Dengue Encephalitis: Don't Forget to List It when the Brain Is Hit

An 8-year-old boy, previously well presented with an acute febrile illness for the past week, followed by recurrent, generalized tonic-clonic seizures from day 4 of illness with persistent altered sensorium thereafter. There was no history of focal motor deficits, headache, vomiting, neck pain, trauma, toxin ingestion, recent vaccination, abnormal body odor or rash. On admission, he had depressed sensorium (Glasgow Coma Scale E1V1M2), blood pressure 110/59 mm Hg, pulse rate 98/min, secondary generalized dystonia, rigidity, brisk deep tendon reflexes, extensor plantar responses, and meningismus. A clinical diagnosis of acute encephalitis syndrome (AES) with raised intracranial pressure (ICP) was made. He was mechanically ventilated and ICP control measures were instituted. Empiric intravenous ceftriaxone (50 mg/kg/dose twice daily), doxycycline (3 mg/kg/dose twice daily), and acyclovir (10 mg/kg/dose thrice daily) were administered ([Table 1]).

Table 1 Investigations done in the index patient

Dengue non-structural protein 1 (antigen) (by rapid diagnostic kit done on day 4 of illness at a local hospital)	Reactive
Hemoglobin	10.9 g/dL
Total leucocyte count	12.07×109/L
Absolute lymphocyte count was	2.88×109/L
Platelet count	1.48×109/L
Aspartate transaminase	102 IU/L, range 2-40
Alanine transaminase	101 IU/L, range 2-40
Enzyme-linked immunosorbent assay-based dengue IgM	Elevated titres
Cerebrospinal fluid analysis (CSF)	Cells: nil Glucose: 72 mg/dL Protein: 52 mg/dL Gram Stain: nil Culture: nil
Polymerase chain reaction for herpes viral DNA	Negative
Enzyme-linked immunosorbent assay-based Japanese encephalitis virus IgM antibody in CSF	ot detected
Dengue antibodies in CSF	Test not available

The rapid diagnostic kit-based dengue nonstructural protein 1 (antigen) was reactive (done at the local hospital on day 4 of illness). His hemoglobin was 10.9 g/dL, total leucocyte count 12.07 × 10⁹/L, and absolute lymphocyte count was 2.88 × 10⁹/L. He had mild thrombocytopenia (1.48 × 10⁹/L), elevated aspartate transaminase (102 IU/L, range 2–40), and alanine transaminase (101 IU/L, range 2–40). Enzyme-linked immunosorbent assay-based dengue IgM titers were elevated. Cerebrospinal fluid analysis (CSF) by lumbar puncture showed absence of cells, glucose 72 mg/dL, protein 52 mg/dL, and absence of bacteria on Gram Stain or culture. Polymerase chain reaction for herpes viral DNA was negative. Antibody titers for Japanese encephalitis virus in CSF by IgM ELISA were not elevated. Dengue antibodies in CSF were not done as it was not available. Magnetic resonance imaging (MRI) of the brain showed features of encephalitis and the characteristic “double doughnut sign” ([Fig. 1A–D]). A final diagnosis of dengue encephalitis was considered. With supportive care, he gradually improved. At discharge, he was able to understand simple commands, recognized parents, and sat with support.

Fig. 1 (A–F): Axial MR images at the level of thalami showing bilateral symmetrical, heterogeneous hyperintensity with interspersed areas of hypointensity on T2-weighted (A) and FLAIR (B). These lesions show hyperintensities on T1-weighted (C) image consistent with subacute hemorrhages. The lesions show susceptibility changes on SWI (D), patchy diffusion restriction on DWI (E), and mild peripheral contrast enhancement on contrast-enhanced T1-weighted images (F). DWI, diffusion-weighted images; FLAIR, fluid attenuated inversion recovery; SWI, susceptibility weighted imaging; MR, magnetic resonance imaging.

Dengue fever is a multisystemic infection caused by the dengue virus. The virus belongs to the Flaviviridae family and is spread by the mosquito Aedes aegypti. Dengue is endemic in most parts of India and peaks after the monsoon season.[1] It is one of the common causes of AES in India after Japanese encephalitis (JE) and scrub typhus.[2] [3] Patients with dengue encephalitis may not have all the typical manifestations of dengue fever such as petechial rash and bleeding manifestations.[4]

The diagnosis in the index case was suspected on the basis of the clinical syndrome of AES, thrombocytopenia, transaminitis, absence of a bacterial picture in the CSF, and dengue antigen and IgM positivity in the serum. MRI in dengue encephalitis may show cortical swelling, signal changes in the cerebral (40%) and cerebellar white matter (31%), brain stem (28%), thalamus (26%), middle cerebellar peduncles (23%), or basal ganglia (6%).[5] Hyperintense signal in bilateral thalami with central diffusion restriction and blooming on susceptibility-weighted imaging has been described as a peculiar “double-doughnut sign” in dengue encephalitis. It is often seen in adult patients.[6] The neurological presentation of JE and dengue encephalitis may be similar, but dengue often presents with marked systemic features such as rash, organomegaly, transaminitis, serous effusions, arthralgia, and myalgia. Therefore, it is important to differentiate among these two illnesses. JE presents with leucopenia, CSF pleocytosis, elevated CSF protein, generalized dystonia, and signal changes in the thalamus and basal ganglia.[7] JE has significant mortality and neurological morbidity, whereas dengue encephalitis has the potential for good recovery with minimal neurological deficits as in the index case.[8] In conclusion, doughnut sign on the MRI is an important clue to dengue encephalitis in children with AES and needs timely recognition.

Publication History

Received: 18 June 2020

Accepted: 28 July 2020

Article published online:
04 September 2020

• References

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