Neurologic complications of acute hepatitis E virus infection

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.

Figure 1. Flowchart of the study design

Figure 2. Location of Ticino in Switzerland and geographical distribution of HEV-NA cases

The residence of the 15 NA cases is approximated by blue dots. The population density in the area is shown in different colors in a red scale (legends on the left). Most of the cases were not located in urban but in rural areas (this map has been obtained from data of the Federal Office of Topography [Swisstopo]). HEV = hepatitis E virus; NA = neuralgic amyotrophy.

Figure 3. Clinical picture of HEV-NA

(A) In bilateral HEV-NA cases (above), winged scapula (black arrows) is recurrent and often asymmetrical. (B) In unilateral HEV-NA cases (below), amyotrophy is often very focal, affecting one muscle and sparing the neighboring muscle (left: involvement of the upper trapezius = green arrow, deltoid spared; right: brachialis muscle affected = red arrow, biceps brachii spared). HEV = hepatitis E virus; NA = neuralgic amyotrophy.