Antecedent infection initiating an immune response often is believed to result in Guillain-Barré syndrome (GBS), with prior infection of the gastrointestinal tract, most commonly by Campylobacter jejuni, or respiratory tract, noted in two-thirds. Other antecedent infections include human immunodeficiency virus (HIV), influenza, cytomegalovirus (CMV), and Epstein-Barr virus (EBV), and less commonly, varicella-zoster virus, herpes simplex virus, hepatitis A, B, C, and E viruses, Haemophilus influenzae, Escherichia coli, and Mycoplasma pneumonia. Zika virus recently has been identified as causally related to GBS. What is the prevalence and clinical spectrum of hepatitis E (HepE) virus-associated GBS and how may it be accurately diagnosed?
Undertaken at the Department of Neurology, University Hospital, Leuven, Belgium, this retrospective cohort study identified all GBS or GBS-variant patients who presented between Jan. 1, 2007, and Nov. 1, 2015, within four weeks of onset of neurological symptoms. Patients were categorized clinically as pure motor GBS, Miller-Fisher syndrome, Bickerstaff brainstem encephalitis, acute ataxic neuropathy, bifacial weakness with distal paresthesiae, acute multiple cranial neuropathies, pharyngeal-cervical-brachial variant, and overlap syndrome. Clinical history and examination findings, results of lumbar puncture and blood work, including antiganglioside or anti-sulfatide antibodies (IgM and IgG against GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b, and sulfatides), and infectious serologic serum tests were reviewed. Patients accepted in transfer following intravenous immunoglobulin treatment and those without usable serum in the laboratory serum bank were excluded. Statistical analysis comprised the Shapiro-Wilk normality test and the two-tailed unpaired Mann-Whitney test, with P < 0.05 considered significant.
Among 88 patients with GBS or its variant, 73 satisfied inclusionary and exclusionary criteria, encompassing 44 men and 29 women, with mean age 52 years, of which 8% (n = 6) had positive IgM HepE assays, consistent with possible acute HepE infection, two of whom also tested positive for EBV or CMV. Elevated alanine aminotransferase (> 1.5 times the upper limit of normal) was found in four of these patients. Thus, 6% (n = 4) of this GBS cohort had probable acute HepE infection, two presenting with a GBS variant (acute ataxic neuropathy or the pharyngeal-cervical-brachial variant) and the two others with classic GBS. Of the two patients who tested positive for both HepE and CMV or EBV, one had mild predominantly sensory GBS and one had classic GBS. Acute HepE infection is associated with GBS, and elevated alanine aminotransferase may be a clue to its presence.
Hyper-endemic in many Asian and African developing countries, where infection is caused by HepE virus 1 and 2, and spread via the fecal-oral route through contaminated water, HepE also is endemic in developed countries, where HepE3 and HepE4 are the culprits, and are porcine zoonoses. Most often asymptomatic, HepE can cause acute and chronic hepatitis, and it is the most common cause of acute viral hepatitis worldwide. HepE is associated with a variety of neurologic disorders, including GBS, which, in 2000, was reported as the first HepE-associated neurologic complication. Other disorders include neuralgic amyotrophy, encephalitis, meningitis, and myelitis. Mononeuritis multiplex often is reported with HepE, as well as a rare report of myositis. Bell’s palsy and vestibular neuronitis have occurred concomitantly with HepE, but a causal relationship remains speculative. Hepatitis is either absent or mild when seen in conjunction with neurologic complications of HepE.