Anti-myelin oligodendrocyte glycoprotein (MOG) antibody disease has been recently implicated as a major etiology for pediatric non-infectious encephalitis [1]. We report a case of acute fulminant encephalitis in a 5 year old child mimicking viral encephalitis, which was eventually diagnosed as anti-MOG antibody encephalitis leading to successful treatment with immunotherapy, thus highlighting this condition as an important differential diagnosis for acute viral encephalitis.

A 5-years-old previously normal Indian girl presented with intermittent fever for 4 days, headache for 2 days followed by encephalopathy. On admission, she was afebrile with normal vital signs and a Glasgow coma scale of 12. Subsequently her GCS deteriorated to 8 within 12 hours necessitating mechanical ventilation, and she developed signs of raised moderate intracranial hypertension and relative bradycardia. Neuro-logical examination showed sluggish brainstem reflexes including pupillary and occulocephalic reflex, brisk deep tendon reflexes and bilateral extensor plantar response. There was no history of seizures, abnormal movements, visual disturbances, bowel or bladder dysfunction, or preceding altered sleep or behavior. There was no history of contact with tuberculosis or recent travel. There was no history of drug ingestion or any toxic exposure. The initial working diagnosis was acute febrile encephalopathy with differential diagnosis of viral encephalitis, acute demyelinating encephalomyelitis (ADEM) or neuro-metabolic disease with acute decompen-sation. Emergent neuroprotection measures and a combination of broad spectrum antimicrobials including Acyclovir were instituted.

MRI brain showed extensive asymmetrical high signal changes involving bilateral cortical regions along with ventromedial thalamus with extensive diffusion restriction suggestive of cytotoxic edema (Fig. 1). Post contrast study showed no evidence of parenchymal or leptomeningeal enhancement. MRI of spine and MR angiogram were normal. On day 2 of admission, patient developed focal seizures with EEG showing bilateral periodic lateralizing epileptiform discharges (PLEDs) highly suggestive of a neurotropic viral encephalitis. Due to the patient’s clinical condition, cere-brospinal fluid (CSF) was deferred until the second week and was unremarkable including negative routine studies, culture and PCR for neurotropic viruses. The patient remained deeply encephalopathic and ventilator dependent for the next two weeks with no response to treatment including acyclovir. In the second week of admission she developed stereotypical flinging repetitive asymmetrical lower limb movements, prompting a trial of methyl prednisolone and immunoglobulins alongside autoimmune and lupus workup including CSF and serum anti-NMDAR (N-methyl-d-aspartate receptor) antibodies and oligoclonal bands which were negative. However, there was no significant clinical improvement. This led to the counselling of the family regarding an acute fulminant encephalitis with poor neurological outcome and need for tracheostomy. After review of the recently published case series by Armangue, et al. [1], serum anti-MOG antibodies (IgG) immunofluorescence test was sent and showed a positive titer of 1:40. Plasma Exchange was then instituted with a total of 5 cycles on alternate days. After the second cycle of plasma exchange itself, the patient showed rapid clinical improvement in the form of improved GCS and was successfully weaned off from ventilation. At the time of discharge two weeks later, the patient could walk unsupported and talk in simple sentences. On follow-up at 4 months after the illness, the patient remained clinically well, and had regained pre-illness developmental status. Her repeat anti-MOG titers were negative and repeat neuroimaging showed no active lesions.

Fig. 1 a) MRI T2-weighted image showing bilateral asymmetrical (left more than right) cortical high intensity signal with cortical swelling along with high signal in the ventromedial thalami, b) MRI diffusion weighted image (DWI) and c) apparent diffusion coefficient (ADC) images showing bilateral cortical cytotoxic edema in the form of diffusion restriction and corresponding drop in the ADC values.

During the last decade, anti-MOG antibodies have been implicated in a wide range of pediatric acquired demyelinating syndromes including optic neuritis, myelitis and ADEM [2]. However a recent multicenter observational study by Armangue, et al highlighted the widening spectrum of anti-MOG antibodies disease [1], demonstrating it as the commonest etiology of non-infectious, non-ADEM encephalitis in the pediatric age group, in addition to the well-established presentations mentioned above. Of the 116 anti-MOG antibody positive patients recruited in the study, 22 (19%) were diagnosed as encephalitis other than ADEM, thus making it an important differential diagnosis in pediatric encephalitis. The clinical presentation included encephalopathy, seizures, status epilepticus, fever, abnormal behavior, motor deficits, abnormal movements and brainstem-cerebellar dysfunction. MRI showed non-ADEM like findings including extensive bilateral cortical involvement (55%) with or without basal ganglia involvement and meningeal enhancement. Another recent publication by Budhram, et al. coined the term FLAMES based on a distinct radiological pattern of unilateral cortical FLAIR-hyperintense lesions in adult anti-MOG encephalitis with seizures [3]. Our case had clinical features of encephalopathy, brainstem dysfunction and abnormal movements while MRI brain showed extensive bilateral cortical and basal ganglia involvement with diffusion restriction but without meningeal enhancement. These observations were in keeping with the findings described in the study by Armangue, et al. [1]

We conclude that anti-MOG encephalitis should be considered in a child with fulminant encephalitis with bilateral cortical involvement with diffusion restriction on MRI, with or without meningeal contrast enhancement. Steroids should be the first line treatment for anti-MOG encephalitis, and usually shows a good response. However, early plasma exchange should be considered in cases with inadequate response to pulse steroids.

1. Armangue T, Olive-Cirera G, Martinez-Hernandez E, et al. Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: A multicentre observational study. Lancet Neurol. 2020;19:234-46.

2. Fernandez-Carbonell C, Vargas-Lowy D, Musallam A, et al. Clinical and MRI phenotype of children with MOG antibodies. Mult Scler. 2016;22:174-84.

3. Budhram A, Mirian A, Le C, et al. Unilateral cortical FLAIR-hyperintense lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES): Characterization of a distinct clinico-radiographic syndrome. J Neurol. 2019; 266:2481-87.