Summary Dengue is the second most common mosquito-borne disease affecting human beings. In 2009, WHO endorsed new guidelines that, for the first time, consider neurological manifestations in the clinical case classification for severe dengue. Dengue can manifest with a wide range of neurological features, which have been noted—depending on the clinical setting—in 0·5–21% of patients with dengue admitted to hospital. Furthermore, dengue was identified in 4–47% of admissions with encephalitis-like illness in endemic areas. Neurological complications can be categorised into dengue encephalopathy (eg, caused by hepatic failure or metabolic disorders), encephalitis (caused by direct virus invasion), neuromuscular complications (eg, Guillain-Barre syndrome or transient muscle dysfunctions), and neuro-ophthalmic involvement. However, overlap of these categories is possible. In endemic countries and after travel to these regions, dengue should be considered in patients presenting with fever and acute neurological manifestations.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(13)70150-9.pdf

Neurological complications of dengue virus infection.

More than 500 million people worldwide are infected each year by any of the four dengue virus (DENV) serotypes. The clinical spectrum caused during these infections is wide and some patients may develop neurological alterations during or after the infection, which could be explained by the cryptic neurotropic and neurovirulent features of flaviviruses like DENV. Using in vivo and in vitro models, researchers have demonstrated that DENV can affect the cells from the blood-brain barrier (BBB) in several ways, which could result in brain tissue damage, neuronal loss, glial activation, tissue inflammation and hemorrhages. The latter suggests that BBB may be compromised during infection; however it is not clear whether the damage is due to the infection per se or to the local and/or systemic inflammatory response established or activated by the BBB cells. Similarly, the kinetics and cascade of events that trigger tissue damage, and the cells that initiate it, are unknown. This review presents evidence of the BBB cell infection with DENV and the response established towards it by these cells; it also describes the consequences of this response on the nervous tissue and compares these evidence with the one reported with neurotropic viruses of the Flaviviridae family. This information will allow us to understand more about the complex disease known as dengue, and its impact on a specialized and delicate tissue like is the nervous tissue.

Dengue Virus Infection of Blood-Brain Barrier Cells: Consequences of Severe Disease.

Dengue virus is an under-recognised causative agent of acute encephalitis syndrome (AES): Results from a four year AES surveillance study of Japanese encephalitis in selected states of India.

Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to a DENV infection leading to maternal and fetus death. Postmortem analysis of fetal organs demonstrated the presence of DENV using reverse transcriptase polymerase chain reaction (RT-PCR) in the fetal brain and DENV non-structural protein 3 (NS3) staining in placenta and several peripheral fetal tissues, such as the brain, liver, lungs, and spleen. Histological analysis of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema, and necrosis in placenta and tissue disorganization in the fetus, such as spongiform parenchyma, microglial inflammation, steatosis, hyalinose arteriolar, inflammatory cells in the alveolar septa, and disorganization of the lymphoid follicle. Increased cellularity (macrophage, Hofbauer cells and TCD8+ lymphocytes) and up-regulation of inflammatory mediators such as IFN-γ, TNF-α, RANTES/CCL5, MCP1/CCL2, and VEGF/R2 were detected in the liver, lung, spleen, brain, and placenta, supporting placental and fetus peripheral tissues inflammation. Maternal infection leading to the production of those vascular mediators may alter the vascular permeability, facilitating the virus entry and tissue and barrier dysfunction.

/pdf/a-stillborn-multiple-organs-investigation-from-a-maternal-1ckpn6albl.pdf

A Stillborn Multiple Organs' Investigation from a Maternal DENV-4 Infection: Histopathological and Inflammatory Mediators Characterization.

Dengue virus, a RNA virus of family Flaviviradae is considered non-neurotropic. Increasing studies and case reports reveal neurological manifestations of dengue virus. In our case series, we have evaluated magnetic resonance imaging (MRI) findings of 3 patients with dengue fever diagnosed by positive dengue NS1 antigen with neurological symptoms, which revealed nonspecific imaging features of dengue encephalitis in two cases and dengue meningoencephalitis in one case. Autopsy findings are also correlated in 2 patients who succumbed to their disease. This case series underlines the consideration of dengue encephalitis in patients of dengue fever with neurological symptoms and relevant imaging findings.

/pdf/mri-features-in-dengue-encephalitis-a-case-series-in-south-4a8rx7a4b7.pdf

MRI features in dengue encephalitis: A case series in South Indian tertiary care hospital

Behcet's disease (BD) is characterised by the triad of recurrent oral and genital aphthous ulceration, skin lesions and ocular inflammation. This disease frequently affects other systems including neurological, locomotor, cardiac or vascular systems. Recurrent oral and genital aphthous ulcerations are the hallmarks of BD. We hereby report a case of rapidly evolving and aggressive form of BD in a young man presenting with extensive ulcerative lesions in orogenital region leading to obstructive uropathy resulting in acquired urethral meatal stenosis due to inflammatory activity.

/pdf/acquired-urethral-meatal-stenosis-a-rare-sequel-of-an-1za2g0yjru.pdf

Acquired urethral meatal stenosis: a rare sequel of an aggressive form of Behçet's disease.

Dengue fever has a variable clinical spectrum ranging from asymptomatic infection to life-threatening dengue haemorrhagic fever and dengue shock syndrome. However, neurological complications, in general, are unusual. Dengue encephalopathy is not an unknown entity; however, dengue encephalitis, a direct neuronal infiltration by the dengue virus, is an extremely rare disease. Although dengue is classically considered a non-neurotropic virus, there is increasing evidence for dengue viral neurotropism, suggesting that, in a proportion of cases, there may be an element of direct viral encephalitis. An MRI brain rarely shows focal abnormalities in dengue encephalitis. We report an interesting case of dengue encephalitis during an outbreak in Delhi, India. The diagnosis was confirmed by blood and cerebrospinal fluid dengue serology and (NS1) antigen assay. The case showed extensive lesions involving the midbrain, cerebellum, thalamus and medial temporal region on both sides of the MRI brain, which is an uncommon manifestation of dengue fever.

/pdf/a-rare-case-of-dengue-encephalitis-1b7xdjtofl.pdf

A rare case of dengue encephalitis.

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Acquired urethral meatal stenosis: a rare sequel of an aggressive form of Behçet's disease.

A rare case of dengue encephalitis.