Published onChildren's Doctor
A 5-year-old female with history of behavioral issues, constipation, and mild developmental delays presents for medical evaluation of headaches, gait abnormality, generalized weakness, and weight loss. Over the course of 3 weeks prior to hospitalization, her mother noticed a change in her gait and behavior in addition to episodes of headaches and emesis, which seemed to begin after a minor trauma.
During her hospitalization, she became increasingly agitated, with episodes of increased sleepiness, prompting neurologic consultation for encephalopathy. Her neurologic exam was notable for meningismus, hyperreflexia, bilateral sustained ankle clonus, dysmetria, and ataxia. A lumbar puncture showed an elevated white blood cell count of 225 (lymphocytic predominance), red blood cell count of 56, elevated protein of 55, and normal glucose. MRI of the brain and spine revealed diffuse patchy areas of abnormal signal in the cerebral peduncles, bilateral thalami, and cortical/subcortical areas bilaterally (Figure 3 A-C) and a longitudinally extensive spinal cord lesion from C2-T2, as well as involvement of the conus medullaris (Figure 3 D) — all suggestive of an inflammatory process.
Figure 3 (above): MRI of the brain and spine T2 Axial FLAIR imaging demonstrating bilateral cortical T2 hyperintensities (A), left thalamic T2 hyperintensity (B), bilateral cerebral peduncle hyperintensities (C), and spinal imaging revealing a longitudinally extensive lesion predominantly affecting the grey matter from C2-T2 (D)
The differential diagnosis included acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), viral encephalomyelitis, and anti-NMDA receptor encephalitis. She was treated with high-dose intravenous steroids followed by a steroid taper leading to significant clinical improvement. Serum antibodies to myelin oligodendrocyte glycoprotein (MOG) were reported positive after the patient was discharged.
The combination of subacute encephalopathy with ataxia and hyperreflexia, neuro-imaging consistent with a demyelinating process, and serum MOG-antibody positivity led to the diagnosis of MOG-antibody associated encephalomyelitis.
MOG-antibody associated disease is an emerging demyelinating disorder that is characterized by a broad range of clinical phenotypes and neuroimaging findings with a disease course that is distinct from multiple sclerosis (MS). MOG is a myelin glycoprotein that is exclusively expressed in the central nervous system and has been identified in about one-third of children diagnosed with an acquired demyelinating syndrome (ADS). The precise function of MOG is poorly understood; however, it likely plays a role in myelin maturation, myelin integrity, and cell surface interactions. The most common clinical phenotype of MOG-antibody associated disorders in children is ADEM, followed by optic neuritis and transverse myelitis. Most studies have found a bimodal distribution of clinical phenotypes, with younger patients predominantly presenting with ADEM and older children presenting with optic neuritis.
Neurodiagnostically, patterns have emerged to distinguish this disorder from other demyelinating diseases. CSF typically demonstrates a pleocytosis with variable protein elevation. CSF oligoclonal bands are not typically identified. Neuro-imaging of the brain classically reveals poorly demarcated, widespread lesions, or confluent white matter changes, but can also be normal. Lesions of the corpus callosum, juxtacortical lesions, and well-defined ovoid lesions are uncommonly described. Neuro-imaging of the spine characteristically shows longitudinally extensive lesions that can affect the cervical cord, but most frequently involves the lower cord, including the conus medullaris.
The disease course is most commonly monophasic but relapses can occur. Complete recovery from the onset attack is common in children both clinically and radiographically, and in general the outcome is favorable. The most common residual deficits are visual impairment, erectile dysfunction, and bladder sphincter dysfunction. The optimal treatment strategy for relapsing disease is currently unknown. In the acute setting, most patients respond well to intravenous steroids followed by a gradual steroid taper over 3 to 4 weeks, though some centers recommend a prolonged steroid taper of up to 6 months.
In children with relapsing disease, studies suggest use of intravenous immunoglobulin (IVIG) and/or disease modifying therapies (DMTs). These studies have demonstrated improvement in annualized relapse rate with the use of mycophenolate, azathioprine, rituximab, and IVIG, and a poor response to standard injectable DMTs used to treat MS, such as interferons and glatiramer acetate. Further research defining the exact pathogenesis, distinct clinical phenotype, and neuro-imaging findings — in addition to clinical trials to identify optimal therapies — will be essential moving forward.