Neurol India Home 

Year : 2019  |  Volume : 67  |  Issue : 1  |  Page : 284--286

Gray variant of acute disseminated encephalomyelitis and its response to immunomodulatory drugs

Sunil Pradhan, Animesh Das 
 Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Correspondence Address:
Dr. Sunil Pradhan
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh

How to cite this article:
Pradhan S, Das A. Gray variant of acute disseminated encephalomyelitis and its response to immunomodulatory drugs.Neurol India 2019;67:284-286

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Pradhan S, Das A. Gray variant of acute disseminated encephalomyelitis and its response to immunomodulatory drugs. Neurol India [serial online] 2019 [cited 2019 Jun 26 ];67:284-286
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Acute disseminated encephalomyelitis (ADEM) is a demyelinating disorder of the central nervous system (CNS). Although predominantly described as a white matter disease, reports of deep gray matter involvement have been reported in the literature. Here, we present a series of two cases with predominant gray matter involvement.

Case 1

A 20-year-old student presented with on and off fever for 2 months. He had status epilepticus on day 20th of the fever, resulting in altered sensorium for 5 days. He was managed symptomatically with antiepileptics and steroids at that time. Magnetic resonance imaging (MRI) of the brain brought at the time of presentation to our hospital showed multiple T2 and fluid-attenuated inversion recovery (FLAIR) hyperintensities in the brain stem, bilateral temporal lobes, globus pallidi interna, and cerebellar vermis. MRI of the spine showed evidence of long-segment myelitis from the cervical cord to conus [Figure 1]. On examination, he was having spastic paraparesis as the sequelae of previous myelitis. Considering the etiological diagnosis of long-segment myelitis and a bizarre MRI involvement of the brain, a parainfectious demyelinating pathology was kept as the first possibility. Cerebrospinal fluid (CSF) analysis revealed increased protein level only, whereas the neurotrophic virus panel done from CSF was negative. Work-up for tuberculosis and HIV was also negative. The vasculitis profile and neuromyelitis optica antibody level were also inconclusive. He was followed up with a repeat MRI of the brain and tapering doses of steroids. After 3 months, MRI brain showed near complete resolution of the lesions [Figure 2]. The patient had only urinary complaints of difficulty in initiation with a poor stream, and a mild spasticity at follow-up.{Figure 1}{Figure 2}

Case 2

A 23-year old male patient was admitted with acute onset paraparesis, girdle like sensation at the subcostal level and incontinence after 2 days of a febrile episode. On day 4 of the illness, he developed slurring of speech and alteration of sensorium which progressed over the next 2 days. He was in deep coma from day 6 of hospital stay. MRI brain was suggestive of multiple T2/FLAIR hyperintensities in the bilateral medial temporal (left > right), thalamic, and hypothalamic regions, whereas MRI of the spinal cord showed long-segment demyelinating lesions in the lower cervical and upper dorsal region [Figure 3]. He was initially treated with intravenous steroids. He did not have any improvement of power in lower limbs even after 2 months of completion of tapering steroid therapy of 6 weeks. Thereafter, he was treated with intravenous immunoglobulin (IVIG) therapy initially at a dose of 2 g/kg followed by two more courses of 1g/kg at an interval of 2 months. He improved dramatically, and during the follow-up visit after 3 months of the second course, he could walk unsupported, albeit with bilateral foot drop, which was attributable to ankle contracture that had developed during the bedridden state for 4 months. Serial MRI of the brain and spine showed gradual resolution of the T2 lesions, and the final MRI after the third course of IVIG showed a total clearance of the lesions [Figure 4]. In this case also, similar to the first case, all the investigations for etiological diagnosis in the form of vasculitic profile, pan neurotrophic virus panel, neuromyelitis optica (NMO) antibody, and human immunodeficiency virus status were negative.{Figure 3}{Figure 4}

The clinical manifestations of ADEM depend on the site of involvement of the CNS by the inflammatory process. Rapid onset of altered sensorium, seizure, visual field defect, aphasia, ataxia and pyschiatric abnormalities are known to occur.[1],[2],[3],[4],[5] Basal ganglia involvement resulting in movement disorders is common among children. These groups of disorders have specific antibodies against basal ganglia.[6] Recovery is also rapid, occurring either spontaneously or following supportive treatment.

Classical MRI findings of ADEM include multifocal lesions in the subcortical white matter, brain stem, middle cerebellar peduncle, corpus callosum, and periventricular white matter.[7],[8],[9] Basal ganglia involvement has been shown in upto 61% patients in a study.[3] In fact, only thalamic and basal ganglia lesions without the involvement of corpus callosum favors ADEM over other demyelinating disorders such as multiple sclerosis.[10] Spinal cord involvement is also not very uncommon.[11] A review of the literature [Table 1] showed variable involvement of the gray matter in ADEM.{Table 1}

Recently, a pattern of disseminated gray matter involvement with additional basal ganglia lesions termed as “cortical grey variant” has been described in the literature in pediatric population.[12] Theoretically, being a perivascular disease, ADEM lesions should involve both gray and white matter as blood vessels are present everywhere in the brain. However, somehow only white matter lesions have been highlighted till now. Both our cases had extensive gray matter involvement along with the spinal cord, without much subcortical white matter involvement. The possibility of nonspecific disseminated encephalitis can be kept in such cases; however, the spinal cord involvement along with response to steroids and IVIG in our cases along with the disappearance of lesions in the follow-up MRI favors a diagnosis of ADEM.

Regarding treatment, there are no controlled trials that have addressed the issue of what should be the first line treatment in an ADEM patient with varying degrees of gray matter involvement as these cases are not common in the adult population. Conventional first line approach is to treat the patients of ADEM with high-dose intravenous steroids, although patients of ADEM may recover spontaneously and completely even without any treatment. In patients not responding to steroids, the equation becomes more complicated. Various case series and randomized controlled crossover trials have shown the effectiveness of plasmapheresis. The dilemma persists regarding the number of plasmapheresis cycles needed for a case of steroid-resistant ADEM. The technical difficulties associated with plasmapheresis also hinder its use as a regular treatment for ADEM. IVIG has been shown to be beneficial in patients who fail to improve after steroids. The second patient was treated by IVIG and recovered to a significant extent, reinforcing the role of IVIG as a second line treatment in cases suffering from steroid-resistant ADEM.

These cases highlight the not so well-known “gray variant” of ADEM in the adult population and reiterates the effectiveness of IVIG in treating steroid-resistant chronic ADEM.

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Conflicts of interest

There are no conflicts of interest.


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