Beyond Binary: Biomarkers Reveal the Coexistence of Acute Motor Axonal Neuropathy (AMAN) and Acute Inflammatory Demyelinating Polyneuropathy (AIDP) in Guillain-Barré Syndrome
Henk-Andre Kroon1, Kunal Kunani1, Eric Humphriss1, Preeti Paliwal1, Zhahirul Islam2, Quazi Deen Mohammad3
1Annexon Biosciences, 2Laboratory Sciences and Services Division, icddr,b, 3National Institute of Neuroscience (NINS)
Objective:
To investigate the metabolic profile of acute motor axonal neuropathy (AMAN) and acute inflammatory demyelinating polyneuropathy (AIDP) in Guillain-Barré syndrome (GBS) patients.
Background:
Complement-fixing autoantibodies target gangliosides in axons and/or myelin of peripheral nerves, leading to common clinical manifestations of GBS. Disease severity and path to recovery vary by patient and geography, which is often attributed to the neuro subtype. However, the binary classification into AMAN and AIDP does not consider that the two subtypes likely coexist. Molecular profiling can be used to more accurately describe the underlying disease process and identify prognostic markers.
Design/Methods:
CSF samples collected at baseline and day 5/8 from GBS patients in Bangladesh with either AMAN (n=15) or AIDP (n=10) were profiled for metabolomics and proteomics. Serum neurofilament light (sNfL), a marker of axonal damage, and sphingomyelin in cerebral spinal fluid (csfSM), a diagnostic biomarker of demyelination, were evaluated.
Results:
Independent of subtype, sNfL was the most prognostic biomarker followed by csfSM. Baseline median sNfL was above the normal range in all patients, with higher levels in AMAN patients (434.0 pg/ml) than AIDP patients (108.5 pg/ml). Higher NfL was associated with worse muscle strength. Levels of csfSM were elevated, more in AIDP than AMAN and continued to increase in patients still deteriorating; csfSM correlated with cholesterol levels (r =0.97, p <0.0001). The NfL/sphingomyelin ratio was 5x higher in AMAN vs AIDP (p=0.002), which is consistent with the neuroimmunology of GBS.
Conclusions:
GBS patients, regardless of neurotype (AMAN or AIDP), have elevated biomarkers indicative of axonal damage and demyelination, suggesting that the two pathological processes coexist to varying degrees in individual patients. NfL is most prognostic, suggesting that the extent of axonal damage is important for the patient’s ability to recover. This study emphasizes the need to move beyond traditional binary neurotype classifications to explain GBS disease heterogeneity.