical (vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O indicates risk of respiratory failure) because treatment cannot immediately reverse respiratory muscle weakness 4, 5
Specific Context: Campylobacter jejuni-Associated GBS
In AMAN (acute motor axonal neuropathy) following C. jejuni infection, molecular mimicry leads to antibodies against gangliosides GM1, GM1b, GD1a expressed on motor axolemma, causing direct axonal degeneration 2
Axonal damage takes longer to recover than demyelination—removing the antibodies with IVIG or plasmapheresis stops further damage but cannot repair axons that have already degenerated 2
Pure motor variants may have different immunopathological mechanisms but respond to the same treatment approach, with recovery still dependent on axonal regeneration timelines 4