Sandbox: KN

Jump to navigation Jump to search
    • NOTOC**

Diagnosis

Guillain-Barré syndrome (GBS) is primarily a clinical diagnosis. The 2023 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline identifies progressive bilateral limb weakness, decreased or absent deep-tendon reflexes, and progression to nadir within 4 weeks as the principal diagnostic features. Cerebrospinal fluid (CSF) examination and electrodiagnostic studies are supportive and may be normal early in the disease; neither should be required to establish the diagnosis in a clinically typical presentation.[1]

Clinical diagnostic features

The diagnosis should be based primarily on the clinical syndrome and its time course.

Feature Diagnostic significance
Progressive bilateral limb weakness Principal clinical feature of GBS
Decreased or absent deep-tendon reflexes Required feature in typical GBS. However, a minority of patients with axonal/motor variants (AMAN) have normal or even exaggerated reflexes throughout the course; initial hyper-reflexia does not exclude GBS and should not delay diagnosis.[2][3]
Progression to nadir within 4 weeks Supports the acute monophasic pattern of GBS
Relatively symmetric involvement Typical, although some asymmetry may occur
Sensory symptoms Common but generally less prominent than motor weakness
Cranial nerve involvement May occur, particularly facial or bulbar weakness
Autonomic dysfunction May occur and can be clinically important

A recent antecedent event within 6 weeks, especially diarrhoeal or respiratory infection, is present in approximately two-thirds of patients and, in the EAN/PNS guideline, supports the diagnosis. Less commonly, antecedent surgery, trauma, malignancy, or certain vaccinations may be reported.[1][3]

Findings that make GBS less likely include marked and persistent asymmetry; fever at onset; a sensory level or extensor plantar responses; severe respiratory dysfunction with only mild limb weakness; predominant sensory signs with mild weakness; abdominal pain or vomiting; nystagmus; altered consciousness (except in Bickerstaff brainstem encephalitis); progression within less than 24 hours or beyond 4 weeks; and CSF white-cell count >50 cells/µL.[1][3]

Cerebrospinal fluid

CSF examination is supportive rather than required for the diagnosis of clinically typical GBS. The characteristic finding is albuminocytologic dissociation — elevated CSF protein (>0.45 g/L) with a normal white-cell count (usually <5 cells/µL, rarely 5–50 cells/µL). A normal CSF protein concentration early in the illness does not exclude GBS because protein elevation is time-dependent: in the IGOS cohort, albuminocytologic dissociation was present in approximately 57% of patients at ≤4 days and approximately 84% at >4 days after onset of weakness (approximately 52% by day 3 and 86% by day 7).[3][1][4]

Normal CSF protein values are higher in older adults, and the sensitivity of albuminocytologic dissociation falls when age-adjusted reference limits or the CSF/serum albumin quotient are used rather than a fixed 0.45 g/L cutoff.[5][6]

Both CSF protein and cell count may be artefactually elevated after intravenous immunoglobulin (IVIg), so the timing of lumbar puncture relative to treatment should be considered.[1]

A normal early CSF protein should not, by itself, prompt a repeat lumbar puncture, because the diagnostic value of CSF protein is limited and a second puncture may itself artefactually raise the result.[4]

A marked CSF pleocytosis should prompt consideration of alternative diagnoses or an associated infectious or inflammatory process rather than being attributed automatically to GBS.[1]

Electrodiagnostic studies

Nerve conduction studies (NCS) and electromyography (EMG) are supportive investigations. They may be normal during the first 1–2 weeks of illness and therefore should not be used to exclude GBS when the clinical presentation is typical.[3][7]

An absent H-reflex is a sensitive early electrodiagnostic abnormality (reported sensitivity >95%). A present H-reflex makes GBS less likely, although electrodiagnostic findings should be interpreted in the context of the complete clinical picture. The sural-sparing pattern — a normal sural sensory response with abnormal or absent median or ulnar sensory responses — is relatively specific (approximately 91–98%) and can support the diagnosis across GBS subtypes.[3]

To maximize diagnostic yield, NCS should examine at least four motor nerves and three sensory nerves and include F-waves and H-reflexes when feasible.[7]

If the initial NCS is non-diagnostic, a repeat study after 2–3 weeks may be considered; approximately one-third of initially non-diagnostic studies may subsequently show a polyneuropathy. However, timing does not substantially increase overall diagnostic yield, and the electrodiagnostic subtype is highly dynamic, with approximately 38–45% of patients changing subtype on serial studies. Therefore, a single NCS should not be used to fix the demyelinating-versus-axonal classification.[8][1][9]

Antibody testing

Antibody testing should be targeted to the clinical phenotype rather than used as a universal screening test.

  • Anti-GQ1b antibodies are particularly useful when Miller Fisher syndrome (MFS) is suspected; they are positive in approximately 90% of MFS cases (sensitivity approximately 92%, specificity approximately 97%). Positive predictive value is lower in overlap phenotypes, including Bickerstaff brainstem encephalitis (approximately 74%) and GBS with isolated ophthalmoplegia (approximately 57%). A negative test does not exclude MFS. A clearly negative result in an atypical presentation should prompt consideration of mimics such as Wernicke encephalopathy, mitochondrial disease, or botulism.[10][11][12]
  • Anti-GM1 and anti-GD1a antibodies are found mainly in axonal/motor (AMAN) and motor-sensory phenotypes and less often in AIDP. Anti-GM1 IgG has variable sensitivity (approximately 20–69%, varying by region and subtype) but high specificity (approximately 94–98%), so a positive result supports a motor-predominant GBS variant while a negative result does not exclude GBS. GM1-complex antibodies can also occur across electrophysiological variants, so their presence should not be used alone to assign an axonal subtype.[1][13][14]
  • Nodal and paranodal antibodies (neurofascin-155, neurofascin-140, neurofascin-186, contactin-1, and CASPR1) define a distinct entity — autoimmune nodopathy — rather than a GBS subtype, although the initial presentation may be clinically and electrophysiologically indistinguishable from GBS. EAN/PNS advises testing for these antibodies specifically in patients with poor response to treatment, continuous worsening, or relapse after treatment. Testing should use cell-based assays confirmed by a second technique (ELISA or immunohistochemistry).[1][3][10]

A negative antibody test does not exclude GBS.

Diagnostic certainty and classification

The Brighton Collaboration criteria grade diagnostic certainty from level 1 (highest) to level 4 (lowest). Higher-certainty levels incorporate supportive CSF and/or electrodiagnostic findings in addition to the clinical picture. The Brighton framework is used primarily for research and vaccine-safety surveillance, whereas clinical care relies on the clinical diagnostic framework of the EAN/PNS guideline.[15][16][9]

Magnetic resonance imaging

MRI is not required to establish a typical diagnosis of GBS. Nerve-root enhancement may support the diagnosis but is nonspecific. MRI is primarily useful when an alternative structural or central nervous system diagnosis must be excluded.

Other imaging and diagnostic studies

CT, chest radiography, and echocardiography do not have characteristic diagnostic findings for GBS. These studies may be performed when clinically indicated to evaluate complications, alternative diagnoses, or other organ-system abnormalities.

Differential diagnosis

The differential diagnosis should be organized according to the suspected anatomic localization and should prioritize conditions in which delayed recognition would alter management.

Localization or mechanism Important alternatives
Spinal cord Transverse myelitis, spinal cord compression, infarction
Anterior horn cell / motor neuron Acute motor neuron disorders and other anterior horn cell syndromes
Peripheral nerve Acute-onset CIDP, toxic or metabolic neuropathies, infectious neuropathies
Neuromuscular junction Myasthenia gravis, botulism
Muscle Acute inflammatory or metabolic myopathies
Central nervous system Brainstem or other central lesions when associated findings indicate central localization
Infectious or inflammatory systemic disease Neuroinfections and systemic inflammatory disorders

Features such as a sensory level, marked persistent asymmetry, prominent sphincter dysfunction, altered consciousness, or another clear central or peripheral localization should prompt evaluation for an alternative diagnosis.[1]

Diagnostic approach

  1. Establish that the patient has an acute or subacute peripheral motor-predominant neurologic syndrome.
  2. Confirm progressive weakness with a time course reaching nadir within 4 weeks.
  3. Assess deep-tendon reflexes and examine for features suggesting an alternative neurologic localization.
  4. Obtain CSF examination when useful for diagnostic support or exclusion of important alternatives, recognizing that normal early CSF protein does not exclude GBS.
  5. Obtain NCS/EMG when diagnostic confirmation, characterization, or an alternative diagnosis is being considered, recognizing that studies may be normal early.
  6. Perform targeted antibody testing when the clinical phenotype suggests a relevant GBS variant or when autoimmune nodopathy should be excluded.
  7. Use MRI or other imaging primarily when an alternative structural or central nervous system diagnosis requires exclusion.

Diagnostic limitations and uncertainty

The EAN/PNS diagnostic framework emphasizes the clinical syndrome, while CSF and electrodiagnostic testing provide supportive evidence. Both modalities have reduced sensitivity early in the illness. CSF protein interpretation is additionally affected by age and by the choice of fixed versus age-adjusted reference limits or albumin quotient. Electrodiagnostic subtype classification is dynamic and may change on serial testing. Diagnostic criteria and laboratory thresholds have not been uniformly validated across all real-world clinical settings.[1][5][6][8]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 van Doorn PA; Van den Bergh PYK; Hadden RDM; et al. (2023). "European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain-Barré syndrome". European Journal of Neurology. 30 (12): 3646–3674. doi:10.1111/ene.16073.
  2. ↑ Kuwabara S; Yuki N (2013). "Axonal Guillain-Barré syndrome: concepts and controversies". Lancet Neurology. 12 (12): 1180–1188. doi:10.1016/S1474-4422(13)70215-1.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Leonhard SE; Papri N; Querol L; et al. (2024). "Guillain–Barré syndrome". Nature Reviews Disease Primers. 10 (1): 97. doi:10.1038/s41572-024-00580-4.
  4. ↑ 4.0 4.1 Al-Hakem H; Doets AY; Stino AM; et al. (2023). "CSF Findings in Relation to Clinical Characteristics, Subtype, and Disease Course in Patients With Guillain-Barré Syndrome". Neurology. 100 (23): e2386–e2397. doi:10.1212/WNL.0000000000207282.
  5. ↑ 5.0 5.1 Rath J; Zulehner G; Schober B; et al. (2021). "Cerebrospinal fluid analysis in Guillain–Barré syndrome: value of albumin quotients". Journal of Neurology. 268 (9): 3294–3300. doi:10.1007/s00415-021-10479-9.
  6. ↑ 6.0 6.1 Hegen H; Ladstätter F; Bsteh G; et al. (2021). "Cerebrospinal fluid protein in Guillain–Barré syndrome: Need for age-dependent interpretation". European Journal of Neurology. 28 (3): 965–973. doi:10.1111/ene.14600.
  7. ↑ 7.0 7.1 Willison HJ; Jacobs BC; van Doorn PA (2016). "Guillain-Barré Syndrome". Lancet. 388 (10045): 717–727. doi:10.1016/S0140-6736(16)00339-1.
  8. ↑ 8.0 8.1 Arends S; de Koning L; Drenthen J; et al. (2026). "Dynamics of Nerve Conduction Studies in Patients With Guillain–Barré Syndrome". Muscle & Nerve. 73 (5): 832–842. doi:10.1002/mus.70152.
  9. ↑ 9.0 9.1 Leonhard SE; Mandarakas MR; Gondim FAA; et al. (2019). "Diagnosis and management of Guillain–Barré syndrome in ten steps". Nature Reviews Neurology. 15 (11): 671–683. doi:10.1038/s41582-019-0250-9.
  10. ↑ 10.0 10.1 Pascual-Goñi E; Caballero-Ávila M; Querol L (2024). "Antibodies in autoimmune neuropathies: what to test, how to test, why to test". Neurology. 103 (4): e209725. doi:10.1212/WNL.0000000000209725.
  11. ↑ Lee SU; Kim HJ; Choi JY; Choi KD; Kim JS (2024). "Expanding clinical spectrum of anti-GQ1b antibody syndrome: a review". JAMA Neurology. 81 (7): 762–770. doi:10.1001/jamaneurol.2024.1123.
  12. ↑ Spatola M; Du Pasquier R; Schluep M; Regeniter A (2016). "Serum and CSF GQ1b antibodies in isolated ophthalmologic syndromes". Neurology. 86 (19): 1780–1784. doi:10.1212/WNL.0000000000002558.
  13. ↑ Kusunoki S; Willison HJ; Jacobs BC (2021). "Antiglycolipid antibodies in Guillain-Barré and Fisher syndromes: discovery, current status and future perspective". Journal of Neurology, Neurosurgery, and Psychiatry. 92 (3): 311–318. doi:10.1136/jnnp-2020-325053.
  14. ↑ Caballero-Ávila M; Pascual-Goñi E; Lleixà C; et al. (2025). "The changing landscape of primary autoimmune neuropathies". Nature Reviews Neurology. 21 (10): 544–555. doi:10.1038/s41582-025-01133-3.
  15. ↑ Fokke C; van den Berg B; Drenthen J; et al. (2014). "Diagnosis of Guillain-Barré Syndrome and Validation of Brighton Criteria". Brain. 137 (1): 33–43. doi:10.1093/brain/awt285.
  16. ↑ Shahrizaila N; Lehmann HC; Kuwabara S (2021). "Guillain–Barré Syndrome". Lancet. 397 (10280): 1214–1228. doi:10.1016/S0140-6736(21)00517-1.
Retrieved from "https://www.wikidoc.org/index.php?title=Sandbox:_KN&oldid=1746409"