Department of Radio diagnosis, JLN Hospital and Research Centre, Sector 9, Bhilai - 490009, Chattisgarh, India

*Corresponding author: Das A, Department of Radio diagnosis, JLN Hospital and Research Centre, Sector 9, Bhilai - 490009, Chattisgarh , India; Mobile: +91 7489740972; E-mail: mukut016@gmail.com

Copyright: © 2022 Das A, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Acquired demyelinating disorders of CNS are rare among the pediatric age group, the common ones among them being ADEM, MOGAD, MS and NMOSD. Clinical history and MRI of the CNS may reveal some soft indicators that help differentiate the demyelinating disorders, which are extremely important from the perspective of treatment and prognosis. However, a few overlapping clinical and imaging features may be seen among these disorders. We present a case of pediatric MOGAD, which had initially mimicked pediatric MS clinically and imaging-wise. We also present his clinico-radiological followup over a period of 6 years.

Pediatric; Demyelinating disorder; Acute disseminated encephalomyelitis; Myelin oligodendrocyte glycoprotein antibody-associated demyelinating disease; Multiple sclerosis; Neuromyelitis optica spectrum disorder

Acquired demyelinating disorders of the central nervous system (CNS) among the pediatric age group have a rare occurrence, with an annual incidence of approximately 0.5-1.66 per 100,000 children. The two most important immunoglobulin G (IgG) antibodies playing a role in the pathogenesis of these disorders are aquaporin-4 antibody (AQP-4 Ab) and myelin oligodendrocyte glycoprotein antibody (MOG- Ab). An MRI of the brain and spinal cord is important in characterizing the demyelinating lesions, both symptomatic and subclinical, and in predicting the probability of further recurrences. Serial MRI may also help in establishing the diagnosis, and monitoring treatment response [1]. This report describes a rare case of pediatric myelin oligodendrocyte glycoprotein antibody-associated demyelinating disease (MOGAD), its clinico-radiological correlation, and its follow-up over 6 years.

An 8-year old male child presented with acute, painless, diminished vision and was unable to read the question sheet. There was no history of (h/o) redness in the eye, increased lacrimation, or watering. No h/o headache, vomiting, seizures, or altered sensorium. There was no h/o preceding fever, cough, cold, loose stools, or recent vaccination before the onset of illness. There was no h/o weakness. There was a past h/o on and off headache since 6 years of age. The patient was also a known case of (k/c/o) bilateral (B/L) myopia, which was corrected with refractive lenses. There is a family h/o stroke in paternal grandmother in 2012. Neurological and fundoscopic examinations showed normal findings. The child was admitted to our hospital for 15 days and evaluated. Cerebrospinal fluid (CSF) analysis during hospital stay revealed no cells, protein of 7 mg/dl, and glucose of 103 mg/dl. Oligoclonal bands (OCB) were detected. CSF anti-aquaporin 4- immunoglobulin G antibodies (APQ4-IgG) were negative. Testing for MOG-Ab was not done.

MRI brain (plain + contrast) study revealed multiple demyelinating T2 FLAIR hyperintense foci in the deep white matter of B/L cerebral parenchyma including the corpus callosum (Figure 1), typical Dawson fingers, and the ‘dot-dash’ signs of early MS, thus demonstrating dissemination in space. However, none of them showed post-contrast enhancement or restriction on DWI. Thus dissemination in time could not be demonstrated. MRI revealed no abnormalities in B/L optic nerves. Even though findings that are typical of Multiple Sclerosis (MS) were seen in this MRI, it did not fulfil the 2017 revised McDonald criteria [3]. Despite this, in view of the CSF OCB being positive, a diagnosis of clinically isolated syndrome/Paediatric MS was made [1].

A diagnosis of ADEM was ruled out as the patient did not have any recent h/o infection or vaccination. Neuromyelitis Optica Spectrum Disorder (NMOSD) was unlikely since the patient was APQ4-IgG negative. The child was treated with pulse methylprednisolone for 5 days followed by oral steroid for 10 days. The child had complete recovery of vision within 6 days following the onset of illness.

Following the first episode, the child was asymptomatic for four years till May 2019, when he gradually developed weakness in his upper and lower limbs, with difficulty in walking and in raising his left arm. There was slurring of speech and change in handwriting over the next 4 days. There was no h/o headache, blurring of vision, vomiting, seizures or altered sensorium during this event. On examination, his vitals were found stable and his higher mental functions were found normal. On cranial nerve examination, difficulty in blowing mouth and whistling was found. On sensory examination, there was a loss of pain sensation in both upper limbs. Power was found to be 4/5 in all limbs.

MRI Brain (Plain + Contrast) study revealed multiple foci of T2 FLAIR hyperintensity in the deep white matter of the cerebrum, confluent hyperintensity in B/L periventricular white matter, B/L middle cerebellar peduncles, B/L dentate nuclei and extending into the white matter of B/L cerebellar hemispheres (Figure 2). No focus of contrast enhancement was seen in the present scan. As compared to the previous MRI scan done in March 2015, new lesions were seen. Also, there was more extensive white matter involvement in the present scan as compared to the previous scan. Thus, dissemination of demyelinating lesions in both space and time could be substantiated, which led to the fulfillment of Modified McDonald criteria 2017 [3]. In view of a relapsing attack and a positive OCB in CSF, a diagnosis of MS was made. However, pediatric MS has a rare incidence. Moreover, B/L symmetrical cerebellar peduncle involvement along with B/L confluent periventricular white matter involvement in the pediatric population is an atypical finding in multiple sclerosis, and more in favor of MOGAD [4]. Phenotypical similarity in MRI findings may also be seen in pediatric leucodystrophies [5]. Spinal cord MRI screening revealed no lesions.

The child was admitted for one week and treated with pulse methylprednisolone for 5 days followed by oral prednisolone for 8-10 days. There was complete recovery of limb weakness by the third day following the initiation of treatment.

The child presented with similar complaints and clinical findings as of those in May 2019. The neuromotor symptoms were predominantly on the left side of the body. MRI Brain (Plain + Contrast) study revealed bilateral white matter T2 FLAIR hyperintense demyelinating lesions, a few of them showing contrast enhancements suggestive of acute lesions (Figure 3). These acute lesions were more concentrated on the right brain, thus correlating with the left-sided neuromotor symptoms. An open ring pattern of enhancement was seen in the right middle cerebellar peduncle lesion with corresponding hyperintensity on T2 FLAIR images. Spinal cord MRI screening, once again, revealed no demyelinating lesion. The child was again treated with pulse methylprednisolone and oral steroids which showed complete recovery within a few days. The child was evaluated for the above symptoms in September 2019 at a referral hospital when he was found to be positive for MOG antibody. A diagnosis of MOGAD was made and was treated with a schedule of tapering oral steroids for 3 months and an escalating schedule of mycophenolate.

The child again developed gradual onset of weakness in his leftsided upper and lower limbs, with occasional falls while walking. There is history of difficulty in grasping objects with the left hand, and slippage of chappals from the left foot. There is also a history of slurring of speech and change in handwriting, which worsened over the next 3 days. There is also h/o mild blurring of vision in his left eye during this event. There is no h/o fever headache, altered sensorium or seizure. The child was evaluated at the referral hospital for the above symptoms. On examination, cerebellar signs such as dysmetria were present (left more than right) and incoordination in the heelshin test. Pyramidal signs on the left were seen. Visual Evoked Potential (VEP) test showed left anterior optic pathway dysfunction. Somatosensory Evoked Potential (SSEP) test done by stimulating the left tibia did not evoke right sensory cortical potentials.

MRI Brain (Plain+Contrast) study revealed confluent areas of T2 hyperintensities in the periventricular white matter and the deep white matter of frontal and parietal lobes (Figure 4). Left cerebellar white matter and left middle cerebellar peduncle showed mild expansion and T2 hyperintensity, which correlated clinically with cerebellar signs. There was no contrast enhancement or diffusion restriction. Classical “T1 black hole sign” was seen in right temporal lobe white matter, which is typical for MS. Since the patient was having recurrent sensorimotor deficits predominantly on the left side, 3D TOF (Time of Flight) MR Angiography was performed, which ruled out any vascular abnormality. Spinal cord screening once again revealed no lesion. The child was given pulse methylprednisolone for 5 days, followed by rituximab. The patient was discharged on a schedule of tapering dose of oral prednisolone, followed by prolonged maintenance on low-dose prednisolone.

A follow-up MRI Brain (Plain + Contrast) was done for the child who had been asymptomatic for the past one year. The findings were similar to the previous scan, with no significant radiological disease progression. Few hyper-enhancing foci were seen in the right peritrigonal white matter suggestive of an acute demyelinating lesion. The MRI findings are shown in Figure 5. Spinal cord MRI screening showed no demyelinating lesion.

Myelin oligodendrocyte glycoprotein (MOG) is a specific protein found in the outer layers of myelin sheath in the CNS. Earlier, MOG was associated with MS as per animal model studies [7]. Recent advances have shown MOG antibodies to be more closely associated with ADEM and AQP4-Ab negative NMOSD [8,9], rather than MS. Also, CNS imaging has shown many differences in the phenotype of MOG antibody-positive patients from AQP4-Ab positive NMOSD and MS [6,10]. These have lead to a conclusion in recent times that MOGAD is a separate clinical entity.

In the case of this child, with MRI showing multiple demyelinating lesions, MOGAD and MS were considered as differentials based on clinical and radiological findings. ADEM was not considered since the patient had no h/o recent vaccination or infection. The discussion on differentials is summarized in Table 1.

Table 1 show that our case had multiple findings in favor of MS as well as MOGAD. Our case did not fulfil the international criteria for MOG-IgG testing [11]. Yet, the positivity of the antibody test clinched the diagnosis of MOGAD. Ramnathan et al. concluded that there is a significant overlap of radiological findings in MS and MOGAD [12]. They recommended testing of all pediatric-onset demyelinating disorders for MOG-IgG due to the high pretest probability of MOGAD in this population.

Few salient features that were noted in our case and worth mentioning were as follows:
Between the 1^st and 2^nd episodes of the disease, there was an asymptomatic period of 4 years. However, a comparison of both the MRIs showed significant progression in the involvement of B/L cerebral white matter. We may conclude that there was an ongoing process of subclinical demyelination during these years.
 Initial disease morphology was classically that of MS, but later follow up MRI started showing features of MOGAD
 The periventricular white matter had more extensive involvement in parietal lobes compared to frontal or temporal lobes.
 Most relapses had predominant ipsilateral and unilateral (left-sided) neuromotor deficits.
 Our case mostly did not show a strong correlation between clinical deficits and imaging findings.
 Imaging findings did not show changes in the optic nerve when clinically optic neuritis was present.

It is extremely important to identify MOGAD apart from MS as there is a difference in the management of the two disease entities. Chronic immune suppression may be recommended for patients with a relapsing disease or who develop steroid dependence, especially if there is incomplete recovery. Commonly used chronic immunosuppressive agents include mycophenolate mofetil, azathioprine, rituximab, and monthly IVIG. Most multiple sclerosis disease-modifying agents are not effective in preventing attacks of MOGAD [13].

Based on our experience with this case and its continuous followup, we would like to recommend pediatric-onset demyelinating disorder for MOG-IgG testing as imaging findings alone can mimic MS.