Response to Letter to the Editor: Clarifying Diagnostic Criteria and the Role of Serum Neurofilament Light Chain in Immune-Mediated Neuropathies

Abstract

We thank Dr. Seok and Dr. Eun for their thoughtful comments on our study of serum neurofilament light chain (sNfL) in immune-mediated polyradiculoneuropathies (IMPs). Their letter raises important points that merit discussion.

Our study demonstrated elevated sNfL levels in patients with acute axonal variants compared with other IMPs, with baseline levels correlating with disease severity and hospitalization duration. The correspondents raise concerns about: (1) the inclusion of patients without initial motor weakness, (2) the application of Rajabally's criteria to Miller Fisher Syndrome (MFS) cases, and (3) the relevance of sNfL in chronic inflammatory demyelinating polyneuropathy (CIDP).

We acknowledge that patients without motor weakness at presentation appear to contradict established diagnostic criteria. However, these patients developed motor symptoms during hospitalization with progressive increases in F-score, reflecting the dynamic nature of acute IMPs [1]. This highlights the importance of serial clinical assessments, as initial presentations may not capture the full manifestation of the disease.

While we acknowledge that a high proportion of our MFS cohort had limb weakness, suggesting an overlap between MFS and Guillain–Barré syndrome (GBS), this is consistent with previous literature showing motor involvement in MFS [2]. We classified patients based on predominant clinical features, and for the sake of clarity, we decided to refer to this group as “MFS” despite some patients having overlapping features.

Our diagnostic approach first defined clinical syndromes using established criteria and then applied Rajabally's electrodiagnostic criteria for further characterization. The retrospective nature of our study limited the availability of complete nerve conduction study (NCS) datasets, a limitation we acknowledge. We agree that a correlation between NCS findings and sNfL levels would be valuable and plan to address this in prospective studies.

Regarding the broader utility of NfL, we would like to emphasize that our focus on axonal GBS is not intended to diminish its potential value in other IMPs, including CIDP. Previous studies have demonstrated the utility of sNfL as a biomarker for CIDP [3]. However, interpretation of sNfL levels requires careful consideration of confounding factors [4]. This is particularly important in heterogeneous diseases such as CIDP, where multiple comorbidities may be present [5].

We believe that our findings contribute to the understanding of the role of sNfL in IMPs, while acknowledging the need for further prospective studies with standardized electrophysiological protocols and careful phenotyping of clinical variants.

Ali Maisam Afzali: writing – original draft, writing – review and editing. Bernhard Hemmer: writing – review and editing.

The authors declare no conflicts of interest.