Clinical outcome of children presenting with a severe manifestation of acute disseminated encephalomyelitis.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an acute, inflammatory-demyelinating disorder of the CNS with a favourable outcome in the majority of cases. OBJECTIVE: The aim of this study was to examine the long-term outcome of children with an initially severe form of ADEM. METHODS: Children with ADEM according to the criteria of the International Pediatric MS Study Group (IPMSSG) referred to the rehabilitation centre Vogtareuth were included. Neurological impairment was evaluated with a standardized telephone-based interview assessing the EDSS score. Neuropsychological outcome was assessed with review of the medical records and a standardized parental questionnaire (KOPKIJ). RESULTS: Twelve children (1 year 9 months to 13 years of age) were included. All children had focal-neurological signs and changes in mental status at presentation and an MRI of the brain showing a range of white and gray matter lesions. 11/12 patients with a mean follow-up of 6.2 years (2-13.6 years) had a monophasic course of the disease. One child had a multiphasic ADEM. Two children had an EDSS score of 0, three an EDSS of 2, five an EDSS between 3 and 5 and two children had an EDSS score of 6 and 9. Results of a standardized parental questionnaire (KOPKIJ) revealed that 7 children had deficits in the categories alertness, memory, school performance, visual-spatial skills and/or impulse control. CONCLUSION: The results of our study indicate that children with an initially severe manifestation of ADEM continue to have in the majority of cases neurological and neuropsychological handicaps.

Endogenous interleukin-10 is required for prevention of a hyperinflammatory intracerebral immune response in Listeria monocytogenes meningoencephalitis.

To analyze the role of interleukin-10 (IL-10) in bacterial cerebral infections, we studied cerebral listeriosis in IL-10-deficient (IL-10(-/-)) and wild-type (WT) mice, the latter of which express high levels of IL-10 in both primary and secondary cerebral listeriosis. IL-10(-/-) mice succumbed to primary as well as secondary listeriosis, whereas WT mice were significantly protected from secondary listeriosis by prior intraperitoneal immunization with Listeria monocytogenes. Meningoencephalitis developed in both strains; however, in IL-10(-/-) mice the inflammation was more severe and associated with increased brain edema and multiple intracerebral hemorrhages. IL-10(-/-) mice recruited significantly increased numbers of leukocytes, in particular granulocytes, to the brain, and the intracerebral cytokine (tumor necrosis factor, IL-1, IL-12, gamma interferon, and inducible nitric oxide synthase) and chemokine (crg2/IP-10, RANTES, MuMig, macrophage inflammatory protein 1alpha [MIP-1alpha], and MIP-1beta) transcription was enhanced compared to that in WT mice. Despite this prominent hyperinflammation, the frequencies of intracerebral L. monocytogenes-specific CD8(+) T cells were reduced and the intracerebral bacterial load was not reduced in IL-10(-/-) mice compared to WT mice. Following intraperitoneal infection, IL-10(-/-) mice exhibited hepatic hyperinflammation without better bacterial clearance; however, in contrast to the mice with cerebral listeriosis, they did not succumb, illustrating that intrinsic factors of the target organ have a strong impact on the course and outcome of the infection.