 Differentials diagnosis of COVID-19 associated polyradiculitis Eur J Transl Myol 32 (1): 10111, 2022 doi: 10.4081/ejtm.2021.10111 - 1 - Consider differentials before diagnosing COVID-19 associated polyradiculitis Josef Finsterer (1), Fulvio Alexandre Scorza (2), Carla Alessandra Scorza (2), Ana Claudia Fiorini (3) (1) Neurology & Neurophysiology Center, Vienna, Austria; (2) Neurocience Department. Federal University of São Paulo (UNIFESP). São Paulo, Brazil; (3) Phonoaudiology Department, Federal University of São Paulo (UNIFESP), Sao Paulo, Brazil. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. Abstract Evidence is accumulating that SARS-CoV-2 infections and SARS-CoV-2 vaccinations can induce Guillain-Barre syndrome (GBS). More than 400 GBS cases after SARS-CoV-2 infection respectively vaccination have been reported as per the end of 2021. GBS is usually diagnosed according to the Brighton criteria, but also the Besta criteria or Hadden criteria are applied. The diagnosis can be supported by MRI with contrast medium of the cranial or spinal nerves showing enhancing nerve roots. As GBS can be complicated by autonomic dysfunction such as pupillary abnormalities, salivatory dysfunction, reduced heart rate variability, bowel disturbance (constipation, diarrhea), urinary hesitancy, urinary retention, or impotence, it is crucial to investigate GBS patients for autonomic involvement. Before diagnosing GBS various differentials need to be excluded, including neuropathy as a side effect of the anti-SARS-CoV-2 medication, critical ill neuropathy in COVID-19 patients treated on the ICU, and compression neuropathy in COVID-19 patients requiring long-term ventilation. Key Words: SARS-CoV-2; COVID-19; neuropathy; Guillain-Barre; polyradiculitis. Eur J Transl Myol 32 (1): 10111, 2022 doi: 10.4081/ejtm.2021.10111 We read with interest the article by Darvishi et al. about a 56 years old male with mild COVID-19 manifesting with fever, chills, headache, myalgia, coughing, diarrhoea, and fatigue since 5 days prior to quarantine.1 Upon administration of the standard anti-COVID-19 therapy according to the national guidelines he recovered almost completely within 2 weeks.1 However, a few days later he developed subacute onset lower limb weakness, paresthesias, and pain progressing to flaccid paraparesis within 12 days. 1 Work-up revealed Guillain-Barre syndrome (GBS), subtype acute, inflammatory, demyelinating neuropathy (AIDP) and he partially profited from immunoglobulins. The study is appealing but raises concerns and comments. The causal relation between SARS-CoV-2 infections and GBS is meanwhile well established. In a recent review about SARS-CoV-2 associated GBS patients, 220 patients had been collected by the end of December 2020.2 An update about the frequency of published cases with SARS-CoV-2 associated GBS described 300 patients as per the end of July 2021, suggesting that at least the frequency of reporting this association declined in the first half 2021 compared to 2020, most likely due to the beneficial effect of SARS-CoV-2 vaccinations (Finsterer, personal communication, submitted). Previous studies showed that peripheral nerve roots enhance upon application of gadolinium on spinal MRI in patients with SARS-CoV-2 associated GBS.3 We should be told if the patient not only underwent spinal CT but also spinal MRI and if lumbar nerve roots or the cauda were enhancing upon administration of gadolinium. GBS is frequently complicated by autonomic dysfunction occurring in 19% of the patients with SARS-CoV-2 associated GBS.4 We should be told if the index patient had autonomic involvement, particularly bowel disturbance (constipation, diarrhea), urinary hesitancy, urinary retention, or impotence. Missing is the medication the patient received during quarantine for COVID-19. Since some of these compounds are neurotoxic, such as daptomycin, linezolid, lopinavir, ritonavir, hydro- chloroquine, cis-atracurium, clindamycin, or glucocorticoids,5 it is conceivable that neuropathy was drug-induced. Toxic neuropathy should be excluded as a differential of SARS-CoV-2 associated GBS. Missing are reference limits in Table 1 why it cannot be assessed if cerebro-spinal fluid (CSF) protein was within normal limits or increased. Diagnosing GBS according to Brighton criteria level-1 requires the presence of a Differentials diagnosis of COVID-19 associated polyradiculitis Eur J Transl Myol 32 (1): 10111, 2022 doi: 10.4081/ejtm.2021.10111 2 dissociation cyto-albuminique.6 The authors describe glove-type sensory deficits, suggesting that at least the sensory system of the upper limbs was additionally involved. We should know the results of nerve conduction studies (NCSs) of the median, ulnar and radial nerves, to assess if there was only sensory or also subclinical motor involvement of upper limb nerves. Overall, the elegant study has some limitations that challenge the results and their interpretation. These limitations should be addressed to further strengthen the conclusions. List of acronyms AIDP: acute, inflammatory, demyelinating neuropathy COVID-19: Coronavirus disease 2019 CSF: cerebro-spinal fluid GBS: Guillain-Barre syndrome NCSs: nerve conduction studies SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2 Authors contributions JF, FAS, CAS, ACF were involved in the conception, drafting and critical revision of the manuscript. All authors approved the final edited typescript. Acknowledgments None Funding None Conflict of Interest The authors declare no competing interests. Ethical Publication Statement We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Corresponding Author Finsterer Josef, MD, PhD, Neurology & Neurophysiology Center, Postfach 20, 1180 Vienna, Austria. Phone +43-1-71165; Fax. +43-1-71165 E-mail: fifigs1@yahoo.de E-mails and ORCID iD of co-authors Fulvio Alexandre Scorza: scorza@unifesp.br ORCID iD: 0000-0002-0694-8674 Carla Alessandra Scorza: carlascorza.nexp@gmail.com ORCID iD: 0000-0001-7810-4748 Ana Claudia Fiorini: acfiorini@pucsp.br ORCID iD: ORCID: 0000-0003-2989-2308 References 1. Darvishi M, Shahali H, Farahani AA. Guillain-Barré Syndrome Associated with SARS-CoV-2 Infection: A Case Report. Eur J Transl Myol. 2021 Aug 31. doi: 10.4081/ejtm.2021.9494. 2. Finsterer J, Scorza FA. Guillain-Barre syndrome in 220 patients with COVID-19. Egypt J Neurol Psychiatr Neurosurg. 2021;57(1):55. doi: 10.1186/s41983-021-00310-7. 3. Akçay N, Menentoğlu ME, Bektaş G, Şevketoğlu E. Axonal Guillain-Barre syndrome associated with SARS-CoV-2 infection in a child. J Med Virol. 2021 Sep;93(9):5599-5602. doi: 10.1002/jmv.27018. 4. Uncini A, Vallat JM, Jacobs BC. Guillain-Barré syndrome in SARS-CoV-2 infection: an instant systematic review of the first six months of pandemic. J Neurol Neurosurg Psychiatry. 2020 Oct;91(10):1105-1110. doi: 10.1136/jnnp-2020- 324491. 5. Finsterer J, Scorza FA, Scorza CA, Fiorini AC. Peripheral neuropathy in COVID-19 is due to immune-mechanisms, pre-existing risk factors, anti- viral drugs, or bedding in the Intensive Care Unit. Arq Neuropsiquiatr. 2021 Jul 19:S0004- 282X2021005016201. doi: 10.1590/0004-282X- ANP-2021-0030. 6. Mateen FJ, Cornblath DR, Jafari H, Shinohara RT, Khandit D, Ahuja B, Bahl S, Sutter RW. Guillain- Barré Syndrome in India: population-based validation of the Brighton criteria. Vaccine. 2011 Dec 6;29(52):9697-701. doi: 10.1016/j.vaccine.2011.09. 123. Submission: September 12, 2021 Accepted for publication: December 18, 2021 mailto:fifigs1@yahoo.de mailto:scorza@unifesp.br mailto:carlascorza.nexp@gmail.com mailto:acfiorini@pucsp.br