We read with interest the article by Zhao et al. about 94 patients with Guillain-Barre syndrome (GBS) and 50 healthy controls who were tested for anti-neurofascin (NF)-155 antibodies [1]. Seven of the GBS patients had elevated anti-NF-155 antibodies [1]. Compared with anti-NF-155 antibody-negative GBS patients, anti-NF-155 antibody-positive GBS patients had a higher GBS disability score at nadir, higher modified Erasmus GBS outcome score, higher rate of reduced compound motor action potential (CMAP) amplitude, higher frequency of prolonged F-wave latency, lower frequency of abnormal sensory conduction velocity or reduced sensory nerve action potential amplitude, more often of the axonal type, and a poorer therapeutic outcome [1]. The study is appealing but raises concerns that warrant further discussion.

The main limitation of the study is that the seven GBS patients with positive anti-NF-155 antibodies were not evaluated for chronic inflammatory demyelinating polyneuropathy (CIDP) or acute-onset CIDP (A-CIDP) [1]. Particularly A-CIDP is commonly mixed up with GBS. CIDP and A-CIDP are usually diagnosed according to the EFNS criteria [2]. A-CIDP is less likely to have autonomic nervous system (ANS) involvement, facial weakness, a preceding infectious illness, or the need for mechanical ventilation, in comparison with acute inflammatory demyelinating polyneuropathy (AIDP) [3]. Electrophysiological features are usually quite similar between GBS and A-CIDP, although follow-up studies may elucidate key differences. Around 8%-16% of GBS patients may show clinical deterioration shortly after improvement or stabilization following initial immunological therapy, known as treatment-related fluctuation (TRF) [3]. Delineation between GBS with TRF and A-CIDP is crucial as treatment and outcome vary between the two and as A-CIDP patients often require maintenance treatment [3]. Strong arguments in favour of A-CIDP in supposed GBS patients with anti-NF-155 antibodies is that GBS has been only rarely reported in association with elevated anti-NF-155 antibodies [4] and that anti-NF-155 antibodies are more often found in CIDP patients [5]. 

Another limitation is that there is no mention which GBS subtype was diagnosed in one of the seven GBS with anti-NF-155 antibodies [1]. Five patients were diagnosed with acute, motor, axonal neuropathy (AMAN) respectively acute, motor and sensory, axonal neuropathy (AMSAN) and one patient with AIDP [1]. We should know the subtype in the seventh patient.

Because anti-NF-155 antibodies are directed against nodal or paranodal structures of nerve fibers, it is more likely that patients with nodopathies present with AMAN or AMSAN rather than AIDP. We should know how to explain AIDP in a patient positive for anti-NF-155 antibodies. 

Overall, the study carries obvious limitations that require re-evaluation and discussion. Clarifying these weaknesses would strengthen the conclusions and could improve the study. GBS patients with anti-NF-155 antibodies should be evaluated for A-CIDP because treatment and outcome can vary significantly between GBS and CIDP.

1. Zhao, N., et al. "Clinical Features of Guillain-Barré Syndrome with Anti-Neurofascin 155 Antibody." Acta Neurologica Scandinavica, vol. 146, no. 5, Nov. 2022, pp. 553–561. https://doi.org/10.1111/ane.13678.

2. Van den Bergh, P.Y.K., et al. "European Academy of Neurology/Peripheral Nerve Society Guideline on Diagnosis and Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Report of a Joint Task Force—Second Revision." Journal of the Peripheral Nervous System, vol. 26, 2021, pp. 242–268. https://doi.org/10.1111/jns.12455.

3. Kanbayashi, T., and M. Sonoo. "[Acute-Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy]." Brain and Nerve, vol. 67, no. 11, Nov. 2015, pp. 1388–1396. https://doi.org/10.11477/mf.1416200311.

4. Tard, C., et al. "Anti-Pan-Neurofascin IgM in COVID-19-Related Guillain-Barré Syndrome: Evidence for a Nodo-Paranodopathy." Neurophysiologie Clinique, vol. 50, no. 5, Oct. 2020, pp. 397–399. https://doi.org/10.1016/j.neucli.2020.09.007.

5. Gao, Y., et al. "Impact of Neurofascin on Chronic Inflammatory Demyelinating Polyneuropathy via Changing the Node of Ranvier Function: A Review." Frontiers in Molecular Neuroscience, vol. 14, 16 Dec. 2021, article 779385. https://doi.org/10.3389/fnmol.2021.779385.