Our first multi-center study showed that the Hughes score at discharge and 3 months after onset were significantly lower in AIDP patients treated with GCs compared to that in AMAN patients. Further analysis found that among AIDP patients, the high-dose group had shorter hospitalization days and significantly lower Hughes score at nadir, at discharge and 3 months after onset than that in the low-dose group. However, among AMAN patients, according to our data, the short-term outcome in the high-dose group was not significantly different from that in the low-dose group.
In regarding to complications, we found that, among AIDP patients, the incidence of pulmonary infections was higher in the low-dose group, which we speculated that the longer hospital stay of patients in the low-dose group may account. Because, as the length of hospital stay increases, says from some kind of significance, the effective activity of patients decreases and the risk of pathogenic bacteria infection greatly increases [15]. On the other side, studies have demonstrated that patients with refractory pulmonary treated with high-dose corticosteroid could achieve defervescence earlier and have a shorter hospitalization [16].
These data above suggest that we can’t dismiss wholesale the role of GCs in the treatment of GBS, subtyping to explore the effects of different doses of GCs on GBS treatment is necessary. After all, in China, especially in the 1990s, GCs were the drug of choice in the treatment of GBS because of their civilian price, and clinical observations found good results in many patients [17].
A study used a rabbit model of the axonal form of GBS initially explored the reasons for the ineffectiveness of GCs in treating AMAN, suggesting that MPS did not reduce complement C3 deposition and sodium (Nav) channel disruption, but significantly reduced macrophage infiltration in the ventral roots and thus delay the axonal regeneration [18]. Studies of pathophysiology about AMAN have shown that macrophages invasion was rare at the acute progressive phase but significantly more frequent at the site of inflammation mainly during the recovery phase, which suggested a role for macrophages in the clearance of damaged myelin and axon fragments and promoting nerve repair and regeneration [19]. Whereas, the classical experimental autoimmune neuritis (EAN) model, which highly replicates human AIDP in terms of clinical manifestations, immunology, histopathology, and electrophysiology [20], indicated that “Classically” activated (M1) macrophages mainly accumulated at the acute phase of EAN and promoted the inflammatory response, while during the recovery phase, macrophages could change their expression profile, M2 macrophages attenuated inflammation and promoted tissue repair [21, 22]. Ultrastructural studies showed that macrophage-mediated nerve injury was a pathological hallmark of AIDP/EAN [21–23]. Macrophages (M1) were involved in this process by regulating cytokines, chemokines, adhesion molecules, NO and matrix metalloproteinases (MMPs), and as major antigen-presenting and effector cells, macrophages played a key role in EAN pathogenesis by expressing antigens and promoting Th1 and Th17 polarization [24].
In summary, we hypothesize that the different mechanisms of macrophages' role in the inflammatory response of AIDP and AMAN may lead to different effects of GCs therapy. We will further test our hypothesis through animal experiments.
As a multicenter study, we derived relatively powerful results, but there exists inevitably some limitations. First, as a retrospective study, the long-term follow-up information was insufficient to further explore the prognosis of patients with different subtypes treated with different doses of GCs, further studies were anticipated; Second, the number of patients with AMAN subtypes in this study was relatively small; Third, because the study was a retrospective review of medical records and database, extracting bias was unavoidable. However, in order to reduce the bias as much as possible, a unified parameter standard in the analysis of NCS was adopted and data were extracted by our team members through strict training.