With interest we read the article by Sidoli et al. on a 90 years-old female who was diagnosed with SARS-CoV-2 related Guillain-Barre syndrome (GBS) subtype acute, motor and sensory, axonal neuropathy (AMSAN), but despite treatment with intravenous immunoglobulins (IVIGs), the patient died about three weeks after admission [1]. The study is excellent but has limitations that are cause of concerns and should be discussed.

We disagree that the index patient had GBS subtype AMSAN. Assuming that a cerebrospinal fluid (CSF) cell count of 21/microL is consistent with mild pleocytosis, the patient did not have dissociation cyto-albuminique, required to meet Brighton’s level A criteria A for the diagnosis of definitive GBS [2]. Although the CSF culture was negative, it cannot be ruled out that the patient had viral central nervous system (CNS) infection other than SARS-CoV-2 or a fungal infection. The patient developed fluctuating vigilance state with a tendency to drowsiness [1]. To rule out CNS infections disease, it would have been necessary to perform a CSF virus panel, fungal culture, and contrast-enhanced cerebral magnetic resonance imaging (MRI) to confirm or rule out viral encephalitis. It would also have been necessary to measure antibodies associated with autoimmune encephalitis (AIE) to rule out AIE. Infectious and immune encephalitis can be easily missed on cerebral computed tomography (CCT), especially when done without contrast medium. In SARS-CoV-2 associated CNS disease cytokines, chemokines, 14-3-3, and glial factors are often elevated in the CSF [3]. 

There is a discrepancy between the statement that “all reported symptoms originated in the last two weeks” (since December 28^th 2020) and the statement that the patient came to the emergency room on December 26^th 2020 due to loss of appetite [1]. This discrepancy should be clarified. The lack of appetite also existed presumably before December 26^th.

There is also a discrepancy between the statement that the patient died at home a few days after discharge from the hospital [1] and the statement that the two-month follow-up showed a further rapid decline [1]. The patient was discharged after 15 days of hospitalisation, i.e. on the 27^th January [1]. If she died a few days later, how can there be a two-months follow-up? 

It was not explained why the patient was SARS-CoV-2 positive for a long time [1]. She is said to have suffered from COVID-19 in the first half of December 2020 and was still SARS-CoV-2 positive on the 26^th December 2020 [1]. Given that the incubation period for SARS-CoV-2 infection is up to 14 days, it is reasonable to assume that she was SARS-CoV-2 positive for around a month. How do the authors explain this long persistence of the virus, or was there evidence that she was infected again after the initial infection?

We disagree that therapy was maximised as stated in the case description. Why didn’t she undergo a second IVIG cycle or plasma exchange? 

Another limitation is that differentials of neuropathy were not appropriately ruled out. Since the patient developed loss of appetite, dysphagia, dehydration, and hypoproteinemia, it is crucial that malignancy, particularly gastro-intestinal, and paraneoplastic neuropathy are adequately ruled out. No explanation for dysphonia, dysarthria and severe difficulty in swallowing was provided. Was this due to bulbar involvement in GBS or due to other causes? Was GBS subtype Bickerstaff encephalitis adequately ruled out?

Another limitation of the study is that reference limits were not reported, neither for blood tests nor for CSF parameters [1]. Knowing reference limits is crucial to assess what parameters were abnormal and to assess severity of abnormality. 

Overall, the interesting study has limitations that call the results and their interpretation into question. Addressing these issues would strengthen the conclusions and could improve the status of the study. GBS should be diagnosed according to the Brighton criteria and before diagnosing GBS, all differential diagnoses need to be thoroughly ruled out.

1. Sidoli, C., et al. “Guillain-Barré Syndrome AMSAN Variant in a 90-Year-Old Woman after COVID-19: A Case Report.” BMC Geriatrics, vol. 23, no. 1, 2023, p. 114. doi:10.1186/s12877-023-03833-1.

2. Mateen, F.J., et al. “Guillain-Barré Syndrome in India: Population-Based Validation of the Brighton Criteria.” Vaccine, vol. 29, no. 52, 2011, pp. 9697–9701. doi:10.1016/j.vaccine.2011.09.123.

3. Gigli, G.L., et al. “HLA and Immunological Features of SARS-CoV-2-Induced Guillain-Barré Syndrome.” Neurological Sciences, vol. 41, no. 12, 2020, pp. 3391–3394. doi:10.1007/s10072-020-04787-7.