Jump to content

Acute Inflammatory Demyelinating Polyneuropathy

Original Editor - Oshomoji Olawale

Top Contributors - Oshomoji Olawale, Vidya Acharya and Alexandra Stead  

Introduction

Acute Inflammatory Demyelinating Polyneuropathy (AIDP) is the most prevalent subtype of Guillain-Barré Syndrome (GBS), a heterogeneous group of immune-mediated polyneuropathies that collectively represent the most common cause of acute neuromuscular paralysis worldwide.[1][2]

Aetiology

AIDP, like other subtypes of GBS, is typically preceded by an infectious trigger that initiates an aberrant immune response targeting the peripheral nervous system[3]. According to a systematic review, AIDP shows a preferential aetiological association with Cytomegalovirus (CMV) and Epstein–Barr virus (EBV), neither of which produces ganglioside-mimicking epitopes (part of an antigen that is recognised by the immune system).[4] This distinguishing AIDP from axonal subtypes, particularly Acute Motor Axonal Neuropathy (AMAN), which are more strongly associated with Campylobacter jejuni.[4]

Campylobacter jejuni has lipooligosaccharide (LOS) epitopes, which structurally mimic monosialotetrahexosylganglioside (GM1) and disialotetrahexosylganglioside (GD1a) gangliosides on axonal membranes, explaining the predominance of axonal pathology. [4] In contrast, the CMV–AIDP association is thought to be mediated by T-lymphocyte (T-cell) driven autoimmunity against myelin proteins, consistent with the predominantly cellular immune pathogenesis of AIDP.[4]

Pathophysiology

Cellular immune mechanisms

A systematic review of 71 articles (2010 to 2024) examined the autoimmune mechanisms underlying AIDP.[5] The review found that T-lymphocytes (T-cell) activation and elevated levels of pro-inflammatory cytokines, particularly tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), were identified as the major contributors to myelin destruction in AIDP. Activated T cells and macrophages invade peripheral nerves and strip myelin from axons through a process termed myelinophagy, in which macrophages penetrate the myelin sheath and progressively strip it from the axon.[6] [1] This cellular immune attack disrupts saltatory conduction, resulting in decreased nerve conduction velocities and conduction block, the electrophysiological hallmark of AIDP.[7]

There's a clear mechanistic distinction between AIDP and axonal GBS subtypes. Humoral immunity, mediated by anti-ganglioside antibodies including anti-GM1 and tetrasialotetrahexosylganglioside (anti-GQ1b), predominates in AMAN and Miller Fisher syndrome (MFS), whereas cytokine-mediated cellular immunity predominates in AIDP.[8]

Reduced circulating regulatory T cell (Treg) numbers are a further hallmark of AIDP.[9] Impaired Treg activity leads to uncontrolled peripheral nerve inflammation, driving progressive demyelination until therapeutic intervention disrupts the process.[8][10]

Nodo-paranodopathy

The 2023 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline introduced the concept of 'nodo-paranodopathy', which describes immune-mediated dysfunction at the node of Ranvier or paranodal regions leading to acute conduction failure without segmental demyelination.[11] [7] This blurs the distinction between AIDP and AMAN in classical histopathological terms and highlights the vulnerability of nodes of Ranvier in the immunopathology of AIDP.

Coronavirus disease 2019 (COVID-19)-associated AIDP

Another systematic review and meta-analysis (2021) pre EAS/PNS guideline found that the electrophysiological pattern in patients who developed GBS after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection was most commonly AIDP (approximately 73%)[12]. Anti-ganglioside antibodies were found in only 18% of COVID-19-associated GBS cases, and SARS-CoV-2 ribonucleic acid (RNA) was nearly undetectable in the cerebrospinal fluid (CSF), making direct viral neuroinvasion an unlikely primary cause.[12] The authors stated that COVID-19-associated AIDP is a post-infectious, cytokine-driven autoimmune process involving bystander immune activation and cytokine storm, mediated by TNF-α, Interleukin-1β (IL-1β), and IL-6, leading to myelin targeting rather than classical ganglioside antibody-dependent processes. The meta-analysis confirmed that SARS-CoV-2 infection was associated with greater than threefold increase in the odds of developing AIDP compared with non-COVID-19 GBS (OR 3.27, 95% CI 1.32–8.09).[12]

Epidemiology

In Western countries, AIDP is the predominant GBS subtype, accounting for approximately 90% of all cases.[13][14] In contrast, the axonal variants AMAN and Acute Motor and Sensory Axonal Neuropathy (AMSAN) are more prevalent in Asia, South and Central America, constituting 30–47% of GBS cases in these regions.[15] Female patients with AIDP were associated with a more severe disease course characterised by chronic fatigue, pain, and reduced mobility, even though the long-term prognosis was generally more favourable than for axonal forms.[16]

A systematic review on gender differences in GBS, including 117 studies published from 2014 to 2024 with 2,312 participants, concluded that overall GBS incidence is higher in males, but among GBS subtypes, AIDP (the demyelinating form) may be proportionally more common for females, whilst AMAN tends to occur more frequently in males.[16] This sex differential may be attributed to the immunomodulatory activity of oestrogen, which may promote a demyelinating rather than axonal autoimmune response pattern.[16]

Clinical presentation

AIDP typically presents as a rapidly progressive, ascending, symmetrical limb weakness accompanied by areflexia (absence of deep tendon reflexes), often preceded by an upper respiratory or gastrointestinal infection.[17] Sensory involvement, particularly hypoaesthesia (reduced tactile sensitivity or numbness), is characteristic and reflects the preferential injury to large myelinated sensory fibres.[18] Autonomic dysfunction, cranial nerve involvement (most commonly facial nerve palsy), and, in severe cases, respiratory muscle weakness may also occur.[19]

A prospective observational cohort study directly compared AIDP of total number of participant (n) =31 with primary axonal GBS (n=26) using Rajabally's electrophysiological classification criteria.[18] In this study, AIDP was associated with a higher prevalence of antecedent upper respiratory tract infections (82.35% versus 54.54% in axonal GBS).[18] Hypaesthesia was identified in 93.5% of AIDP cases compared with 50% of axonal cases, reflecting the preferential destruction of large myelinated sensory fibres in AIDP, a statistically significant difference with direct clinical relevance.[18] Neck muscle weakness was less frequent in AIDP (29%) than in axonal GBS (65.38%).

In COVID-19-associated AIDP specifically quadriparesis (weakness in all four limbs)(OR 2.54) and facial nerve involvement (OR 2.34) were significantly more prevalent in COVID-19-associated AIDP, providing additional clinical distinguishing features.[20]

Differential diagnosis

Several conditions can mimic the clinical presentation of AIDP and must be systematically excluded, particularly when AIDP occurs in the context of acute illness. A systematic review[21] noted that AIDP in the context of COVID-19 must be distinguished from:

  • Viral myositis: may present with limb weakness and elevated inflammatory markers, but typically lacks the areflexia, sensory involvement, and CSF albuminocytological dissociation seen in AIDP.[22][23]
  • Critical illness polyneuropathy: occurs in the context of prolonged ICU admission and systemic sepsis; differentiated by electrophysiological evidence of axonal, rather than demyelinating, pathology.[22]
  • Toxic neuropathies and myopathies: may produce ascending weakness resembling AIDP but are distinguished by history of toxic exposure and absence of the characteristic demyelinating electrophysiological profile.[22]

All of which may present similarly but lack the typical CSF albuminocytological dissociation or demyelinating electrophysiological profile of AIDP.[24] The evidence underpinning these differential diagnoses is limited, as the systematic review consisted predominantly of case reports and case series; study designs that carry a high risk of bias due to their susceptibility to systematic errors that may affect the validity of results.[25]

Medical management

Based on the 2023 European Academy of Neurology/Peripheral Nerve Society guideline, the treatment of AIDP is the use of immunotherapy. The guideline identifies IVIg and plasmapheresis as the principal therapeutic options because of their broad immunomodulatory actions.[11]

A double-blind Randomised Controlled Trial (RCT) demonstrated that validated poor-prognosis scoring tools in AIDP do not translate into improved outcomes with escalated immunotherapy, reinforcing that a poor prognosis should not prompt a reflex second Intravenous immunoglobulin (IVIg) course.[26] Where patients remain significantly disabled following first-line IVIg, rehabilitation (including physiotherapy) should be optimised, as further immunotherapy has not been shown to confer additional benefit.[26]

Physiotherapy management

Treatment of AIDP with physiotherapy should be based on the biological basis of recovery: the regeneration of the myelin sheath. The design of physiotherapy in AIDP, therefore, needs to support and capitalise on this window of remyelination, building up intensity and complexity as the peripheral nervous system rebuilds myelin, to enhance proprioceptive acuity, motor strength, postural control, gait quality, and functional independence during the acute, sub-acute, and chronic phases of recovery.[7]

Additional details can be found on the main GBS page

Prognosis

The prognosis of AIDP is generally more favourable than for axonal GBS subtypes, reflecting the greater regenerative capacity of remyelination compared with axonal regrowth. Respiratory involvement is similarly less frequent in AIDP. A study reported that AIDP patients had significantly less severe motor involvement at nadir compared with axonal GBS, as measured by the Medical Research Council (MRC) sum score (31.16 in AIDP group versus 18.23 in axonal group).[18] None of the AIDP patients in this cohort required required mechanical ventilation, compared with 15.3% of axonal patients, consistent with the more favourable respiratory profile of AIDP.[18] However, this finding should be contextualised against the wider literature: across all GBS subtypes, up to one-third of patients may require invasive mechanical ventilation.[27] Physiotherapist should therefore monitor signs of respiratory deterioration in all patients with AIDP.[28]

Similarly, there's a slower neurological deterioration in AIDP, evidenced by a longer mean time from onset to hospitalisation (8.1 days versus 5.35 days in axonal GBS) which provides a wider window for diagnosis and initiation of appropriate immunotherapy and physiotherapy.[18]

A systematic review identified a gender-specific prognostic dimension, noting that although the overall prognosis of AIDP is more favourable than for axonal GBS, women with AIDP frequently continue to experience fatigue, pain, and reduced mobility beyond the acute phase, indicating the need for prolonged physiotherapy involvement.[16]

Summary of AIDP

AIDP is an autoimmune disease that causes neuromuscular paralysis. It often triggered by a preceding infection and shows preferential aetiological association to ones without ganglioside-mimicking epitopes (e.g CMV, EBV). Pathogenesis is based on myelinophagy and epidemiology is more prevalent in Western countries. Medical management includes use of IVIg and plasmapheresis.

Additional details can be found on the main GBS page

References

  1. ↑ 1.0 1.1 Vallat JM, Mathis S. Pathology explains various mechanisms of auto‐immune inflammatory peripheral neuropathies. Brain Pathology. 2024 Mar;34(2):e13184.
  2. ↑ Bellanti R, Rinaldi S. Guillain‐Barré syndrome: a comprehensive review. European journal of neurology. 2024 Aug;31(8):e16365.
  3. ↑ Palombo G, Hoppe B. Review of acute inflammatory demyelinating polyradiculoneuropathy. JBJS Journal of Orthopaedics for Physician Assistants. 2022 Jan 1;10(1):e21.
  4. ↑ 4.0 4.1 4.2 4.3 Ramesh A, Subbarayan R, Srinivasan D, Balakrishnan R, Shrestha R, Chauhan A. Infectious Triggers and Immune Dynamics in Guillain–Barré Syndrome: Revisiting Campylobacter jejuni and the Silent Role of Haemophilus influenzae. MicrobiologyOpen. 2025 Dec;14(6):e70177.
  5. ↑ Oshomoji OI, Ajiroba JO, Semudara SO, Olayemi MA, Adeoye SO. Autoimmune mechanisms in Guillain-Barré syndrome subtypes: a systematic review. Bulletin of Faculty of Physical Therapy. 2024 Dec 18;29(1).
  6. ↑ Koike H, Katsuno M. Macrophages and autoantibodies in demyelinating diseases. Cells. 2021 Apr 8;10(4):844.
  7. ↑ 7.0 7.1 7.2 Joshua AM, editor. Physiotherapy for adult neurological conditions. Springer Nature; 2022 Jun 20.
  8. ↑ 8.0 8.1 Zhu W, Li K, Cui T, Yan Y. Detection of anti-ganglioside antibodies in Guillain-Barré syndrome. Annals of Translational Medicine. 2021 Apr 21;11(7):289.
  9. ↑ Chi LJ, Wang HB, Zhang Y, Wang WZ. Abnormality of circulating CD4+ CD25+ regulatory T cell in patients with Guillain–Barré syndrome. Journal of Neuroimmunology. 2007 Dec 1;192(1-2):206-14.
  10. ↑ Olson KE, Mosley RL, Gendelman HE. The potential for treg-enhancing therapies in nervous system pathologies. Clinical and experimental immunology. 2023 Feb 1;211(2):108-21.
  11. ↑ 11.0 11.1 van Doorn PA, Van den Bergh PY, Hadden RD, Avau B, Vankrunkelsven P, Attarian S, Blomkwist‐Markens PH, Cornblath DR, Goedee HS, Harbo T, Jacobs BC. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of Guillain–Barré syndrome. Journal of the Peripheral Nervous System. 2023 Dec;28(4):535-63.
  12. ↑ 12.0 12.1 12.2 Palaiodimou L, Stefanou MI, Katsanos AH, Fragkou PC, Papadopoulou M, Moschovos C, Michopoulos I, Kokotis P, Bakirtzis C, Naska A, Vassilakopoulos TI. Prevalence, clinical characteristics and outcomes of Guillain− Barré syndrome spectrum associated with COVID‐19: a systematic review and meta‐analysis. European journal of neurology. 2021 Oct;28(10):3517-29.
  13. ↑ Ziganshin RH, Ivanova OM, Lomakin YA, Belogurov AA, Kovalchuk SI, Azarkin IV, Arapidi GP, Anikanov NA, Shender VO, Piradov MA, Suponeva NA. The pathogenesis of the demyelinating form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and immunological profiling of physiological fluids. Molecular & Cellular Proteomics. 2016 Jul 1;15(7):2366-78.
  14. ↑ Ginanneschi F, Giannini F, Sicurelli F, Battisti C, Capoccitti G, Bartalini S, Mignarri A, Volpi N, Cioncoloni D, Franci L, De Stefano N. Clinical features and outcome of the Guillain–Barre Syndrome: a single-center 11-year experience. Frontiers in Neurology. 2022 Jun 29;13:856091.
  15. ↑ Vucic S, Kiernan MC, Cornblath DR. Guillain-Barré syndrome: an update. Journal of clinical neuroscience. 2009 Jun 1;16(6):733-41.
  16. ↑ 16.0 16.1 16.2 16.3 Oshomoji OI, Oti IK, Ajiroba JO, Semudara SO. Gender differences in Guillain-Barré syndrome presentations and outcomes: a systematic review. Bulletin of Faculty of Physical Therapy. 2025 Mar 3;30(1):14.
  17. ↑ van Doorn PA. Guillain-Barré syndrome. InDysimmune Neuropathies 2020 Jan 1 (pp. 5-29). Academic Pres
  18. ↑ 18.0 18.1 18.2 18.3 18.4 18.5 18.6 Khedr EM, Shehab MM, Mohamed MZ, Mohamed KO. Early electrophysiological study variants and their relationship with clinical presentation and outcomes of patients with Guillain-Barré syndrome. Scientific reports. 2023 Aug 26;13(1):14000.
  19. ↑ Dimachkie MM, Barohn RJ. Guillain-Barré syndrome and variants. Neurologic clinics. 2013 Feb 19;31(2):491.
  20. ↑ Yusari IG, Sudira PG, Samatra DP. Clinical characteristics of Guillain–Barre syndrome in COVID-19: a systematic review and meta-analysis of observational studies. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery. 2023 Mar 27;59(1):40.
  21. ↑ Sriwastava S, Kataria S, Tandon M, Patel J, Patel R, Jowkar A, Daimee M, Bernitsas E, Jaiswal P, Lisak RP. Guillain Barré Syndrome and its variants as a manifestation of COVID-19: A systematic review of case reports and case series. Journal of the neurological sciences. 2021 Jan 15;420:117263.
  22. ↑ 22.0 22.1 22.2 Morgan L, Hollist M, Au K, Ayari L, Betts C, Kirmani BF. Neuromuscular disorders associated with COVID-19. Neuroscience Insights. 2023 May;18:26331055231176251.
  23. ↑ Balcom EF, Nath A, Power C. Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease. Brain. 2021 Dec 1;144(12):3576-88.
  24. ↑ Ziganshin RH, Ivanova OM, Lomakin YA, Belogurov AA, Kovalchuk SI, Azarkin IV, Arapidi GP, Anikanov NA, Shender VO, Piradov MA, Suponeva NA. The pathogenesis of the demyelinating form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and immunological profiling of physiological fluids. Molecular & Cellular Proteomics. 2016 Jul 1;15(7):2366-78.
  25. ↑ Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ evidence-based medicine. 2018 Feb 2.
  26. ↑ 26.0 26.1 Walgaard C, Jacobs BC, Lingsma HF, Steyerberg EW, van den Berg B, Doets AY, Leonhard SE, Verboon C, Huizinga R, Drenthen J, Arends S. Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial. The Lancet Neurology. 2021 Apr 1;20(4):275-83.
  27. ↑ Rodríguez-Méndez AA, Briseño-Ramírez J, Rivas-Ruvalcaba FJ, Solis-Estrada J, Alcázar-García LB, Díaz-Ramírez K, Lira-Jaime G, Sánchez-Román EJ, Zúñiga-Ramírez C. Clinical predictors for mechanical ventilation assistance in Guillain-Barré syndrome. Frontiers in neurology. 2024 May 9;15:1385945.
  28. ↑ Palombo G, Hoppe B. Review of acute inflammatory demyelinating polyradiculoneuropathy. JBJS Journal of Orthopaedics for Physician Assistants. 2022 Jan 1;10(1):e21.
Retrieved from "https://www.physio-pedia.com/w/index.php?title=Acute_Inflammatory_Demyelinating_Polyneuropathy&oldid=380993"