Neurological Complications during Treatment of Middle East Respiratory Syndrome

Kim, Jee-Eun; Heo, Jae-Hyeok; Kim, Hye-ok; Song, Sook-hee; Park, Sang-Soon; Park, Tai-Hwan; Ahn, Jin-Young; Kim, Min-Ky; Choi, Jae-Phil

and critical information from laboratory studies was also not available. However, we cautiously supported a diagnosis of ICU-acquired weakness in patient 2, because a paraparetic presentation (as observed in this patient) is extremely rare in GBS and because dysautonomia and cranial nerve palsy, which frequently accompany GBS, were not observed in this patient. 18, 21 Acute sensory neuropathy was the probable diagnosis in patients 3 and 4, which may have resulted from a toxin and/ or drug or viral infection. These two patients both received pegylated interferon alpha-2a, ribavirin, and lopinavir/ritonavir to treat MERS-CoV. Interferon alpha-2a rarely induces peripheral neuropathy, 22 and several studies have found complications associated with sensory neuropathy, vasculitic neuropathy, Bell's palsy, GBS, chronic inflammatory demyelinating polyneuropathy, and autonomic neuropathy. 23, 24 Ribavirin is not associated with peripheral neuropathy, 24 while lopinavir/ritonavir is another possible causative drug. However, many people living with human immunodeficiency virus have been treated with this protease inhibitor for many years, and the risk of peripheral neuropathy in patients receiving lopinavir/ritonavir remains unclear. 25 CoVs are a group of enveloped RNA viruses that include the Alphacoronavirus and Betacoronavirus [including MERS-CoV and severe acute respiratory syndrome (SARS) CoV] genera. 26 These viruses have neurotrophic and neuroinvasive characteristics, and CoV RNA has been detected in the central nervous systems of patients with various neurological diseases. 26, 27 A recent in vitro study evaluated the human tissue tropism of MERS-CoV in diverse cell lines, and revealed that it has the ability to infect human neuronal cells (NT2). 28 The neuropathological effects of MERS-CoV infections are suggested to result from immune-mediated processes, either directly by viral invasion or via molecular changes that arise from systemic inflammatory response syndrome. The delayed onset of neurological complications, the absence of the virus in the CSF, and the development of GBS-which is one of the prototypical immunological diseases observed in our patients-might support the immunological mechanisms of these phenomena. This topic requires further microbiological and pathological studies.