an adult case of multiphasic disseminated
TRANSCRIPT
Internal Medicine Vol.53An Adult Case of Multiphasic Disseminated
Encephalomyelitis Manifesting with Optic Neuritis
Hong-Qi Yang 1,2, Wen-Cong Zhao 3, Shu-Man Feng 1 and Jian-Jun Ma 1
Abstract
A 25-year-old woman presented with a fever, headache, vomiting and somnolence. Cranial magnetic reso-
nance imaging (MRI) showed multiple lesions in the cerebellum, brainstem, cerebral cortex and subcortex.
Oligoclonal bands were positive in the cerebral spinal fluid (CSF). She experienced a good recovery after
steroid treatment. Four months later, she developed right vision loss. Repeated MRI showed multiple cranial
lesions different from those involved in the first attack in both size and distribution. An abnormal high signal
was also observed in the front and intraorbital regions of the right optic nerve. The patient’s vision progres-
sively improved, and she obtained a full recovery following the administration of steroids. A diagnosis of
multiphasic disseminated encephalomyelitis manifesting with optic neuritis was made.
Key words: acute disseminated encephalomyelitis, optic neuritis, oligoclonal band, magnetic resonance
imaging, multiple sclerosis
Introduction
myelinating disorder of the central nervous system that typi-
cally occurs after infection or vaccination. The clinical
course is usually monophasic, and affected patients often re-
spond well to steroid therapy. Although rare, some ADEM
patients presented with a multiphasic course that is clinically
difficult to differentiate from that of multiple sclerosis (MS).
According to the definitions proposed in 2007 by Krupp et
al. (1), such patients can be diagnosed with multiphasic dis-
seminated encephalomyelitis (MDEM). However, these cases
are usually reported in the pediatric population. We herein
report an adult case of ADEM followed by an attack of op-
tic neuritis (ON) that mimicked MS. After performing a
careful clinical evaluation, a diagnosis of MDEM manifest-
ing with optic neuritis was established. This study was ap-
proved by the ethics committee of Henan Provincial Peo-
ple’s Hospital.
of fever, headache and vomiting. She reported having no
history of infection or vaccination. Following the admini-
stration of antibiotics and mannitol, the headache was re-
lieved; however, an intermittent febrile state persisted. Four
days later, abdominal distension and numbness in all four
limbs were noted. A routine blood test showed a white
blood cell count of 10.1×109/L, with a neutrophil percentage
of 77.3 (50-70)% and a lymphocyte percentage of 16.9 (20-
40)%. The erythrocyte sedimentation rate was 7 (0-20) mm/
h. Despite the continued administration of antibiotics, the
patient’s clinical symptoms deteriorated, and she developed
urine incontinence and somnolence. On a physical examina-
tion, her temperature was 38.4, her heart rate was 93
beats per min and her blood pressure was 125/80 mmHg.
She exhibited apathy and disorientation (Glasgow Coma
Scale: 13 points). A muscle strength test revealed symmetri-
cal weakness in the proximal and distal limbs (4/5). No sen-
sory disturbances were detected. The deep tendon reflexes
Department of Neurology, Henan Provincial People’s Hospital, China, Department of Neurology, People’s Hospital of Zhengzhou University,
China and Department of Pharmacology, Zhengzhou Maternal and Child Health Hospital, China
Received for publication June 27, 2013; Accepted for publication November 25, 2013
Correspondence to Dr. Hong-Qi Yang, [email protected]
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1012
Figure 1. MRI findings of the patient during the first (A-C) and second (D-F) episodes and follow- up study (G-I). During the first attack, axial T2-weighted (A) and fluid-attenuated inversion recovery images (B) showed multiple lesions of various sizes in the cerebral cortex and subcortex. Nodular, linear and even ring-shaped enhancement was observed following the administration of gadolinium (C). During the second episode, axial T2-weighted images showed multiple high-signal intensity le- sions of various sizes in the temporal and occipital lobes, with some lesions exhibiting an egg-yolk appearance (D). Ring-shaped enhancement was noted following the administration of gadolinium (E), and the front portion of the right optic nerve was thickened and enhanced (F). On the follow-up study conducted 18 months later, most of the lesions had disappeared on both T1- and T2-weighted images (G, H). No signal enhancement was detected (G-I).
were normal; however, Babinski’s sign was positive. No
neck stiffness was observed. Initial cranial magnetic reso-
nance imaging (MRI) showed multiple, patchy, high-signal
intensity lesions of various sizes in the cerebellum, brain-
stem, cerebral cortex and subcortex. Nodular, linear and
even ring-shaped enhancement was noted following the ad-
ministration of gadolinium (Fig. 1A-C). Enhancement was
also observed in the upper cervical spinal cord and
meningeal region of the skull base. The results of an elec-
troencephalogram were moderately abnormal, although the
findings of a chest CT scan were normal. A cerebral spinal
fluid (CSF) examination (Table) showed an open pressure of
190 mmH2O, and oligoclonal bands (OCB) were positive.
Intravenous methylprednisolone was administered, followed
by oral prednisolone, tapered over the next eight weeks. The
patient exhibited progressive improvements. Two weeks
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1013
Table. Laboratory Examinations of the Blood and CSF during the Two Episodes
ADA: Adenosine Deaminotransferase, CSF: Cerebral Spinal Flu-
id, LDH: Lactate Dehydrogenase, MBP: Myelin Basic Protein,
NSE: Neuron-specific Enolase, OCB: Oligoclonal Bands, WBC:
White Blood Cells
Protein (0.15~0.45 g/L)
Glucose (2.5~4.5 mmol/L)
Chloride (120~135 mmol/L)
ADA ( 0~8 U/L)
LDH (10~25 U/L)
Q Alb (CSF/Ser)×10 -3 (<5.0)
Q IgG (CSF/Ser)×10 -3(<5.0)
6.0
0.95
0.12
5.9
5.6
3.9
2.5
11.9
1.6
4.0
in urination, and the abdominal distension and numbness
were alleviated. MRI showed that the lesions had mostly
disappeared, no signal enhancement was observed.
Four months later, only 40 days after the discontinuation
of the steroid therapy, the patient suddenly presented with a
headache and right eye pain without any known cause.
Blurred vision, diplopia and ataxia subsequently developed.
Her symptoms gradually progressed, and blindness ulti-
mately occurred in the right eye five days later. Upon pres-
entation, the patient exhibited slight lethargy and confusion,
although she denied symptoms of dysautonomia. There were
no signs of meningeal irritation. The two pupils were round
in shape and equal in size (diameter =3 mm), and the direct
pupillary light reflex in the right eye was diminished. No
sensory disturbances were noted, and Babinski’s sign was
negative. Brain MRI showed multiple, patchy, high-signal
intensity lesions of various sizes in the bilateral, temporal,
occipital and frontal lobes, internal and external capsules
and bilateral cerebellum. These lesions were different from
those involved in the first attack in both size and distribu-
tion. Three lesions with an egg-yolk appearance and a di-
ameter over 2 centimeters were detected (Fig. 1D). Nodular
and ring-shaped enhancement was observed following the
administration of gadolinium (Fig. 1E). The front portion of
the right optic nerve was thickened, and the signals were en-
hanced in this area (Fig. 1F). The CSF pressure was 200
mmH2O; other indexes are listed in Table. OCB and neuro-
myelitis optic (NMO)-IgG were negative. The patient was
again treated with methylprednisolone followed by oral
prednisolone. Her vision progressively improved, and she
obtained a full recovery two weeks later. A follow-up visit
conducted at 18 months showed that she remained in recov-
ery without any residual symptoms. A MRI scan revealed
that most of the lesions had disappeared on both T1- and
T2-weighted images, and no signal enhancement was ob-
served following gadolinium administration (Fig. 1G-I). The
clinical course of the patient is illustrated in Fig. 2.
Discussion
In the absence of biological markers, criteria for a diagno-
sis of ADEM have not been fully developed. The first epi-
sode observed in the present patient fulfilled the criteria for
ADEM proposed by Krupp et al. (1), including the presenta-
tion of encephalopathy and involvement of multifocal white
matter lesions. The multiple lesions detected on MRI in this
case mimicked those of intracranial tuberculosis. However,
the latter usually present in association with increased pro-
tein and decreased glucose and chloride in the CSF and
positive acid-fast bacilli staining. Therefore, a diagnosis of
tuberculosis was not taken into consideration. The patient’s
response to steroid therapy and almost complete recovery in
symptoms and MRI findings add weight to the diagnosis of
ADEM.
treatable inflammatory central nervous system (CNS) disor-
ders, and MS is more likely to be associated with the in-
trathecal synthesis of OCB (2). Previous research suggests
that the absence of OCB is more indicative of ADEM (3).
Positive findings for OCB and cerebral white matter lesions
on the initial presentation of ADEM possibly indicate a
higher risk (82%) for developing MS (4). An elevated IgG
index and the presence of OCB are more often observed in
children who develop MS (5). However, the incidence of
OCB in patients with ADEM varies. Some authors have re-
ported negative OCB findings in ADEM patients (6), while
others have shown a rate of 10-30% (2, 7), and still others
have reported rates as high as 65% (8). Under these circum-
stances, the presence of OCB cannot be used to discriminate
ADEM from MS (2, 8).
Another point that favors a diagnosis of ADEM is the
MRI findings. The MRI lesions in this case were bilateral,
asymmetric and variable in size. No periventricular lesions
were observed, a finding that is correlated with MS out-
comes (9). Callen et al. proposed MRI criteria in 2009 such
that any two of the following findings favor a diagnosis of
MS (10): (1) the absence of a diffuse bilateral lesion pattern;
(2) the presence of black holes; and (3) the presence of two
or more periventricular lesions. This criterion is most useful
for differentiating a first attack of MS from monophasic
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1014
Figure 2. The clinical course of the patient. The clinical symptoms, treatments (indicated by verti- cal arrows) and clinical results are illustrated.
ADEM (11). According to these criteria, a diagnosis of
ADEM should be favored in the present case. In addition,
the egg-yolk appearance observed during the second attack
(Fig. 1D) has been repeatedly reported previously in ADEM
patients (12, 13). Furthermore, encephalopathy is not typi-
cally associated with MS (1).
The key point in this case is the second attack. Was it a
recurrent or multiphasic form of ADEM or NMO? Since the
profile of the patient’s symptoms and the features of the le-
sions on MRI definitively distinguished the second attack
from the first episode, a diagnosis of recurrent ADEM is
less likely. The negative NMO-IgG results and clinical fea-
tures of the patient do not support a diagnosis of NMO (1).
The clinical presentation of the second attack included en-
cephalopathy and multiple lesions on MRI, thus satisfying
the criteria for an MDEM diagnosis (1).
Schwarz et al. (8) reported that, in their study, 35% of
ADEM patients ultimately developed MS after 38 months of
follow-up. Many patients have been reported to have
ADEM; however, the present patient may represent one of
the few patients who strictly fulfil the criteria for MDEM
proposed by Krupp.
Most cases of MDEM have been reported in pediatric pa-
tients (2, 14), and the development of MDEM followed by
ON is rare. Huppke et al. recently reported a series of pedi-
atric ADEM patients who also exhibited recurrent or mono-
phasic ON attacks (15). All of these patients demonstrated
negative OCB findings at the time of ADEM diagnosis and
all displayed high titers of serum anti-myelin oligodendro-
cyte glycoprotein (MOG) antibodies. However, repeated cra-
nial MRI performed during the ON attacks and on follow-up
did not reveal new lesions in any of the patients. These pa-
tients may represent a distinct clinical phenotype among
ADEM patients (15). It is possible that the present case was
associated with anti-MOG antibodies, which are usually ob-
served in pediatric patients with ADEM. However, the cur-
rent patient can be distinguished from those reported by
Huppke (15) in that the patient was an adult, OCB were
positive during the ADEM attack and the MRI findings dur-
ing the ON attack were positive.
In summary, we herein reported an extremely rare case of
adult MDEM that manifested with optic neuritis. We ac-
knowledge that our study has several limitations, including
the lack of measurements of MOG antibodies, possibility of
other diagnoses and unknown future prognosis, etc. The
follow-up period in this case was 18 months; thus, long-
term (years or even decades) follow-up is warranted in order
to confirm the diagnosis.
The authors state that they have no Conflict of Interest (COI).
References
1. Krupp LB, Banwell B, Tenembaum S; International Pediatric MS
Study Group. Consensus definitions proposed for pediatric multi-
ple sclerosis and related disorders. Neurology 68(Suppl 2): S7-S
12, 2007.
2. Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville
BG. Acute disseminated encephalomyelitis, multiphasic dissemi-
nated encephalomyelitis and multiple sclerosis in children. Brain
123: 2407-2422, 2000.
3. Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS,
Kean MJ. Clinical and neuroradiologic features of acute dissemi-
nated encephalomyelitis in children. Neurology 56: 1308-1312,
2001.
4. Sharief MK, Thompson EJ. The predictive value of intrathecal im-
munoglobulin synthesis and magnetic resonance imaging in acute
isolated syndromes for subsequent development of multiple sclero-
sis. Ann Neurol 29: 147-151, 1991.
5. Neuteboom RF, Boon M, Catsman Berrevoets CE, et al. Prognos-
tic factors after a first attack of inflammatory CNS demyelination
in children. Neurology 71: 967-973, 2008.
6. Tenembaum S, Chamoles N, Fejerman N. Acute disseminated en-
cephalomyelitis: a long-term follow-up study of 84 pediatric pa-
tients. Neurology 8: 1224-1231, 2002.
7. Franciotta D, Columba-Cabezas S, Andreoni L, et al. Oligoclonal
IgG band patterns in inflammatory demyelinating human and
mouse diseases. J Neuroimmunol 200: 125-128, 2008.
8. Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-
Hagenlocher B. Acute disseminated encephalomyelitis: a follow-
up study of 40 adult patients. Neurology 56: 1313-1318, 2001.
9. Alper G, Heyman R, Wang L. Multiple sclerosis and acute dis-
seminated encephalomyelitis diagnosed in children after long-term
follow-up: comparison of presenting features. Dev Med Child
Neurol 51: 480-486, 2009.
10. Callen DJ, Shroff MM, Branson HM, et al. Role of MRI in the
differentiation of ADEM from MS in children. Neurology 72:
968-973, 2009.
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1015
CE, Hintzen RQ; Dutch Pediatric MS Study Group. A comparison
of MRI criteria for diagnosing pediatric ADEM and MS. Neurol-
ogy 74: 1412-1415, 2010.
12. Singh S, Alexander M, Korah IP. Acute disseminated encephalo-
myelitis: MR imaging features. AJR Am J Roentgenol 173: 1101-
1107, 1999.
13. Dale RC, Branson JA. Acute disseminated encephalomyelitis or
multiple sclerosis: can the initial presentation help in establishing
a correct diagnosis? Arch Dis Child 90: 636-639, 2005.
14. Chen S, Wu A, Zhang B, et al. A case of exacerbated multiphasic
disseminated encephalomyelitis after interferon beta treatment. J
Neurol Sci 325: 176-179, 2013.
15. Huppke P, Rostasy K, Karenfort M. Acute disseminated encepha-
lomyelitis followed by recurrent or monophasic optic neuritis in
pediatric patients. Mult Scler 19: 941-946, 2013.
2014 The Japanese Society of Internal Medicine
http://www.naika.or.jp/imonline/index.html
Hong-Qi Yang 1,2, Wen-Cong Zhao 3, Shu-Man Feng 1 and Jian-Jun Ma 1
Abstract
A 25-year-old woman presented with a fever, headache, vomiting and somnolence. Cranial magnetic reso-
nance imaging (MRI) showed multiple lesions in the cerebellum, brainstem, cerebral cortex and subcortex.
Oligoclonal bands were positive in the cerebral spinal fluid (CSF). She experienced a good recovery after
steroid treatment. Four months later, she developed right vision loss. Repeated MRI showed multiple cranial
lesions different from those involved in the first attack in both size and distribution. An abnormal high signal
was also observed in the front and intraorbital regions of the right optic nerve. The patient’s vision progres-
sively improved, and she obtained a full recovery following the administration of steroids. A diagnosis of
multiphasic disseminated encephalomyelitis manifesting with optic neuritis was made.
Key words: acute disseminated encephalomyelitis, optic neuritis, oligoclonal band, magnetic resonance
imaging, multiple sclerosis
Introduction
myelinating disorder of the central nervous system that typi-
cally occurs after infection or vaccination. The clinical
course is usually monophasic, and affected patients often re-
spond well to steroid therapy. Although rare, some ADEM
patients presented with a multiphasic course that is clinically
difficult to differentiate from that of multiple sclerosis (MS).
According to the definitions proposed in 2007 by Krupp et
al. (1), such patients can be diagnosed with multiphasic dis-
seminated encephalomyelitis (MDEM). However, these cases
are usually reported in the pediatric population. We herein
report an adult case of ADEM followed by an attack of op-
tic neuritis (ON) that mimicked MS. After performing a
careful clinical evaluation, a diagnosis of MDEM manifest-
ing with optic neuritis was established. This study was ap-
proved by the ethics committee of Henan Provincial Peo-
ple’s Hospital.
of fever, headache and vomiting. She reported having no
history of infection or vaccination. Following the admini-
stration of antibiotics and mannitol, the headache was re-
lieved; however, an intermittent febrile state persisted. Four
days later, abdominal distension and numbness in all four
limbs were noted. A routine blood test showed a white
blood cell count of 10.1×109/L, with a neutrophil percentage
of 77.3 (50-70)% and a lymphocyte percentage of 16.9 (20-
40)%. The erythrocyte sedimentation rate was 7 (0-20) mm/
h. Despite the continued administration of antibiotics, the
patient’s clinical symptoms deteriorated, and she developed
urine incontinence and somnolence. On a physical examina-
tion, her temperature was 38.4, her heart rate was 93
beats per min and her blood pressure was 125/80 mmHg.
She exhibited apathy and disorientation (Glasgow Coma
Scale: 13 points). A muscle strength test revealed symmetri-
cal weakness in the proximal and distal limbs (4/5). No sen-
sory disturbances were detected. The deep tendon reflexes
Department of Neurology, Henan Provincial People’s Hospital, China, Department of Neurology, People’s Hospital of Zhengzhou University,
China and Department of Pharmacology, Zhengzhou Maternal and Child Health Hospital, China
Received for publication June 27, 2013; Accepted for publication November 25, 2013
Correspondence to Dr. Hong-Qi Yang, [email protected]
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1012
Figure 1. MRI findings of the patient during the first (A-C) and second (D-F) episodes and follow- up study (G-I). During the first attack, axial T2-weighted (A) and fluid-attenuated inversion recovery images (B) showed multiple lesions of various sizes in the cerebral cortex and subcortex. Nodular, linear and even ring-shaped enhancement was observed following the administration of gadolinium (C). During the second episode, axial T2-weighted images showed multiple high-signal intensity le- sions of various sizes in the temporal and occipital lobes, with some lesions exhibiting an egg-yolk appearance (D). Ring-shaped enhancement was noted following the administration of gadolinium (E), and the front portion of the right optic nerve was thickened and enhanced (F). On the follow-up study conducted 18 months later, most of the lesions had disappeared on both T1- and T2-weighted images (G, H). No signal enhancement was detected (G-I).
were normal; however, Babinski’s sign was positive. No
neck stiffness was observed. Initial cranial magnetic reso-
nance imaging (MRI) showed multiple, patchy, high-signal
intensity lesions of various sizes in the cerebellum, brain-
stem, cerebral cortex and subcortex. Nodular, linear and
even ring-shaped enhancement was noted following the ad-
ministration of gadolinium (Fig. 1A-C). Enhancement was
also observed in the upper cervical spinal cord and
meningeal region of the skull base. The results of an elec-
troencephalogram were moderately abnormal, although the
findings of a chest CT scan were normal. A cerebral spinal
fluid (CSF) examination (Table) showed an open pressure of
190 mmH2O, and oligoclonal bands (OCB) were positive.
Intravenous methylprednisolone was administered, followed
by oral prednisolone, tapered over the next eight weeks. The
patient exhibited progressive improvements. Two weeks
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1013
Table. Laboratory Examinations of the Blood and CSF during the Two Episodes
ADA: Adenosine Deaminotransferase, CSF: Cerebral Spinal Flu-
id, LDH: Lactate Dehydrogenase, MBP: Myelin Basic Protein,
NSE: Neuron-specific Enolase, OCB: Oligoclonal Bands, WBC:
White Blood Cells
Protein (0.15~0.45 g/L)
Glucose (2.5~4.5 mmol/L)
Chloride (120~135 mmol/L)
ADA ( 0~8 U/L)
LDH (10~25 U/L)
Q Alb (CSF/Ser)×10 -3 (<5.0)
Q IgG (CSF/Ser)×10 -3(<5.0)
6.0
0.95
0.12
5.9
5.6
3.9
2.5
11.9
1.6
4.0
in urination, and the abdominal distension and numbness
were alleviated. MRI showed that the lesions had mostly
disappeared, no signal enhancement was observed.
Four months later, only 40 days after the discontinuation
of the steroid therapy, the patient suddenly presented with a
headache and right eye pain without any known cause.
Blurred vision, diplopia and ataxia subsequently developed.
Her symptoms gradually progressed, and blindness ulti-
mately occurred in the right eye five days later. Upon pres-
entation, the patient exhibited slight lethargy and confusion,
although she denied symptoms of dysautonomia. There were
no signs of meningeal irritation. The two pupils were round
in shape and equal in size (diameter =3 mm), and the direct
pupillary light reflex in the right eye was diminished. No
sensory disturbances were noted, and Babinski’s sign was
negative. Brain MRI showed multiple, patchy, high-signal
intensity lesions of various sizes in the bilateral, temporal,
occipital and frontal lobes, internal and external capsules
and bilateral cerebellum. These lesions were different from
those involved in the first attack in both size and distribu-
tion. Three lesions with an egg-yolk appearance and a di-
ameter over 2 centimeters were detected (Fig. 1D). Nodular
and ring-shaped enhancement was observed following the
administration of gadolinium (Fig. 1E). The front portion of
the right optic nerve was thickened, and the signals were en-
hanced in this area (Fig. 1F). The CSF pressure was 200
mmH2O; other indexes are listed in Table. OCB and neuro-
myelitis optic (NMO)-IgG were negative. The patient was
again treated with methylprednisolone followed by oral
prednisolone. Her vision progressively improved, and she
obtained a full recovery two weeks later. A follow-up visit
conducted at 18 months showed that she remained in recov-
ery without any residual symptoms. A MRI scan revealed
that most of the lesions had disappeared on both T1- and
T2-weighted images, and no signal enhancement was ob-
served following gadolinium administration (Fig. 1G-I). The
clinical course of the patient is illustrated in Fig. 2.
Discussion
In the absence of biological markers, criteria for a diagno-
sis of ADEM have not been fully developed. The first epi-
sode observed in the present patient fulfilled the criteria for
ADEM proposed by Krupp et al. (1), including the presenta-
tion of encephalopathy and involvement of multifocal white
matter lesions. The multiple lesions detected on MRI in this
case mimicked those of intracranial tuberculosis. However,
the latter usually present in association with increased pro-
tein and decreased glucose and chloride in the CSF and
positive acid-fast bacilli staining. Therefore, a diagnosis of
tuberculosis was not taken into consideration. The patient’s
response to steroid therapy and almost complete recovery in
symptoms and MRI findings add weight to the diagnosis of
ADEM.
treatable inflammatory central nervous system (CNS) disor-
ders, and MS is more likely to be associated with the in-
trathecal synthesis of OCB (2). Previous research suggests
that the absence of OCB is more indicative of ADEM (3).
Positive findings for OCB and cerebral white matter lesions
on the initial presentation of ADEM possibly indicate a
higher risk (82%) for developing MS (4). An elevated IgG
index and the presence of OCB are more often observed in
children who develop MS (5). However, the incidence of
OCB in patients with ADEM varies. Some authors have re-
ported negative OCB findings in ADEM patients (6), while
others have shown a rate of 10-30% (2, 7), and still others
have reported rates as high as 65% (8). Under these circum-
stances, the presence of OCB cannot be used to discriminate
ADEM from MS (2, 8).
Another point that favors a diagnosis of ADEM is the
MRI findings. The MRI lesions in this case were bilateral,
asymmetric and variable in size. No periventricular lesions
were observed, a finding that is correlated with MS out-
comes (9). Callen et al. proposed MRI criteria in 2009 such
that any two of the following findings favor a diagnosis of
MS (10): (1) the absence of a diffuse bilateral lesion pattern;
(2) the presence of black holes; and (3) the presence of two
or more periventricular lesions. This criterion is most useful
for differentiating a first attack of MS from monophasic
Intern Med 53: 1011-1015, 2014 DOI: 10.2169/internalmedicine.53.1257
1014
Figure 2. The clinical course of the patient. The clinical symptoms, treatments (indicated by verti- cal arrows) and clinical results are illustrated.
ADEM (11). According to these criteria, a diagnosis of
ADEM should be favored in the present case. In addition,
the egg-yolk appearance observed during the second attack
(Fig. 1D) has been repeatedly reported previously in ADEM
patients (12, 13). Furthermore, encephalopathy is not typi-
cally associated with MS (1).
The key point in this case is the second attack. Was it a
recurrent or multiphasic form of ADEM or NMO? Since the
profile of the patient’s symptoms and the features of the le-
sions on MRI definitively distinguished the second attack
from the first episode, a diagnosis of recurrent ADEM is
less likely. The negative NMO-IgG results and clinical fea-
tures of the patient do not support a diagnosis of NMO (1).
The clinical presentation of the second attack included en-
cephalopathy and multiple lesions on MRI, thus satisfying
the criteria for an MDEM diagnosis (1).
Schwarz et al. (8) reported that, in their study, 35% of
ADEM patients ultimately developed MS after 38 months of
follow-up. Many patients have been reported to have
ADEM; however, the present patient may represent one of
the few patients who strictly fulfil the criteria for MDEM
proposed by Krupp.
Most cases of MDEM have been reported in pediatric pa-
tients (2, 14), and the development of MDEM followed by
ON is rare. Huppke et al. recently reported a series of pedi-
atric ADEM patients who also exhibited recurrent or mono-
phasic ON attacks (15). All of these patients demonstrated
negative OCB findings at the time of ADEM diagnosis and
all displayed high titers of serum anti-myelin oligodendro-
cyte glycoprotein (MOG) antibodies. However, repeated cra-
nial MRI performed during the ON attacks and on follow-up
did not reveal new lesions in any of the patients. These pa-
tients may represent a distinct clinical phenotype among
ADEM patients (15). It is possible that the present case was
associated with anti-MOG antibodies, which are usually ob-
served in pediatric patients with ADEM. However, the cur-
rent patient can be distinguished from those reported by
Huppke (15) in that the patient was an adult, OCB were
positive during the ADEM attack and the MRI findings dur-
ing the ON attack were positive.
In summary, we herein reported an extremely rare case of
adult MDEM that manifested with optic neuritis. We ac-
knowledge that our study has several limitations, including
the lack of measurements of MOG antibodies, possibility of
other diagnoses and unknown future prognosis, etc. The
follow-up period in this case was 18 months; thus, long-
term (years or even decades) follow-up is warranted in order
to confirm the diagnosis.
The authors state that they have no Conflict of Interest (COI).
References
1. Krupp LB, Banwell B, Tenembaum S; International Pediatric MS
Study Group. Consensus definitions proposed for pediatric multi-
ple sclerosis and related disorders. Neurology 68(Suppl 2): S7-S
12, 2007.
2. Dale RC, de Sousa C, Chong WK, Cox TC, Harding B, Neville
BG. Acute disseminated encephalomyelitis, multiphasic dissemi-
nated encephalomyelitis and multiple sclerosis in children. Brain
123: 2407-2422, 2000.
3. Hynson JL, Kornberg AJ, Coleman LT, Shield L, Harvey AS,
Kean MJ. Clinical and neuroradiologic features of acute dissemi-
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