# Case Report: Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E

Xavier Moisset, Nicolas Vitello, Elodie Bicilli, Romain Courtin, Anna Ferrier, Frederic Taithe, Clément Lahaye, Ali Ait Hssain, Cyril Garrouste, Clavelou Pierre

<figure><img src="image_1.png" /></figure>

To cite this version:

Xavier Moisset, Nicolas Vitello, Elodie Bicilli, Romain Courtin, Anna Ferrier, et al.. Case Report: Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E. F1000Research, 2014, 2, pp.259. 10.12688/f1000research.2-259.v2 . hal-05484723

HAL Id: hal-05484723

https://hal.science/hal-05484723v1

Submitted on 30 Jan 2026

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons CC BY 4.0 - Attribution - International License
<figure><img src="image_3.png" /></figure>

## CASE REPORT

**REVISED** Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E [v2; ref status: indexed, http://f1000r.es/2q8]

Xavier Moisset<fnref n="1" />,<fnref n="2" />, Nicolas Vitello<fnref n="1" />,<fnref n="3" />, Elodie Bicilli<fnref n="1" />, Romain Courtin<fnref n="4" />, Anna Ferrier<fnref n="1" />, Frederic Taithe<fnref n="1" />, Clément Lahaye<fnref n="5" />, Ali Ait Hssain<fnref n="6" />, Cyril Garrouste<fnref n="3" />,<fnref n="7" />, Clavelou Pierre 1-3

## v2

First Published: 26 Nov 2013, 2:259 (doi: 10.12688/f1000research.2-259.v1)

Latest Published: 06 Jan 2014, 2:259 (doi: 10.12688/f1000research.2-259.v2)

### Abstract

**Introduction:** Several acute neurological syndromes can be triggered by immune events. Hepatitis E virus (HEV), an emerging infectious disease, can be one of these triggers.

**Case report:** We report the case of a 36-year-old man that presented nausea and a dull abdominal pain for a week and then felt an acute neuralgic pain involving both shoulders that lasted for 8 to 10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs, corresponding to an amyotrophic neuralgia. Two days after the shoulder pain, the patient presented a dysphagia necessitating tube feeding. A blood sample confirmed hepatitis caused by hepatitis E virus (HEV; genotype 3F). Oral feeding resumed progressively after five months. The patient was fully independent for the activities of daily living but was still unable to work after six months.

**Conclusion:** Amyotrophic neuralgia and hepatitis E are both under-diagnosed. It is noteworthy that HEV can trigger amyotrophic neuralgia. Antiviral drugs, oral steroids and intravenous immunoglobulins can be proposed, but the optimal treatment has not yet been determined.

### Article Status Summary

#### Referee Responses

Referees

1

2

3

4

v1

published
26 Nov 2013

<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /></figure>

<figure><img src="image_6.png" /></figure>

<figure><img src="image_7.png" /></figure>

v2

published
06 Jan 2014

REVISED

1. **Bruce Brew**, St Vincent's Hospital, Sydney Australia

2. **Thierry Coton**, Hôpital d'instruction des Armées Laveran France

3. **José Manuel Echevarría**, National Centre of Microbiology, Carlos III Health Institute Majadahonda Spain

4. **Michelle Cheung**, King's College Hospital UK

### Latest Comments

No Comments Yet

<footnote n="1">¹CHU Clermont-Ferrand, Service de Neurologie, CHU Gabriel Montpied, Clermont-Ferrand, F-63000, France</footnote>

<footnote n="2">²Neuro-Dol, Inserm U1107, Douleur Trigéminale et Migraine, Faculté de Chirurgie Dentaire, F-63000, F-63000, France</footnote>

<footnote n="3">³Clermont Université, Université d'Auvergne, Clermont-Ferrand, F-63000, France</footnote>

<footnote n="4">⁴CHU Clermont-Ferrand, Service d'Ophtalmologie, CHU Gabriel Montpied, Clermont-Ferrand, F-63000, France</footnote>

<footnote n="5">⁵CHU Clermont-Ferrand, Service de Rhumatologie, CHU Gabriel Montpied, Clermont-Ferrand, F-63000, France</footnote>

<footnote n="6">⁶CHU Clermont-Ferrand, Service de Réanimation Médicale, CHU Gabriel Montpied, Clermont-Ferrand, F-63000, France</footnote>

<footnote n="7">⁷CHU Clermont-Ferrand, Service de Néphrologie, CHU Gabriel Montpied, Clermont-Ferrand, F-63000, France</footnote>
**Corresponding author:** Xavier Moisset (xavier.moisset@gmail.com)

**How to cite this article:** Moisset X, Vitello N, Bicilli E et al. (2014) Severe bilateral amyotrophic neuralgia associated with major dysphagia secondary to acute hepatitis E [v2; ref status: indexed, http://f1000r.es/2q8] *F1000Research* 2014, *2*:259 (doi: 10.12688/f1000research.2-259.v2)

**Copyright:** © 2014 Moisset X et al. This is an open access article distributed under the terms of the [Creative Commons Attribution Licence](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the [Creative Commons Zero "No rights reserved" data waiver](http://creativecommons.org/licenses/by/4.0/data-waiver) (CC0 1.0 Public domain dedication).

**Grant information:** The author(s) declared that no grants were involved in supporting this work.

**Competing Interests:** No competing interests were disclosed.

**First Published:** 26 Nov 2013, 2:259 (doi: 10.12688/f1000research.2-259.v1)

**First Indexed:** 20 Dec 2013, 2:259 (doi: 10.12688/f1000research.2-259.v1)
**REVISED** Amendments from Version 1

We thank the reviewers for their comments. In addition to our detailed
responses to reviewers at the bottom, the following is a summary of
the changes made in response to reviewer's comments:

There is no validated treatment for neuralgic amyotrophy, with only
one retrospective series reporting a benefit of corticosteroids. This
point has been corrected in the text.

A sentence and a reference (Abbas and Afzal. 2013) have been
added to justify the use of ribavirin.

Anti-HEV antibody testing of CSF was not performed and this is now
clearly specified.

Concerning biological exams, it is now specified that the prothrombin
time didn't increase, the immunological screening is detailed and PCR
was not initially realized in stools.

The duration of the ribavirin therapy is now specified (35 days).

We now state in the discussion that this case concerned genotype
3f virus that is predominant in France (Luciano et al. 2012).

See referee responses

**Introduction**

Neurological syndromes such as Guillain-Barré Syndrome, trans-
verse myelitis, encephalitis or amyotrophic neuralgia can be trigger-
gered by immune events. Hepatitis E virus (HEV), discovered in
the 1980s, can be one of these triggers. Epidemics of hepatitis E
occur periodically throughout the developing world, but autoch-
thonous HEV infections have also been reported in most devel-
oped countries during the last decade. Several HEV-associated
neurological syndromes have been described but are probably
under-diagnosed¹.

**Case report**

We report the case of a 36-year-old French man, Caucasian truck
driver, without any significant medical history. The clinical symp-
toms started in May 2012 with nausea and a dull abdominal pain.
No sign of chronic liver disease or of portal hypertension was
noted. High liver enzymes were diagnosed after assay for: alanine
aminotransferase (ALT) 1707 µmol/L (normal range: N<78),
aspartate aminotransferase (AST) 554 µmol/L (N<37), gamma-
glutamyltranspeptidase (GGT) 737 U/L (N<95) and alkaline phos-
phatase at 311 U/L (N<136). Total bilirubin level was at 54 µmol/L
(N<17). There was no hepatitis A, B or C, no HIV and no sign
of autoimmune disease. The immunological screening included
antinuclear antibodies, anti-smooth muscles antibodies, anti-
mitochondria antibodies, anti LKM antibodies, anti-hepatic cytosol
antibodies, complement (C3, C4, CH50), rheumatoid factor, antineu-
trophil cytoplasmic antibody (ANCA), antiganglioside antibodies
(GM1, GM2, GD1a, GD1b, GQ1b) and onconeural antibodies
(Hu, Ri, Yo, PNMA2, CV2, Amphiphysine). Liver ultrasound was
normal. The prothrombin time stayed within the normal range
throughout the monitoring period.

Around one week after the first digestive symptoms, the patient felt
an acute neuralgic pain involving both shoulders that lasted for 8 to

10 hours. Immediately after, the patient presented a severe bilateral muscular weakness of the proximal part of both upper limbs. Two days after the shoulder pain, the patient presented with hypophonia and dysphagia. The MRI did not show any brain abnormality. The spinal cord and the brachial plexus were unharmed. The cerebrospinal fluid (CSF) was normal (2 white blood cells/mm³; CSF Protein = 0.37 g/L) and there was no intrathecal antibody synthesis, although it was not tested for the synthesis of specific anti-HEV antibodies. Electromyography (EMG) and nerve conduction studies (NCS) showed normal amplitudes and conduction velocity but bilateral denervation in the supraspinatus, infraspinatus, subscapularis and deltoid muscles. An acute hepatitis E infection was suspected due to the presence of IgM and confirmed by PCR (genotype 3f). The initial serum HEV RNA count was 5.2 log-copies/ml. The PCR was negative in the CSF and was not initially performed in stools.

A treatment with intravenous immunoglobulins (Tegeline®, LFB laboratory, France; 0.4 g/kg/day) was given for 5 days. Ribavirin (600 mg/day) was also introduced. Nine days after ribavirin initiation, the PCR showed 2.02 log-copies/ml and was negative after 18 days in both blood and stools. Ribavirin treatment was discontinued after 35 days. After three weeks, the patient still required nasogastric tube-feeding and a gastric feeding tube was placed endoscopically. There was no contraction of the shoulder girdle muscles. Oral feeding resumed progressively after five months. After six months follow-up and intensive rehabilitation, there was a 3/5 muscular strength in the affected muscles, corresponding to a movement possible against gravity, but not against resistance by the examiner. The patient was fully independent for the activities of daily living but still unable to work.

**Discussion**

This is the first report of both severe bilateral amyotrophic neu-
ralgia and dysphagia caused by an acute hepatitis E infection.
Amyotrophic neuralgia (AN) is a peripheral neuropathy consisting
of multiple symptoms including abrupt onset of shoulder pain, usu-
ally unilaterally, followed by motor weakness, with an annual inci-
dence above 2 per 100,000 inhabitants². Concomitant involvement
of other peripheral nervous system structures (such as the lumbosa-
cral plexus or phrenic nerve) is described. AN can be triggered by
immune events but also by trauma or surgery. Many patients are left
with residual disabilities that affect their ability to work and their
everyday life. It is noteworthy that a particularly severely affected
subgroup presents sign of liver dysfunction, as seen in HEV infec-
tions³. The only proposed treatment (with a low level of evidence)
is corticosteroids but this may have been dangerous in this case
of acute hepatitis E³. Some authors have also reported a positive
effect of intravenous immunoglobulins and this was the option we
selected⁴⁻⁶.

HEV-associated neurological syndromes include both central and
peripheral nervous system involvement⁷. Such cases have been
described in the Asian sub-continent (probably due to HEV1) but
also in Western Europe with acute and chronic HEV3 infection.
The present case concerned genotype 3f virus that is predominant
in France⁸. For patients with chronic HEV infections, neurological symptoms completely resolved or significantly improved when viral clearance was achieved¹. Moreover, several authors suggest treating severe acute HEV infections in order to preclude the development of acute liver failure⁹. This is the reason why we tried antiviral treatment. Unfortunately, although viral clearance was achieved quickly, this did not lead to fast clinical improvements.

An alternative diagnosis of pharyngeal-cervical-brachial variant of Guillain-Barré syndrome could have been made. This pathology is characterized by oropharyngeal, neck, and upper limb muscle involvement. However, in the present case, this diagnosis was excluded (no neck involvement, atypical EMG, no albuminocytologic dissociation of the cerebrospinal fluid and negative GQ1b antibody).

## Conclusion

Post-infectious neurological diseases following HEV infection must be recognized to avoid unnecessary and potentially invasive procedures such as liver biopsy. Further studies are needed in order to determine the optimal treatment. In the meantime, antiviral drugs, steroids and IV-immunoglobulins are all possibilities.

## Consent

Written informed consent for publication of clinical details was obtained from the patient.

## Author contributions

XM: wrote the manuscript. NV: revised the first draft. EB, RC and CL: managed the patient in the rheumatology and neurology departments. AF: suggested HEV diagnosis. FT: did the EMG. AAH: managed the patient in the intensive care unit. FT, CG and PC: decided on the treatment plan. All authors were involved in the revision of the manuscript and have agreed to the final content.

## Competing interests

No competing interests were disclosed.

## Grant information

The author(s) declared that no grants were involved in supporting this work.

## References

1. Kamar N, Bendall R, Legrand-Abravanel F, et al.: Hepatitis E. Lancet. 2012; 379(9835): 2477-2488.
PubMed Abstract | Publisher Full Text

2. Van Alfen N: Clinical and pathophysiological concepts of neuralgic amyotrophy. Nat Rev Neurol. 2011; 7(6): 315-322.
PubMed Abstract | Publisher Full Text

3. Van Alfen N, Van Engelen BG, Hughes RA: Treatment for idiopathic and hereditary neuralgic amyotrophy (brachial neuritis). Cochrane Database Syst Rev. 2009; 8(3): CD006976.
PubMed Abstract | Publisher Full Text

4. Johnson NE, Petraglia AL, Huang JH, et al.: Rapid resolution of severe neuralgic amyotrophy after treatment with corticosteroids and intravenous immunoglobulin. Muscle Nerve. 2011; 44(2): 304-305.
PubMed Abstract | Publisher Full Text

5. Moriguchi K, Miyamoto K, Takada KM, et al.: Four cases of anti-ganglioside antibody-positive neuralgic amyotrophy with good response to intravenous immunoglobulin infusion therapy. J Neuroimmunol. 2011; 238(1-2): 107-109.
PubMed Abstract | Publisher Full Text

6. Naito K, Fukushima K, Suzuki SM, et al.: Intravenous immunoglobulin (IVIg) with methylprednisolone pulse therapy for motor impairment of neuralgic amyotrophy: clinical observations in 10 cases. Intern Med. 2012; 51(12): 1493-1500.
PubMed Abstract | Publisher Full Text

7. Cheung MC, Maguire J, Carey IM, et al.: Review of the neurological manifestations of hepatitis E infection. Ann Hepatol. 2012; 11(5): 618-622.
PubMed Abstract

8. Luciano L, Martel C, De Pina JJ, et al.: Genotype 3f predominance in symptomatic acute autochthonous hepatitis E: a short case series in south-eastern France. Clin Res Hepatol Gastroenterol. 2012; 36(3): e54-5.
PubMed Abstract | Publisher Full Text

9. Abbas Z, Afzal R: Hepatitis E: when to treat and how to treat. Antivir Ther. 2013.
PubMed Abstract | Publisher Full Text
<figure><img src="image_8.png" /></figure>

## Referee Responses for Version 1

<figure><img src="image_9.png" /></figure>

Michelle Cheung

King's College Hospital, London, UK

**Approved: 23 December 2013**

**Referee Report: 23 December 2013**

This is a report of an emerging viral infection with well-documented but still uncommon neurological symptoms, and adds to the knowledge of the natural history and potential treatment of this clinical syndrome. It is clearly written and the case is described well.

I have the following minor comments:

1. The referenced Cochrane review found no evidence from randomised trials to support any form of treatment for neuralgic amyotrophy, with only one retrospective series reporting a benefit. Therefore it seems an over-statement to say that corticosteroids are a validated treatment for the condition.

2. Are there any cases of prednisolone use specifically for HEV-induced neuralgic amyotrophy? What is the evidence of using ribavirin to treat acute (rather than chronic) HEV, which is a self-limiting infection?

3. The authors state that 'a severely affected subgroup present with signs of liver dysfunction, as seen in HEV' - do you mean that cases associated with HEV infection (and therefore presenting with liver dysfunction) have a more severe clinical course compared to neuralgic amyotrophy associated with other causes?

4. Please justify the conclusion that recognition of HEV infection avoids invasive procedures?

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

**Competing Interests:** No competing interests were disclosed.

<figure><img src="image_10.png" /></figure>

José Manuel Echevarría

Department of Virology, National Centre of Microbiology, Carlos III Health Institute Majadahonda, Madrid, Spain

**Approved: 20 December 2013**

**Referee Report: 20 December 2013**

The manuscript describes the association of a convincingly diagnosed case of acute hepatitis E due to HEV genotype 3 infection with the development of severe amyotrophic neuralgia and major dysphagia in
the patient. Reports of neurological complications among otherwise healthy patients after acute HEV-3 infection are scarce (I found just six cases from three reports since 2009, five of them reported in 2011), and the manuscript adds significant knowledge to the background.

Pathogenic mechanisms underlying neurological complications of hepatitis E are still unclear. Such diseases after viral infection may involve the invasion of the nervous system or may be of a pure, post-infectious, immune-mediated nature. Reports involving immunocompromised patients (Kamar et al., 2011; four patients) found HEV genome in CSF from all of them and detected anti-HEV IgM in one, which confirmed CNS invasion at the time of the onset of the neurological symptoms.

Among the six healthy patients mentioned above (Loly et al., 2009; Kamar et al., 2011; Despierres et al., 2011), CSF testing for HEV markers was performed in three cases. One tested positive for both HEV RNA and anti-HEV IgM, and one tested negative for both markers (Despierres et al., 2011). CSF from the remaining patient was tested for viral RNA only and was found negative. It seems likely therefore, that both mechanisms may be involved, in absence of immune impairment.

The patient mentioned in the present report tested negative for HEV RNA in CSF, but I understand from the text that anti-HEV testing of CSF was not performed (if the sentence "there was no intrathecal antibody synthesis" refers to immunoglobulins and not to HEV-specific antibody, which should be stated more clearly). It would have provided useful information if the patient's CSF had been tested for anti-HEV IgG and IgM. The lack of a viral genome at the time of sampling does not exclude CNS invasion, and demonstration of intrathecal synthesis of a specific antibody provides the diagnosis once viral particles are no longer present. As far as I know, nobody has yet communicated results from the evaluation of the intrathecal synthesis of a specific antibody to HEV in these cases (only the presence of anti-HEV IgM has been documented), so I would suggest performing such an evaluation if anti-HEV was detected. From my former experience with the diagnosis of neurological infections caused by varicella-zoster virus, testing for specific IgG antibody optimizes the yield, and the most useful criteria of evaluation is the antibody to albumin index, though several others can be used (see Echevarría et al. 1997).

**I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.**

**Competing Interests:** No competing interests were disclosed.

<figure><img src="image_11.png" /></figure>

Thierry Coton

Service de Pathologie Digestive, Hôpital d'instruction des Armées Laveran, Marseille, France

**Approved: 20 December 2013**

**Referee Report: 20 December 2013**

This is a very interesting article about an emerging complication of acute hepatitis E.

The following information is missing however:

1. the gender of the patient.

2. if prothrombin time increased during hepatitis.

3. which auto antibodies were screened for.

4. if PCR was realised in stools.

5. the duration of the ribavirine therapy.
Additionally in the discussion, the authors must highlight that this case concerned a genotype 3f virus which is predominant in France (Luciano et al. 2012).

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

**Competing Interests:** No competing interests were disclosed.

<figure><img src="image_12.png" /></figure>

Bruce Brew

Department of Neurology, St Vincent's Hospital, Sydney, NSW, Australia

Approved: 04 December 2013

Referee Report: 04 December 2013

This is an important case report highlighting HEV as a cause for brachial neuritis. Recognition of this association is clinically important as treatment with corticosteroids should be avoided.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.

**Competing Interests:** No competing interests were disclosed.