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January 2020; 7 (1) ArticleOpen Access

Neurologic complications of acute hepatitis E virus infection

Paolo Ripellino, Emanuela Pasi, Giorgia Melli, Claudio Staedler, Monserrat Fraga, Darius Moradpour, Roland Sahli, Vincent Aubert, Gladys Martinetti, Florian Bihl, Enos Bernasconi, Benedetta Terziroli Beretta-Piccoli, Andreas Cerny, Harry Roland Dalton, Cinzia Zehnder, Barbara Mathis, Chiara Zecca, Giulio Disanto, Alain Kaelin-Lang, Claudio Gobbi
First published December 5, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000643
Paolo Ripellino
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Emanuela Pasi
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Giorgia Melli
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Claudio Staedler
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Monserrat Fraga
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Darius Moradpour
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Roland Sahli
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Vincent Aubert
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Gladys Martinetti
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Florian Bihl
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Enos Bernasconi
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Benedetta Terziroli Beretta-Piccoli
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Andreas Cerny
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Harry Roland Dalton
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Cinzia Zehnder
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Barbara Mathis
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Chiara Zecca
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Giulio Disanto
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Alain Kaelin-Lang
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Claudio Gobbi
From the Department of Neurology (P.R., G.M., C.S., C.Z., G.D., A.K.-L., C.G.), Neurocenter of Southern Switzerland, Lugano, CH; Laboratory of Microbiology EOLAB (E.P., G.M.), Bellinzona, CH; Faculty of Biomedical Sciences, USI (G.M., C.Z., A.K.-L., C.G.), Lugano, CH; Division of Gastroenterology and Hepatology, Lausanne University Hospital (M.F., D.M.), Lausanne, CH; Institute of Microbiology, Lausanne University Hospital (R.S.), Lausanne, CH; Laboratory of Immunology, Lausanne University Hospital (V.A.), CH; Department of Hepatology, Hospital of Bellinzona (F.B.), CH; Division of Infectious Diseases (E.B.), Hospital of Lugano, CH; Epatocentro Ticino (B.T.B.-P., A.C.), Lugano, CH; Queens Park (H.R.D.), London, UK; Synlab Ticino (C.Z.), Bioggio, CH; and Unilabs Ticino (B.M.), Lugano, CH.
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Full PDF
Citation
Neurologic complications of acute hepatitis E virus infection
Paolo Ripellino, Emanuela Pasi, Giorgia Melli, Claudio Staedler, Monserrat Fraga, Darius Moradpour, Roland Sahli, Vincent Aubert, Gladys Martinetti, Florian Bihl, Enos Bernasconi, Benedetta Terziroli Beretta-Piccoli, Andreas Cerny, Harry Roland Dalton, Cinzia Zehnder, Barbara Mathis, Chiara Zecca, Giulio Disanto, Alain Kaelin-Lang, Claudio Gobbi
Neurol Neuroimmunol Neuroinflamm Jan 2020, 7 (1) e643; DOI: 10.1212/NXI.0000000000000643

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Abstract

Objective To assess the prevalence and clinical features of neurologic involvement in patients with acute hepatitis E virus (HEV) infection in Southern Switzerland.

Methods Among 1,940 consecutive patients investigated for acute hepatitis E, we identified 141 cases of acute of HEV infection (anti-HEV immunoglobulin M and immunoglobulin G both reactive and/or HEV RNA positive) between June 2014 and September 2017. Neurologic cases were followed up for 6 months. We compared patients with and without neurologic symptoms.

Results Neurologic symptoms occurred in 43 acute HEV cases (30.4%) and consisted of neuralgic amyotrophy (NA, n = 15, 10.6%) and myalgia (n = 28, 19.8%). All NA cases were immunocompetent. Men had higher odds (OR = 5.2, CI 1.12–24.0, p = 0.03) of developing NA after infection with HEV, and in 3 couples simultaneously infected with HEV, only men developed NA. Bilateral involvement of NA was predominant (2:1) and occurred only in men. Seven NA cases were viremic (all genotype 3), but HEV was undetectable in their CSF. In the acute phase of NA, 9 patients were treated with intravenous immunoglobulin and 4 with prednisone, reporting no side effects and improvement in pain and strength. Myalgia occurred both without (n = 16) or with (n = 12) concomitant elevated serum creatinine kinase. Seven cases with myalgia in the shoulder girdle did not have muscle weakness (“forme fruste” of NA).

Conclusions Neurologic symptoms occurred in one-third of acute HEV infections and consisted of NA and myalgia. NA seems to occur more frequently in men infected by HEV and has a predominant (but not exclusive) bilateral involvement.

Glossary

ALT=
alanine aminotransferase;
ANA=
antinuclear antibodies;
CK=
creatinine kinase;
GBS=
Guillain-Barré syndrome;
HEV=
hepatitis E virus;
IFN=
interferon;
IVIg=
intravenous immunoglobulin;
NA=
neuralgic amyotrophy

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • The Article Processing Charge was funded by the authors.

  • Received September 16, 2019.
  • Accepted in final form October 11, 2019.
  • Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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