ABSTRACT
Extrahepatic manifestations linked to hepatitis B Virus (HBV) are usually indirect consequences of immune-mediated mechanisms triggered by the virus replication. Strong evidence of brain HBV replication is missing and direct involvement of HBV in nervous system symptoms has been rarely reported. We report two cases of neurological manifestations contemporary to HBV infection. In both cases, HBV-DNA and HBsAg could be quantified in the cerebrospinal fluid (CSF) at relatively high levels. Differential quantification of HBsAg and HBV viral load both in CSF and in blood as well as phylogenic studies on HBV genomic sequences obtained from blood and CSF provided strong arguments for central nervous system viral replication in both cases. Direct causality of HBV replication in the central nervous system in these clinical situations is certainly not demonstrated but these findings could expand the list of hepatitis viruses possibly involved in neurological disorders. Further studies should be promoted to better document possible HBV replication in the brain tissues and its consequences.
Subject(s)
Central Nervous System Diseases/virology , Hepatitis B/cerebrospinal fluid , Hepatitis B/complications , Aged, 80 and over , Central Nervous System Diseases/cerebrospinal fluid , DNA, Viral/cerebrospinal fluid , Hepatitis B Surface Antigens/cerebrospinal fluid , Humans , Male , Middle AgedABSTRACT
Although many extrahepatic manifestations have been described in patients with acute or chronic hepatitis B, there are few reports about neurological disorders. We describe a 55-year-old man who contracted acute hepatitis B virus (HBV) infection and transverse myelitis. His neurological findings were gradually reduced along with the recovery from hepatitis. The cerebrospinal fluid (CSF) was revealed to be positive for HBsAg and HBV DNA. Full-length sequences of HBV in his serum and CSF were determined, and it was revealed that these two isolates had mutations at nucleotide (nt) 1762/1764 in the core promoter region and nt 1896 in the precore region. They were identical to each other except for two ambiguous codes at nt 2020 and 2631 in the CSF isolate. After cloning of the amplicons, substitutions at nt 2020 and 2631 were found in 6 (38%) of the 16 CSF clones. One clone of the 6 CSF clones had an additional substitution at nt 2119. These substitutions were not found in 16 serum clones. The presence of HBV clones unique to CSF suggests that HBV was a possible causative agent of the myelitis.
Subject(s)
Cerebrospinal Fluid/virology , DNA, Viral/genetics , Genome, Viral , Hepatitis B virus/genetics , Hepatitis B/virology , Myelitis, Transverse/virology , Serum/virology , Base Sequence , DNA, Viral/blood , DNA, Viral/cerebrospinal fluid , DNA, Viral/chemistry , Hepatitis B/complications , Hepatitis B Core Antigens/genetics , Hepatitis B Surface Antigens/blood , Hepatitis B Surface Antigens/cerebrospinal fluid , Hepatitis B virus/isolation & purification , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Molecular Sequence Data , Myelitis, Transverse/complications , Point Mutation , Promoter Regions, Genetic , Radiography , Sequence Analysis, DNA , Spinal Cord/diagnostic imagingABSTRACT
A 17 year-old boy with chronic hepatitis B who developed left-sided muscle wasting is reported. When other possible known diseases as the cause of the neurogenic muscle disease were excluded it was hypothesised that there was a relation between the chronic hepatitis B infection and the neurogenic muscle disease. An immunopathogenesis could be explained by the presence of HBsAg in the cerebral spinal fluid.
Subject(s)
Hepatitis B, Chronic/complications , Neuromuscular Diseases/virology , Adolescent , Biopsy , Female , Hepatitis B Surface Antigens/cerebrospinal fluid , Humans , Male , Neural Conduction , Neurologic Examination , Neuromuscular Diseases/cerebrospinal fluid , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/immunologyABSTRACT
An acute disintegrative disorder in a child with acute hepatitis B virus (HBV) infection is described. Both hepatitis B surface antigen (HBsAg) and HBV-DNA were detected in cerebrospinal fluid (CSF) by means of enzyme-linked immunosorbent assay (ELISA) and the polymerase chain reaction (PCR) technique respectively. A markedly elevated level of CSF adenylate kinase (AK), which normalised as the patient recovered spontaneously, suggested an organic brain disorder. Demonstration of intra-blood-brain barrier production of IgG supported the possibility of local infection by HBV within the central nervous system.
Subject(s)
Hepatitis B virus/isolation & purification , Hepatitis B/complications , Psychotic Disorders/etiology , Adenylate Kinase/cerebrospinal fluid , Child, Preschool , DNA, Viral/cerebrospinal fluid , Hepatitis B/cerebrospinal fluid , Hepatitis B Surface Antigens/cerebrospinal fluid , Hepatitis B virus/immunology , Humans , Male , Psychotic Disorders/cerebrospinal fluid , Psychotic Disorders/virology , Remission, SpontaneousABSTRACT
HBs antigen was found in the cerebrospinal fluid of a patient with acute type B virus hepatitis and Guillain-Barré syndrome. At the onset of the neurologic disease, immunological study of the spinal fluid revealed local synthesis of immunoglobulins and, in particular, anti-double-stranded DNA IgG antibodies. These abnormalities disappeared when the neurologic syndrome remitted. These findings suggest the extension of viral aggression to the central nervous system, perhaps at the onset of the neurologic disease.
Subject(s)
Antibodies, Antinuclear/cerebrospinal fluid , Hepatitis B Surface Antigens/cerebrospinal fluid , Hepatitis B/immunology , Polyradiculoneuropathy/immunology , Acute Disease , Adult , Albumins/cerebrospinal fluid , DNA/immunology , DNA, Single-Stranded/immunology , Hepatitis B/complications , Humans , Immunoglobulin G/biosynthesis , Male , Polyradiculoneuropathy/complications , Serum Albumin/analysis , Time FactorsABSTRACT
The AA, taking the latest reports as a starting point, are attempting a first epidemiological reconsideration of Hepatitis, Virus B. They have found that the disease, which was generally thought not to be contagious, is actually deceptive in its potential for transmission from person to person. Hospital personnel, in particular, are greatly at risk as are their families.
Subject(s)
Hepatitis B Surface Antigens/analysis , Hepatitis B/immunology , Saliva/immunology , Enzyme-Linked Immunosorbent Assay , Hepatitis B/epidemiology , Hepatitis B/transmission , Hepatitis B Surface Antigens/cerebrospinal fluid , Humans , Immunoglobulins/analysis , ItalyABSTRACT
A 76-yr-old male presented with Guillain-Barré syndrome after acute hepatitis B virus infection. Main immunologic features were: (a) high levels of circulating hepatitis B surface antigen-containing immune complexes in serum and cerebrospinal fluid during the acute neurologic syndrome, and (b) clearance of immune-complex material with recovery. Our data indicate that these immune complexes in cerebrospinal fluid reflect leakage from the systemic circulation via a deranged blood-brain barrier and are not generated in the cerebrospinal compartment. Possibly deposition of such immune complexes along nerve structures is important in the immunopathogenesis of some cases of Guillain-Barré syndrome.
Subject(s)
Antigen-Antibody Complex/analysis , Hepatitis B Surface Antigens/analysis , Polyradiculoneuropathy/immunology , Aged , Antigen-Antibody Complex/cerebrospinal fluid , Blood-Brain Barrier , Complement C3/analysis , Hepatitis B/complications , Hepatitis B Surface Antigens/cerebrospinal fluid , Humans , Male , Polyradiculoneuropathy/physiopathologyABSTRACT
Spinal fluid and serum samples from 19 patients, with acute viral hepatitis, type B, already known to have HBs antigenemia, were tested for the detection of HBsAg by two techniques; Hemagglutination Inhibition (H.I.) and Enzyme Linked Immuno Sorbent assay (ELISA). HBsAg was detected in all serum samples by both techniques while all spinal fluid samples were free of that antigen except one sample that was found to contain HBsAg by the ELISA technique only. This sample was also proved to contain occult blood as shown by the positive benzidine reaction.
Subject(s)
Anesthesiology , Hepatitis B Surface Antigens/cerebrospinal fluid , Hepatitis B/cerebrospinal fluid , Occupational Diseases/etiology , Acute Disease , Adolescent , Adult , Female , Hepatitis B/transmission , Humans , MaleABSTRACT
Cerebrospinal fluids (CSF) or sera or both from 57 chronic schizophrenics and 18 senile demented patients were examined by various tests for HBsAg. both CSF and serum were positive in 2 schizophrenics while in six HBsAg was detected in the CSF only. Elevated values of circulating immune complexes were found in positive patients. Most CSF positive for HBsAg also contained neutralizing antibodies to Herpesvirus hominis type 1. Ultramicroscopic structures similar to hepatitis B virus (HBV) components and herpesviral particles were visualized in the CSF of one patient on electron microscope (EM) grids coated with anti-human IgG serum. Most HBsAg positive patients appeared to be liver-symptoms-free carriers. In the CSF of a 79 years old senile demented man HBsAg was proved serologically. Several herpesviral particles complexed with globular material and spherical structures for 15 to 25 nm in diameter were visualized in the same CSF on EM grids coated with anti-human IgG serum. The findings support the importance of herpesviruses in mental illness. Penetration of HBsAg through the blood-brian barrier might be involved as an iatrogenic factor in the course of late psychoses.
Subject(s)
Antibodies, Viral/cerebrospinal fluid , Dementia/cerebrospinal fluid , Hepatitis B Surface Antigens/cerebrospinal fluid , Schizophrenia/cerebrospinal fluid , Simplexvirus/immunology , Adult , Aged , Chronic Disease , Dementia/microbiology , Female , Hepatitis B virus/ultrastructure , Humans , Male , Middle Aged , Schizophrenia/microbiology , Simplexvirus/ultrastructureSubject(s)
Hepatitis B Surface Antigens/cerebrospinal fluid , Hepatitis B/complications , Polyradiculoneuropathy/etiology , Adult , Female , Hepatitis B/diagnosis , Hepatitis B/immunology , Hepatitis B Surface Antigens/analysis , Humans , Polyradiculoneuropathy/cerebrospinal fluid , RadioimmunoassayABSTRACT
Hepatitis B surface antigen (HBsAg) was detected in the cerebrospinal fluid (CSF) of five of nine leukemia patients with HBsAg-positive sera. These five CSF samples were shown to be free of occult blood using a sensitive hemoglobin extraction technique. The presence of HBsAg in CSF was unrelated to cranial irradiation, prior lumbar punctures, or current chemotherapy. The findings indicate that many blood-free CSF specimens from HBsAg-positive patients, as well as all blood-contaminated specimens, contain detectable HBsAg. This suggests that CSF from patients who are HBsAg-positive should be handled with care, as it may be capable of transmitting hepatitis B to health care personnel caring for these patients and laboratory personnel handling their specimens.