|Year : 2022 | Volume
| Issue : 2 | Page : 107-109
Myelin oligodendrocyte glycoprotein encephalomyelitis: An unusual cause of blindness
Nimrat Sandhu, BM Sunil Kumar
Department of Pediatrics, M S Ramaiah Medical College, MSRIT, Bengaluru, Karnataka, India
|Date of Submission||15-Feb-2022|
|Date of Decision||26-Apr-2022|
|Date of Acceptance||02-May-2022|
|Date of Web Publication||30-May-2022|
Dr. Nimrat Sandhu
Department of Pediatrics, M S Ramaiah Medical College, MSRIT, Bengaluru - 560 054, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Myelin oligodendrocyte glycoprotein encephalomyelitis (MOG-EM) includes patients with (i) monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, or encephalitis; (ii) magnetic resonance imaging (MRI) or electrophysiological evidence of central nervous system (CNS) demyelination; and (iii) MOG-immunoglobulin G (IgG) seropositivity. Clinical Description: A 4-year-old girl presented with fever and excruciating headache for 10 days. Her vitals were stable and systemic examination was normal. Cerebrospinal fluid (CSF) analysis revealed 10 lymphocytes and normal biochemistry. After 5 days, she developed a fever and a seizure. Repeat CSF showed increased cells (60% lymphocytes), normal protein, and sugar. MRI brain was normal. She was managed symptomatically. CSF meningoencephalitis panel was negative. The child improved and was discharged. After 2 weeks, the headache recurred with associated blurring of vision. Bilateral papillitis, MRI brain abnormalities suggestive of acute disseminated encephalomyelitis (EM), and bilateral prolonged latency on visual evoked potential (VEP) were found. Anti-MOG antibodies were positive. The final diagnosis was MOG-EM. Management: The child was started on methylprednisolone therapy as per standard protocol. The vision improved and headache disappeared. She is on regular follow-up and is asymptomatic. Conclusion: MOG-IgG testing should be done in patients with (i) monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, or encephalitis; (ii) radiological or VEP findings compatible with CNS demyelination; and (iii) at least 1 of 25 delineated findings on MRI, fundoscopy, CSF, histopathology, clinical phenotype, or treatment response.
Keywords: Acute disseminated encephalomyelitis, myelin oligodendrocyte glycoprotein antibody disease, optic neuritis, seizures
|How to cite this article:|
Sandhu N, Sunil Kumar B M. Myelin oligodendrocyte glycoprotein encephalomyelitis: An unusual cause of blindness. Indian Pediatr Case Rep 2022;2:107-9
|How to cite this URL:|
Sandhu N, Sunil Kumar B M. Myelin oligodendrocyte glycoprotein encephalomyelitis: An unusual cause of blindness. Indian Pediatr Case Rep [serial online] 2022 [cited 2022 Jul 4];2:107-9. Available from: http://www.ipcares.org/text.asp?2022/2/2/107/346258
Acute encephalitis syndrome (AES) is characterized by fever, with mental confusion, disorientation, delirium, or coma. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating condition that predominantly affects the white matter of the brain and the spinal cord., ADEM is a rare heterogenous autoimmune disease often triggered by a viral infection or rarely by vaccines. Due to variable manifestations, the diagnosis is often missed.
In this report, we describe a young child with AES who presented initially with features of meningeal involvement but later developed optic neuritis. Neuroimaging suggested ADEM. The presence of myelin oligodendrocyte glycoprotein (MOG) antibodies clinched the diagnosis of MOG encephalomyelitis (MOG-EM). Prompt detection is associated with better outcomes.
| Case Report|| |
A 4-year-old girl presented with fever and headache for 10 days. The fever was moderate grade, intermittent, resolving with medication. The headache was frontal, persisted throughout the day, and resulted in excessive crying. There was no history of lethargy, loss of consciousness, seizures, or behavioral manifestations. There was no history of cough, cold, sore throat, breathing difficulty, rashes, ear infection, watering of the eyes, vomiting, loose stools, or urinary complaints. The child did not receive any antibiotics. There was no significant past medical or family history. She was immunized and developing typically.
On admission, she was febrile, hemodynamically stable, and normotensive. The weight (18 kg), height (100 cm) and body mass index (17) were normal for age. There was no pallor, lymphadenopathy, or rashes. The throat and joints were normal. She was conscious (modified Glasgow Coma Scale score: 15/15), oriented to time, place, and person, but irritable. Higher mental functions (attention, memory and speech) were age appropriate. Both pupils were equal in size and reactive. The fundus was normal. There were no cranial or focal neurological deficits. The motor and sensory examinations were normal. There were no signs of meningeal involvement, increased intracranial pressure, or ataxia. Hepatosplenomegaly was absent. The remaining systemic examination was normal. The differential diagnoses considered in view of the subacute fever, severe headache, irritability, and absence of localizing features were an acute central nervous system (CNS) infection, viral fever, or viral hemorrhagic fever. Malaria and enteric fever were considered less likely due to the absence of organomegaly.
| Management and Outcome|| |
Initial investigations revealed hemoglobin of 8.4 gm/dl; normal total leukocyte count of 8040 cells/mm3, with a differential count of 51% neutrophils, 43% lymphocytes, 2% eosinophils, and 4% monocytes; and platelet count of 3.2 lakhs/mm3. The C-reactive protein was normal (0.1 mg/dl). Cerebrospinal fluid (CSF) analysis showed 12 cells with 100% lymphocytes and normal protein and sugar levels. Samples were sent for CSF viral studies, and the child was started on antibiotics, acyclovir, and symptomatic management.
There was slight improvement between the 2nd and 4th days of admission, with decrease in fever and reduction in headache. The CSF meningoencephalitis panel was negative. On the 5th day of admission, she developed fever with chills, increasing drowsiness, and right focal seizures. The GCS was 12/15 (E3V4M5). There was no other change in the examination. She was euglycemic, normocalcemic, and had no dyselectrolytemia. She was started on antiepileptic drugs. Cerebral malaria was suspected and antimalarials started. However, the tests for malaria were negative. Magnetic resonance imaging (MRI) of the brain was normal. A repeat CSF examination showed an increase in cells (63 total, 60% lymphocytes and 40% neutrophils), normal sugar (40 mg/dl), but mildly increased proteins (52 mg/dl). The electroencephalogram was normal. The child improved clinically. Fever abated by day 3 and there was no recurrence of seizures. She was discharged after 7 days without any neurological sequelae and a clinical diagnosis of viral meningoencephalitis.
After 3 weeks, the child returned with complaints of blurring of vision and headache. There was no pain upon eye movement, or nystagmus. There was no history of fever, seizures, or altered sensorium. A repeat MRI (brain) revealed widespread diffuse asymmetrical diffuse hyperintensities in the T2 images involving the brainstem, basal ganglia, and peduncles, suggestive of ADEM [Figure 1]. Salient ophthalmological findings were normal visual acuity and fundus, bilateral papillitis, and bilateral prolonged latency on visual evoked potential (VEP), as depicted in [Figure 2]. Since ADEM is one of the most common presentations of MOG antibody disease (MOGAD), accounting for almost 50% of pediatric MOGAD patients, CSF and serum samples were sent for anti-neuromyelitis optica (NMO) and anti-MOG antibodies, and a trial of steroids started. The child was given pulse methylprednisolone (25 mg/kg/day) for 5 days, continued for 4 weeks, tapered, and stopped. The report that anti-MOG antibodies were positive became available midcourse. By this time, the child's headache had disappeared (end of the 1st week) and vision had improved (by the 2nd week). Currently, after 3 months, the child is stable and asymptomatic. The final diagnosis is MOG-EM (as per latest nomenclature).
|Figure 1: VEP report with bilateral prolonged latencies. VEP: Visual evoked potential|
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|Figure 2: MRI (brain) T2 image showing widespread diffuse asymmetrical hyperintensities in the brainstem, basal ganglia, and peduncles suggestive of ADEM. ADEM: Acute disseminated encephalomyelitis, MRI: Magnetic resonance imaging|
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| Discussion|| |
ADEM is usually a diagnostic challenge for a clinician due to its multifocal presentation that includes multiple neurological deficits and encephalopathy. The manifestations include fever (67%), lethargy (60%), vomiting (57%), weakness (50%), ataxia (50%), and headache (17%)., Kotlus et al., reported 6 of 10 pediatric ADEM patients with optic neuritis. Half of them had bilateral involvement. Other ocular manifestations described were decreased visual acuity, pain upon eye movement, nystagmus, and peripapillary hemorrhages. Other neurologic features were ataxia, hemiparesis, hypoesthesia, and dysarthria. ADEM presenting as isolated optic neuritis is uncommon.
MOG is a glycoprotein of the myelin sheath that plays an important role in the adhesion of myelin fibers and the regulation of oligodendrocyte stability. Their epitopes are highly immunogenic, and modulate the immune system. Anti-MOG antibodies have been reported in 40%–68% of children with ADEM. The current gold standard for the identification of immunoglobulin G (IgG) antibodies to MOG is cell-based assay utilizing fluorescence-activated cell sorting or indirect fluorescence test. Full-length human MOG should be used as target antigen and Fc-specific or IgG1-specific secondary antibodies to avoid cross-reactivity with IgM and IgA antibodies.
MOGAD was the term that was previously used for the autoimmune inflammatory demyelinating disorder that presented with optic neuritis, myelitis, and encephalitis. According to recent recommendations, the term MOG-EM should be used in patients who meet all of the following criteria: (i) monophasic or relapsing acute Optic Neuritis (ON), myelitis, brainstem encephalitis, or encephalitis, or any combination of these syndromes; (ii) MRI or electrophysiological (VEP in patients with isolated ON) findings compatible with CNS demyelination; and (iii) seropositivity for MOG-IgG as detected by means of a cell-based assay employing full-length human MOG as target antigen
The indications for MOG-IgG testing in adult and adolescent patients presenting with an acute CNS demyelination disorder of autoimmune etiology are as follows: (i) monophasic or relapsing acute optic neuritis, myelitis, brainstem encephalitis, encephalitis, or any combination thereof; (ii) radiological or, only in patients with a history of optic neuritis, electrophysiological (VEP) findings compatible with CNS demyelination; and (iii) at least one of the 25 delineated findings on MRI, fundoscopy, CSF, histopathology, clinical phenotype, and treatment response. In young children with acquired demyelinating disease, the indications for MOG-IgG testing are not as rigorous, since MOG-EM is significantly more frequent in this age group.
Once a diagnosis of MOG-EM is suspected, early treatment with steroids should be started. Intravenous immunoglobulin (IVIG) can be used if steroid-unresponsive, at a total dose of 2 g/kg for 2–5 days. Upcoming trials show that early initiation of IVIG might be beneficial.
ADEM with persistent MOG antibody is at risk of developing any of the three demyelinating conditions: multiphasic ADEM, NMO spectrum disorder with longitudinally extensive transverse myelitis, or recurrent optic neuritis. Therefore, regular follow-up is essential to monitor these children.
Declaration of patient consent
The authors certify that they have obtained appropriate patient consent form. In the form, the patient's parents have given their consent for images and other clinical information to be reported in the journal. The parents understand that name and initials of the patient will not be published and due efforts will be made to conceal the patient's identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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