Hepatitis E and diaphragmatic dysfunction: Case series and review of the literature.

INTRODUCTION: The causes of diaphragmatic paresis are manifold. An association between neuralgic amyotrophy (NA) and hepatitis E virus (HEV) infection has been reported. We wondered about the prevalence of diaphragmatic disfunction and hepatitis E infection in our clinic. METHODS: From July 1st, 2020 to August 31st, 2023, patients presenting with diaphragmatic dysfunction and simultaneous clinical symptoms of an acute NA, or a history of NA, as well as patients with previously unexplained diaphragmatic dysfunction were examined for HEV infection. RESULTS: By August 31st, 2023, 13 patients with diaphragmatic dysfunction and HEV infection were diagnosed (4 women, 9 men). Mean age was 59 ± 10 years. Liver values were normal in all patients. The median latency to diagnosis was five months (range: 1-48 months); nine patients, 4 of them with typical symptoms of NA, presented with acute onset three patients showed bilateral diaphragmatic dysfunction. All patients had a positive IgG immunoblot. Seven patients, three with NA, had an elevated hepatitis E IgM titer and six of them also a positive IgM immunoblot. In all cases, O2C hepatitis genotype 3 was identified. In eight cases, all those with a high IgG titer >125, the O2 genotype 1 was also detected. CONCLUSION: NA that shows involvement of the phrenic nerve resulting in diaphragmatic dysfunction and dyspnoea, may be associated with HEV infection. The observation of 13 patients with diaphragmatic dysfunctions and HEV infection within a period of three years indicates a high number of undetected HEV-associated diaphragmatic dysfunction in the population, especially in the absence of NA symptoms. Therefore, even in diaphragmatic dysfunction without NA symptoms and causative damaging event, HEV infection should be considered, as it may represent a subform of NA with only phrenic nerve involvement. Therapy of HEV-associated diaphragmatic dysfunction in the acute phase is an open question. In view of the poor prognosis for recovery, antiviral therapy should be discussed. However, no relevant data are currently available.

Herpes zoster increased risk of neuralgic amyotrophy: a retrospective, population-based matched cohort study.

Although neuralgic amyotrophy (NA) has occasionally been reported to be associated with reactivated herpes zoster, their associated risk remains unknown. The aim of this study was to assess the risk of developing NA following preceding herpes zoster. The authors used the National Health Insurance Research Database of Taiwan to select 41,548 patients with newly diagnosed herpes zoster during the period 2000 to 2010 and randomly extracted 166,192 matched control subjects. All participants in the study and control groups were followed for 3 months after the diagnosis to identify those who developed NA. Cox proportional hazards regression analyses were performed to evaluate the subsequent risk of NA. Twenty-one subjects from the group with herpes zoster (0.05%) developed NA over the 3-month period and 46 from the group without herpes zoster (0.03%). The patients with herpes zoster had a higher risk of developing NA (adjusted hazard ratio = 1.408, 95% confidence interval = 1.013-2.319, P = 0.030). In the patients with herpes zoster, female sex, age ≥ 65, hepatitis E virus (HEV), and having had a recent infectious event including pneumonia and influenza were risk factors for developing NA (adjusted HR 2.746, 1.998, 2.735, 2.016, and 1.718, respectively, all P < 0.05). Patients with herpes zoster attack have a higher risk of developing NA over a 3-month period after diagnosis, especially those who are female, age ≥ 65, HEV, or have experienced a recent infectious event or pneumonia and influenza.

Visceral disseminated varicella zoster virus infection with brachial plexus neuritis detected by fluorodeoxyglucose positron emission tomography and computed tomography.

Varicella zoster virus (VZV) infection sometimes result in visceral disseminated VZV infection (VD-VZV), which is a fulminant disease featured by abdominal pain and the absence of skin lesions, particularly occurs in the immunosuppressive patients. Brachial plexus neuritis (BPN) is another rare type of VZV infection usually appears without blisters. Few diagnostic images of both VD-VZV and BPN-VZV have been reported. A 25-year-old woman receiving allogeneic hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia. Unexplained severe pain in the left upper extremity followed by severe stomachache, liver dysfunction and unconsciousness appeared on day 344 post-HSCT. Computed tomography (CT) showed left brachial plexus hypertrophy and edematous changes to the hepatoduodenal ligament, fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased uptake in both lesions. Intravenous acyclovir therapy was started and successfully resolved all symptoms. Several days later, blisters appeared all over the body and positive VZV DNA from blood using polymerase chain reaction test was obtained. FDG-PET and CT may offer supportive findings for detecting or diagnosing blister-less VZV infectious diseases.

Pathological Cerebrospinal Fluid Findings in Patients With Neuralgic Amyotrophy and Acute Hepatitis E Virus Infection.

There is growing evidence that hepatitis E virus (HEV) infection can present with extrahepatic manifestations including neurological disorders. Among these, neuralgic amyotrophy (NA) has been reported to occur in some industrialized countries. We investigated 35 patients with NA and a control group for markers of HEV infection. Acute HEV infection was found in NA patients only and was associated with an inflammatory response in the central nervous system. Shedding of HEV RNA into the cerebrospinal fluid and intrathecal production of anti-HEV immunoglobulin M occurred in 1 patient, suggesting that HEV is neurotropic.

Hepatitis E virus in neurological disorders: a case of Parsonage-Turner syndrome.

Hepatitis E virus (HEV) infection is an emerging disease in developed countries with a broad clinical spectrum. In the absence of immunodeficiency or pregnancy, it is a mild and almost asymptomatic condition in most cases. However, extrahepatic manifestations, including neurological conditions, are common and may occasionally lead to permanent neurological sequelae. Herein, we report the case of an immunocompetent patient who was admitted to our hospital with paresthesia and weakness in both the upper extremities associated with anicteric-elevated transaminases. The diagnosis was Parsonage-Turner syndrome (neuralgic amyotrophy) secondary to HEV infection. The diagnosis was reached via electromyography and serology tests. Neuralgic amyotrophy (NA) is a demyelinating axonal disease that affects the brachial plexus and is associated with HEV infection in up to 10% of cases. We also emphasize the importance of requesting HEV serology in patients with neurological disease, especially with the involvement of the peripheral nervous system. Although the role of ribavirin remains to be fully determined, early diagnosis and treatment may result in an improved prognosis, thereby minimizing neurological sequelae.

Parsonage-Turner syndrome due to autochthonous acute genotype 3f hepatitis E virus infection in a nonimmunocompromised 55-year-old patient.

Hepatitis E virus (HEV) infection is an emerging autochthonous disease in industrialized countries. Extra-hepatic manifestations, in particular neurologic manifestations, have been reported in HEV infection. Only a few cases of hepatitis E-associated Parsonage-Turner syndrome have been reported, and HEV genotypes were rarely determined. Here, we report the case of a Parsonage-Turner syndrome associated with an acute autochthonous HEV infection in a 55-year-old immunocompetent patient. HEV genomic RNA was detected in serum and cerebrospinal fluid samples (CSF), and molecular phylogenetic analysis of HEV was performed. The interest of this case lies in its detailed description notably the molecular analysis of HEV RNA isolated from serum and CSF. HEV infection should be considered in diagnostic investigations of neurologic manifestations associated with liver function perturbations.

Hepatitis E virus and neurological disorders.

Hepatitis E is the most common cause of hepatitis worldwide. While originally considered a disease of developing countries, it is increasingly recognised in developed countries, probably related to contaminated pork meat, and where infection is often asymptomatic. However, several non-liver manifestations have become apparent, the most important of which are neurological, including Guillain-Barré syndrome (acute inflammatory demyelinating polyradiculoneuropathy (AIDP)), neuralgic amyotrophy and meningoencephalitis. We recommend testing all patients with AIDP and neuralgic amyotrophy for hepatitis E and consider testing any patient with an unexplained neurological illness and abnormal liver function tests for the virus.

Hepatitis E virus infection as a direct cause of neuralgic amyotrophy.

INTRODUCTION: We describe a patient who developed neuralgic amyotrophy (NA) related to hepatitis E virus (HEV) infection. METHODS: The patient underwent neurological and electrodiagnostic examinations, high-resolution analysis of serological changes, and HEV load profile, and was treated with intravenous immunoglobulin. RESULTS: There was evidence of bilateral, asymmetric acute inflammatory cervical polyradiculopathy and possible brachial plexopathy. Positive serum anti-HEV IgM was followed by seroconversion to anti-HEV IgG positivity. A calculated anti-HEV antibody index was compatible with intrathecal synthesis, and HEV genotype 3 RNA was found in serum and cerebrospinal fluid (CSF). Liver function tests returned to normal within 6 weeks. CONCLUSIONS: Bilateral involvement of cervical nerve roots and/or plexus, elevated liver function tests, and abnormal CSF are typical features of HEV-associated NA. The pathogenesis involves possible immune-mediated mechanisms. However, our findings support the hypothesis that HEV-related NA is associated with direct infection. Muscle Nerve 54: 325-327, 2016.

Varicella zoster virus brachioplexitis associated with granulomatous vasculopathy.

Varicella zoster virus (VZV) causes the common childhood disease chickenpox (varicella), or upon reactivation, the dermatomal vesiculopustular eruption seen in shingles (herpes zoster). The clinical course of herpes zoster in immunocompromised patients is often recurrent, protracted and multidermatomal, and it can result in myelitis, meningoencephalitis, and cerebral or small-vessel vasculopathic or vasculitic changes. Commonly, the vesicular rash settles with aciclovir therapy and does not involve motor neuropathy. We report a 63-year-old man with a prolonged, multidermatomal, nonvesicular rash, and limb paresis secondary to brachioplexitis. PCR for VZV was positive, and the histological results were consistent with granulomatous vasculopathy. Prolonged treatment with valaciclovir was required to resolve the eruption and help improve the patient's motor function. We discuss the problems faced in clinical decision-making about immunosuppressive treatment of granulomatous vasculopathy and motor neuropathy, when any increase in immunosuppressive therapy may increase the likelihood of central nervous system complications.

Neuralgic amyotrophy associated with dengue fever: case series of three patients.

Dengue is an acute mosquito borne viral infection caused by one of the four distinct serotype of dengue viruses (type 1-4), belonging to flavivirus family. Dengue fever, an arboviral infection is known to cause various neurological complications. Commonly reported neurological manifestations associated with dengue infection are encephalopathy, myelopathy, stroke, Guillain-Barre syndrome and hypokalemic paralysis. Brachial amyotrophy associated with dengue infection were not described previously. Here, we describe three patients presenting with brachial neuritis associated with dengue infection. Dengue infection should be considered in the etiological list of brachial neuritis in dengue endemic areas, especially if preceded by history of febrile illness compatible with dengue illness.

Extended Neuralgic Amyotrophy Syndrome in a Confirmed COVID-19 Patient After Intensive Care Unit and Inpatient Rehabilitation Stay.

ABSTRACT: The cause of neuralgic amyotrophy is often unknown but is commonly associated with a recent upper respiratory viral tract infection. Since the beginning of the COVID-19 pandemic, there has been a tireless effort to understand the sequelae of the virus. A 46-yr-old woman who presented after a COVID-19 hospitalization complicated by hypoxic respiratory failure requiring intubation and mechanical ventilation for 23 days was subsequently found to have lower limb sensorium changes as well as upper limb weakness. Left shoulder abduction and extension were both 3/5 in motor strength, and left hip flexion strength was 4/5 with diminished sensation to crude touch in the left lateral thigh. Nerve conduction studies and electromyography findings included a mild left median neuropathy at the wrist and motor unit recruitment pattern consistent with a chronic left upper trunk plexopathy with reinnervation. The case presented describes an extended neuralgic amyotrophy syndrome from an atraumatic mechanism in a previously diagnosed COVID-19 patient. An extended neuralgic amyotrophy syndrome has at least three immune mediated etiologies postulated (1) direct neuropathogenicity, (2) molecular mimicry, and (3) direct cytotoxic effects on peripheral nerves. As COVID-19 survivors continue to be seen in outpatient settings, practitioners should remain aware of diffuse neurological complications as sequelae of the virus persist.

Parsonage-Turner syndrome associated with hepatitis E infection in immunocompetent patients.

Introduction The hepatitis E virus (HEV) is the leading cause of acute hepatitis around the world. In recent years, knowledge has increased concerning extrahepatic manifestations caused by HEV, including neurological manifestations such as Parsonage-Turner syndrome (PTS). PTS is characterized by severe shoulder or arm pain and patchy paresis with muscle weakness. The aim of the present study was to assess the association between HEV and PTS. Materials and Methods We reported two cases of PTS associated with HEV, which were diagnosed in a short period of time in the same village. PTS was diagnosed by physical examination and electrophysiological studies, and serology testing for IgM, low-avidity IgG, and RNA of HEV established the diagnosis of acute HEV infection. Results A 44-year-old man who presented cervicobrachial pain accompanied by paresthesia, dyspnea, and isolated derangement of liver enzymes and 57-year-old women with cervical pain radiated to upper limbs, paresthesia, and liver cytolysis, although, this patient was initially diagnosed as having drug-induced hepatitis. Finally, the diagnosis was Parsonage- Turner syndrome associated with hepatitis e virus. In both patients, symptoms were bilateral and they required hospital admission. Both consumed vegetables are grown in a local patch and the phylogenetic analysis showed genotype 3f. Then, we reviewed the literature on PTS and HEV and we found 62 previously described cases that were more likely to be men (86.20 %) with more frequent bilateral symptoms (85.71 %). Genotype 3 is the most commonly associated. Three of those cases were diagnosed in Spain. Conclusions According to our findings, HEV should be considered in patients with neuralgic amyotrophy, including those with the absence of liver cytolysis.

[Neurologic disorders and Hepatitis E: Review of literature]. / Trouble neurologique et hépatite E : revue de la littérature.

INTRODUCTION: Hepatitis E is an emerging, worldwide disease. It is often asymptomatic. Nevertheless, in few cases, clinical manifestation such as neurological disorder could be present. The aim of this article is to realize a literature review of the neurological symptoms associated with hepatitis E. METHODS: We searched the Pubmed database using the term "hepatitis E", "neurological disorder AND hepatitis E". RESULTS: One hundred and thirty cases have been described between 2000 and 2017. The majority of cases were associated with the genotype 3 and were reported in Europe or in Asia. It preferentially affected immunocompetent (93%) men with a median age of 52 years. The main neurologic disorders were Guillain-Barré syndrome (54 cases), Parsonage-Turner syndrome (35 cases), multiplex mononeuropathy (6 cases), meningitis and meningoencephalitis (9 cases). The diagnosis was done with HEV IgM serology in most cases (98%). Aminotranferases increase and cholestasis were found in 88% and 82% respectively. The outcome varied according to the neurological syndrome. Antiviral or immunomodulatory therapies did not seem to improve symptoms. CONCLUSION: Hepatitis E seems to be associated with acute, wide neurological disorders. These data should be confirmed with a long term prospective study.

Neuralgic amyotrophy triggered by hepatitis E virus: a particular phenotype.

The neuralgic amyotrophy may be of difficult diagnosis, due to phenotypic variability, with different initial presentations (upper plexus multiple mononeuropathy, lumbosacral involvement, distal reached, phrenic involvement). To date, there is little guidance on these patients' therapeutic management, especially those for which neuralgic amyotrophy is triggered by hepatitis E virus (HEV-NA). The study aims to identify specific features that characterize patients bearing the neuralgic amyotrophy triggered by HEV. We first describe a new case report of HEV-neuralgic amyotrophy, with delayed diaphragmatic reach. Then, the literature was searched for reports of HEV-NA (n = 39), and neuralgic amyotrophy with phrenic paresis (n = 42) from 1999 to June 2016. Relevant data were retrieved, analyzed and compared with the parameters of idiopathic neuralgic amyotrophy (n = 199) of the largest cohort, described by Van Alfen and Van Engelen in 2006. Compared to the published cohort, HEV-NA patients were more likely to be men (M/F 34/5 vs. 136/63, p = 0.017), with more frequent bilateral symptoms (86.8% cases vs. 28.5%, p < 0.0001) as well as phrenic paresis (18.0 vs. 6.6%, p = 0.028). The clinical improvement is poor, with 15.6% of cases with remission only. A particular phenotype characteristic of the HEV-induced neuralgic amyotrophy has arisen. Our findings call for action in validating the above-mentioned features that illustrate the HEV-NA cases as an early diagnosis would prevent complications, especially the phrenic damage often associated with a worse functional outcome.

[Neurological symptoms with a hepatitis E virus infection]. / Neurologische symptomen bij hepatitis E-infectie.

BACKGROUND: Infection with hepatitis E virus genotype 3 (HEV3) is an emerging zoonosis in the industrialized world. The infection usually proceeds asymptomatically. Extrahepatic sequelae including neurological symptoms have been described. CASE DESCRIPTION: A 52-year-old man presented at the emergency department with pain, muscle weakness and sensory disorders in both shoulders and arms. He was found to have bilateral neuralgic amyotrophy accompanying an HEV3 infection. CONCLUSION: An HEV3 infection can have neurological sequelae, but very little is known about its incidence and spectrum of symptoms.

Hepatitis E and neuralgic amyotrophy: Five cases and review of literature.

Hepatitis E virus infection - mainly genotype 3 - is increasingly common in industrialized countries. Infection is usually asymptomatic, but cases of central or peripheral neurological symptoms with hepatitis E have been described. The most frequent is Guillain-Barre but somes cases of neuralgic amyotrophy have been described. In our center, since 2010, we have identified five cases of neuralgic amyotrophy associated with acute hepatitis E in immunocompetent patients. For all these patients, neuralgic amyotrophy was diagnosed with electromyogram and positive IgM for hepatitis E, and detectable HEV RNA in 4 of the cases. Including our patients, we count 26 cases in literature. The mean age of the patients was 44 years old, with a large predominance of males (88%). The disorder is bilateral and asymmetric in 69% of cases. Peripheral nerves other than the brachial plexus were affected in 6 patients (23%). In industrialized countries, any neuralgic amyotrophy, particularly if there is bilateral, asymmetric associated with involvement of nerves outside the brachial plexus, should lead physicians to consider a diagnosis of acute hepatitis E.

Neuralgic amyotrophy complicating acute hepatitis E infection: a rare association.

Hepatitis E virus infection (HEV) is an emerging pathogen that is under-recognised in developed countries. Preceding infection manifested by acute transaminitis has been associated with neurological manifestations, predominately involving the peripheral nervous system, even in immunocompetent patients. We present a case of a 65-year-old previously fit and well Caucasian man with bilateral neuralgic amyotrophy (NA) and acute transaminitis. Serology testing for immunoglobulin (Ig) M and G established the diagnosis of acute HEV infection. The patient received immunomodulatory treatment with an excellent long-term outcome. The temporal association of the clinical presentation of bilateral NA and acute transaminitis from HEV infection suggested the causal association of HEV to NA. We propose screening for HEV in patients presenting with NA and acute hepatitis.

Neuralgic amyotrophy and hepatitis E virus infection.

OBJECTIVE: To determine whether there is an association between an acute preceding hepatitis E virus (HEV) infection and neuralgic amyotrophy (NA), and if so, whether patients with HEV-related NA differ from patients without an associated HEV infection. METHODS: HEV testing was conducted in a retrospective cohort of 28 Cornish patients with NA (2011-2013) and a prospective cohort of 38 consecutive Dutch patients with NA (2004-2007). Acute-phase serum samples were analyzed for the presence of anti-HEV immunoglobulin (Ig) M and IgG and HEV RNA (quantitative real-time PCR). RESULTS: Five cases (10.6%) of acute hepatitis E infection were identified in a total group of 47 patients with NA of whom serum samples were available. In 4 patients, HEV RNA was detected in serum samples taken at presentation. All patients with HEV-associated NA had clinical and electrophysiologic evidence of bilateral brachial plexus involvement. Anti-HEV IgM positivity was not related to age, sex, disease severity, disease course, or outcome. CONCLUSIONS: Acute hepatitis E is found in 10% of patients with NA from the United Kingdom and the Netherlands. Further research is required to investigate the role of HEV in NA in other geographical locations and to determine pathophysiologic mechanisms.

Brachial plexus neuritis in the context of acute HIV seroconversion illness: a case report.

We report an unusual case of bilateral brachial plexus neuritis occurring during the seroconversion stage of an HIV infection in a 45-year-old man. Brachial plexus neuritis is thought to be an immune mediated inflammatory reaction resulting in acute onset of shoulder pain followed by muscle weakness and wasting. There is often a history of viral illness, diagnosis is clinical, and treatment is supportive. Many sufferers are left with residual defects. Clinicians should consider the possibility of HIV infection when managing a patient with brachial plexus neuritis.

Bilateral brachial neuritis secondary to varicella reactivation in an HIV-positive man.

We present the case of a 48-year-old HIV-positive man, who developed acute onset of pain in both upper limbs associated with proximal weakness and distal paraesthesia. Eight weeks prior to this presentation he had had varicella zoster affecting his right S1 dermatome. CD4 count was 355 cells/mm(3) and he was antiretroviral therapy (ART) naive. Power was 0/5 proximally and 4/5 distally in the upper limbs. Reflexes were absent and there was sensory loss in the C5, C6 and T1 dermatomes. Cerebrospinal fluid (CSF) examination showed a lymphocytosis with low glucose; however, CSF Mycobacterium tuberculosis (TB), and herpes simplex virus polymerase chain reaction (HSV PCR) were negative as was syphilis serology. Electromyography showed marked motor axonal loss. Magnetic resonance imaging (MRI) did not show any cervical spinal lesion. Varicella zoster virus (VZV) PCR was positive in the CSF. He was treated with high-dose intravenous aciclovir with good resolution of his syndrome over time and was commenced on ART. We believe this to be the first case report of varicella reactivation causing bilateral neuralgic amyotrophy in an HIV-positive patient.