With interest we read the review article by Koike et al., [1] about the association between SARS-CoV-2 vaccinations and Guillain-Barre syndrome (GBS) [1]. It was concluded that the risk of GBS is not considered a legitimate reason to limit administration of currently available vaccines, because only a trivial association or no association with GBS [1]. The review is appealing but has a number of limitations which evoke the following comments and concerns.We do not agree with the statement that GBS is “mainly categorised into a demyelinating and an axonal subtype” [1]. GBS is not only categorised according to electrophysiological criteria into “axonal” and “demyelinating” but also according to clinical criteria, particularly if only peripheral nerves or also cranial nerves or both, or even the central nervous system (CNS) are involved. Accordingly, in addition to acute, inflammatory demyelinating polyneuropathy (AIDP) and acute, motor (and sensory), axonal, neuropathy (AMAN/AMSAN), Miller-Fisher syndrome (MFS), polyneuritis cranialis (PNC), the pharyngeal, cervical, and brachial (PCB) variant, and brainstem Bickerstaff encephalitis (BBE) are delineated [2]. All subtype of GBS are diagnosed according to the Brighton criteria.We do not agree with the notion that there is only a “trivial” or “no” association between SARS-CoV-2 vaccinations and GBS. According to a recent mini review at least 17 cases with SARS-CoV-2 vaccination associated GBS have been published so far [submitted]. In all cases GBS developed after the first dose of the vaccine. In two patients an mRNA-based vaccine and in 15 patients a vector-based vaccine was applied. Latency between vaccination and occurrence of GBS ranged between one day and 39 days. Eleven patients received IVIGs, two steroids, and one additionally plasma exchange. The outcome was fair in most cases.
We do not agree with the notion that the causal relation between SARS-CoV-2 and GBS is controversial [2]. In a recent review about SARS-CoV-2 associated GBS, 220 cases were found to have been published as per the end of December 2020 [2]. Considering that the majority of patients with SARS-CoV-2 associated GBS have not been published at all or were not even recognised because of mild symptoms or because of developing GBS during ICU treatment, it is conceivable that SARS-CoV-2 plays indeed a causal role in the development of SARS-CoV-2 associated GBS, probably in most of these cases. We do not agree that only IVIGs and plasma exchange are beneficial for SARS-CoV-2 associated GBS [1]. In a recent review of 220 cases with SARS-CoV-2 associated GBS, two patients were treated only with steroids, one from Spain and one from Italy. The patient from Spain recovered completely, the Italian patient partially [2]. Seven of the 220 patients did not receive any treatment but one of these patients recovered completely, 5 partially, and 1 died [2].
We do not agree that there is a causal relation between GQ1b antibodies and MFS [1]. GQ1b can be found in up to 100% of the MFS cases but this fact does not proof causality. Since GQ1b negative patients with MFS have been reported [3], another pathophysiological mechanisms may be more relevant for the development of the disease than these antibodies.
We do not agree that GBS develops “by chance” [1], GBS is an immune-reactive disorder and there is usually trigger that activates an immune response potentially harmful for certain compartments.
Overall, the interesting study has several limitations which challenge the results and their interpretation. Those receiving SARS – CoV - 2 vaccinations and experiencing side effects need to be taken seriously. Even if they may report mild symptoms they need to be carefully investigated, and in case of progressive motor, sensory, or autonomic deficits, GBS needs to be considered.
Ito H. et al. “Anti-ganglioside complex antibody profiles in a recurrent complicated case of GQ1b-seronegative Miller Fisher syndrome and Bickerstaff brainstem encephalitis: a case report.” BMC Neurology, vol. 18, no. 1, 2018, pp. 1–5. https://doi.org/10.1186/s12883-018-1077-5.
Josef F. and F.A. Scorza. “Guillain-Barré syndrome in 220 patients with COVID-19.” The Egyptian Journal of Neurology, Psychiatry, and Neurosurgery, vol. 57, no. 1, 2021, p. 55. https://doi.org/10.1186/s41983-021-00310-7.
Shoraka A.R. et al. “Ataxia and ophthalmoplegia: an atypical case of Miller Fisher syndrome (MFS) with anti-GAD antibody.” International Journal of Neuroscience, 2020, pp. 1–5. https://doi.org/10.1080/0020 7454.2020.1859502.