Dengue in Children’s Brains: Pakistani Radiologists Map the Virus’s Imaging Fingerprints

Dengue fever has long been thought of as a disease of high fever, aching joints, and, in its severe forms, dangerous plasma leakage and hemorrhage. Yet in recent years clinicians across the tropical world have become increasingly aware that the dengue virus can also attack the nervous system, producing encephalitis, spinal cord inflammation, and even paralysis in children. A team of radiologists at Aga Khan University Hospital in Karachi, Pakistan, has now compiled a systematic pictorial review of what pediatric dengue looks like on magnetic resonance imaging, organizing the findings by the underlying disease mechanisms that produce them. The review, published in Pediatric Radiology, is intended as a practical diagnostic atlas for physicians working in dengue-endemic regions, where recognizing these patterns quickly can change the course of a child’s illness.

Pakistan has experienced repeated large dengue outbreaks, including a major epidemic in 2022 that prompted the World Health Organization to issue a formal disease outbreak notice. In such settings, children presenting with fever and new neurological symptoms pose a difficult diagnostic problem. The symptoms of dengue-related brain involvement, ranging from seizures and altered consciousness to weakness and confusion, overlap heavily with those of other viral encephalitides, autoimmune conditions, and metabolic derangements. Magnetic resonance imaging is often the decisive tool, but only if radiologists know which patterns to look for and how to distinguish them from close mimics. The Karachi group, led by Kumail Khandwala and Kiran Hilal, set out to fill that gap by illustrating the full spectrum of dengue-related neuroradiological findings in children and correlating each pattern with the published literature.

The review’s central organizing principle is pathophysiology. Rather than listing findings haphazardly, the authors divide the imaging manifestations of pediatric dengue into three broad mechanistic categories: direct viral invasion of nervous tissue, immune-mediated injury, and reversible edema syndromes. This framework matters because the categories carry different prognoses and demand different clinical responses. Direct viral invasion tends to produce the most severe imaging abnormalities and the gravest illness, while the reversible edema patterns, as their name implies, often resolve completely with supportive care. Immune-mediated disease occupies an intermediate position, sometimes responding dramatically to immunomodulatory treatment. Understanding which category a given scan belongs to is therefore not an academic exercise but a practical step toward appropriate management.

Within the direct-invasion category, the review describes meningoencephalitis, involvement of the deep gray matter nuclei, and rhombencephalitis, which is inflammation centered on the brainstem. The most striking and diagnostically valuable findings in this group are two named signs that have become associated with severe dengue encephalitis. The first is the so-called double doughnut sign, in which symmetric lesions in the thalami develop a central area of necrosis surrounded by a ring of edema, producing a pattern on axial images that resembles two doughnuts side by side. This appearance reflects acute necrotizing encephalopathy, a fulminant form of viral brain injury in which the damage is driven partly by a cytokine storm rather than by the virus alone. The review notes that dengue-associated acute necrotizing encephalopathy is now considered by many investigators to be a true variant of that syndrome rather than a mere mimic, a conclusion supported by a recent systematic review of published cases.

The second named pattern is the Jack-o’-lantern sign, seen in dengue rhombencephalitis. On imaging, the brainstem shows scattered, patchy areas of abnormal signal within the pons that give the structure a carved, hollowed-out appearance reminiscent of a Halloween pumpkin. Brainstem involvement in dengue is uncommon but clinically dangerous, because the pons and medulla control breathing, heart rate, and other vital functions. The review highlights that this sign has been reported to be reversible in some patients who survive the acute illness, which underscores the importance of recognizing it early and providing aggressive supportive care rather than assuming a uniformly fatal course. Distinguishing dengue rhombencephalitis from other causes of brainstem inflammation, such as Listeria infection or other flaviviruses, relies on the clinical context, serological testing, and the specific distribution of lesions.

The immune-mediated category encompasses two related but distinct white matter disorders. The first is acute leukoencephalopathy with restricted diffusion, a condition in which the brain’s white matter shows marked restriction of water molecule movement on diffusion-weighted imaging, indicating acute cytotoxic injury. The second is acute disseminated encephalomyelitis, a post-infectious autoimmune demyelinating syndrome in which the body’s immune response, triggered by the virus, mistakenly attacks the myelin sheaths of its own neurons. The review emphasizes that these two entities can be told apart by their diffusion characteristics and their timing relative to the infection. Acute leukoencephalopathy with restricted diffusion typically appears during the acute phase and shows true restricted diffusion, whereas acute disseminated encephalomyelitis tends to emerge days to weeks after the febrile illness and shows different diffusion behavior along with lesions that may enhance after contrast administration. This distinction has direct therapeutic consequences, because the autoimmune condition is the one that typically warrants corticosteroids or other immunotherapy.

The third category, reversible edema syndromes, includes two entities with reassuring outcomes when properly identified. Reversible splenial lesion syndrome involves a characteristic lesion in the splenium, the posterior portion of the corpus callosum that connects the brain’s two hemispheres. On MRI the lesion appears as a small, round area of restricted diffusion, and, crucially, it typically disappears completely on follow-up imaging as the child recovers. Dengue has been reported as a cause of this syndrome in multiple case reports from Asia and elsewhere. The second, less commonly reported entity in the dengue context is posterior reversible encephalopathy syndrome, a condition in which the parietal and occipital regions of the brain develop vasogenic edema, often in association with severe hypertension, seizures, and visual disturbances. The Karachi group has previously studied pediatric posterior reversible encephalopathy syndrome in depth, examining how blood pressure relates to imaging severity and atypical MRI features, and that expertise informs the current review’s treatment of the dengue-associated form.

Beyond the brain, the review extends its atlas to the spinal cord and peripheral nerves. Dengue-associated myelitis, inflammation of the spinal cord, can produce transverse myelitis with weakness and sensory loss below the affected level, and MRI plays a central role in defining the extent and character of the cord lesion. Guillain-Barré syndrome, the autoimmune peripheral neuropathy that causes ascending weakness and can progress to respiratory failure, has also been increasingly linked to dengue infection, with recent systematic reviews cataloging the clinical characteristics, outcomes, and predictors of severity in these patients. The review stresses that MRI is valuable in differentiating dengue-related myeloradiculopathies from other infectious and inflammatory causes, a distinction that determines whether antiviral, immunomodulatory, or purely supportive strategies are most appropriate.

Perhaps the most practically useful single insight in the review concerns hemorrhage. The authors highlight that intralesional hemorrhagic changes, detected on susceptibility-weighted imaging or gradient recalled echo sequences, particularly within the deep gray nuclei and the brainstem, represent a valuable marker that favors dengue over several viral and inflammatory mimickers. Susceptibility-weighted sequences are exquisitely sensitive to blood breakdown products, and their ability to reveal microhemorrhages in characteristic locations gives radiologists an additional clue that can tip the diagnostic balance in dengue’s favor. In a region where Japanese encephalitis, tuberculosis, and other neurotropic infections circulate alongside dengue, such pattern-recognition tools can meaningfully shorten the path to the correct diagnosis.

The broader significance of the Karachi review lies in its synthesis. By systematically illustrating the full range of pediatric dengue neuroradiology and anchoring each pattern in its pathophysiological mechanism, the authors aim to improve diagnostic confidence among radiologists and clinicians who may encounter only a handful of such cases in a career. As climate change expands the geographic range of the Aedes mosquito vectors and dengue incidence rises globally, the neurological complications of the virus will increasingly be seen outside traditional endemic zones, in emergency departments where familiarity with these imaging signatures is limited. A pattern-based approach, grounded in the double doughnut and Jack-o’-lantern signs, the diffusion characteristics that separate leukoencephalopathy from demyelination, and the hemorrhagic markers that distinguish dengue from its mimics, offers a practical framework for timely recognition and management of one of the more feared complications of a rapidly spreading tropical disease.

Subject of Research: Neuroradiological manifestations of pediatric dengue central nervous system infection on MRI

Article Title: The varying neuroradiological manifestations of pediatric dengue central nervous system infection: a pictorial review from Pakistan with literature correlation

Article References: Khandwala, K., Hasan, S. M., Mateen, S. K., Nadeem, N., & Hilal, K. (2026). The varying neuroradiological manifestations of pediatric dengue central nervous system infection: a pictorial review from Pakistan with literature correlation. Pediatric Radiology. https://doi.org/10.1007/s00247-026-06771-3

Image Credits: AI Generated

DOI: 10.1007/s00247-026-06771-3

Keywords: dengue, pediatric neurology, neuroradiology, MRI, encephalitis, double doughnut sign, Jack-o'-lantern sign, acute disseminated encephalomyelitis, reversible splenial lesion syndrome, Guillain-Barré syndrome, Pakistan, viral infection