Starry Sky Appearance on Diffusion Imaging in Chikungunya Encephalitis

A 78-year-old male with a history of diabetes mellitus and coronary artery disease presented with fever and joint pains for 2 days, followed by gradually worsening sensorium over the next 6 days. On examination, he was drowsy, opening his eyes to pain with minimal limb movements. Blood tests for Salmonella typhi, malaria parasite screening, dengue, scrub typhus, and chikungunya virus (CHIKV) enzyme-linked immunosorbent assay (ELISA) IgM were negative. Cerebrospinal fluid (CSF) routine examination revealed protein 92 mg/dl, glucose 126 mg/dl (corresponding serum glucose 263 mg/dl), and total cells 85/mm3 (all lymphocytes). CSF CHIKV IgM was negative, while both serum and CSF CHIKV real time reverse transcription polymerase chain reaction (rt-PCR) were positive. Magnetic resonance imaging (MRI) of the brain revealed bilateral near-symmetrical periventricular “starry sky” lesions showing restriction on diffusion-weighted imaging (DWI) and apparent diffusion coefficient sequences [Figure 1]. T2-weighted imaging (T2W) and fluid-attenuated inversion recovery (FLAIR) sequences revealed hyperintense white matter near-symmetrical confluent lesions [Figure 2]. No posterior fossa, cortical, or deep grey matter involvement was seen. No contrast enhancement was noted. He was treated with intravenous methylprednisolone 1 g daily over 5 days, followed by 120 g intravenous immunoglobulin over 3 days. He gradually partially recovered over 17 days and was sent for home care.Figure 1: Axial DWI MR images show a “starry sky” appearance (top row) with restriction on corresponding ADC images (bottom row) at presentation of chikungunya encephalitis. ADC: apparent diffusion coefficient, DWI: diffusion-weighted imaging, MR: magnetic resonanceFigure 2: Axial T2W (top row) and FLAIR (bottom row) MR images [corresponding to DWI and ADC images of Figure 1] show bilateral symmetrical white matter hyperintense confluent lesions at presentation of chikungunya encephalitis. ADC: apparent diffusion coefficient, DWI: diffusion-weighted imaging, FLAIR: fluid-attenuated inversion recovery, MR: magnetic resonance, T2W: T2 weightedHe was readmitted 2 months later with extensive bilateral pneumonia and septicemia due to Escherichia coli. CSF routine examination was normal. A repeat MRI of the brain (2 months after the first MRI) revealed near-complete resolution of the DWI starry sky lesions seen previously [Figure 3]. Ventricular dilation was noted, compared to previous imaging, and it was suggestive of white matter volume loss in the interim period. The patient succumbed to his present illness of pneumonia after 6 days.Figure 3: Follow-up axial DWI MR images (top row) after 2 months of chikungunya encephalitis show significant resolution of the “starry sky” appearance without any restriction on ADC images (bottom row) with a mild increase in ventricular size. ADC: apparent diffusion coefficient, DWI: diffusion-weighted imaging, MR: magnetic resonanceCHIKV infections are widely seen as outbreaks in tropical countries, especially during summer. The neurologic manifestations of CHIKV infection have been sporadically reported. In a recent review article (including published cases of CHIKV infection with neurologic involvement up to the year 2017) on the range of neurologic involvement, encephalitis/encephalopathy was seen in 47% of these patients, mostly affecting the young or the elderly with significant morbidity and mortality.[1] DWI showing diffusion restriction in a starry sky-like appearance has been rarely observed in CHIKV encephalitis, mostly in case reports or short series.[2-4] In a series of 43 patients who were serum CHIKV rt-PCR positive with neurologic manifestations and underwent MRI of the brain, 13 patients had normal findings, while in 14 patients (30%), restricted diffusion of varying patterns including the starry sky pattern was seen on MRI. Others had either T2 or FLAIR focal hyperintensities with or without restricted diffusion. Restricted diffusion pattern distribution was not specified.[4] A strikingly similar starry sky appearance on DWI showing diffusion restriction has been rarely observed in children with the tick-borne disease, Rocky Mountain spotted fever encephalitis, caused by Rickettsia rickettsii. It is assumed that organisms hematogenously reach the small blood vessels of the brain of the periventricular and subcortical regions, disrupting the blood–brain barrier and leading to minute vasculitic infarcts in a perivascular distribution, which on imaging give a starry sky appearance.[5] We suggest similar mechanisms to be involved in those CHIKV encephalitis patients who exhibit these unique starry sky restriction patterns on MRI of the brain. Similar looking, but not identical, DWI abnormalities have been described in other noninfective conditions like fat embolism or other thromboembolic phenomena. However, in these conditions, there is a lack of symmetricity as in this case. All documented CHIKV encephalitis patients were positive for either serum or CSF CHIKV ELISA IgM or CHIKV rt-PCR.[2-4] In our case, both serum and CSF CHIKV ELISA IgM tests were negative, but CHIKV rt-PCR was positive. This observation also highlights the fact that in appropriate clinical settings, in suspected cases of CHIKV encephalitis, if serum and/or CSF CHIKV ELISA IgM is negative, testing for CHIKV rt-PCR can be helpful in both serum and CSF, especially if done early within the first 1–2 weeks of illness, as CHIKV rt-PCR tends to turn negative during and after the second week. However, CHIKV ELISA IgM can remain positive for more than 3 months. In an appropriate clinical context, as during epidemics of CHIKV, recognition of similar findings of starry sky pattern of restricted diffusion on MRI of the brain can help suspect CHIKV encephalitis, more so if serum CHIKV ELISA IgM is negative and serum or CSF CHIKV rt-PCR has not been performed or is unavailable. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.