Acute Disseminated Encephalomyelitis: An
MRI/MRS Longitudinal Study
Lidia V. Gabis, MD*, David J. Panasci, MD†, Mary R. Andriola, MD*, and
Wei Huang, PhD†
A clinical and radiologic diagnosis of acute disseminated encephalomyelitis was made in two children: a
6-month-old female who presented with focal seizures
and thalamic and cerebral white matter lesions, and a
4.5-year-old male who presented with tremor and
dystonia and had bilateral basal ganglia lesions, without evidence of active brain infection. Serial clinical
and laboratory evaluations were supplemented by neuroimaging including routine magnetic resonance imaging and 1H magnetic resonance spectroscopy. They
were treated symptomatically, without using steroids
or intravenous immunoglobulin, and both children
recovered. Single voxel 1H magnetic resonance spectroscopy data were acquired from the involved areas
and from normal-appearing white matter. Abnormalities in N-acetyl-aspartate, choline, and lactate peaks
were evident during the symptomatic phase, and persistence of low N-acetyl-aspartate was observed during
recovery. These spectroscopic findings are consistent
with neuropathologic findings of neuronal dysfunction,
cellular membrane turnover, cellular infiltration, and
metabolic stress in the acute phase, and with neuronal
loss in the chronic phase. © 2004 by Elsevier Inc. All
rights reserved.
Gabis LV, Panasci DJ, Andriola MR, Huang W. Acute
disseminated encephalomyelitis: An MRI/MRS longitudinal study. Pediatr Neurol 2004;30:324-329.

Introduction
Acute disseminated encephalomyelitis has been characterized as a demyelinating disorder involving mainly the
white matter and occurring after an infection or vaccination. It presents with focal neurologic signs and encephalopathy and is differentiated from multiple sclerosis by its

From the Departments of *Neurology and †Radiology, State University
of New York, Stony Brook, New York.

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monophasic course [1]. Mortality can be as high as
10-20%, but in most, complete recovery occurs. Pathologically, there are multifocal widespread demyelinating lesions with perivascular mononuclear cell infiltration [2].
Characteristic neuroimaging findings have been reported
and are one criterion for diagnosis [3]. On computed
tomography the lesions are observed as areas of decreased
attenuation with contrast enhancement in the subacute
phase of the disease [1]. At present, magnetic resonance
imaging is the modality of choice for evaluation of
children suspected of having acute disseminated encephalomyelitis. Lesions are usually bilateral, asymmetric, and
most commonly in the frontal and parietal lobes. Corpus
callosal involvement similar to that observed in multiple
sclerosis has been described. Basal ganglia and thalamic
involvement is less frequent and typically symmetric [4,5].
Lesions in the acute phase of the illness typically enhance
after administration of gadolinium. Most lesions will
either resolve or improve over time although progression
to necrosis and gliosis can occur. Interestingly, there is no
clear correlation between the severity of the magnetic
resonance imaging findings and the symptoms [6].
Diffusion-weighted magnetic resonance imaging is a
sensitive technique for detecting cellular ischemia. There
is restriction of motion of water molecules within ischemic
neurons. In one case report, diffusion-weighted magnetic
resonance imaging in a child with acute disseminated
encephalomyelitis revealed diffusion abnormalities in lesions observed on T2-weighted sequences with rapid
normalization over time [7].
Immunomodulatory treatments, such as steroids, plasmapheresis, or intravenous immunoglobulins are reported
as beneficial in multiple case reports [8-11], with concomitant partial resolution of magnetic resonance imaging–
documented lesions [3]. To date, there is no controlled and
blinded study to validate these data [12].

Communications should be addressed to:
Dr. Gabis; Pediatric Neurology; Safra Children’s Hospital;
Sheba Medical Center; Tel Hashomer, Israel 52621.
Received August 13, 2003; accepted November 13, 2003.

© 2004 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2003.11.005 ● 0887-8994/04/$—see front matter

1

H magnetic resonance spectroscopy has become a
valuable in vivo technique for obtaining biochemical
information in patients with neurologic disorders because
of its ability to monitor noninvasively metabolic processes
in the brain on a regional basis. With both long and short
echo time (TE), 1H magnetic resonance spectroscopy
concurrently measures N-acetyl-aspartate (NAA), total
creatine, choline-containing compounds, and lactate. NAA
has been considered as the marker of neuronal integrity,
whereas the levels of choline and lactate are indicative of
cell membrane turnover and anaerobic glycolysis [13]. A
recent case study of acute disseminated encephalomyelitis
with 1H magnetic resonance spectroscopy reported reduced NAA but normal levels of other metabolites in the
brain lesions [14]. Magnetic resonance spectroscopy has
been used for longitudinal follow-up of lesions in relapsing-remitting multiple sclerosis, as well as evaluation of
normal-appearing white matter, and of treatment effects.
NAA reduction in normal-appearing white matter has been
found to inversely correlate with disability and biochemical abnormalities in lesions correlated with treatment
response [15,16]. Because of the higher sensitivity of
magnetic resonance spectroscopy changes compared with
magnetic resonance imaging appearance in patients with
multiple sclerosis, it has been suggested that magnetic
resonance spectroscopy be used as a secondary outcome
measure in treatment trials [17].
In this study, we report the clinical and imaging findings
in two children with acute disseminated encephalomyelitis. Magnetic resonance imaging (including routine sequences and diffusion-weighted magnetic resonance imaging) and 1H magnetic resonance spectroscopy both in
the acute and subacute phases of the disease were employed to detect possible structural and neurochemical
abnormalities. Both children recovered without immunomodulatory treatment.
Patients and Methods
Patient History
Case report 1: A 6-month-old female presented with new onset focal
seizures involving the right upper extremity, irritability, and low-grade
fever preceded 2 weeks earlier by otitis and rash. Electroencephalogram
on admission indicated an epileptogenic focus originating from the left
temporoparietal area. Seizures resolved with antiepileptic treatment, but
mild hemiparesis of right upper extremity persisted. Initial laboratory
tests, including cerebrospinal fluid, were normal. Subsequent cerebrospinal fluid after 4 days indicated 40 cells (100% monocytes) and protein 58
mEq/dL (normal 15-45 mEq/dL). Blood count, electrolytes, and liver
enzymes were in the normal range. Mycoplasma, Epstein-Barr virus,
antibodies to nuclear antigens, and viral titers were all negative. Cerebrospinal fluid, urine and blood bacterial cultures, and herpes polymerase
chain reaction were negative as well. Evaluation for a disorder of
coagulopathy (factor V Leiden, antibodies to nuclear antigens, anticardiolipin antibodies) and a metabolic disorder (ammonia, lactate, organic
acids, amino acids) were negative. After the first 4 days she began to
improve clinically, and she slowly began to regain use of her right upper
extremity. Acyclovir was discontinued after 4 days. Immunomodulatory
treatment was not administered because of a delay in herpes polymerase

chain reaction results and subsequent recovery. After 1 month she had
full passive and active motion of upper and lower extremities, but at 6
months follow-up she manifested left preference, which suggested a
residual right hemiparesis. She continued to attain age-appropriate
developmental milestones.
Case report 2: A clinical and radiologic diagnosis of acute disseminated encephalomyelitis was made in a 4.5-year-old child who had abrupt
onset of abnormal movements, preceded by an upper respiratory infection. Head computed tomography was reported as revealing bilateral
basal ganglia lesions. After 9 days he was transferred to our hospital
owing to decreased activity and feeding, and frequent tremors of arms.
Examination revealed dystonia, dysarthria, and choreoathetosis. Laboratory results including blood count, electrolytes, liver function tests,
cerebrospinal fluid cell count and protein, lactate in blood and cerebrospinal fluid, serum amino acids, ceruloplasmin, carnitine and acyl
carnitines, and urine organic acids were all within normal limits.
Serologic titers for Epstein-Barr virus, Mycoplasma, Lyme disease,
antibodies to nuclear antigens, and antistreptolysin-O test were negative.
Echocardiogram performed before his transfer was normal. After his
transfer, he began to improve clinically and the immunomodulatory
treatment was deferred. Over the next month the patient continued to
improve, with minimal residual speech and balance difficulties. He
received only supportive treatment and physical therapy. At 6 months
follow-up, his language and physical examination were normal for his
age.

Brain Magnetic Resonance Imaging and 1H Magnetic
Resonance Spectroscopy
The two patients underwent brain magnetic resonance imaging/
magnetic resonance spectroscopy scanning sessions after hospital admission and as follow-up. Magnetic resonance imaging was performed for
clinical purposes, and the addition of magnetic resonance spectroscopy
was approved by the State University of New York Stony Brook
Institutional Review Board. Brain magnetic resonance imaging and 1H
magnetic resonance spectroscopy examinations were performed using
a 1.5-T GE Signa whole-body scanner. Patients were sedated during
the procedure. The routine magnetic resonance imaging protocol at
our institution includes T1- and T2-weighted, as well as fluid-attenuated
inversion-recovery images obtained in axial, sagittal, and coronal
planes. Contrast agent was not injected. Multislice diffusion-weighted
magnetic resonance imaging was obtained in Case #1 with b ⫽ 1000
s/mm2. T2-weighted axial images were used as scout images for
single-voxel 1H magnetic resonance spectroscopy data acquisition from
regions of T2 magnetic resonance imaging signal hyperintensity, and
from regions of normal-appearing white matter. A stimulated echo
acquisition mode (STEAM) sequence was employed to collect proton
spectra with TE ⫽ 40 ms, mixing time (TM) ⫽ 14 ms, repetition time
(TR) ⫽ 2 s, and 128 scan averages. The magnetic resonance
spectroscopy voxel location, size, and acquisition parameters were
kept the same for each patient during follow-up studies by using
anatomic landmarks and measured size. Because of the large size of
lesions in both cases, voxels positioned in the lesion areas incorporated
mainly abnormal tissue.
The raw spectral data were processed using 3-Hz line broadening,
Fourier transformation, and phase and baseline corrections. Resonance
peaks of NAA, creatine, choline, and lactate were identified and fitted
using a nonlinear-least-squares fitting procedure with a LevenbergMarquardt algorithm. The peak area ratios of metabolites to creatine were
calculated and used as measures of metabolite levels. Correction for
underlying macromolecular signal was made using base corrections with
polynomial functions. Peak position of lactate (1.33 ppm) and lipids
(1.45 ppm) could overlap, and the existence of lactate was judged on the
basis of the characteristic doublet peak.

Gabis et al: 1H MRS in ADEM 325

Figures 1 (Top) and 2 (Bottom). Patient 1: Axial T2-weighted images (TE 40 ms) demonstrating focal region of abnormally increased signal in the
parietal white matter. Voxel localization and magnetic resonance spectroscopy spectra in acute (Fig 1) and in chronic phases (Fig 2).

Results
Case 1
Initial magnetic resonance imaging obtained 2 days
after the onset of symptoms demonstrated multiple bilateral hyperintense lesions in the peripheral white matter of
the left frontal and parietal lobes, right frontal lobe, and
the left thalamus, without appreciable mass effect (Fig 1).
The lesions were characteristic in that they were discrete,
nonhemorrhagic, asymmetrical, and initially correlated
with clinical symptoms and signs. Diffusion-weighted

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magnetic resonance imaging demonstrated restricted diffusion in the left frontal lesion only. This phenomenon was
observed as increased signal on the diffusion-weighted
magnetic resonance imaging trace images with corresponding decreased signal on the apparent diffusion coefficient (ADC) maps.
Magnetic resonance spectroscopy obtained at this time
revealed mildly decreased NAA in the left basal ganglia
and elevated choline and lactate in both the left parietal
area where a lesion was visualized on magnetic resonance
imaging, as well as in right normal-appearing white matter
(Fig 1).

Figure 3. Patient 2: Axial T2-weighted image (TE 40 ms) demonstrates abnormally increased signal in the caudate and putamen with mild compression
of the adjacent frontal horns of the lateral ventricles. Voxel localization and magnetic resonance spectroscopy spectra in the acute phase are illustrated.

Follow-up magnetic resonance imaging obtained 1
month later revealed interval increase in size of the left
parietal lesion, which had become contiguous with the left
frontal lesion. The right frontal and left thalamic lesions
had decreased in size. No new lesions had developed.
Diffusion-weighted magnetic resonance imaging indicated
decreased signal in the left parietal area.
Magnetic resonance spectroscopy obtained at this time
indicated normalization of choline and lactate. However,
there was an interval decrease in NAA in the left parietal
lesion, whereas NAA in the left basal ganglia remained
low (Fig 2).
A final magnetic resonance imaging obtained 8 weeks
after the initial study demonstrated complete resolution of
the right frontal lesion. The left thalamic and parietal
lesions were unchanged. The left frontal lesion evolved
into an area of volume loss and cortical necrosis. No new
lesion developed (Fig 3).
Magnetic resonance spectroscopy documented additional decrease in NAA in the left parietal lesion and small
NAA recovery in the left basal ganglia area (Table 1).
Case 2
Initial magnetic resonance imaging obtained 9 days
after the onset of symptoms demonstrated bilateral, symmetric, abnormally increased signal on fluid-attenuated
inversion-recovery and T2-weighted images in the caudate
and putamen with relative sparing of the globus pallidus.
There was mass effect as evidenced by compression of the
adjacent frontal horns of the lateral ventricles. The white
matter and cortical gray matter of the cerebral and cerebellar hemispheres were normal (Fig 3).

Repeat magnetic resonance imaging obtained 4 weeks
later revealed persistent hyperintensity in the caudate and
putamen although it was less pronounced and without
associated mass effect. No new lesions developed between
the two studies. Clinically, the patient displayed improvement with minimal residual speech (stutter) and balance
difficulties.
Figure 3 presents proton spectra acquired from the right
basal ganglia region in the initial phase. Both initial and
follow-up spectra indicated that when compared with
spectra from the same region of age-matched healthy
control subjects, NAA peak was decreased, whereas choline and lactate peaks were elevated. However, the follow-up magnetic resonance spectroscopy indicated a slight
increase in NAA peak and a slight decrease in lactate peak.
The choline peak remained elevated. The subcortical
normal-appearing white matter spectra in both studies of
this child (not shown here) revealed normal NAA peak,
but elevated choline peak.
The metabolite ratios from different brain regions
obtained in the magnetic resonance spectroscopy studies
of both patients are listed in Table 1. Corresponding
literature metabolite ratios from age-matched healthy control subjects are also listed for comparison. These values
are mean values from the cited studies after correction for
the differences in pulse sequence type and parameters
[18,19].
Discussion
The young age, antecedent infection, monophasic
course, and the multifocal neurologic and radiologic findings in these two patients are compatible with the diagno-

Gabis et al: 1H MRS in ADEM 327

Table 1. Regional brain metabolite ratios in AM children with acute
disseminated encephalomyelitis and age-matched healthy control subjects
MRS Voxel
ADEM Case 1
Left parietal WM (lesion)
Left BG (lesion)
Right frontal WM
Left parietal WM (lesion)
Left BG (lesion)
Right frontal WM
Left parietal WM (lesion)
Left BG (lesion)
Right frontal WM
Age-matched controls
BG
WM
ADEM Case 2
BG
WM
BG
WM
Age-matched controls
BG
WM
Abbreviations
BG ⫽ Basal ganglia
Cr ⫽ Creatine
Cho ⫽ Choline
Lac ⫽ Lactate

Study

NAA/Cr

Cho/Cr

Lac/Cr

Initial
Initial
Initial
1 month
1 month
1 month
2 months
2 months
2 months

3.20
1.23
2.15
1.17
1.27
3.02
0.41
1.44
2.10

2.50
0.90
1.13
1.00
0.90
0.80
1.22
0.90
0.80

29.4
0.00
13.3
0.00
0.00
0.00
0.50
0.00
0.00

1.80

0.82
2.14

0.00
0.90

0.00

0.71
1.62
0.83
1.38

0.76
0.91
0.88
1.10

0.51
0.00
0.21
0.00

2.33
1.45

0.65
0.80

0.00
0.00

Initial
Initial
Follow-up
Follow-up

MRS ⫽ Magnetic resonance spectroscopy
NAA ⫽ N-acetyl-aspartate
WM ⫽ White matter

sis with acute disseminated encephalomyelitis. Case 1 had
typical magnetic resonance imaging findings of asymmetric cerebral white matter and deep gray (thalamic) lesions.
Case 2 was unusual in that lesions were limited to the
basal ganglia without cerebral white matter involvement.
This uncommon distribution of acute disseminated encephalomyelitis lesions has been previously described
[4,5].
Immunomodulatory treatment was deferred and both
patients recovered. The sequence of the appearance of the
lesions on magnetic resonance imaging pictures correlated
with the clinical evolution; however, clinical recovery
preceded the magnetic resonance imaging improvement.
The addition of diffusion-weighted magnetic resonance
imaging sequence in the first patient predicted the severity
of one lesion, which evolved similar to the appearance of
a stroke.
In the children described, as compared with the corresponding metabolite ratios from similar brain regions of
age-matched normal healthy children reported in several
prior magnetic resonance spectroscopy studies [15,16],
NAA was decreased in neuroradiologicaly involved areas,
whereas choline and lactate were elevated in areas in
which lesions were visualized, as well as in normalappearing white matter. The lactate elevation likely reflects an early inflammatory process. The reduction in
NAA suggests neuronal dysfunction in the involved areas
of the disease that is at least partially reversible, as
indicated by increase in NAA/creatine values during the

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phase of clinical recovery. The NAA value at long-term
follow-up suggests neuronal loss. The choline elevation,
which is likely the result of increased membrane turnover
during demyelination or macrophages infiltration, seems
to be more global rather than regional specific. In Case 2,
the increase of NAA and the decrease of lactate in
involved areas after 1 month coincided with reduced areas
of enhancing lesions documented in magnetic resonance
imaging and with clinical improvement. Although NAA
was still lower than normal in involved areas, there were
apparently sufficient surviving neurons to support recovery of normal function. Metabolic analysis using magnetic
resonance spectroscopy may provide valuable information
from lesions and from normal-appearing areas in acute
disseminated encephalomyelitis, aiding in diagnosis with
anatomic structure from magnetic resonance imaging.
Magnetic resonance spectroscopy might be useful in
longitudinal neuroimaging studies for monitoring disease
activity and further assessing the need for, and result of,
interventions, such as immunomodulatory or neuroprotective agents.
Despite significant neurologic and radiologic abnormalities during the acute and subacute phase, those two
patients with acute disseminated encephalomyelitis regained function and continue to improve. It is unknown if
treatment would have hastened or optimized the outcome.
This uncertainty emphasizes the need for multicenter
randomized controlled trials, using magnetic resonance
spectroscopy as an additional follow-up measure, and

evaluating indications for immunomodulatory treatments
in acute disseminated encephalomyelitis.

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