SUPPLEMENTARY Informationin Format Provided by Dalton, H.R.Et Al

SUPPLEMENTARY INFORMATIONIn format provided by Dalton, H.R.et al.

Associated with

Supplementary information S1 (table) | Review – neurological manifestations associated with HEV

Study / n and sex / Country / Age (years) / Type of patient / HEV infection at neurologicalsymptoms (acute or chronic phase) / HEV genotype / HEV IgG/IgM / Serum HEV RNA / ALT (IU/l) / Bilirubin (µmol/l) / HEV RNA in CSF / Neurological symptoms / Treatment / Outcome
Soodet al.(2000)1 / 1M / India / 50 / IC / Acute / NR / NR/+ / NR / 114 / 24 / NR / GBS / None / Complete recovery
Kejariwalet al.(2001)2 / 1F / India / 28 / IC / Acute / NR / NR/+ / NR / 1,890 / 55 / NR / Meningoencephalitis / None / Improved
Kamaniet al.(2005)3 / 1F / India / 58 / IC / Acute / NR / NR/+ / NR / 1,448 / 41 / NR / GBS / PP, IVIg / Complete recovery
Dixit et al.(2006)4 / 1M / India / 32 / IC / Acute / NR / NR/+ / NR / 1,000 / NR / NR / Bell palsy / None / Complete recovery
Mandalet al.(2006)5 / 1F / India / 12 / IC / Acute / NR / NR/+ / NR / NR / NR / NR / Acute transverse myelitis / None / Complete recovery
Joshi et al.(2007)6 / 1M / India / 22 / IC / Acute / NR / NR/+ / NR / 575 / 138 / NR / Encephalitis / Antiepileptic drugs / Improved
Fonget al.(2009)7 / 1M / UK
(back fromEquator) / 53 / IC / Acute / NR / NR/+ / NR / 2,547 / 20 / NR / Neuralgicamyotrophy / None / Complete recovery
Lolyet al. (2009)8 / 1M / Belgium / 66 / IC / Acute / NR / NR/+ / NR / 1,813 / NR / NR / GBS / IVIg / Near-complete recovery
Rianthavornet al.(2010)9 / 1M / Thailand (back fromIndia) / 49 / IC / Acute / 3 / NR/+ / + / 795 / 32 / NR / Neuralgicamyotrophy / None / Partial recovery
Kamaret al.(2011)*‡10
Kamaret al.(2010)*11
Dalton et al.(2011)*12 / 6M, 1F / France (n=4)
UK (n=3) / Median44(range 35–60) / 3 IC,4 IS / Acute (n=3)
Chronic (n=4) / 3a (n=1)
3e (n=2)
3f (n=4) / +(n=6)/
+(n=7) / +(n=7) / Median171 (range 105–1,160) / Median14 (range 9–70) / –(n=2)
+(n=4)
NR(n=1) / Neuralgicamyotrophy (n=3)
GBS (n=2)
Encephalitis (n=2) / IVIg (n=2)
Immunosuppressant dose modification (n=3)
Peg-IFN/ribavirin (n=1) / Complete recovery (n=4)
Partial recovery (n=2)
No improvement (n=1)
Cronin et al.(2011)13 / 1M / Ireland / 40 / IC / Acute / NR / NR/+ / NR / 127 / NR / NR / GBS / PP, IVIg / Complete recovery
Maurissenet al. (2012)14 / 1F / Belgium / 51 / IC / Acute / NR / +/+ / + / 2,074 / NR / NR / GBS / IVIg / Complete recovery
Despierreset al. (2011)15 / 1F
1M / France / 54
49 / IC / Acute / 3 / NR/+ / + / 566
78 / Normal / +(n=1) / Meningitis
Polyradiculoneuropathy / None / Complete recovery
Del Bello et al.(2012)16 / 1M / France / 60 / IS / Acute / 3f / +/+ / + / 2,000 / NR / – / GBS and myositis / IVIg, ribavirin / Partial recovery
Tse et al.(2012)17 / 1F / Hong Kong / 60 / IC / Acute / NR / NR/+ / NR / 2,858 / 60 / NR / GBS / PP / Complete recovery
Inghileriet al.(2012)18 / 1M / France / 28 / IC / Acute / NR / NR/+ / NR / 1,007 / NR / NR / Neuralgicamyotrophy / Unavailable / Unavailable
Jhaet al.(2012)19 / 1M / India / 28 / IC / Acute / NR / NR/+ / NR / 1,200 / 204 / NR / Bell palsy / None / Complete recovery
Carliet al.(2012)20 / 1M / France / 30 / IC / Acute / NR / NR/+ / + / 1,518 / NR / NR / Neuralgicamyotrophy / None / Partial recovery
Cheung et al.(2012)21 / 1M / UK / 56 / IC / Acute / NR / NR/+ / + / NR / NR / NR / Neuralgicamyotrophy / None / No recovery
Periet al.(2013)22 / 1M / Italy / 53 / IC / Acute / 3 / +/+ / + / 1,768 / 129 / NR / Neuralgicamyotrophy / None / Complete recovery
Sharma et al.(2013)23 / 1M / India / 27 / IC / Acute / NR / NR/+ / NR / NR / Increased / NR / GBS / IVIg / Partial recovery
Santos et al.(2013)24 / 1M / Portugal / 50 / IC / Acute / 3a / –/+ / + / 2,320 / 114 / NR / GBS / IVIg / Partial recovery
Motte et al.(2014)25 / 1M / France / 52 / IC / Acute / 3f / +/+ / + / 590 / NR / – / Neuralgicamyotrophy / None / Unavailable
Moissetet al.(2013)26 / 1M / France / 36 / IC / Acute / 3f / NR/– / + / 1,707 / 54 / – / Neuralgicamyotrophy / IVIg, ribavirin / Sequelae
Maddukuriet al.(2013)27 / 1M / USA / 64 / IS / Chronic / 3 / +/+ / + / 362 / NR / + / Peirpheralneuropathy and encephalitis / Peg-IFN,immunosuppressant dose reduction / Death
Geurtsvankesselet al.(2013)28 / 11 (sexNR) / Bangladesh / NR / IC / Unknown / 1 (only IgM+patients were tested) / +(n=4)/ +(n=11) / 1 (only IgM+ patients were tested) / NR / NR / NR / GBS / Unavailable / Unavailable
De Vrieset al.(2014)29 / 1F / Netherlands / 66 / IS / Chronic / 3 / +/+ / + / 299 / 8 / + / Encephalopathy / Immunosuppressant dose reduction, ribavirin / Partial recovery
Comontet al.(2014)‡30 / 1M / France / 73 / IC / Acute / 3f / +/+ / + / 822 / 101 / + / GBS / IVIg / Complete recovery
Scharnet al.(2014)31 / 1M / Germany / 50 / IC / Acute / 3c / +/+ / + / 334 / NR / - / GBS / IVIg / Partial recovery
Derouxet al.(2014)32 / 2M / France / 38
41 / IC / Acute / 3f (n=1)
Second patient was not tested / NR/+ / + / 479 and1,612 / Normal / +(n=1)
Second patientwas not tested / Encephalitis (n=1)
Neuralgicamyotrophy (n=1) / None / Complete recovery
Belbezieret al.(2014)33 / 1M / France / 33 / IC / Acute / 3f / –/+ / + / 190 / NR / – / Myastheniagravis / Prostigmin, ribavirin, IVIg, azathioprine / Complete recovery
Chen et al.(2014)34 / 1F / China / 64 / IC / Acute / NR / –/+ / NR / 1,461 / 157 / NR / GBS and encephalitis / IVIg / Complete recovery
van den Berg et al.(2014)35 / 6M, 4F) / Netherlands / Median60 (range 32–69) / IC / Acute / 3 / +(n=9)/ +(n=10) / +(n=3) / Median70 (range 26–921) / Median 10 (range 3–46) / –(n=5)
NRin the other patients / GBS / Unavailable / Partial recovery (n=7)
Complete recovery (n=3)
Van Eijket al.(2014)36 / 4M, 1F / Netherlands
and UK / Median36 (range 34–40) / IC / Acute / 3 (n=1) / +/+ / + / Median 129.5 (range 34–313) / Median 4 (range 3–8) / NR / Neuralgicamyotrophy / Unavailable / Partial recovery
Woolsonet al. (2014)37 / 7M, 1F / UK / Median40 (range 34–92) / 7 IC,1 IS* / Acute (n=7)
Chronic (n=1) / 3 (n=5; other patients not tested) / +/+ / + / Median 471 (range 27–1504) / Median 13 (range 4–158) / + in 1of 3 tested patients / Neuralgicamyotrophy (n=3)
Neuromyopathy (n=1)
GBS (n=1)
Vestibular neuritis (n=1)
Small-fibre neuropathy (n=1)
Peripheral neuropathy (n=1) / Peg-IFN/ribavirin (n=1) / Complete remission (n=3)
Partial remission (n=5)
Bennettet al.(2015)38 / 1F / Scotland / 77 / IC / Acute / NR / +/+ / + / 1,606 / 25 / NR / Paraesthesia / None / Complete recovery
BlascoPerrin et al.(2015)‡39 / 8M, 7F / France / Median55 (range 25–77) / IC / Acute / 3f (n=9;other patients not tested) / +(n=13)/+(n=15) / +(n=11 out of 14 tested patients) / Median 495 (range 49–3641) / Median 15 (range 7–101) / +(n=2 out of 6 tested patients) / Mononeuritis multiplex (n=6)
Neuralgicamyotrophy (n=4)
Meningoradiculitis (n=3)
Acute demyelinating neuropathy (n=2) / None (n=8)
IVIg (n=3)
IVIg + ribavirin(n=2)
Ribavirin (n=1)
Steroids (n=1) / Complete recovery (n=9)
Partial recovery (n=6)
Decardet al.(2015)40 / 1M / Switzerland / 47 / IC / Acute / NR / +/+ / NR / 106 / NR / NR / Neuralgicamyotrophy / None / Near-complete recovery
Theochariet al. (2015)41 / 1M / UK / 65 / IC / Acute / NR / +/+ / NR / 1,368 / NR / NR / Neuralgicamyotrophy / None / Complete recovery
Martinez-Rodriguez et al.(2015)43 / 1M / Spain / 41 / IC / Acute / NR / NR/+ / NR / 1,270 / NR / NR / Neuralgicamyotrophy / None / Unknown
Yazakiet al.(2015)43 / 1M / Japan / 67 / IC / Acute / 4 / NR/+ / + / 3,866 / 445 / NR / Bell palsy / None / Complete recovery
Dartevelet al.(2015)44 / 3M, 2F / France / Median54 (range 40–59) / IC / Acute / 3f (n=3; other patients not tested) / +(n=2)/+(n=5) / +(n=4)§ / Median 924 (range 88–1,036) / 8 (in 1patient) / –(in the 3 testedpatients) / Neuralgicamyotrophy / None (n=3)
Physiotherapy (n=1)
IVIg (n=1) / No recovery (n=1)
Partial recovery (n=3)
Complete recovery (n=1)

The term “HEV” was searched on PubMed against the following terms: “neurology”, “neurological symptoms”, “neurological manifestations”, “Guillain–Barré syndrome”, “neuralgic amyotrophy”, “encephalitis” and“peripheral nerve”. *A case reported by Kamaret al.(2010)11 and a case reported by Dalton et al.(2011)12were included in the study by Kamaret al.(2011)10. ‡Some of these cases are also reported in the study by Blasco-Perrin et al.(2015)39. Cases from this study have been previously reported in the study by Kamaret al.(2011)10. In summary, 7 cases were reported in more than one study (2 cases that occurred in IS patients and 5 other cases in IC patients).§HEV RNA was not detected in the serum but it was present in the stools in 1 patient.ALT, alanine aminotransferase; CSF, cerebrospinal fluid; GBS, Guillain–Barré syndrome; HEV, hepatitis E virus; IC, immunocompetent; IS, immunosuppressed; IVIg, intravenous immunoglobulin; NR, not reported; Peg-IFN, pegylated interferon;PP, plasmapheresis. Of note, in a large number of reports, HEV RNA was not assessed in the serum at the time of diagnosis ofneurological manifestations.

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