073&725X/86 S3.00 + .I0 Copyright b 1986 Pergsmon Press Lid Magnric Resonance Imagfng. Vol. 4. pp. 25-32.1986 Printed in the USA. All rights rservcd. ?? MRI in Pediatrics MRI IN CHILDREN WITH POSTINFECTIOUS DISSEMINATED ENCEPHALOMYELITIS VAL DUNN,* JAMES F. BALE,JR.,?ROBERT A. ZIMMERMAN,* ZACK PERDUES AND WILLIAM E. BELL? *Department of Radiology, American Fork Hospital, 170 North 1100 East, American Fork, Utah 84003, TPediatric Neurology Division, SDepartment of Neurology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, *Neuroradiology Section, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania 19 104. Acute disseminated encephalomyelitis,an inflammatory and demyelinating disorder of central nervous system white matter, typically occurs following childhood viral infections. Although CT may demonstrate abnormalities, many children have normal CT studies in spite of widespread neurologicabnormalities. We report a series of five patients with the typical clinical presentation of disseminated encephalomyelitis who were studied using magnetic resonance imaging (MRI). Ineach case the children presented with progressive subacute neurologic abnormalities including headache, diplopia, ataxia, hemiparesis, seizures, dysarthria, and/or coma. CT was nondiagnostic. MRI clearly demonstrated multifocal white matter lesions of the cerebnun, brainstem, and cerebellum which corresponded to progressiveresolutionof clinical signs. The patients improveddramatically with corticosteroidtherapy. MRIshowed multifocal lesions in conj~ction with clinical improvement. Keywortis: myelitis. MRI,Encephalomyelitis, Encephalitis, Postinfectious encephalomyelitis,Acute diinated encephah+ elitis was made infrequently because the constellation of symptoms and signs resembles viral encephalitis, toxic encephalopathy, or acute MS.‘v3 A clear latent period helps differentiate this entity from viral encephalitis. Fever and meningism in children are rare in MS. Pathologically, acute-disseminated encephalomyelitis is characterized by mononuclear cell infiltration and demyelination around small veins. Multifocal areas of perivascular demyelination may coalesce to form larger lesions, but do not resemble multiple sclerosis plaques. Disseminated encephalomyelitis usually occurs in young children, but similar parainfectious syndromes such as acute hemorrhagic encephalitis have been reported in adults. Some authors feel that hemorrhagic encephalitis is a more severe form of disseminated encephalomyelitis. In children, the neurologic symptoms typically begin 1-3 weeks after a viral illness or vaccination. Numerous infectious agents, including influenza virus, Epstein-Barr virus, and the viruses responsible for childhood examthems have been associated but in many cases no specific cause can be identified. Common neurologic features include sei- Magnetic resonance imaging (MRI) has demonstrated significantly greater sensitivity than x-ray computed tomography (CT) in detecting a wide variety of brain pathology.2 In particular, the multifocal demyelinating white matter lesions of multiple sclerosis (MS) are often well demonstrated by MRI when CT is negative.’ We have observed a similar increased sensitivity of MRI over CT in a childhood disorder with multiple foci of demyelination, postinfectious disseminated encephalomyelitis. MRI has been of significant clinical benefit in the diagnosis and management of this condition. Disseminated encephalomyelitis is a childhood disorder characterized by neurologic abnormalities and lesions of the central nervous system white matter. The disease is not rare, being said to constitute one-third of all encephalidites reported in the United States.’ Because most cases follow childhood viral infections or vaccination, the disorder is felt to be immunologically mediated. The terms postencephalitis demyelination and postinfectious multifocal leucoencephalopathy probably refer to the same entity. In the past, the antemortem diagnosis of disseminated encephalomyRECEIVED 7122185; ACCEPTED 7/30/85. 25 26 Magnetic Resonance Imaging 0 Volume 4, Number 1, 1986 zures, coma, papilledema, ataxia, and motor deficits. The CSF is often normal, but elevated pressure may be noted. CSF leucocytosis may be present, most commonly with lymphocytosis, but leucocytosis may occur in early stages. The EEG usually shows slowing in delta and theta frequencies. In the past, this disorder was often progressive with permanent defecits and even death. The prognosis is variable and spontaneous resolution often occurs. More recently, studies indicate that with appropriate diagnosis and therapy it is a disease that can be effectively treated.5 Most children respond to corticosteroid therapy and do not have residual neurologic deficits. Several recent reports have demonstrated that CT may show brain stem swelling, cortical enhancement, or hypodense lesions of white matter which correspond to areas of edema or demyelination. However, CT was not clinically helpful in most cases.3-5 In a large percentage, CT was negative. In others there was only a limited correlation between clinical signs and the location of CT abnormalities demonstrated. In many cases CT is normal despite significant neurologic deficits. CASE MATERIAL AtiD METHODS clinical features of disseminated encephalomyelitis were recently examined by MRI at the University of Iowa Hospitals and Clinics Five cases with typical (Cases 1, 2, and 4), Vanderbilt University (Case 3), and the University of Pennsylvania (Case 5). The criteria for inclusion in the series include (1) a clinical diagnosis consistent with disseminated encephalomyelitis, (2) MRI showing multifocal white matter lesions and (3) response to steroid therapy. Imaging was performed on a Picker .5 T Vista MR in Cases 1, 2, and 4. Case 3 was performed on a .5 T superconducting Technicare system and Case 5 on a 1.5 T General Electric system. CT was performed in each case prior to MRI during the acute presentation of symptoms. A more detailed discussion of Cases l-3 is reported elsewhere.6 Case 1 A 7-year-old girl presented with diplopia and pharyngitis. Heat CT was normal. Two weeks later she developed anorexia, malaise, increasing headache, unsteady gate, and slurred speech. CT was again normal. She was transferred to the University of Iowa on 5/5/84 and found to have papilledema, ataxia, and hyperreflexia. Multiple blood and CSF cultures were negative. After a brief improvement she was readmitted on 5/19/84. She was unable to walk without assistance, had a mild left hemiparesis and impairment of position sense of the left side. CT on 5/18/84 demonstrated a subtle region of hypodensity in the region of the right internal capsule and apparent narrowing of the frontal horn of the right lateral Fig. 1. Transverse T*-weighted spin-echo images (TE/TR = 80/2300) demonstrate multiple ill-defined lesions of increased signal intensity in both cerebral and cerebellar white matter. Areas of involvement include bilateral middle cerebellar peduncles (left), the right internal capsule (center), and the gray-white interface adjacent to the cerebral cortex (right). MRI in postinfectious disseminated encephalomyelitis 0 VAL DUNN ETAL. 21 Fig. 2. Transverse MRI demonstrates multifocal lesions in the midbrain and anterior, superior right cerebellum (left), the right thalamus (center), and bilateral cerebral white matter (arrows). ventricle. On 5/24/84 MRI was performed and demonstrated multiple bilateral white matter lesions of the cerebrum and cerebellum (Fig. 1). The most prominent regions of abnormality were near the right internal capsule and cerebellar peduncles. Intravenous methylprednisolone therapy was instituted with dramatic improvement. Neurologic examination on 6/17/84 showed nearly complete resolution of neurologic deficits with persistance of mild intension tremor of the left upper extremity. Subsequent MRI studies demonstrated resolution of the multifocal lesions. Fig. 3. Parasagittal spin-echo image demonstrates multiple white matter abnormalities, including involvement of the corpus collosum, midbrain, cerebellum, and region of the internal capsule (TE/TR = 120/1000). Case 2 A 5-year-old girl experienced an episode of difficulty using her right hand and foot with eye deviation and facial twitching. After a second similar episode she had residual right hemiparisis and aphasia. CT and electroencephlogram (EEG) were within normal limits. She was treated with anticonvulsants. Two weeks later she developed double vision and was found to have bilateral papilledema and acuity of 20/200 in the left eye. CT, EEG, and spinal fluid studies were normal. After a week of prednisone therapy her vision was 20/30 bilaterally and papilledema had resolved. She did well for about 1 year until November, 1985 when ataxia, left hemiparesis, and urinary retention developed. CT was interpreted as negative and laboratory examinations were unrevealing. MRI demonstrated multiple white matter lesions of the brainstem, cerebrum, and cerebellum (Fig. 2). Based on MRI findings, acute disseminated encephalomyelitis was suspected and therapy with hydrocortisone initiated. Within three days her left hemiparesis had resolved and ataxia had significantly decreased. She was treated with oral prednisone for 3 months with complete resolution of her neurologic abnormalities. Repeat MRI demonstrated significant decrease in the size and number of abnormal areas. Case 3 A 5-year-old boy was admitted 7/17/84 because of headache and visual loss. He had received a DPT immunization 17 days earlier. Examination revealed bilateral optic neuritis and unenhanced CT was normal. During hospitalization he developed fever and an Fig. 4. Case 4 transverse T2- and T,-weighted images show lesions in the left midbrain and ports (arrows). Spin-echo images (TE/TR = 80/2300) show focal areas of increased signal intensity in the left cerebral peduncle (left) and the left middle cerebellar peduncle (center). Inversion recovery image shows the same lesion in the left cerebellar peduncle adjacent to the fourth ventricle as a region of decreased signal intensity (TI/TR = 60/2100). Fig. 5. Case 4 followup. The two lesions described in Fig. 4 have resolved following steroid therapy. Clinical signs and symptoms also resolved. Cerebral and cerebellar peduncles appear normal (TE/TR = 80/2300 left and center; TI/ TR = 600/2300 right). MRI in postinfectious disseminated encephalomyelitis 0 VAL DUNN ET AL. elevated white count and sedimentation rate. Multiple cultures for bacterial, fungal, and viral pathogens were negative. He improved gradually without treatment and was discharged. In September, 1984 he again developed headache and visual loss. Examination demonstrated optic atrophy, tremulousness, ataxia, and hyperreflexia of the lower extremities. MRI revealed multiple lesions involving the corpus callosum, cerebellum, brainstem, and area of the internal capsule (Fig. 3). He was treated with prednisone and subsequently improved. 29 with slight contrast enhancement [Fig. 6(B)]. MRl demonstrated abnormal areas in the white matter of the right parietal, right frontal, and both temporal lobes (Fig. 7). The areas of involvement appear to be patchy and discontinuous. The patient was started on prednisone with dramatic improvement and clearing of dysarthria. The hyperreflexia in the knees and bilateral extensor plantar responses remained. The patient was discharged on steroids and phenobarbital with a diagnosis of postencephalitis demyelination. After two Case 4 A S-year-old boy developed chicken pox on 3/ 1 1 / 8 5 with resolution of lesions 5 days later. Within the next few days, he developed increasing somnolence, lethargy, vomiting, and eventually hypothermia. On examination, he was stuporous with disconjugate gaze and an upgoing right plantar response. MRI showed lesions compatible with demyelination in the left midbrain and middle cerebellar peduncle (Fig. 4). Steroid therapy was initiated and within two days he was awake and responding appropriately. Right lower extremity weakness was apparent as his mental status improved. After 5 weeks the patient was asymptomatic and the neurologic examination essentially normal. Followup MRI study showed resolution of previously described lesions (Fig. 5). Case 5 A 6-year-old girl was admitted January, 1985 for evaluation of recurrent lethargy and recent onset of seizures. As age 3 she had become comatose following gastroenteritis and CT reportedly showed diffuse edema. CSF revealed 113 neutrophiles, 30 lymphocytes, 7 RBC. She was treated with steroids and recovered to a normal neurologic status. Thirty-two months later she again developed lethargy and vomiting, and became unresponsive following a seizure. CT was reported as normal. The patient was discharged on phenobarbitol. During the intervening 3 weeks between discharge at another hospital and admission at the Children’s Hospital of Philadelphia, the patient complained of headaches and was lethargic. Physical examination revealed knee jerks to be increased bilaterally and plantar responses to be bilaterally extensor. CSF showed a WBC of 68 cells/mm3 with a differential of 63% neutrophils, 37% monocytes. The CSF protein was 46 and the glucose 60. EEG showed diffuse delta slowing with occasional paroxysmal discharges on the anterior leads. CT showed hypodensity on the right parietal region with vague contrast enhancement [Fig. 6(A)]. During the ensuing weeks the patient became dysarthric. At this point CT was repeated and showed suggestion of hypodensity in the left temporal lobe Fig. 6. (A) CT in Case 5 demonstrates decreased density in the right parietal white matter and an area of possible contrast enhancement anterior to this region (arrow.). (B) CT one week later shows similar vague contrast enhancement (arrow) and hypodensity in the left temporal lobe. Magnetic Resonance Imaging ??Volume 4, Number 1, 1986 Fig. 7. Transverse [(A) and (B)] and coronal (C) spin-echo images demonstrate multiple areas of abnormal signal intensity, most prominent in the right parietal white matter. Small separate foci are also present in both temporal lobes and the left frontal white matter. There is a tendancy to involve the graywhite interface adjacent to the cerebral cortex in a patchy, discontinuous distribution (TE/TR - 30/2000). weeks, she returned for reevaluation. CT showed hypodensity in the right parietal region with contrast enhancement. MRI showed that the previous areas of abnormal signal intensity were reduced in size and number (Fig. 8). DISCUSSION These patients have very similar clinical and MRI features. The diagnosis of disseminated encephalomyelitis was based predominantly on the clinical presentation. Cultures for bacterial, viral, and fungal patho- gens, as well as studies to detect other causes of demyelination, were negative. Clinical improvement was dramatic following steroid therapy. Although initial CT was normal in each case, subsequent scans disclosed poorly demarcated lesions of white matter in two cases. MRI dramatically demonstrated multifocal white matter lesions which corresponded to the abnormal neurologic signs. Subsequent MRI studies showed resolution of these lesions and correlated well with clinical improvement. In four of the five patients, MRI was very similar with multiple lesions involving cerebrum, cerebellum, and brainstem. In one case (Case MRI in postinfectious disseminated encephalomyelitis @ VAL DUNN ETAL. 31 Fig. 8. Followup spin-echo MRI 29 days following initial examination (Fig. 7). Transverse (A) and coronal (B) projections show that the previous areas of increased signal intensity in white matter have decreased in size and intensity. Cortical involvement has resolved. Ventricles and sulci appear larger than on the previous study (TE/TR - 30/2000). 4), two distinct abnormal foci were identified but were limited to the cerebral and cerebellar peduncles. Previously published studies indicate that CT may be abnormal in acute disseminated encephalomyelitis. In one series CT demonstrated lesions in 7 of 11 patients with this disease.5 The findings included midbrain swelling, cortical enhancement, and hypodense lesions of white matter representing edema or demyelination. However, these investigators found a limited correlation between clinical signs and CT abnormalities and the four patients with normal CT could not be distinguished clinically from patients with abnormal studies. In another series, of seven cases of steroidresponsive encephalomyelitis, only two patients had abnormal CT.4 In this group, pontine swelling and hypodense lesions of the cerebellum were identified. The remaining five children had normal CT studies despite abnormal neurologic signs, and abnormal EEG or CSF profiles. In our patients, CT was normal initially, but became abnormal in two. The abnormalities were very subtle and did not have a characteristic pattern. MRI, on the other hand, demonstrated multiple definite abnormalities in each case. In four cases the pattern and distribution was very distinctive and may be specific for this disorder. The only other condition with a similar appearance is multiple sclero- sis. However, the lesions of disseminated encephalomyelitis appear to be more poorly defined and are located less frequently in the periventricular white matter. In fact, lesions tend to involve the gray-white interface adjacent to the cerebral cortex. The age and clinical history of these patients is also very different from multiple sclerosis. Magnetic resonance appears to be the imaging method of choice in evaluating patients with postinfectious neurologic abnormalities. As in MS and childhood leucodystrophies,8 MRI appears to be more sensitive than CT. In addition, the MRI appearance of disseminated encephalomyelitis may be quite chracteristic and allow a specific diagnosis to be made. CONCLUSIONS Although experience is still small, MRI appears to be the imaging method of choice in steroid-responsive postinfectious disseminated encephalomyelitis in children. MRI is more sensitive than CT and may allow a specific diagnosis to be made when multiple bilateral poorly marginated white matter lesions are seen in a child. In the past, this disorder was often fatal, but with appropriate diagnosis and therapy it is a curable disease with no permanent sequelae in many cases. 32 Magnetic Resonance Imaging 0 Volume 4, Number 1, 1986 REFERENCES I. Behan, P.O.; Moore, M.J.; Lisak, R.P. Acute disseminated encephalomyelitis. Brirish J C/in Pruct 28:243245; 1974. 2. Brant-Zawadzki, M.; Norman, D.; Newton, T.H.; Kelly, W.M.; Kjos, B.; Mills, C.M.; Dillon, W.; Sobel, D.; and Crooks, L.E. Magnetic resonance of the brain: the optima1 screening technique. Radiology 52:71-77; 1984. 3. Byers, R.K. Acute Hemorrhagic leukoencephalitis: report of three cases and review of the literature. Pediatrics 56~727-735; 1975. 4. Lukes, S.A.; Norman, D. Computed tomography in acute disseminated encephalomyelitis. Ann Neural 13:567-572; 1983. 5. Pasternak, J.F.; DeVivo. D.C.; Prensky, A.L. Steroidresponsive encephalomyelitis in childhood. Neurology 30:48 l-486; 1980. 6. Perdue, Z.; Bale, J.F.; Dunn, V.; Bell, W.E. Magnetic resonance imaging in childhood disseminated encephalomyelitis (submitted to Pediatric Neurology). 7. Runge, V.M.; Price, A.C.; Kirshner, H.S.; Allen, H.S.; Partain, CL.; James, A.E., Jr. Magnetic resonance imaging of multiple sclerosis: a study of pulse technique efficacy. AJR 143:1015-1026; 1984. 8. Young, R.S.K.; Osbakken, M.D.; Alger, P.M. Magnetic resonance imaging in leukodystrophies of childhood. Ped Neurol 1:15-19; 1985.