Bax, F.

Gigli, G. L.

Marini, A.

Pellitteri, G.

Scalise, A.

Surcinelli, A.

Valente, M.

English

Gigli G. L.

Bax F.

Marini A.

Pellitteri G.

Scalise A.

Surcinelli A.

Valente M.

Archivio istituzionale della ricerca - Università degli Studi di Udine

Vol.:(0123456789) Journal of Neurology https://doi.org/10.1007/s00415-020-09911-3LETTER TO THE EDITORSGuillain‑Barré syndrome in the COVID‑19 era: just an occasional cluster?Gian Luigi Gigli1,2,3  · Francesco Bax2 · Alessandro Marini2  · Gaia Pellitteri2  · Anna Scalise1  · Andrea Surcinelli2 · Mariarosaria Valente1,2 Received: 24 April 2020 / Revised: 11 May 2020 / Accepted: 12 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020Dear Sirs,In terms of epidemiology, Guillain-Barré syndrome (GBS) accounts for 1–2 new cases/100.000 inhabitants per year [1, 2]. During the last two weeks, in coincidence with the descending slope of the pandemic peak in our region (Friuli Venezia-Giulia, Italy), we noted an unusual cluster of patients affected by GBS. The Neurology of the Udine University Hospital is the only Neurology Unit for the entire territory of the province, making unlikely the pos-sibility of missing new cases, since this is the only facility for neurophysiological investigation and cerebrospinal fluid (CSF) examination in an area of 4,969.3 km2. Solicited by this observation and by a recent paper reporting the asso-ciation of GBS with COVID-19 infection [3], we decided to re-examine the frequency of GBS cases during the March–April months of the last three years and to compare it with the admissions for GBS during the same months of the current year (up to April 16th).After having the possibility to perform a quick test (Cellex™ q rapid test [4]) for the presence of IgM and IgG against SARS-CoV-2 nucleocapsid protein (N-protein), we tested the four patients still present in our ward and two more patients already discharged who accepted to come back to the hospital. Furthermore, we briefly described clinical, laboratory and neuro-physiological data of patients admit-ted this year in Table 1. Data dealing with COVID-19 are reported in Table 2.The total number of GBS in the March–April interval of the previous three years is four. In 2020, from March 1st to April 15th, we observed instead seven new cases diag-nosed as GBS, in addition to a relapse in one more patient. This means 0.67 cases/month of observation (four cases in six months) in the previous three years, compared to 3.5 cases/month (seven cases in two months) during the current year, which increases to 4 cases/month (eight cases in two months), if we consider also the patient with relapse. Consid-ering a population of 535,516 inhabitants in the province of Udine (2017 census), the monthly incidence in March–April period of previous years was 0.12 new cases/100.000 inhab-itants per month (in line with the epidemiological literature [1, 2]) versus 0.65 cases/100.000 inhabitants per month dur-ing the ongoing pandemic. Accordingly, compared to years 2017–2019, the increase of GBS cases in 2020 is 5.41-fold.The suspicion that this striking difference could be due to the pandemic curve in our region is, therefore, legitimate. In fact, it is well known that GBS and related syndromes are often post-infectious (as for the influenza epidemics and more recently for Zika virus [5]), with an usual latency of 10–14 days after infection [2]. However, in our series, only one patient (twice negative at swab test) had positive serol-ogy and thorax CT scan. Despite the serologic and swab negativity of the others, we think that the association with the descending slope of SARS-CoV-2 infection should still be evaluated, since the specificity and sensitivity of these tests are not yet completely assessed and the exact slope of the humoral immune response curve to this new virus is still unknown. It could also be possible that asymptomatic or paucisymptomatic infections may not develop an antibody response sufficient enough to be detected, especially consid-ering that the available test is only qualitative.We wonder if similar clusters have been observed elsewhere. * Alessandro Marini  alemarini00@gmail.com1 Clinical Neurology Unit, Santa Maria della Misericordia University Hospital, Udine, Italy2 Department of Medicine (DAME), Neurology Unit, University of Udine, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy3 DMIF, University of Udine, Udine, Italy Journal of Neurology1 3Table 1  Demographic, clinical, CSF and neurophysiological findings in the observed population with GBSID patient identification number, GBS Guillain-Barré syndrome, CSF cerebrospinal fluid, M male, F female, AMSAN acute motor-sensory axonal neuropathy, AIDP acute inflammatory demyelinating polyneuropathy, MFS Miller-Fisher syndrome, c.n. cranial nerve, r normal range for labo-ratory, NA not availablea During patient’s first episode of AIDP, with onset on December 2019, CSF examination showed a protein content of 930 mg/L, with 0.8/µL cells. On the occasion of the clinical relapse, lumbar puncture was not performedID Age, Sex Previous infection symptomsGBS symptoms Symptoms onset CSF proteins (r: 150–450 mg/L)CSF leuco-cytes (r: 0–3/µL)Neurophysiological studies1 76, M No TetraparesisDysarthriaDysautonomia27/02/2020 228 mg/L 0.6/µL AMSAN2 70, M Diarrhea ParaparesisParaesthesiaAtaxia07/02/2020 216 mg/L 0.6/µL AIDP3 80, M No ArthromyalgiaLow back painParaesthesiaParaparesis20/03/2020 933 mg/L 0/µL AIDP4 59, M No Emifacial paresthesiaFacial weakness (VII c.n.)Dysarthria (XII c.n.)24/03/2020 701 mg/L 2.8/µL Altered blink reflex, demy-elinating damage (MFS)5 59, F FeverCoughCommon coldLow back painParaesthesiaTetraparesis01/03/2020 1124 mg/L 0.4/µL AIDP6 82, M Fever Asymmetric paraparesis 28/03/2020 827 mg/L 0.8/µL AIDP7 53, M FeverDiarrheaParaesthesiaAtaxia01/04/2020 1928 mg/L 2.6/µL AIDP8 59, F No TetraparesisParaesthesia11/02/2020 (relapse) NAa (relapse) NA (relapse) AIDP relapseTable 2  Data dealing with COVID-19 in the population with GBSID COVID-19 common  symptomsaSwab test Thorax imaging sug-gestive for COVID-19(Rx or thorax CT scan)SARS-CoV-2 serol-ogyPCR for SARS-CoV-2 on CSFSerology or PCR for other infectionsSerum anti-gan-gliosides antibodies1 No 24/03/2020 negative Interstitial pneumo-niaNA NA Negative Multiplex  PCRb (CSF)Negative serology for  Borreliac and TBE (CSF), WNV (serum)Negative2 Yes 24/03/2020 negative No Negative (blood) NA Negative serology for Borrelia and TBE (serum)Negative3 No 15/04/2020 negative No Negative (blood) Negative Negative Multiplex PCR (CSF)Negative serology for Borrelia and TBE (CSF)NA4 No 27/03/2020 negative No Negative (blood) Negative Negative Multiplex PCR (CSF)Negative serology for Borrelia and TBE (serum and CSF)NegativeJournal of Neurology 1 3ID patient identification number, CT computed tomography, PCR polymerase chain reaction, CSF cerebrospinal fluid, NA not available, CMV Cytomegalovirus, EBV Epstein-Barr virus, HSV-1 Herpes simplex virus 1, HSV-2 Herpes simplex virus 2, HHV-6 Human herpes virus 6, HPeV Human parechovirus, VZV Varicella-zoster virus, TBE Tick-borne encephalitis, WNV West-Nile virusa We intend symptoms such as fever, cough, cold and diarrheab Mutliplex PCR: EBV, CMV, Enterovirus, HSV-1, HSV-2, HHV-6, HPeV, VZVc Borrelia burgdorferiAuthor contributions Data access, responsibility, and analysis: AM had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Funding None.Compliance with ethical standards Conflicts of interest On behalf of all authors, the corresponding author states that there is no conflict of interest.Ethical standard statement This study followed the tenets of the Dec-laration of Helsinki and was performed according to the guidelines of the Institutional Review Board of University of Udine Medical School.References 1. Sejvar JJ, Baughman AL, Wise M, Morgan OW (2011) Population incidence of Guillain-Barré syndrome: a systematic review and meta-analysis. Neuroepidemiology 36(2):123–133. https ://doi.org/10.1159/00032 4710 2. Yuki N, Hartung H-P (2012) Guillain-Barré syndrome. N Engl J Med 366(24):2294–2304. https ://doi.org/10.1056/NEJMr a1114 525 3. Zhao H, Shen D, Zhou H, Liu J, Chen S (2020) Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol. https ://doi.org/10.1016/S1474 -4422(20)30109 -5 4. Cellex qSARS-CoV-2 IgG/IgM Rapid Test (2020) https ://fda.gov/media /13662 5/downl oad. Accessed 8 May 2020 5. Parra B, Lizarazo J, Jiménez-Arango JA et al (2016) Guillain-Barré syndrome associated with Zika virus infection in Colom-bia. N Engl J Med 375(16):1513–1523. https ://doi.org/10.1056/NEJMo a1605 564ID COVID-19 common  symptomsaSwab test Thorax imaging sug-gestive for COVID-19(Rx or thorax CT scan)SARS-CoV-2 serol-ogyPCR for SARS-CoV-2 on CSFSerology or PCR for other infectionsSerum anti-gan-gliosides antibodies5 Yes 20/03/2020 negative No Negative (blood) NA Negative Multiplex PCR (CSF)Negative6 Yes 07/04/2020 negative No Negative (blood) Negative NA NA7 Yes 06/04/2020 negative14/04/2020 negativeBilateral ground-glass opacitiesPositive IgM and IgG(blood and CSF)Negative Negative PCR for influenza A and B viruses (nasal swab)Negative serology for Borrelia and TBE (CSF)Negative8 No 30/03/2020 negative06/04/2020 negative15/04/2020 negativeGround-glass opaci-tiesPeri-bronchovascular thickeningsNA NA NA GD1a + GT1b, anti-sulfatide low titer + Table 2 Continued

Guillain-Barré syndrome in the COVID-19 era: just an occasional cluster?

https://air.uniud.it/bitstream/11390/1188373/2/Gigli2020_Article_Guillain-Barr%c3%a9SyndromeInTheCOV.pdf

Guillain-Barr\ue9 syndrome in the COVID-19 era: just an occasional cluster?

Guillain-Barr\ue9 syndrome in the COVID-19 era: just an occasional cluster?

Abstract

Similar works

Full text

Available Versions

Archivio istituzionale della ricerca - Università degli Studi di Udine