Chikungunya and the nervous system: what we do and do not know.

Chikungunya virus (CHIKV), an alphavirus transmitted by mosquitoes of the Aedes genus, has recently re-emerged, causing epidemics on Indian Ocean Islands and the Indian subcontinent, and an unexpected outbreak in north-eastern Italy. CHIKV infection was first reported to affect the nervous system in the 1960s; in the early 1970s it was found to be associated with meningoencephalopathy, myelitis, and choroiditis, and animal studies appeared to confirm that CHIKV was neurotropic. Nonetheless, CHIKV has never been considered as a 'true' neurotropic virus. The re-emergence of CHIKV infection in areas with efficient clinical facilities has allowed CHIKV-related neurological disease to be better defined both in adults and children. Encephalopathy appears to represent the most common clinical manifestation among newborns infected through mother-to-child transmission. Although data are still scarce, the ratio between cases with and without CNS involvement for CHIKV appears to be comparable with that for other neurotropic viruses. Unfortunately, the neurotropism of CHIKV has not been completely defined, and different animal studies show inconsistencies with regard to the capacity of the virus to invade and replicate in the brain parenchyma. This merits further investigation in light of the emergence of the virus in previously unaffected areas and of the clinical evidence of CNS involvement in a considerable proportion of symptomatic cases.