Myelin oligodendrocyte glycoprotein antibody–positive acute disseminated encephalomyelitis following hepatitis A infection: A paediatric case report

INTRODUCTION

Acute disseminated encephalomyelitis (ADEM) is an inflammatory, immune-mediated demyelinating disorder of the central nervous system that most commonly affects children. It presents with the sudden onset of polyfocal neurological deficits, along with encephalopathy and changes consistent with demyelination on brain magnetic resonance imaging (MRI). Although ADEM can occur at any age, most paediatric series report a mean age of onset between 5 and 8 years with a slight male predominance. The estimated annual incidence in children ranges from 0.1 to 0.6/100,000. ADEM post Hepatitis A is extremely rare in the paediatric population.^[1] In our literature search, we were able to identify only three previously documented cases. We report a 13-year-old male patient who developed ADEM after a Hepatitis A infection, representing the first reported case from India and the first known instance of myelin oligodendrocyte glycoprotein (MOG) antibody-positive ADEM post-hepatitis A infection.

CASE REPORT

A 13-year-old boy presented with the chief complaint of confusion for 1 week, accompanied by loss of balance. He also reported blurring of vision in his left eye for 2 days associated with a headache. His mother also noticed difficulty in speech. Three weeks before this, he had an episode of fever and jaundice. Liver function tests were deranged with elevated bilirubin and transaminases. Fever and jaundice resolved with symptomatic management, which was followed by a 2-week interval without any new symptoms. He had no recent history of other infections or immunisations. On examination, he was mildly disoriented with a glasgow coma scale (GCS) score of 14/15-E4V4M6. Neurological examination showed reduced visual acuity in the left eye (6/60) with fundoscopy findings of grade 2–3-disc oedema. Bilateral dysdiadochokinesia, impaired finger-to-nose coordination, wide-based gait, and inability to perform tandem walking were also noted. Cranial nerves (except the left optic nerve) were intact; no facial asymmetry or extraocular movement limitation was noted. Motor examination showed normal tone, bulk, and power in all four limbs. Deep tendon reflexes were symmetrical, and plantar responses were flexor bilaterally. Sensory examination was normal. No signs of raised intracranial pressure were noted. Examination revealed no meningeal signs or involuntary movements. The combination of encephalopathy, visual impairment, and multifocal cerebellar signs, as well as a recent history of febrile jaundice, suggested a post-infectious demyelinating process.

MRI of the brain revealed multifocal T2/fluid-attenuated inversion recovery hyperintensities involving the bilateral cerebellar hemispheres, bilateral globus pallidus, subcortical white matter of the bilateral frontal lobes, bilateral centrum semiovale, and left temporal lobe. The MRI brain findings of the child are shown in Figure 1. There was no evidence of diffusion restriction on diffusion-weighted imaging and blooming on susceptibility-weighted imaging. Post-contrast study shows no evidence of enhancement. Anti-MOG immunoglobulin (Ig)G antibodies were strongly positive. Serum hepatitis A IgM antibodies were also positive. Cerebrospinal fluid (CSF) analysis was unremarkable.

Close

Figure 1:

(a) Ill-defined confluent FLAIR hyperintensities noted involving the white matter of the bilateral cerebellar hemispheres (red arrows). (b) Ill-defined FLAIR hyperintensities noted involving the left basal ganglia and genu of the left internal capsule (red arrow). (c) Multifocal patchy ill-defined FLAIR hyperintensities noted involving the subcortical white matter of bilateral frontal lobes (red arrows). (FLAIR: Fluid-attenuated inversion recovery).

Export to PPT

The patient was treated with intravenous methylprednisolone (30 mg/kg/day for 5 days), which resulted in significant clinical improvement, including resolution of vision, sensorium, cerebellar signs, and gait disturbances. Subsequently, he was switched to oral prednisolone (1 mg/ kg/day), which was tapered and discontinued over 6 weeks. Treatment was well tolerated with no adverse events. There was significant clinical improvement, and no new neurological signs during the follow-up visit 3 months later.

DISCUSSION

ADEM manifests abruptly within days to weeks after an infection or immunisation.^[2] Common preceding infections include influenza, Epstein–Barr virus, cytomegalovirus, herpes simplex, enterovirus, varicella, measles, mumps, rubella, and Mycoplasma pneumoniae.^[1] The development of ADEM may have a genetic predisposition, although there is no concrete evidence to support this. In contrast, ADEM following Hepatitis A virus (HAV) infection is exceptionally rare. HAV is a positive-sense RNA virus most commonly transmitted through the faecal-oral route. While hepatitis A usually causes a self-limited illness, there have been reports of neurological sequelae such as Guillain–Barré syndrome, hepatic myelopathy, acute transverse myelitis, acute cerebellar ataxia, opsoclonus-myoclonus ataxia syndrome, ADEM, and meningoencephalitis.^[3-7] In this case, a detailed history ruled out the possibility of other infections, and there is no recent history of immunisation. It represents the first paediatric MOG-antibody positive ADEM associated with Hepatitis A infection in India.

ADEM is hypothesised to arise through molecular mimicry, whereby pathogens have antigens similar to myelin, which triggers T-cell activation leading to a cytokine-mediated inflammatory response, which results in perivenular sleeves of demyelination, oedema, and infiltration of inflammatory and microglial cells.^[2]

ADEM can present with prodromal symptoms of lethargy, fever, headache, vomiting, and seizures, including status epilepticus. One of the hallmark features of ADEM is encephalopathy. Common neurological signs that develop later include visual loss, ataxia, cranial neuropathies, and sensory and motor deficits, along with bowel/bladder dysfunction if the spinal cord is involved. The condition rapidly progresses over days.^[1] Our patient demonstrated features that were consistent with paediatric ADEM, including acute onset of neurological deficits, including cerebellar involvement and encephalopathy.

ADEM is a diagnosis of exclusion, as there are no definitive biomarkers or laboratory investigations available. Important differential diagnoses to consider include multiple sclerosis (MS), MOG antibody disease, and vascular pathologies. Monophasic ADEM can be differentiated from relapsing demyelinating conditions like paediatric MS based on clinical presentation, laboratory findings, and MRI characteristics. An isolated clinical event with a polysymptomatic presentation, along with the presence of encephalopathy and multifocal neurological deficits, as in this case, favours ADEM over MS. Furthermore, there was no clinical evidence of new neurological symptoms to suggest dissemination in time that can happen in MS. The presence of oligoclonal bands in the CSF and ovoid periventricular lesions with well-defined borders on MRI are hallmark features of MS, but would be atypical findings in ADEM.^[2]

Most cases of ADEM, including ours, are monophasic, with one single episode, but Oleszak et al. describe the case of a multiphasic disseminated encephalomyelitis following HAV infection.^[2,8]

MRI brain is the imaging modality of choice for patients with suspected ADEM. MRI typically shows poorly demarcated, diffuse, and large (measuring more than 1–2 cm) T2 hyperintense lesions predominantly involving the white matter, thalamus, or basal ganglia,^[2] which is consistent with the findings in our patient. In our patient, the MRI of the brain did not show optic nerve involvement. The unilateral optic disc oedema observed on fundoscopy was consistent with papillitis (inflammatory optic nerve head involvement), which contrasts with the case described by Alehan et al. in which bilateral papilledema was due to increased intracranial pressure from severe cerebral involvement.^[9]

CSF examination may be normal or show pleocytosis and elevated protein.^[2] Among the previously reported paediatric cases of ADEM following HAV, two (Oleszak et al. and Alehan et al.) had abnormal CSF findings, whereas Unay et al. had a normal CSF profile similar to our case. Notably, none of these three cases documented MOG-antibody positivity. However, up to 50% of cases of ADEM are associated with MOG Ab-positivity in the serum, which could be due to the MOG antibody testing modality being relatively new.^[8-10]

As with other demyelinating disorders, ADEM is commonly treated with high-dose intravenous corticosteroids, typically methylprednisolone 20–30 mg/kg/day for 5 days with a maximum dose of 1000 mg/day, followed by oral prednisolone 1–2 mg/kg/day (maximum 40–60 mg/day) tapered over 4–6 weeks. For refractory cases, intravenous IG (IVIG) (2g/kg administered over 2–5 days) or plasmapheresis (5–7 exchanges every other day) is effective. (1) Our patient demonstrated an excellent response to corticosteroids. Among the previously reported paediatric cases, the 12-year-old female in Unay et al. responded well to IVIG, whereas the 7-year-old female in Oleszak et al. received corticosteroids, IVIG, and plasmapheresis.^[8,10]

Overall, ADEM generally has a good prognosis, but in a few cases, cognitive deficits and behavioural changes have been reported, especially in children younger than 5 years.^[1,2] In our case, the patient made a full recovery, consistent with the outcomes reported by Unay et al. and Oleszak et al. Conversely, in Alehan et al., a 30-month-old male developed papilledema. He rapidly progressed to coma, ultimately dying 3 weeks after the onset of symptoms, which underscores the potential severity of ADEM in younger children.^[8-10]

CONCLUSION

Given the high prevalence of hepatitis A infection in developing countries due to poor sanitation, it is important to recognise that ADEM may rarely follow HAV infection. Clinicians should monitor patients for neurological symptoms after recovery and consider recent HAV infection when evaluating children presenting with acute demyelinating syndromes. Routine immunisation against HAV would indirectly help in reducing the incidence of post-infectious demyelinating syndromes.