Eur Radiol DOI 10.1007/s00330-014-3473-6

NEURO

Dengue encephalitis with predominant cerebellar involvement: Report of eight cases with MR and CT imaging features Vinay Hegde & Zarina Aziz & Sharath Kumar & Maya Bhat & Chandrajit Prasad & A. K. Gupta & M. Netravathi & Jitender Saini

Received: 16 July 2014 / Revised: 20 September 2014 / Accepted: 15 October 2014 # European Society of Radiology 2014

Abstract Objectives CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in eight cases of dengue encephalitis. Materials and methods We retrospectively searched cases of dengue encephalitis in which imaging was performed. Eight cases (three men, five women; age range: 8–42 years) diagnosed with dengue encephalitis were included in the study. MR studies were performed on 3-T and 1.5-T MR clinical systems. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and imaging features. Results All eight cases exhibited MRI abnormalities and the cerebellum was involved in all cases. In addition, MRI signal changes were also noted in the brainstem, thalamus, basal ganglia, internal capsule, insula, mesial temporal lobe, and cortical and cerebral white matter. Areas of susceptibility, diffusion restriction, and patchy post-contrast enhancement were the salient imaging features in our cohort of cases.

V. Hegde : M. Bhat : C. Prasad : A. K. Gupta : J. Saini (*) Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, Karnataka, India e-mail: [email protected] Z. Aziz Department of Radiology, Sri Sathya Sai Institute of Medical Science, Bangalore, India S. Kumar Department of Neuroradiology, Apollo Hospital, Jayanagar, Bangalore, India M. Netravathi Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India

Conclusion A pattern of symmetrical cerebellar involvement and presence of microbleeds/haemorrhage may serve as a useful imaging marker and may help in the diagnosis of dengue encephalitis. Key Points • MR images of eight cases diagnosed with dengue encephalitis were retrospectively reviewed. • Symmetrical cerebellar involvement may serve as an imaging marker on MRI. • Presence of microbleeds/haemorrhage and diffusion restriction are other salient features. Keywords Dengue infection . Encephalitis . Cerebellitis . Microbleeds . MRI Abbreviations FLAIR Fluid-attenuated inversion recovery DWI Diffusion-weighted MR imaging WM White matter SWI Susceptibility-weighted MR imaging

Introduction Dengue infection is an Arbovirus infection, commonly transmitted to humans by the Aedes aegypti mosquito. Clinically, the disease manifests as a febrile illness which may be complicated by the development of haemorrhagic features and shock (dengue haemorrhagic fever/dengue shock syndrome). CNS involvement in the dengue virus infection is relatively less common. Neurological manifestations include encephalopathy, encephalitis, myelitis, Guillain Barre Syndrome (GBS), cranial nerve palsies, stroke, and post-infectious acute disseminated encephalomyelitis [1, 2].

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Previous reports of CNS dengue infection describe nonspecific imaging features with no distinctive tropism for selective brain regions [3–5]. However, isolated reports have described focal signal abnormalities in CNS dengue infection. Focal signal changes have been described in the basal ganglia [5], hippocampus [6], thalamus [7], temporal lobe, brainstem, spinal cord [8], and cerebellum [9, 10]. In this report we describe the imaging features of eight laboratory-confirmed dengue infection patients hospitalized with neurological features. In addition, lesion characteristics on diffusion-weighted MR imaging (DWI) and gradient imaging are discussed.

Materials and methods Patients This retrospective case series included eight cases (three men, five women; age range: 8–42 years; mean age: 21.2 years) who were diagnosed with dengue encephalitis. Cases were identified from the case records of the hospital. Cases were diagnosed with CNS dengue infection based on clinical features, results of laboratory investigations, and positive serology for dengue virus in CSF or serum. Diagnosis of dengue fever was as per standard WHO criteria [1, 11] – highly suggestive dengue: IgM-positive in one serum sample, or IgG-positive in one serum sample with haemagglutination inhibition titre of 1280

or greater. Confirmed cases of dengue had one of the following: polymerase chain reaction (PCR)-positivity, virus culture-positivity, IgM seroconversion in paired serum samples, IgM seroconversion in paired serum samples, or four-times IgG titre increase in paired serum samples. Dengue encephalitis was suggested by the presence of focal signs, seizures, CSF pleocytosis, and NS1 antigen in CSF or positive CSF PCR for dengue. If not contraindicated, a CSF examination was performed. In cases where a CSF examination could not be performed, clinical presentation and positive serological tests for dengue virus in serum were used to make the diagnosis of probable dengue encephalitis. Cases were also evaluated for other possible causes of viral encephalitis, like Japanese and herpes encephalitis. In our study all cases in which CSF or serological investigations were performed and were found to be positive for dengue infection were included. Patients who underwent only CT or those in whom MRI was not available for review were excluded. MR studies were performed on 3T (Achieva, Philips Medical Systems, Best, The Netherlands) and 1.5-T (Aera, Seimens Medical systems, Enlargen, Germany) MR clinical systems. Studies were performed at different hospitals and MR images included transverse T1-weighted (TE 4.6–11 ms/TR 405– 500 ms/slice thickness 3–5 mm/acquisition time 105–129 s), fast spin-echo T2-weighted (TE 80 ms/TR 3380 ms/slice thickness 3 mm/acquisition time 60 s), transverse fluid-attenuated inversion recovery (FLAIR) (TE 86–125 ms/TR 9000–

Table 1 Summary of clinical features and laboratory investigations S. no Age Sex Duration Blood examination of Illness

CSF examination

Immunological investigations

1.

21

M

3 days

Platelet count 77,000, Leucopenia

ELISA-(Dengue) IgM positive in blood NS1 antigen positive in blood

2.

10

F

3 days

Platelet count 87,000, Leucopenia

3.

24

F

4 days

Platelet count 143,000, Leucopenia

4.

25

F

1 day

Platelets 74,000, Leucopenia

Proteins 266 mg% Glucose 91 mg% Cells-Nil Proteins 480 mg% Glucose 113 mg% Cells-113 Proteins- 177 mg% Glucose-78 % Cells-11 Not done due to raised ICP

5

20

M

5 days

Platelets 12,000, Leucopenia

6.

42

M

7 days

Leucopenia and thrombocytopenia, Platelet count 40,000

7.

8

F

3 days

8

22

F

7 days

CSF after 25 days, proteins 22, Glucose 62, Cells 2

ELISA for IgM antibodies for dengue – positive in blood and CSF ELISA for IgM antibodies for dengue – positive in blood and CSF. NS1 antigen positive in blood ELISA for IgM antibodies for Dengue positive in blood ELISA for IgM negative, NS1 Ag positive in blood

CSF: clear, 133 cells/mm3, protein ELISA for IgM antibodies for dengue – 58 g/L, glucose 54 g/L positive in blood and CSF. NS1 Ag positive in blood. RT-PCR positive for DENV-3 ELISA for IgM antibodies for dengue – Leucopenia and thrombocytopenia CSF: 300 cells/mm3 Protein 112 g/L Glucose 59 g/L positive in blood and CSF, NS1 Ag positive in blood. RT-PCR positive for DENV-3 Leukocytosis and thrombocytopenia, Not done ELISA for IgM antibodies for Dengue Platelet count 54,000 positive in blood. NS1 Ag positive in blood.

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11000 ms/TI 2800 ms/slice thickness 3 mm/acquisition time 176–262 s), and gradient echo images or susceptibilityweighted MR imaging (SWI). Contrast-enhanced T1W images were available for review in all the cases. All patients underwent imaging during the acute phase of illness. DWIs were acquired using single-shot spin-echo echoplanar sequences in seven cases. Diffusion-sensitizing gradients were applied in three orthogonal planes with abfactor of 0 and 1,000 s/mm2. The isotropic DWIs were reviewed. Apparent diffusion coefficients (ADCs) were calculated using vendor supplied workstations. Two neuroradiologists retrospectively reviewed the MR images and analysed the type of lesions, as well as their distribution and conspicuity, on various MR imaging sequences. Image evaluation was done with consensus.

Results Clinical records of eight cases were reviewed and the findings are summarized in Table 1. All cases presented with fever and were commonly associated with headache and focal neurological deficits. Diminished sensorium was present in most of the cases. Other clinical features commonly present were seizures, signs of meningism, ataxia, and nystagmus. All eight cases showed abnormalities on MR imaging. The lesions appeared hyperintense on T2-weighted and isointense to hypointense on T1-weighted images (Fig. 1). Gradient Fig. 1 A 21-year-old male presented with a 3-day history of fever, weakness, and altered sensorium. Axial non-contrastenhanced CT (a) shows hypodensity in bilateral cerebellar hemispheres. Axial T2WI MRI (b, c) reveals hyperintensity in bilateral cerebellar hemispheres, thalami. Gradient MR image (d) shows features of bleeding within the cerebellar lesion which appear hyperintense on T1WI (e). Follow-up CT (f) shows gliotic changes in the cerebellum

images were available for review in seven cases. Areas of susceptibility within the lesions were seen in six cases (Figs. 1, 2 and 3). DWI was available in seven cases, showed restricted diffusion in five, while in the remaining two cases lesions showed facilitated diffusion (Fig. 2). Cerebellar involvement was noted in all the cases. Involvement of the brainstem was noted in four cases, thalamus in six cases, basal ganglia in two cases, internal capsule in three cases, insula in one case, mesial temporal lobes in two cases, and cortical and cerebral white matter in six cases, with frontoparietal regions being most commonly involved (Fig. 4). Follow-up Clinical follow-up was available in all cases. Two patients succumbed to the illness, whereas the rest of the patients recovered. Three patients had persistent cerebellar and/or dystonic symptoms which hindered their daily activities. Three other patients recovered completely and had no residual symptoms. In four patients follow-up imaging was available for review which showed complete resolution of the brain lesions in one patient (Fig. 4) and gliotic brain areas in the remaining three patients (Figs. 1 and 3). Imaging findings are summarized in Table 2.

Discussion In the present series we evaluated imaging findings in eight cases of dengue encephalitis. Imaging studies were abnormal

Eur Radiol Fig. 2 An 8-year-old female presented with fever, difficulty walking, and altered sensorium for 2 days. Axial T2WI (a, b) and fluid-attenuated inversion recovery (FLAIR) images (c) reveal hyperintensity in bilateral cerebellar hemispheres. Gradient MR images (d) show haemorrhagic foci within the cerebellar lesion. On diffusion-weighted imaging (e) and apparent diffusion coefficient (ADC) maps (f) diffusion restriction is evident

in all the patients. All patients showed focal signal changes in the cerebellum while brainstem and supratentorial structures

Fig. 3 A 20-year-old male patient presented with fever, vomiting, ataxia, slurring of speech, and unsteadiness of gait followed by altered sensorium for 5 days. Axial T1WI (a) revealed hyperintense lesions within the vermis and both cerebellar hemispheres. Axial and coronal T2WI (b, c) images reveal hyperintensity with a rim of hypointensity. Gradient MR image (d) shows a haemorrhagic component within the cerebellar lesion. On diffusion-weighted imaging (e) the lesions showed diffusion restriction. Follow-up CT (f) shows gliotic lesions in the right cerebellar hemisphere

were also found to be abnormal in some of the patients. Lesions appeared hyperintense on T2W images and

Eur Radiol Fig. 4 A 22-year-old female presented with post-partum seizures and fever. Axial T1WI (a) reveals ill-defined hypointense signals involving both cerebellar hemispheres. Axial T2WI and fluid-attenuated inversion recovery (FLAIR) (b, c) images reveal corresponding areas showing hyperintense signals. Involvement of the frontoparietal cortex and underlying white matter is seen in the superior sections on FLAIR axial (d) images. No post-contrast enhancement was evident (e). Follow-up imaging (f) revealed complete resolution of the findings

hypointense on T1W images. Gradient/SWI images showed the presence of small haemorrhages within the lesions. CNS lesions showed both restricted and facilitated diffusion. Two distinct imaging features were observed in our case series: firstly presence of cerebellar signal abnormalities and secondly presence of micro-haemorrhages within parenchymal lesions. These findings are important as the majority of previous neuroimaging studies in patients with CNS dengue infection have reported variable findings and have concluded that changes are nonspecific [4, 12]. Findings of newer imaging contrasts like SWI and DWI in CNS dengue infection have been rarely reported in previous studies. These imaging findings may be useful in cases of suspected infectious cerebellitis, and in the presence of appropriate clinical features, dengue infection may be suggested as one possible aetiology. MRI findings in CNS dengue infection include normal study, diffuse cerebral oedema, and parenchymal signal changes [5–10]. Diffuse cerebral oedema is the most common imaging feature of CNS dengue infection [8, 12]. Other less commonly described findings include meningeal enhancement on post-contrast MRI [6] and subdural [13] and parenchymal haematomas [14]. Focal parenchymal lesions have also been reported in the thalamus, cerebral cortex, internal capsules, and corpus callosum [5–10, 12]. Focal cerebellar involvement in dengue infection has been described in a few isolated case reports [9, 10, 15–18]. In one report cerebellar syndrome was part of the post-infectious immune-mediated process [15, 16]. Another series reported three cases of cerebellar syndrome in association with dengue infection. Two of the cases were probably post-infection, while one possibly had acute infective cerebellitis, and imaging in this case showed

symmetrical hyperintense lesions in the cerebellar hemispheres on T2W images [10]. In other recent reports, symmetrical involvement of the cerebellar hemispheres has been described along with involvement of the midbrain, thalamus, and medial temporal regions in dengue encephalitis [17, 18]. Cerebellar infection in dengue encephalitis is also supported by pathological studies which have shown the presence of viral antigen in the cerebellar granular layer and purkinje cells [19, 20]. On imaging, focal lesions appeared hyperintense on T2W images and hypointense on T1W images. DWI and SWI have not been systematically evaluated in previous studies. In the series by Bhoi et al. [5] few of the focal lesions were shown to have an increased signal on DWI. In our series, lesions showed restricted diffusion in three cases, facilitated diffusion in two cases, and in the remaining two cases a combination of restricted and facilitated diffusion was seen. Increased blood brain barrier permeability is one of the hallmarks of dengue infection. This results in vasogenic oedema which manifests as facilitated diffusion on DWI. However, restricted diffusion may be attributed to the presence of inflammatory cells, associated haemorrhage, or presence of ischemia. SWI and gradient images showed evidence of susceptibility in the areas of signal alterations in most of the cases. The majority of parenchymal lesions showed microbleeds (

Dengue encephalitis with predominant cerebellar involvement: report of eight cases with MR and CT imaging features.

CNS dengue infection is a rare condition and the pattern of brain involvement has not been well described. We report the MR imaging (MRI) features in ...
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