[Acute disseminated encephalomyelitis associated with hepatitis A virus infection]. / Encéphalomyélite aiguë disséminée associée à une infection au virus de l'hépatite virale A chez l'adulte.

INTRODUCTION: Hepatitis virus A (HVA) infection is usually a benign infection, but it can lead to severe manifestations and neurological symptoms. CASE REPORT: We report the case of a 44-year-old man who was admitted for pyramidal tetraparesis, loss of proprioceptive sensitivity and cranial nerve involvement. He had developed concomitally jaundice and fatigue. Brain MRI and cerebrospinal fluid examination were normal. Blood tests revealed elevated serum transaminase and anti-hepatitis A virus (IgM and IgG) levels. Acute disseminated encephalomyelitis (ADEM) was diagnosed and the patient was treated with high dose intravenous then oral corticosteroid therapy. The clinical condition continued to deteriorate and the patient died at eight months. DISCUSSION: ADEM is exceptionally associated with HVA infection or after vaccination for hepatitis A. Other neurological complications, including either peripheral or central nervous system, are reported. The clinical presentation and the outcome of our patient are atypical.

Molecular epidemiology of hepatitis A virus in a group of Portuguese citizens living in Lisbon area.

Hepatitis A virus (HAV) is the most important cause of acute infectious hepatitis worldwide. In Portugal, due to improvements in sanitation epidemic outbreaks of HAV infection have become less frequent. This report is the first, to our knowledge that characterized HAV in Portugal. For the detection and molecular characterization of HAV cases in a group of Portuguese individuals in the Lisbon area, 31 serum samples were tested: 8 from symptomatic children from an acute hepatitis A outbreak in a Roma (Gipsies) community (2004-2005), and 22 from patients with acute HAV from sporadic cases (2005-2006). A sample of CSF involved in a case of meningitis was also included. IgM anti-HAV detection and nested reverse transcription (RT-PCR), with primers located at the VP1-P2a region, was undertaken to detect HAV genome. In positive samples, molecular characterization was followed by phylogenetic analysis. All samples (n = 31) were positive for IgM anti-HAV. HAV RNA was found in 96.7% of cases. All isolates were classified as genotype I: 22 belonged to sub-genotype IA (73.3%), and 8 to sub-genotype IB (26.7%). All strains obtained from an acute HAV outbreak had sub-genotype IA, in which seven isolates (87.5%) had identical sequences. In HAV sporadic cases sub-genotypes IA and IB were identified, and this may reflect the co-circulation of these two sub-genotypes in Portugal. Molecular epidemiology of HAV infection in this group of Portuguese appears to be similar to other European countries. HAV phylogenetic studies can provide important information for the design of appropriate public health measures.

[Detection of HBSAG in cerebrospinal fluid by means of a radioimmunoassay technique (author's transl)]. / Radioimmunoglogischer HBSAg-Nachweis im Liquor cerebrospinalis

HBSAg was demonstrated radioimmunologically in cerebrospinal fluid in 7 out of 11 seropositive children with acute viral hepatitis B (1/2), fulminant viral hepatitis (0/1), chronic active hepatitis (2/4), chronic persistent hepatitis (1/1), cirrhosis (1/1), and asymptomatic carrier status (2/2). Counterelectrophoresis and complement fixation test lacked the necessary sensitivity to detect the antigen even in patients with high serum concentrations. The pass over of the cerebrospinal barrier appears to be dependent of the serum titer. Some neurologic symptoms in the early stage of acute viral hepatitis are probably connected with the appearance of HBSAg in cerebrospinal fluid. It is however unlikely that central-nervous-system dysfunctions observed in association with fulminant viral hepatitis and coma result from a direct effect of HBSAg or hepatitis B-virus. In chronic carriers the cerebrospinal fluid probably contains the antigen more frequent. The cerebrospinal fluid of HBSAg-positive patients has to be regarded as an infectious agent.

Guillain-Barré syndrome associated with acute hepatitis A.

A case of Guillain-Barré syndrome in a 49-year-old male is described. The syndrome presented as tetraplegia with sensory impairment and the pre-icteric phase of acute hepatitis A. Both viral hepatitis and neurologic disturbances improved, although neurologic changes lasted for 3 months after the onset. HA IgM antibody in cerebrospinal fluid was first manifest with onset of neurologic symptoms. On the basis of this finding and some reports in the literature it seems possible that the Guillain-Barré syndrome may be related to the immunopathogenetic mechanism of hepatitis A virus infection.

Presence of oligoclonal T cells in cerebrospinal fluid of a child with multiphasic disseminated encephalomyelitis following hepatitis A virus infection.

We have investigated the clonality of beta-chain T-cell receptor (TCR) transcripts from the cerebrospinal fluid (CSF) and peripheral blood from a 7-year old child who developed a multiphasic disseminated encephalomyelitis following an infection with hepatitis A virus. We amplified beta-chain TCR transcripts by nonpalindromic adaptor (NPA)-PCR-Vbeta-specific PCR. TCR transcripts from only five Vbeta families (Vbeta13, Vbeta3, Vbeta17, Vbeta8, and Vbeta20) were detected in CSF. The amplified products were combined, cloned, and sequenced. Sequence analysis revealed in the CSF substantial proportions of identical beta-chain of TCR transcripts, demonstrating oligoclonal populations of T cells. Seventeen of 35 (48%) transcripts were 100% identical, demonstrating a major Vbeta13.3 Dbeta2.1 Jbeta1.3 clonal expansion. Six of 35 (17%) transcripts were also 100% identical, revealing a second Vbeta13 clonal expansion (Vbeta13.1 Dbeta2.1 Jbeta1.2). Clonal expansions were also found within the Vbeta3 family (transcript Vbeta3.1 Dbeta2.1 Jbeta1.5 accounted for 5 of 35 transcripts [14%]) and within the Vbeta20 family (transcript Vbeta20.1 Dbeta1.1 Jbeta2.4 accounted for 3 of 35 transcripts [8%]). These results demonstrate the presence of T-cell oligoclonal expansions in the CSF of this patient following infection with hepatitis A virus. Analysis of the CDR3 motifs revealed that two of the clonally expanded T-cell clones exhibited substantial homology to myelin basic protein-reactive T-cell clones. In contrast, all Vbeta TCR families were expressed in peripheral blood lymphocytes. Oligoclonal expansions of T cells were not detected in the peripheral blood of this patient. It remains to be determined whether these clonally expanded T cells are specific for hepatitis A viral antigen(s) or host central nervous system antigen(s) and whether molecular mimicry between hepatitis A viral protein and a host protein is responsible for demyelinating disease in this patient.