Recurrent acute disseminated encephalomyelitis: A favorable outcome among recurrent brain diseases in pediatric patient.

Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disease of the central nervous system (CNS) and considered mostly a monophasic course. Recurrence of ADEM is rare entity, posing diagnostic dilemma with multiple sclerosis (MS). There were no definite diagnostic criteria or established treatment for ADEM. International Pediatric MS Study Group laid down first consensus definition. We report a boy presented with recurrent episodes of fever, paraparesis, seizure, and unconsciousness. Magnetic resonance imaging (MRI) brain revealed the recurrence of lesions in the same brain site of the previous event. The first and second events were at age of three and five, respectively, with no neurological deficit, clinically and MRI, in between period of 24 months. We found that he responded dramatically both episodes with intravenous immunoglobulin treatment and no CNS deficit was found on 3-year prospective evaluation to exclude MS. We diagnosed recurrent ADEM.

Introduction

Acute disseminated encephalomyelitis (ADEM) is a mostly monophasic course.[12] The incidence of the second episode is occurred in 10–18%[34] cases.

Recurrent ADEM (RADEM) is defined (International Pediatric MS Study Group)[4] as occurrence of new episode with a recurrence of the first symptoms and signs, 3 or more months after the first ADEM event and after at least 1 month completing therapy, without new central nervous system (CNS) lesion (clinical or neuroimaging). RADEM is rare,[5] two children are reported in the literature.[67]

There is no established controlled trial treatment or guidelines for ADEM.[89] On the basis of anecdotal data, methylprednisolone is common therapy for ADEM.[10]

Case Report

A 3-year-old boy, third child of nonconsanguineous marriage, was presented in 2009 with fever, sudden onset paraparesis, aphasia, generalized tonic–clonic convulsion, and became unconscious-evolved over 3 days. He had unremarkable family history, no developmental delay, no recent immunization, or illness. On examination, Glasgow coma score - 7/15, head circumference-for-age: >50th percentile, right lower motor facial nerve palsy, brisk deep tendon reflexes, bilateral extensor planter reflex and no meningeal signs, involvement of bowel/bladder, and sensory deficit. Systemic examinations were normal. Blood picture and biochemical investigations were within normal limits, cerebrospinal fluid (CSF) study within normal range: Sugar 82 mg/dl, protein 15 mg/dl, cell count 8/cmm (99% lymphocytes), negative for Gram-stain or Ziehl–Neelsen stain, and no growth in culture.

Magnetic resonance imaging (MRI) brain showed focal hyperintense lesions (fluid attenuated inversion recovery and T2) in subcortical white matter of both cerebral hemispheres, both basal ganglia, pons, medulla [Figure 1-MRI 2009], middle cerebellar peduncles, and no abnormal parenchymal or meningeal enhancement in a gadolinium-based MRI contrast study. Thalamus and corpus callosum showed normal signal characteristics. He put on intravenous immunoglobulin (IVIG) for 5 days then oral prednisolone (P) for 6 weeks and recovered within 7 days. After 3 months, MRI brain was normal.

Figure 1

Magnetic resonance imaging brain showing focal hyperintense lesion (T2) in paraventricular and subcortical white matter indicating demyelination of brain in the first episode

After 2 years, in 2011, 5-year-old boy admitted with same complaints as previous episode and examination revealed similar findings. CSF study normal limits with no oligoclonal bands. MRI brain showed focal hyperintense, demyelinating lesions [Figure 2-MRI 2011], in same brain territory as in the previous episode [Figure 3-MRI; arrow showing affection of similar areas of brain]. Immunological markers: Antinuclear antibody, antineutrophil cytoplasmic antibody, anticardiolipin antibody, lupus anticoagulant, polymerase chain reaction (PCR) for Herpes simplex virus nucleic acid, and Japanese B antibodies (serum, CSF) were negative. Serum lactate, electroencephalography, and nerve conduction study were normal. His treatment was IVIG for 5 days, oral P for 6 weeks, improved within 3 days. After follow-up for 3 years, clinically/MRI brain was normal.

Figure 2

Magnetic resonance imaging brain showing focal hyperintense lesion (T2) in the second episode indicates demyelination of brain

Figure 3

Magnetic resonance imaging brain arrow showing similar size and number of lesions in the same sites of the brain

Discussion

The index case presented with recurrent acute neurological deficit with lesions in bilateral basal ganglia region. The differential diagnosis of recurrent CNS diseases is considered [Table 1].

Table 1

The differential diagnosis of recurrent central nervous system diseases

Of those, systemic disease with CNS involvement collagen vascular diseases, recurrent encephalitis, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes is excluded by the absence of clinical features of systemic diseases or immunological markers, viral PCR of CSF, serology for viral antibody, no family history, and normal serum lactate level, respectively.

Multiple sclerosis (MS) and ADEM, the two major CNS inflammatory demyelinating diseases of children, are difficult to differentiate in the initial episode. MS is a continuous demyelinating disease with characteristically relapsing–remitting course. Furthermore, relapsing cohort may be a part of spectrum of MS.[4]

Although recurrence is characteristic of MS, but a second ADEM is described. Furthermore, there is no definite guidelines to differentiate MS and ADEM.[4] Encephalopathy, seizure, absent oligoclonal band in CSF, and[2] bilateral basal ganglia MRI lesions are suggestive of ADEM.[4] In addition, the unique feature of the index case is stereotyped reappearance of initial symptoms and affected same brain site in MRI as in initial event and complete cliniconeuroradiological recovery in between 24 months-clinch to the diagnosis RADEM. Multiphasic ADEM excluded as no new CNS lesion, clinical, or neuroradiological.

Of previous studies, there are two children with RADEM have been reported.[67] Cohen et al.[5] authored a case series of five adult's, designated as the largest one.[7] There was a report[6] of longest intervals of 12 years with three episodes of RADEM. However, more than two ADEM should be suspicious for MS.[4] Neuropsychiatric symptoms are common in adult,[5] not found in this case during recurrence similar to previously reported case in a child.[7]

Authors hypothesized[58] recurrences occur because there is continuing of subclinical inflammatory demyelination in affected sites.

Early treatment is the most determining outcome factor[9] and MP can have an uncertain role after early course of ADEM.[10] Therefore, we treated with IVIG. Sometimes, IVIG is an option for MP nonresponder.[8] However; MP was given in previously reported RADEM.[5] All RADEM responded well with treatment.[567] Follow-up should have done to distinguish it from MS.[4]

The MRI lesions may have enlarged in recurrence,[4] but our patient showed comparatively smaller MRI lesion than earlier. That MRI was taken 36 h after treatment initiation. Therapy was started on clinical diagnosis; as ADEM was diagnosed in the previous study based on clinical scenario.[9]

Conclusion

RADEM can be diagnosed clinically, initiated treatment at earliest because it is most important for outcome. We do emphasis IVIG treatment for RADEM and do follow-up to exclude MS.

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Conflicts of interest

There are no conflicts of interest.