Acute myelopathies are a heterogeneous group of disorders with distinct etiologies, clinical and radiologic features, and prognoses. Acute transverse myelitis is one form of acute myelopathy with a reported incidence between 1 and 8 new cases per million people per year (1). Many viruses including varicella, rubella, mumps, echovirus, coxsackie, influenza, and measles have been reported to be associated with transverse myelitis (1). Postinfectious myelopathy associated with hepatitis virus is a rare entity, with most of the reported cases being adults (2,3). There are few reports of this complication in the pediatric population (4,5). Pathogenesis of the myelitis associated with hepatitis virus is still uncertain. We report a child who presented with myelopathy after hepatitis A infection and provide an insight into its pathogenesis.
A developmentally normal 8-year-old boy was brought with complaints of sudden-onset weakness of all limbs associated with neck and back pain. He had associated bowel and bladder retention. There was no preceding history of loose stools, trauma, or myalgia. Three weeks before the present illness, he had developed fever, vomiting, and yellowish discoloration of sclera for which they had not sought any medical attention. The fever subsided within 10 days and the icterus also gradually resolved.
On examination, he was conscious, with stable vital parameters. There was no spinal tenderness. Neurological examination revealed decreased power in all 4 limbs (Medical Research Council [MRC] grade: 4/5 in all muscle groups of upper limbs, 3/5 in lower limbs). Deep tendon reflexes were brisk and plantar response was extensor bilaterally. He had persistent bladder distension necessitating catheterization. Examination of the sensory system and cranial nerves did not reveal any abnormality. He had a hemoglobin 11.5 g/dL, total count of 12,400 cells per cubic millimeter with neutrophilic preponderance and normal platelet counts. Liver function tests were normal (aspartate transaminase 18 IU/L, alanine transaminase 20 IU/L, total bilirubin 0.8 mg/dL). A provisional clinical diagnosis of acute transverse myelitis was made. Magnetic resonance imaging done on the second day of admission revealed spinal cord edema and demyelination extending from C1 segment to D10 segment, which confirmed the clinical diagnosis of myelitis. In view of the history of jaundice preceding the weakness, workup for infective hepatitis was done. Immunoglobulin (Ig)M antihepatitis A virus (HAV) was positive. Hepatitis B surface antigen, IgG antihepatitis C virus, IgM antihepatitis E virus, and human immunodeficiency virus enzyme-linked immunosorbent assay were negative. Examination of the cerebrospinal fluid (CSF) revealed 18 lymphocytes per cubic millimeter. CSF protein content was 40 mg/dL. CSF bacterial culture was sterile and IgM anti-HAV antibody in the CSF was positive. Nested reverse transcriptase RNA polymerase chain reaction (PCR) for HAV in the CSF was negative. A diagnosis of HAV-associated parainfectious myelopathy was considered and the child started receiving pulse methyl prednisolone therapy (100 mg/kg divided for 3 days). Within 48 hours, power of the upper limbs improved to MRC 5/5, and on day 3 lower limb power improved to MRC 4/5 and the child was able to walk with support. From day 5, bowel and bladder control were regained and he was discharged on day 8. On follow-up at 3 months after discharge, the child was able to walk without support with no residual weakness, and the neurological examination was normal.
Viral myelopathy can have varying presentations. Acute transverse myelitis is one of the forms of viral myelitis. Our patient did not have sensory deficits, which are common with acute transverse myelitis. Hence, we have used the term acute parainfectious myelopathy. The transverse myelitis syndrome most often occurs as an autoimmune phenomenon after an infection or vaccination (60% of the cases in children) (6). In 30% to 60% of cases with idiopathic transverse myelitis, there is an antecedent respiratory, gastrointestinal, or systemic illness (7,8). Hepatitis A infection is a self-limited disease in most cases, but in some patients it can lead to systemic complications (9). Although hepatitis A is a common infectious agent among children, especially in endemic countries, the association with transverse myelitis is rarely reported in the English-language literature (4,5). This may be because a significant proportion of young children with HAV infection remain anicteric during the illness (10). In our patient, we investigated for infective hepatitis because there was a definite history of jaundice preceding the myelopathy. Positive serum IgM points toward a recent hepatitis A infection.
Neurologic injury in infection-associated myelitis may be caused by direct microbial infection or because of injury from a systemic immune response. In myelitis associated with herpes simplex 1 and 2, varicella zoster, cytomegalovirus, Epstein-Barr virus, and enterovirus, viral PCR assays in the CSF would show presence of viral particles within the central nervous system pointing to direct cytolytic effect of the neurons as the possible mechanism. Immune-mediated damage is the mechanism behind myelitis associated with Campylobacter jejuni and hepatitis B infections (6). The pathogenesis of myelitis associated with HAV is not certain. Direct virus infection and virus-induced autoimmunity (humoral or cell-mediated, possibly vasculitic) are the proposed disease mechanisms (11). A single case report of HAV-associated transverse myelitis has shown absence of viral particles in the CSF (9), but HAV RNA has been demonstrated in the CSF by reverse transcriptase PCR in a child with demyelinating encephalomyelitis (12). Our report adds credence to the argument in favor of an immune-mediated mechanism. In our patient, the IgM antibody for HAV was positive in the CSF, but the HAV RNA PCR was negative. This observation is suggestive of an immune-mediated myelitis rather than a direct invasion of virus into the spinal cord. Such cases of acute myelitis following hepatitis infection have been found to respond favorably to immunomodulatory therapy (11). The dramatic response observed within 3 days of initiation of steroid therapy is noteworthy because it favors an autoimmune mechanism as the underlying cause.
Considering the fact that hepatitis A infection is a common infection among children in endemic countries such as India, with a significant proportion of the young children remaining anicteric during the illness (10), the possibility of HAV infection should be considered in the etiologic workup of children with myelitis in these endemic countries. The exact burden of this rare complication of HAV can be ascertained only if routine testing is carried out in all myelitis patients. Such a study may be worthwhile considering the fact that an effective vaccine is available for HAV, which can prevent the occurrence of this serious condition in children. Moreover, a better understanding of the mechanism of myelopathy associated with HAV can help in the management because neural injury secondary to systemic immune response, as we observed in our patient, responds well to immunomodulatory therapy.
We thank Dr Rahul, Assistant Professor, Department of Microbiology, for helping us with the serological diagnosis of hepatitis A and Dr Ramesh, Assistant Professor, Department of Radio-diagnosis (both from JIPMER, Pondicherry), for helping us with the imaging. We also thank Dr Kavita Lole, Senior Scientist, Hepatitis Division, National Institute of Virology, for performing the PCR for hepatitis A virus in CSF.
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