Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Masquerading as Herpes Simplex Virus Encephalitis
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Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune demyelinating disorder of the central nervous system caused by immunoglobulin G antibodies (Abs) directed against myelin oligodendrocyte glycoprotein (MOG). This condition can result in subacute inflammation of the optic nerve (optic neuritis), spinal cord (transverse myelitis), and brain (acute disseminated encephalomyelitis). Approximately 25% of children with MOGAD experience at least one relapse, which typically occurs around three years after the initial manifestation [1-4]. Here, we present a case of MOGAD that initially presented as herpes simplex virus (HSV) encephalitis.
A 9-year-old boy, born to non-consanguineous parents with a history of normal birth and development, presented with 4 days of fever and vomiting. On the 4th day, he developed recurrent right-sided focal seizures, followed by altered sensorium characterized by excessive sleepiness and a lack of response to commands. There was no history of rash, visual impairment, or bowel or bladder incontinence. On examination, his head circumference was 50 cm and weight was 22 kg; vital parameters, including heart rate and blood pressure, were normal. He had a Glasgow Coma Scale score of 13/15 and normal cranial nerve findings, including the facial nerve. Power in the right upper and lower limbs was reduced (3/5, modified Medical Research Council grade), with decreased tone but no involuntary movements, no ataxia, and no meningeal signs.
Laboratory investigations revealed hemoglobin of 12.2 g/dL (reference, 11.5 to 15.5 g/dL), a total leukocyte count of 17.1×10³/μL (reference, 5–13×10³/μL), and a platelet count of 200,000/μL (reference, 150–450×10³/μL). Liver function showed normal bilirubin, but serum aspartate aminotransferase was elevated at 104 U/L (normal up to 40 U/L), and alanine aminotransferase at 106 U/L (normal up to 40 U/L). Renal function, ammonia, lactate, and bicarbonate levels were all normal. Cerebrospinal fluid (CSF) analysis showed normal protein and glucose, with three lymphocytes. A CSF and blood acute encephalitis panel, which included Japanese encephalitis, scrub typhus, dengue virus, and chikungunya virus, was negative. Magnetic resonance imaging (MRI) of the brain revealed T2/fluid-attenuated inversion recovery hyperintensities in the bilateral medial temporal lobes (more pronounced on the left) with diffusion restriction and no contrast enhancement (Fig. 1). Electroencephalogram (EEG) demonstrated left-sided periodic lateralized epileptiform discharges (PLEDs) (Fig. 2). Viral meningoencephalitis due to HSV was considered the leading diagnosis, and acyclovir was initiated.
Brain magnetic resonance imaging. A fluid-attenuated inversion recovery axial image (A) and a T2 weighted axial image (B) show hyperintense areas in the medial temporal lobes, left more than right (black arrows). Hypointense areas (white arrows) in the medial temporal lobes are seen on a T1-weighted inversion recovery axial image (C). On a post-contrast T1-weighted axial image (D), the bilateral medial temporal lobes are not enhanced.
On electroencephalography, a bipolar longitudinal montage shows spikes and spike-wave 1–2 Hz, 100–200 μV arising from F3, Fp1, T3, and T5 at the intervals of 2 to 3 seconds, suggestive of left-sided periodic lateralized epileptiform discharges.
Despite treatment, the child remained encephalopathic with persistent drowsiness. CSF HSV DNA polymerase chain reaction (PCR) was negative, so acyclovir was discontinued. MOGAD was then considered, and anti-MOG Abs were found to be strongly positive. The patient was treated with methylprednisolone pulse therapy (30 mg/kg/day) for 5 days, followed by oral steroids. CSF HSV PCR was repeated after 7 days and remained negative. Since both CSF HSV PCR tests were negative and the child's clinical status improved following steroid therapy, a diagnosis of MOGAD was established. Fundoscopic examination was normal at this time. The patient’s sensorium improved, and oral prednisolone was continued at 2 mg/kg/day for 2 weeks, followed by tapering doses: 1.5 mg/kg/day for 2 weeks, 1 mg/kg/day for 2 weeks, and 0.5 mg/kg/day, gradually discontinued over 6 weeks. At 3 months’ follow-up, the child was clinically normal, without focal deficits, and both EEG and MRI findings had normalized.
We report a 9-year-old boy with acute febrile encephalopathy, focal seizures, PLEDs on EEG, and temporal lobe signal changes on MRI secondary to MOGAD. The clinical and radiological spectrum of MOGAD has broadened to include encephalitis-like, leukodystrophy-like, and other atypical presentations [5]. In HSV-1 encephalitis, MRI has over 90% sensitivity, and PLEDs are highly characteristic [5].
This case is unique compared to the previous 50 cases in our series because the clinical, radiological, and electrographic features closely mimicked HSV encephalitis [6]. In our cohort, MRI abnormalities were present in 86% of children: 48% cortical, 22% basal ganglia, 10% cerebellum, 10% brainstem, 8% internal capsule, and 6% midbrain involvement [6]. In this patient, MRI demonstrated asymmetric bilateral temporal lobe involvement and EEG showed PLEDs, both more suggestive of HSV infection.
However, there was no significant improvement; the child remained encephalopathic. CSF HSV DNA PCR, performed twice, was negative (test sensitivity 96% to 98%, with very high specificity) [7,8], and MRI showed asymmetric lesions. Thus, MOGAD was considered, and anti-MOG Abs were sent, returning strongly positive. To date, no prior cases have been reported of MOGAD presenting as herpes encephalitis. There are, however, reports of MOGAD occurring alongside HSV infection in adults [9,10]. Second-line treatments such as intravenous immunoglobulin and plasmapheresis were not required as the child improved dramatically with steroids. In patients with encephalitic syndromes and MRI abnormalities in the brain and/or spinal cord, MOG Ab testing should be part of the initial work-up, as MOG Abs are more frequently detected in these patients than all other neuronal auto-Abs combined [1]. Management is specific, and long-term follow-up for recurrence is needed.
MRI in MOGAD typically demonstrates involvement of all lobes, with frequent basal ganglia, optic nerve, and spinal cord involvement, while HSV commonly affects the temporal lobes and thalami. CSF in HSV encephalitis usually shows lymphocytosis, occasional red blood cells, normal to low glucose, and normal protein, while in MOGAD, CSF may reveal neutrophilic leukocytosis, low glucose, and be negative for HSV PCR.
In conclusion, MOGAD can mimic HSV encephalitis; this newly recognized, treatable disease should be considered, as management and long-term outcomes differ substantially. HSV requires acyclovir, and immunosuppression may worsen its course; conversely, MOGAD requires immunosuppression and careful monitoring for recurrence.
This study was approved by the Institutional Review Board of Indira Gandhi Institute of Child Health (approval number: IEC/IGICH/34/2025).
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Author contribution
Conceptualization: VKG, MV. Data curation: VKG, MV, VSRC. Formal analysis: VKG. Methodology: VKG, MV, VSRC. Visualization: VSRC. Writing - original draft: MV, VSRC. Writing - review & editing: VKG, VSRC.