A total of nine patients were included in the study, seven diagnosed with WNV and two with TOSV neuroinvasive disease, six males and three females (22.5% of the 40 patients hospitalized with infection; age range: 30–77 years, mean age: 64 years, SD: 16.5 years).

The most common prodromal symptoms were fever and headache (7/9). All cases demonstrated one or more neurological symptoms: the most common were headache (7/9) and altered level of consciousness (6/9). Other neurological symptoms recorded were altered speech (2), seizures (2), neck stiffness or pain (1), nystagmus (1), facial nerve palsy (1). The spectrum of symptoms presented by the patients with neuroinvasive involvement in our study was similar to that described in the literature, with prodromal symptoms of fever, headache, and gastrointestinal discomfort, followed by disorientation and a progressive decline in the level of consciousness, leading to coma in six patients.

In our case series only two patients (22.2%) had a complete clinical recovery, one treated for WNV one for TOSV infection. Two patients were discharged from the hospital with moderate persistent symptoms: one had only partial recovery from facial nerve paralysis, although with progressive improvement, while the other demonstrated residual hypokinesia (TOSV leptomeningitis). Three patients with WNV neuroinvasive disease were still hospitalized four months after diagnosis due to persistent neurological symptoms. Two patients who suffered from WNV encephalitis died.

According to the literature, none of the brain CT scans performed in our patients showed abnormalities. CT is commonly the first imaging exam performed in patients with CNS involvement, due to its ready availability and quick execution. However, it stands to reason that brain abnormalities take longer to develop compared to symptoms, which need to be more severe before oedema becomes visible on CT images.

MRI is more sensitive and specific than CT for the detection of parenchymal abnormalities. In five out of seven cases of WNV infection MRI showed abnormalities [Table 1]. 

In four of the brain MRI, we detected findings referable to oedema due to encephalitis, consisting of an increase in signal intensity in T2/FLAIR sequences. The most affected areas by these signal alterations were in the deep gray matter (thalami [Fig. 1, 2], basal nuclei [Fig. 3], and dentate nuclei [Fig. 1]), but also in the cerebellar hemispheric gray matter [Fig. 1] and in the white matter of the corona radiata. Usually, the abnormalities were bilateral and relatively symmetrical. Patients with these findings demonstrated the most severe clinical conditions, with progressive alteration of the state of consciousness and the onset of coma.

Two MRI examinations demonstrated signs of recent ischemia, one in the cerebellum and one in the cortico-subcortical parietal region, characterized by high T2/FLAIR signal and diffusion restriction (high signal on DWI and low ADC signal) [Fig. 4]. It is recognized that viral infections of the CNS, through immune system activation and the systemic inflammatory response, can stimulate the development of a prothrombotic state and contribute to the onset of ischemic stroke.

In one patient, MRI highlighted thickening and increased contrast enhancement of the left 7th cranial nerve along the canalicular, labyrinthine, tympanic, and mastoid segments, findings consistent with facial neuritis [Fig. 5]. The clinical presentation was facial palsy compatible with viral neuritis. This report is consistent with descriptions in the literature of cranial nerve neuritis caused by arbovirosis.

One MRI performed for TOSV neuroinvasive disease did not demonstrate any pathological findings, whereas the other showed diffuse thickening with enhancement of the leptomeningeal structures on FLAIR sequences after gadolinium administration [Fig. 6], consistent with the presentation of leptomeningitis, which is the most frequent manifestation of neuroinvasion by TOSV, as described in the literature.