Acute disseminated encephalomyelitis following dengue fever

Acute disseminated encephalomyelitis following dengue fever

J Infect Chemother (2002) 8:175–177 © Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2002 CASE REPORT Yuuji Y...

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J Infect Chemother (2002) 8:175–177

© Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2002

CASE REPORT Yuuji Yamamoto · Tomohiko Takasaki Ken-ichirou Yamada · Mikio Kimura Kazushige Washizaki · Kouki Yoshikawa Akihiro Hitani · Tetsuya Nakamura · Aikichi Iwamoto

Acute disseminated encephalomyelitis following dengue fever

Received: November 9, 2001 / Accepted: December 14, 2001

Abstract A 58-year-old man suffered from acute disseminated encephalomyelitis (ADEM) after dengue fever. ADEM has not been described as the cause of neurological complications in dengue fever. However, the increasing use of magnetic resonance imaging in endemic areas may help to identify ADEM as being responsible for neurological complications in dengue fever. Key words Dengue fever · Acute disseminated encephalomyelitis · Magnetic resonance image

mumps, influenza, parainfluenza, Epstein-Barr (EB) virus infection, and nonspecific respiratory infections. The illness is sudden in onset, with a monophasic course; it may be selflimited or may leave permanent neurological deficits. We recently experienced a patient with acute onset of neurological disturbance after classical dengue fever. Although there have been no reports of ADEM following dengue fever, we made the diagnosis of ADEM in this patient from the typical clinical course and magnetic resonance images. We report here this ADEM case for further understanding of the pathogenesis of ADEM and dengue fever.

Introduction Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammation caused by antecedent viral infection and vaccination. The molecular mechanism of ADEM is thought to be that host immunity to the virus and vaccine crossreacts with proteins in the central nervous system. The pathological hallmark consists of widely scattered small foci of perivenular inflammation and demyelination. Postinfectious ADEM usually begins late in the course of viral infections, including measles, chickenpox, rubella,

Y. Yamamoto · A. Hitani · T. Nakamura (*) · A. Iwamoto Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan Tel. ⫹81-3-5449-5338; Fax ⫹81-3-5449-5427 e-mail: [email protected] T. Takasaki · K. Yamada First Department of Virology, National Institute of Infectious Diseases, Tokyo, Japan M. Kimura The Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan K. Washizaki Division of Neurology, Akasaka Sannou Hospital, Tokyo, Japan K. Yoshikawa Division of Radiology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

Case report A 58-year-old Japanese man who had been in Brazil for several months had a fever with a temperature of over 39°C and anorexia on January 15, 2000. He was admitted to a hospital in Brazil on January 20 because of persistent fever. On admission, he was found to have erythema on both arms and legs. His platelet count was 50 000/μl; aspartate aminotransferase (AST) was 199 U/ml (normal range, 10–31 U/ ml); and alaninire aminotransferase (ALT) was 123 U/ml (normal range, 9–36 U/ml). IgM antibody to dengue virus in his serum was negative on January 19, but was positive on January 25 (UMLISA Dengue IgM; Centro de Immunologia Molecular, Havana, Cuba), and a diagnosis of dengue fever was made (serotype 2). Although the patient’s fever, liver dysfunction, and thrombocytopenia had improved spontaneously by January 27, he had begun to complain of dysuria since January 21. He also experienced other neurological symptoms, including sensory disturbance and mild paraplegia of the lower extremities, which appeared on January 24 and rapidly worsened to complete paraplegia below the Th7 level by January 27. Cerebrospinal fluid (CSF) collected on January 28 showed mild elevation of protein (89 mg/ml) and pleocytosis (21 cells/μl). Magnetic resonance (MR) imaging of the spinal cord was performed on January 28, but did not show


abnormal findings at this time. In addition to the neurological symptoms, visual acuity had deteriorated in the left eye since February 7 and then in the right eye since February 19. Visual acuity in both eyes then gradually deteriorated. He was transferred to our hospital in Japan on February 25 for further evaluation and treatment. When admitted to our hospital, the patient was alert and afebrile. Visual acuity in both eyes was numerus digitorum. Because fundoscopic examination and cerebral MR images revealed no abnormal findings, optic neuropathy was suspected as the cause of his visual disturbance. The functions of cranial nerves other than the optic nerves were normal. Both lower extremities were completely paralysed, and deep tendon reflexes (DTRs) were absent. The plantar responses were extensor bilaterally. The upper extremities had normal muscle strength and DTRs. Sensations of pinpricks and temperature were severely disturbed under the sixth thoracic dermatome, whereas sensations of vibration and light touch were relatively preserved. Routine laboratory tests revealed no particular abnormalities in blood cell counts, liver function, kidney function, and electrolytes. We confirmed that his serum collected on February 25 was positive for both IgG and IgM antibodies to dengue virus, using a Rapid Immunochromatographic Test (PanBio, Brisbane, Australia) and IgM capture enzymelinked immunosorbent assay (ELISA; Focus Technologies, Herndon, VA, USA). T2-weighted MR images of the spinal cord showed multiple high-intensity spotty lesions from Th7 to Th-11, which were further enhanced on postcontrast T1-weighted images, using an extracellular gadolinium agent (Fig. 1). MR images of the brain revealed no abnormal findings in the cerebrum, cerebellum, and optic nerves. From his characteristic clinical course and MR images, we diagnosed acute disseminated encephalomyelitis (ADEM) following dengue fever. To improve his neuro-

Fig. 1A–C. Magnetic resonance (MR) images of the patient’s spinal cord. A T2-weighted MR image and B T1-weighted MR image before and C after gadolinium contrast on February 25 revealed multiple high-intensity spots from Th-7 to Th-11 of the spinal cord. The Th-8 vertebral body had a deformity caused by an old compression fracture

logical symptoms, treatment was started with methylprednisolone (1000 mg/day) for 3 days, beginning March 1. The administration of methylprednisolone was then carried out three times per week, and the bilateral sensory disturbance and paraplegia, as well as the visual disturbance, improved step-by-step after each treatment. After the third cycle of methylprednisolone treatment, the high-intensity spots in the spinal MR images disappeared. The patient was soon able to walk with the help of a stick, although mild bilateral visual disturbance, dysuria, and dyschezia remained.

Discussion The diagnosis of dengue fever in our patient was confirmed serologically, using serial serum samples. We were unable to detect dengue virus RNA by polymerase chain reaction in either the serum or the CSF collected in our hospital, probably because the samples were obtained after the viremic period. Neurological complications are rare in dengue virus infection.1 A few sporadic cases of dengue encephalopathy have been reported in patients with dengue hemorrhagic fever whose manifestations consisted of abrupt onset of hyperpyrexia, nontransient alteration of consciousness, headache, and vomiting.2,3 In these patients, the neurological symptoms were thought to be associated with non-viral etiology, including vasculitis, cerebral hemorrhage, and severe liver failure. On the other hand, a small number of patients with dengue encephalitis who have either CSF pleocytosis, focal neurological signs, or convulsion have also been reported.2–5 Because dengue virus was isolated from some of these patients,2 direct invasion of dengue virus into the central nervous system (CNS), as occurs with other


flaviviruses, could partly explain the pathogenesis of the encephalitis. However, the precise mechanism of dengue encephalitis remains unknown. The patient in this report had neither metabolic abnormalities nor hemorrhagic lesions in the CNS (both of which features are often observed in dengue encephalopathy). Rather, the CSF pleocytosis and focal neurologic signs indicated the presence of encephalomyelitis. The key point of the diagnosis of ADEM in this patient was that his neurological symptoms had appeared during the late phase of hyperpyrexia and that the visual disturbance occurred after he had become completely afebrile. This characteristic time course of the symptoms strongly suggested postinfectious encephalomyelitis; i.e., ADEM. Although the spinal MR findings of ADEM are nonspecific, high-intensity lesions distributed asymmetrically in the white matter of the cord, extending over several segments (from Th-7 to Th-11 in our patient) on T2-weighted images are consistent with the spinal form of ADEM.6–8 Although gadolinium enhancement is not consistent in ADEM, it can be identified in the acute stages and can be suppressed by corticosteroid therapy,9 as observed in our patient. From the extent that we surveyed the database, we could not find reports of ADEM which occurred following dengue fever. Solomon et al.4 analyzed findings in 21 patients with dengue fever with neurological complications, and found that 10 were complicated with encephalopathy, 9 with encephalitis; and 2 with myelitis. The neurological symptoms in the 11 patients with encephalitis or myelitis started 1–9 days after the initial onset of fever. Although there was a possibility of postinfectious encephalomyelitis in the patients whose neurological symptoms started during the late phase of hyperpyrexia, the limited availability of MR images could have made the diagnosis difficult. Had brain MR imaging been performed in these patients, some of them may have been diagnosed as having ADEM.

Dengue fever patients with encephalomyelitis usually have favorable clinical courses regarding survival, but some patients suffer from persistent neurological complications.3,4 Because glucocorticoid is effective in the active phase of ADEM, early diagnosis and the administration of glucocorticoid seem to be critical for the functional prognosis of patients with ADEM following dengue fever. Acknowledgments We thank Ms. Maiko Nakarai for careful reading of the manuscript. This work was partly supported by grants-in-aid for AIDS research from the Ministry of Health, Labor and Welfare of Japan.

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