Neurologic Alterations Due to Respiratory Virus Infections

Bohmwald, Karen; Gálvez, Nicolás M. S.; Ríos, Mariana; Kalergis, Alexis M.

The first detection of hRSV RNA in CSF was from a 4-month-old boy hospitalized by pneumonia and febrile convulsion (Zlateva and Van Ranst, 2004 ; Figure 1 ). In this study, the authors were able to identify that the hRSV strain found belonged to the serogroup B (Zlateva and Van Ranst, 2004) . To achieve a better understanding of the effects of hRSV-infection in the CNS, the CSF of an 11-month-old boy that exhibited neurological abnormalities were analyzed, to evaluate the contribution of cytokines in this phenomenon (Otake et al., 2007) . The results showed an increase of IL-6 in the CSF but not in serum, which suggests a local effect, implicating that CNS cells-such as astrocytes and microglia-can be the source of these cytokines (Otake et al., 2007; Figure 1 ). Moreover, an increase of IL-6 was also found in three cases of infants younger than 2-years-old in which it was possible to detect hRSV RNA-serogroup A-in CSF ; Figure 1 ). The authors suggest that their result support the idea of a direct invasion of the CNS by hRSV . Interestingly, the same group found in another cohort of children infected with hRSV the presence of viral RNA, which correlated with low levels of TNF-α in CSF (Kawashima et al., 2012) . Also, most of the patients showed an increase in the production of several chemokines such an IL-8, CCL2 and CCL4 which may play an essential role in this disease (Kawashima et al., 2012 ; Figure 1 ). The encephalopathies caused by hRSV are classified in four groups: (1) metabolic error type; (2) cytokine storm type; (3) excitotoxicity type; and (4) hypoxic encephalopathies (Morichi et al., 2011) . The encephalopathy caused by metabolic error is an abnormality of the brain function that can be reversible and involves an alteration of metabolites. Remarkably, it was found in one of nine patients in this study (Morichi et al., 2011) . In the second type of encephalitis, a high increase of several cytokines at systemic levels-which also affect other organs-can be detected. These were reported in only one of the patients (Morichi et al., 2011) . In five of the total of patients, excitotoxic encephalopathy was found, which is characterized by febrile convulsion status epilepticus (Mizuguchi et al., 2007; Morichi et al., 2011) . Two patients manifested encephalopathies associated with hypoxia, which is a condition that does not include any sign of the others classifications (Morichi et al., 2011) . Importantly, hRSV RNA was found in CSF in five of the nine patients analyzed, and the levels of IL-6 were increased only in the patients who exhibited excitotoxic or cytokine storm encephalopathy type (Morichi et al., 2011 ; Figure 1) . Moreover, in all the patients the levels of nitric oxide (NO) were significantly increased independently of the encephalopathy type (Morichi et al., 2011) . These results are consistent with the previous report of these authors where they described the finding of hRSV RNA in five of eight patients and also elevated NO levels when compared to influenzaassociated encephalopathies (Morichi et al., 2009 ). Despite the low frequency of neurological complications associated with hRSV-infection, the cases reported exhibit similar profiles, which considers elevated levels of IL-6 in CSF (Miyamoto et al., 2013) .