Home » Volumes » Volume 40 March/April 2007 » Acute disseminated encephalomyelitis in classic dengue

Acute disseminated encephalomyelitis in classic dengue

Carlos A.A. BritoI, II; Silvana SobreiraIII; Marli Tenório CordeiroI, IV; Norma Lucena-SilvaI, V

IAggeu Magalhães Research Center, Oswaldo Cruz Foundation, Recife, PE IIDepartamento de Medicina Clínica, Universidade Federal de Pernambuco, Recife, PE IIIHospital Memorial São José, Recife, PE IVDr. Milton Bezerra Laboratory, Laboratório Central, Recife, PE VInstituto Materno Infantil de Pernambuco Prof. Fernando Figueira, Recife, PE

DOI: 10.1590/S0037-86822007000200019


Neurological manifestation is uncommon in dengue infection. The pathogenesis of central nervous system involvement is controversial. We report a rare case of acute disseminated encephalomyelitis in classic dengue, with isolation of serotype 3 in liquor. This condition was associated with significant structural damage detected by magnetic resonance.

Key-words: Acute disseminated encephalomyelitis. Dengue. Neurological symptoms.


Manifestação neurológica é incomum em dengue. A patogênese do acometimento do sistema nervosa central é controversa. Nós relatamos um raro caso de encefalomielite disseminada aguda em dengue clássica, com isolamento do sorotipo 3 em líquor. O quadro estava associado a significativo dano estrutural detectado pela ressonância magnética.

Palavras-chaves: Encefalite disseminada aguda. Dengue. Manifestações neurológicas.



Dengue is an infectious disease caused by a flavivirus, in which neurological signs are uncommon. Nevertheless, central nervous system (CNS) involvement has been reported with different clinical forms (meningitis or encephalitis), as well as peripheral nervous system disease with clinical signs of polyradiculoneuritis3 8. The frequency of dengue etiology in patients with encephalitis, based on the presence of anti-dengue IgM in the serum, has been shown to range from 5 to 20%5 11. The pathogenesis of the neurological manifestation is not clearly defined, but some reports have attributed it to the encephalopathy present in severe cases of dengue hemorrhagic fever (DHF)1 8. Acute disseminated encephalomyelitis (ADEM) is a neurological manifestation rarely described in association with dengue. Four ADEM cases have been published, but only two of them showed abnormalities on nuclear magnetic resonance (NMR) imaging, which were associated with systemic vascular alterations, consumption of platelets and hepatic dysfunctions. The dengue virus was not isolated in liquor in any of these cases3 7 12.

The present report details the case of a 37-year-old woman was attended at the emergency services of Memorial São José Hospital in Recife. She presented with asthenia, headache, myalgia and arthralgia, and was using dipyrone as a painkiller. Five days after her symptoms started, she had difficulty in pronouncing some words, and this evolved to progressive impairment in spontaneous speech. She presented weakness in the left hand, which was most pronounced in the first and second fingers. This made the use of tweezers difficult, thereby compromising her professional activity (dentist). She had a sensation of heaviness in her left leg, with repercussions on her gait, and this was the principal preoccupation leading to consultation with a neurologist.

The initial neurological examination showed speech disturbances characterized by phonemic paraphasia and dysnomia, with the preservation of understanding. This was associated with grade III movement deficit in the left hand, which was predominantly in the first and second fingers, and grade IV deficit in the left leg. The superficial and deep reflexes were normal, with slight hypostasis for painful tactile stimulus of the left hand. The cranial pairs were also normal.

Blood assays showed platelets and hepatic enzymes at normal levels (Table 1). NMR gave a low signal on T1 and a high signal on T2, and showed a variety of contrast impregnations (retentions) with ventricular white substance, at the callosal-septal interface, right-side centrum semiovale, corona radiata and thalamus bilaterally.



The dengue etiology was confirmed by isolating the virus from the liquor followed by RT-PCR and immunofluorescence for dengue serotyping. Hemagglutination inhibition (HI) assay detected seroconversion for anti-dengue specific antibodies to DEN-3, as shown in Table 2. A positive HI for other serotype indicates previous dengue infection.



The patient underwent pulse therapy with 1g of methylprednisolone for 5 days.

A sample of liquor was sent to our laboratory for examination on the fifth day of symptoms when she was seen by the physician for the first time. It was only on the ninth day of disease, after laboratory confirmation of dengue in the liquor, that a new blood sample was collected, when virus isolation is more difficult. Anti-dengue IgM was also negative in both the serum and liquor. Negative ELISA has also been reported in 25% out of 614 cases of acute infection confirmed by hemagglutination inhibition4.

Neurological manifestations have not been directly attributed to the effect of the virus, but to dengue encephalopathy caused by systemic vascular alterations. Such alterations might be due to the homeostasis, vascularized endothelium or hepatic dysfunction that is present in severe cases of dengue hemorrhagic fever (DHF)1 8.

The molecular pathogenesis of neurological dengue has become a subject for study because of the increasing numbers of reports of neurological symptoms among patients with mild DHF or classic dengue5 10. Additionally, some necropsy studies have been suggesting that local inflammatory activity is due to the presence of the virus in the CNS2 6 9.

ADEM is an uncommon neurological manifestation involving peripheral nerves that has also been associated with dengue infection. Two recently reported cases of ADEM suggested this association, but no clinical and laboratory evidence has been produced to support the hypothesis that the virus has a cytopathic effect on the CNS3 12.

Out of 41 reported cases of dengue with neurological manifestations among Brazilian patients, 22 were classified as encephalitis, 16 as peripheral nervous disease, two as transversal myelitis and one as ADEM. In the ADEM case, no virus was isolated from liquor, nor were there any abnormalities on NMR. There was no information about the clinical form of the dengue, platelet counts or hepatic dysfunction to add to the discussion on the genesis of these neurological manifestations3.

There has been another report of ADEM, on a Japanese patient infected in Brazil, in which the NMR images of the spinal cord showed multiple high-intensity spotty lesions from Th-7 to Th-11. This case showed a notable decrease in platelet count (50,000/µl) and also hepatic dysfunction, thus suggesting a mechanism associated with dengue encephalopathy12.

We have reported an ADEM case that was associated with dengue virus detected in the liquor and significant structural damage detected by NMR. This was classified as a classic dengue case without evidence of the hepatic dysfunction, circulatory collapse, hypoxia or metabolic imbalance that occur secondarily to encephalopathy. These features emphasize that a cytopathic effect was occurring due to the presence of the virus in the CNS. Future studies will be needed to clarify whether the neurological manifestations are due to neural tropism or the virulence of a variant virus of the dengue virus.



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 Address to:
Dra. Norma Lucena-Silva
Centro de Pesquisa Aggeu Magalhães/FIOCRUZ
Av. Moraes Rego, S/N, campus da UFPE, Cidade Universitária
50670-420 Recife, PE, Brazil
Tel: 55 81 2122-4764
e-mail: nlucena@cpqam.fiocruz.br

Recebido para publicação em 28/9/2006
Aceito em 8/2/2007
Support: This work was supported by the PDTSP program at Fiocruz.