“Dual Double-Doughnut” Sign in Dengue Encephalitis

The patient presented with a clinical profile of fever, chills, vomiting, and headache for 5 days, which progressively worsened with an increase in fever, vomiting, and altered sensorium. Upon examination, the patient had a Glasgow Coma Scale (GCS) score of 6 (E2V1M3), reactive pupils, exaggerated deep tendon reflexes, and absence of meningeal signs. The patient had multiple episodes of documented seizures. The patient was intubated, placed on mechanical ventilation, and transferred to the intensive care unit. Laboratory tests revealed neutrophilic leukocytosis (15,000/mm³), thrombocytopenia (93,000 platelets/mm³), hemoglobin of 16 g/dl, and hematocrit of 48%. The cerebrospinal fluid (CSF) analysis revealed a protein level of 110 mg/dl, glucose levels of 108/blood glucose 148 mg/dl, 200 red blood cells per cubic millimeter, and a total leukocyte count of 5 (100% mononuclear) per mm³. The CSF Gram stain yielded negative results, and the culture was found to be sterile. Both the GeneXpert and culture sensitivity tests for Mycobacterium tuberculosis were negative. The results of Potassium hydroxide (KOH) mount, India ink staining, and fungal culture sensitivity were negative for the presence of any fungal growth. The CSF polymerase chain reaction (PCR) tests showed negative findings for Japanese encephalitis (JE), West Nile virus, and dengue encephalitis (DE). The patient tested positive for dengue NS-1 antigen in serum. PCR for herpes simplex virus 1 and IgM antibodies for JE and Leptospira were negative. Despite treatment, the patient’s encephalopathy and multiorgan dysfunction continued to worsen, ultimately resulting in death on the sixth day of admission.

Magnetic resonance imaging (MRI) of the brain revealed symmetrical areas of low T1 signal intensity and high T2/Fluid-attenuated inversion recovery (FLAIR) signal intensity in the bilateral thalami, periventricular and deep white matter, and bilateral cerebellar white matter. In addition, there were areas of blooming in the central regions of the bilateral thalami and cerebelli on susceptibility-weighted images (SWI), surrounded by a rim of diffusion restriction. This resulted in a distinct dual “double-doughnut” appearance, which is a rare but highly specific radiologic finding. Furthermore, multiple foci of diffusion restriction and micro-hemorrhages were observed in both the periventricular and deep white matter [Figure 1].

Figure 1.

Axial T2-WIs (a and d) reveal bilateral symmetrical hyperintensities with central hypointense areas in the thalami and cerebelli, along with confluent hyperintensity in the periventricular region. Susceptibility-weighted imaging (b and e) shows central blooming, indicating the presence of hemorrhages. Furthermore, diffusion-weighted imaging (c and f) reveals peripheral diffusion restriction surrounding the central hemorrhagic core. T2-WIs: T2-weighted images

Dengue fever can lead to various neurologic complications such as encephalitis (DE), encephalopathy, acute stroke (hemorrhagic and ischemic), transverse myelitis, and neuromuscular and neuro-ophthalmic problems.[1] In these cases, MRI is a critical tool for evaluating the extent of dengue infection and associated neurologic issues. Neuroimaging results may show signs of encephalitis and meningitis caused by the virus invading the nervous system. Other systemic complications, including metabolic or seizure-related encephalopathy and hemorrhagic stroke due to thrombocytopenia, may also be observed. In addition, the activation of autoimmunity can result in acute disseminated encephalomyelitis. MRI commonly reveals T2/FLAIR hyperintensities with restricted diffusion and internal hemorrhagic areas in various regions of the brain, such as the thalami, basal ganglia, brainstem, cortex, and subcortical white matter in the cerebral hemispheres.[2]

The “double-doughnut” sign on MRI has been observed in several case reports and case series of patients with DE,[3,4] showing a symmetrical T2/FLAIR high signal intensity in both thalami, restricted diffusion on diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC), and blooming in the central region on gradient echo (GRE)/SWI due to hemorrhages. The dengue virus has a direct effect on neurons, causing cerebral swelling and vascular leakage, which can result in hemorrhages. This is typically seen in the bilateral basal ganglia and thalami and is visually depicted as a “double-doughnut” sign on neuroimaging. The severity of thrombocytopenia does not directly correlate with the presence of hemorrhagic changes in the “double-doughnut” phenomenon. However, in cases of dengue fever, the likelihood of hemorrhagic strokes is increased in individuals with severe thrombocytopenia.

The “dual double-doughnut sign” was identified in our case, as we observed its presence in both the thalamic and cerebellar hemispheres. This unique finding, not previously reported, may suggest a potential grave and unfavorable prognosis.

The “double-doughnut” sign has been documented in several Flaviviridae diseases, including JE and West Nile encephalitis. Given the rarity of DE and the lack of reliable MRI findings, establishing the specificity and sensitivity of this sign will be challenging. Nevertheless, when faced with severe thrombocytopenia, equivocal serology findings, and the potential risks of conducting a lumbar puncture for CSF investigation, detecting this sign on an MRI can assist clinicians in making a diagnosis.[5] The prognostic value of this sign is currently unclear due to limited evidence.

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Conflicts of interest

There are no conflicts of interest.