Childhood encephalitis in Sweden: etiology, clinical presentation and outcome.

Acute encephalitis is a relatively uncommon but potentially harmful CNS inflammation usually caused by infection. The diagnosis is difficult to establish and the etiology often remains unclear. Furthermore, the long-term prognosis of acute encephalitis in children is poorly described. In this study, we characterize childhood encephalitis from a Swedish perspective in regard to etiology, clinical presentation and sequele. We retrospectively studied all children (n=93) who were admitted for acute encephalitis at Karolinska University Hospital in Stockholm during 2000-2004. A confirmed etiological agent was identified in eight cases and a probable one in 37; in 48 cases no etiological agent could be found. Tick-borne encephalitis virus, enterovirus, respiratory syncytial virus, varicella zoster virus and influenza virus predominated and represented 67% of all the confirmed or probable etiologies. Encephalopathy was present in 80% of the children, 81% had fever, 44% had focal neurological findings, and seizures occurred in 40%. EEG abnormalities were seen in 90% and abnormal neuroimaging was present in 30%. The cerebrospinal fluid showed pleocytosis in 55%. There was no mortality, but 60% of the children had persisting symptoms at the time of discharge, 41% of which were moderate to severe. We conclude that the etiology of encephalitis among Swedish children is at large the same as in other European countries with similar vaccination programs. Fever and encephalopathy were seen in a majority of children and the most sensitive tool for making the diagnosis was EEG examination. Furthermore, many children display persisting sequele at discharge for which the strongest predictive factor was focal neurological findings at presentation.

De novo SCN1A mutations in migrating partial seizures of infancy.

OBJECTIVE: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). METHODS: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. RESULTS: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. CONCLUSION: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy.

A case of diffuse leptomeningeal oligodendrogliomatosis associated with HHV-6 variant A.

We describe a rare case of diffuse leptomeningeal oligodendrogliomatosis associated with the human herpes virus 6 variant A (HHV-6 A). A 2-year-old boy presented with progressive neurological symptoms and hydrocephalus. The patient had a VP shunt placement but did not fully recover. HHV-6 A was detected in both CSF and serum by nested PCR. His symptoms improved repeatedly, but temporarily, on antiviral treatment. An open brain biopsy, ten months after presentation, revealed leptomeningeal tumour as well as the presence of viral DNA in the tumour tissue. The role of HHV-6 A could be that of a reactivated opportunist. However, this case also raises the question whether this neurotropic virus, with malignant transforming properties in vitro, may have a role in pathogenesis in some cases of brain malignancy.