Research Case Report/Case Series Transverse Myelitis Plus Syndrome and Acute Disseminated Encephalomyelitis Plus Syndrome A Case Series of 5 Children Allen DeSena, MD, MPH; Donna Graves, MD; Michael C. Morriss, MD; Benjamin M. Greenberg, MD, MHS IMPORTANCE Classically, transverse myelitis and acute disseminated encephalomyelitis are considered central nervous system demyelinating conditions. In both conditions, the spinal cord is involved to varying degrees, and there is a variety of presentations, usually involving some degree of progressive paralysis of the upper and/or lower extremities. Treatment usually consists of high-dose intravenous steroids in addition to plasma exchange and/or intravenous immunoglobulin. In some cases, immunosuppressive medications, such as intravenous cyclophosphamide, have been used with variable success. Cases with atypical features on examination, imaging, or with neurophysiological studies may be helpful in shedding light on the etiology and/or pathophysiology because many of these patients have permanent disabilities despite appropriate treatment. OBSERVATIONS This case series presents 5 pediatric cases observed from 2009-2012 at our medical center, Children’s Medical Center Dallas. These cases were notable because they provided evidence of autoimmune events affecting the central nervous system but with Author Affiliations: Children’s additional peripheral axonal pathology. Medical Center Dallas, Dallas, Texas (Morriss); Department of Neurology and Neurotherapeutics, University of CONCLUSIONS AND RELEVANCE We describe these cases with respect to findings that suggest Texas Southwestern, Dallas (DeSena, a variant of these conditions that have concomitant nerve-root involvement. These patients Graves, Greenberg); Department of had worse outcomes than typical patients with transverse myelitis/acute disseminated Pediatrics, University of Texas encephalomyelitis, and these observations build on previous work by other investigators that Southwestern, Dallas (DeSena, Graves, Greenberg); Department of highlighted persistent flaccid paralysis and electrophysiological evidence of axonal loss Radiology, University of Texas portending a poorer prognosis. Furthermore, these cases suggest a potential role for Southwestern, Dallas (Morriss). approaching how we classify subtypes of transverse myelitis and acute disseminated Corresponding Author: Benjamin M. encephalomyelitis. Greenberg, MD, MHS, Department of Neurology and Neurotherapeutics, University of Texas Southwestern, JAMA Neurol. 2014;71(5):624-629. doi:10.1001/jamaneurol.2013.5323 5323 Harry Hines Blvd, Dallas, TX Published online March 17, 2014. 75390-8806 (benjamin.greenberg @utsouthwestern.edu). ransverse myelitis (TM) and acute disseminated encephalomyelitis (ADEM) are infrequent causes of Report of Cases T acute paralysis in children, affecting both the upper and lower extremities and, in severe cases, resulting in blad- Children’s Medical Center Dallas institutional review board ap- der and bowel dysfunction. Early recognition is crucial proval was obtained, allowing for retrospective medical rec- because prompt aggressive treatment may reduce the ord review; patient consent was waived. extent of the sequelae of the disease. Despite early aggres- sive treatment, a percentage of children will go on to have Case 1 disabilities resulting in permanent functional impairment.1 A 13-year-old girl presented in late September 2009 with an as- At our center, we identified a subset of children who were cending paralysis over the course of 48 hours. On initial pre- initially identified as having TM, TM with brainstem exten- sentation, she was noted to have severe flaccid weakness in sion, or ADEM based on examination and imaging, but both of her lower extremities, with her left lower extremity af- follow-up magnetic resonance imaging (MRI) was found to fected more than her right lower extremity. Her reflexes were have either proximal ventral nerve-root enhancement or absent at her patellars and ankles bilaterally, and she had a diffuse cauda equina enhancement. These patients may downgoing plantar response bilaterally. She had a sensory level represent a novel subset of TM and ADEM or an entirely dis- on the right at the T10 dermatome. Sensation was impaired to tinct entity. pin, temperature, and light touch, although it was normal in 624 JAMA Neurology May 2014 Volume 71, Number 5 jamaneurology.com Copyright 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Transverse Myelitis and ADEM Case Report/Case Series Research Figure 1. Magnetic Resonance Imaging for Case 1 A B C D A, The patient presented with multifocal areas of increased T2 signal in the distal spinal cord on magnetic resonance imaging consistent with acute disseminated encephalomyelitis (arrowhead). B, At initial presentation, there was no abnormal enhancement in the roots of the cauda equina. On follow-up imaging 2 weeks later, the patient had developed intense contrast enhancement in the ventral roots of the cauda equina in a typical pattern for Guillain-Barré syndrome (C and D, arrowheads). her lower extremities distally to vibration and propriocep- chronic denervation and reinervation in all L4-L5 muscles of tion. She had an MRI of her spinal cord that showed intramed- the left leg and absent motor units in her left tibialis anterior. ullary increased T2 signal from T11 to L2, predominantly af- Although initially nonambulatory, she was able to improve sub- fecting the gray and white matter of the anterior spinal cord stantially with near-normal strength in her right lower extrem- bilaterally, without contrast enhancement on postcontrast T1- ity (at least 4/5 in all muscle groups) and more severe weak- weighted images. She had a white blood cell (WBC) count of 0 ness in her left hip flexors (4−/5) and left dorsiflexors (2/5). She μL and red blood cell (RBC) count of 0 μL in her cerebrospinal currently is able to ambulate with unilateral support for short fluid (CSF) and normal CSF glucose and protein levels. The and moderate distances, and her urinary retention present on workup findings were negative for enterovirus, herpes sim- initial admission has resolved (Figure 1). plex virus (HSV), Epstein-Barr virus (EBV), fungal and acid- fast bacilli infections, syphilis, neurosarcoidosis, and neuro- Case 2 myelitis optica. The IgG synthesis rate and index were normal. A 14-year-old boy presented in June 2009 with a rapidly pro- Despite not meeting typical criteria for idiopathic TM, the pa- gressive flaccid paralysis and burning pain involving both lower tient received 5 days of high-dose steroids, with no clear re- extremities over approximately 72 hours along with severe uri- sponse, followed by 5 rounds of plasma exchange, with some nary retention. He was presumptively treated with intrave- improvement. Approximately 2 weeks after her initial presen- nous immunoglobulin (IVIG) owing to initial concern for Guil- tation, a repeat MRI of the spinal cord was performed, and the lain-Barré syndrome. After failure to improve, he was patient was noted to have developed diffuse contrast enhance- transferred to our facility and was noted to have weakness in ment of ventral nerve roots. A nerve conduction study (NCS)/ all muscle groups in his lower extremities, rated as a 2/5 in large electromyogram (EMG) was not obtained acutely, although muscle groups in both legs, and absent reflexes in his patel- NCS/EMG obtained approximately 8 months later showed se- lars and ankles bilaterally. On initial assessment, he said he had verely decreased amplitudes in the left peroneal motor re- pain in his lower extremities, with some decrease to pain and sponses with a normal distal latency and conduction veloc- light touch noted only in his feet bilaterally. His spinal cord was ity. And she had EMG findings consistent with active and imaged by MRI, revealing increased intramedullary T2 signal jamaneurology.com JAMA Neurology May 2014 Volume 71, Number 5 625 Copyright 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Research Case Report/Case Series Transverse Myelitis and ADEM within the anterior spinal cord from T11 to the conus medul- ralysis of his lower extremities progressing to weakness in his laris and diffuse enhancement of his ventral nerve roots on con- upper extremities, dysarthria, and dysphagia. He had marked trast-enhanced T1-weighted images. An NCS/EMG revealed find- weakness in his lower extremity hip flexors, hamstrings, and ings consistent with an acute motor axonal neuropathy. A repeat dorsiflexors (1/5) bilaterally and mild weakness in his upper ex- of this study approximately 12 months later again showed de- tremities (ranging from a 4−4+/5, depending on the muscle creased amplitudes, consistent with an axonal neuropathy, in group). Reflexes were intact in his upper extremities, being 2+/4 bilateral tibial and peroneal nerves, which was worse on his right bilaterally and were symmetric, and he had absent ankle re- side. Analysis of the CSF showed a WBC count of 8/μL, RBC flexes bilaterally and an absent right patellar reflex, although count of 0/μL, an elevated CSF protein level to 148 mg/dL, and his left was 2+/4. He had no noted sensory level, and his sen- a normal CSF glucose level. The workup results were negative sation to pain, temperature, vibration, and proprioception was for EBV, varicella zoster (VZV), HSV, West Nile (WN) virus, cy- normal in his upper and