Acute disseminated encephalomyelitis following varicella‐zoster virus infection: Case report of effective treated both in clinical symptom and neuroimaging

Abstract Introduction Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disorder of the central nervous system (CNS). Early treatment is the key for neurological recovery. Methods A case of ADEM associated with varicella‐zoster virus infection was presented, in which magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) examinations were included. Results Magnetic resonance imaging of the brain revealed multiple hyperintense lesions at the subcortical level on fluid‐attenuated inversion recovery (FLAIR), and MRI of the spinal cord revealed longitudinally segmented hyperintense lesions at the spinal cord on T2‐weighted images. The patient was treated with methylprednisolone and gancyclovir, and had a favorable recovery. Subsequent MRI of the brain and cervical cord showed the previous abnormal hyperintensities had markedly disappeared. Conclusion A rare case of ADEM with longitudinal segmented hyperintense lesions at the spinal cord on T2‐weighted images was presented. Excellent response to ADEM treatment with high‐dose steroids was reported resulting in a remarkable neurological recovery. A long‐term follow‐up is needed for prognosis.

patients make a full recovery, whereas a few patients remained neurologically impaired.

| C A S E REP ORT
A 13-year-old girl was brought to our hospital with complaints of numbness and weakness of the limbs and urinary retention for 3 days. Eighteen days after the disappearance of measles rashes due to a varicella-zoster virus infection, the patient felt numbness of limbs, face, and tongue. Gradually, lower limb weakness progressed to both upper limbs. At the same time, she presented with urinary retention. No history of previous virus infection was reported. At early ages, she received routine vaccinations, including poliomyelitis, chickenpox, hepatitis B, and pertussis and no allergies were recorded after vaccinations. Neurological examinations revealed no obvious abnormalities in cortical function. Muscle strength of both upper extremities was grade 4, and grade 2 of both lower extremities. Bilateral tendon reflex was symmetrically brisk. Pinprick sensation was weak below the neck, and vibration sensation was weak below the anterior superior spine. There was dysmetria on fingerto-nose tests on both sides of the body. The Hoffmann reflex and Babinski sign were positive on both sides of the body. There were no signs of meningeal irritation. She underwent an MRI of the brain and the spinal cord on the first hospital day (HD) and HD #2 that revealed multiple hyperintense lesions at the subcortical level on FLAIR ( Figure 1) and longitudinally segment hyperintense lesions at the spinal cord on T2-weighted images (Figures 2 and 3). She also underwent a lumbar puncture on HD #1 that revealed pressure was more than 300 mmH 2 O, with cerebrospinal fluid (CSF) containing 200 × 10 6 /L white blood cells of which 95% were mononuclear cells, glucose levels of 2.4 mmol/L, and protein levels of 869.1 mg/L. CMV-IgG antibody and HSV-IgG antibody were found positive in serum.
Three days of 1,000 mg (patient weight: 80 kg) of intravenous methylprednisolone pulse therapy was given and the dose decreased by half afterward. She was also treated with gancyclovir for a total of 3 weeks.
After treatment with high-dose steroids for 6 days, her muscle strength of both upper extremities was grade 4+, and grade 3 of both lower extremities. A lumbar puncture was repeated on HD #7, in which were negative. Gradually, her sensorium became better, and she was independent in her activities, except urinary retention. No apparent changes in lesions were found in MRIs of the brain and cervical cord on HD #17 and HD #20 (see Figure 4). After continued steroid treatment, we removed her urethral catheter safely on HD #21. She was subsequently discharged on HD #22 on a prolonged oral steroid tapering for 4 weeks. Further improvements and full strength of the limbs were found after 3 months of outpatient follow-up.

| D ISCUSS I ON
Acute disseminated encephalomyelitis is an acute, sometimes subacute, multifocal, immune-mediated, monophasic inflammatory disease of the central nervous system (CNS; Wender, 2011). Molecular mimicry associated with infectious agents or direct inflammatory damage to myelinated neurons is a possible mechanism (Marin & Callen, 2013).
The brain and spinal cord may appear normal or be congestion with swelling; however, the disease manifests microscopically including perivenous sleeves of demyelination with mild perivascular inflammation. Clinical presentation is characterized by acute encephalopathy, seizures, multifocal neurologic abnormalities, and meningeal signs.
In this report, we presented a case of ADEM in which the patient had acute transverse myelitis according to neuroimaging. Overall in ADEM cases, spinal cord involvement is relatively common and has been described in 11%-28% of children (Tenembaum, Chamoles, & Fejerman, 2002). In a cohort of 176 adults, spinal cord involvement was reported in 83% of patients (Marchioni et al., 2013). It is unclear whether cases only involved the spinal cord can diagnosed as an ADEM variant.
Magnetic resonance imaging of the brain is critical for the differential diagnosis of ADEM. The most common MRI finding is multifocal lesions predominantly involving white matter. Abnormalities are more readily visible on FLAIR images than T1-and T2-weighted images. Studies reported that sagittal scans rarely revealed extended longitudinal lesion beyond one spinal segment (Tillema & Pirko, 2013). A contiguous lesion over three vertebral segments was considered a longitudinally extensive transverse myelitis (Pandit, 2009) in neuromyelitis optica. Relapse of longitudinal lesions was reported to be high (Weinshenker et al., 2006) and for lesions that extend to seven segments were poor (Carnero Contentti et al., 2017). ADEM typically involves the thalamus and/or basal ganglia, but not in multiple sclerosis (MS) that it can be used as a differential diagnosis (Dale et al., 2000). Supratentorial lesions in ADEM tend to be asymmetrical, whereas symmetrical lesions were found in the thalamus and basal ganglia (Tenembaum et al., 2002). A recent study found that, in adults, lesions in the putamen were associated with ADEM whereas neuromyelitis optica (NMO) lesions were commonly found in the hypothalamus (Zhang et al., 2014). ADEM lesions in the brainstem were often bilateral and symmetrical (Lu et al., 2011).
We observed inflammation with pleocytosis and/or elevated protein in CSF in the ADEM patient. It is necessary to exclude acute CNS infection. OCBs in the CSF can also be found, but this is less common than in patients with MS. Children account for 64%-95% of MS patients, but only 0%-29% of ADEM patients (Dale et al., 2000). Several studies have identified AQP4 antibodies in a subset of ADEM patients (Okumura et al., 2015). The presence of CMV and HSV-IgG antibodies in the serum suggested the potential contribu- There are two recurrent forms of ADEM. Multiphasic ADEM is a recurrent form that involves new brain sites not previously affected, whereas recurrent ADEM has a tendency to involve the previously affected brain region (Cohen et al., 2001). When multiphasic ADEM is diagnosed, a differential diagnosis of MS needs to be considered.  (Lattanzi et al., 2015;Rio et al., 2014). A long-term follow-up is warranted.

| CON CLUS IONS
Acute disseminated encephalomyelitis rarely presents longitudinally with segmented hyperintense lesions at the spinal cord on T2-weighted images. With limited case reports, the prognosis is unknown. Excellent response to ADEM treatment with high-dose steroids was reported resulting in a remarkable neurological recovery. A long-term follow-up is needed for prognosis.

CO N FLI C T O F I NTE R E S T
The authors declare that they have no conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
All data from this study are included in the article.