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Serial magnetic resonance imaging in children with postinfectious encephalitis
Brain & Development 1996; 18: 461-465
Orginal article
Serial magnetic resonance imaging in children with postinfectious encephalitis Seiji Kimura
*,
Atsuo Nezu, Noriyuki Ohtsuki, Takuya Kobayashi, Saori Uehara
Hitoshi Osaka,
Yokohama City Uniuersity, Urafune Hospital, Deparrment of Pediatn’cs, 3-46, Urafune-cho, Minami-ku, Yokohama, 232 Kanagawa, Japan
Received 27 December 1995; accepted 27 April 1996
We analyzed follow-up magnetic resonance images (MRI) in eight children with clinical postinfectious encephalitis (PIE), and discussed their pathogeneses. Three categories of MRI findings were apparent: (1) multifocal lesions in the white matter with/without basal ganglia involvement consistent with acute disseminated encephalomyelitis (ADEM) (three patients); (2) single or multifocal lesions localized only in the gray matter (two patients); and (3) localized lesions in the brain stem, basal ganglia or cerebellum. Some lesions in the patients in Categories 1 and 2 migrated or were resolved quickly, sometimes within 10 days. Gadolinium caused linear or spotty enhancement in the patients in Category 2. These findings suggest that Categories 1 and 2 are a self-limiting allergic angiopathy without demyelination. In contrast, the lesions in the patients in Category 3 were fixed, and not resolved within 6 months (three patients). The pathogenesis of Category 3 is not known. All except one patient had no prednisolone (PSL) therapy, however; all lesions were resolved completely or markedly reduced in size, which indicates PSL therapy is not always necessary in patients with PIE. Keywords: Encephalitis; Postinfectious encephalomyelitis; acute disseminated encephalomyelitis; Allergic encephalitis; Angiopathy
1. INTRODUCTION Postinfectious encephalomyelitis (PIE) is believed to be an allergic phenomenon initiated by a viral pathogen, and has been considered to be synonymous with acute disseminated encephalomyelitis (ADEM) [l--S]. However, the magnetic resonance imaging (MRI) findings in PIE vary, and features typical of ADEM are not common. Although PIE is commonly considered to be a demyelinating disorder, lesions are sometimes located in the gray matter. In addition, the lesions in the white and gray matter were usually resolved rapidly, which is not typical of demyelinating lesions. The purpose of this study is to clarify the pathogenesis of PIE by analyzing follow-up MRI findings in eight patients.
2. MATERIALS
AND METHODS
We analyzed MRI findings in eight Japanese children with PIE who had preceding infections and who showed MRI evi-
* Corresponding author. Fax: (81) (45) 243-3886. 0387.7604/96/$15.00
dence of lesions in the central nervous system (CNS). There were four females and four males aged 7 months to 14 years. Each child exhibited normal development and the family history was not contributory. Prednisolone (PSL) was not administered except to Patient 4. We now present each case in brief.
3. CASE REPORTS Patient 1: an 11 -month-old boy developed a fever 6 days after receiving the 1st oral poliomyelitis vaccination. He developed ataxia and intention tremor one day after reduction of the fever (day 1). On admission (day 81, he exhibited truncal ataxia, tremor and dysmetria. CSF analysis showed 28/mm3 leukocytes, and CSF protein and glucose concentrations were within normal ranges. Oligoclonal IgG band, myelin-basic protein (MBP) and neuron specific enolase (NSE) were not evaluated. Viral culture was negative. MRI showed widespread lesions in the white matter of the cerebrum and cerebellum, and basal ganglia lesions; high signals on T2-weighted images and mildly low signals on Tl-weighted images. His symptoms had resolved by day 12. Follow-up MRI performed on day 12 showed more expanded
Copyright 0 1996 Elsevier Science B.V. All rights reserved.
PIZ SO387-7604(96)00046-O
462
Fig. 1. Patient 1. a: diffuse high-signal been resolved by day 23.
S. Kimura et al. /Brain
& Development
white matter lesions were seen on T2-weighted
than the first MRI. The third MRI performed on day 23 showed improvement of the lesions; the cerebellar white matter lesions had almost been resolved (Fig. 1). MRI performed on day 54 showed disappearance of the white matter lesions. Patient 2: a 3-year-old girl had a persistent fever for about 1 month. She then developed a static and an intention tremor, and was admitted to our hospital (day 1). She was unable to sit or eat because of the severity of the tremor. CSF analysis showed a leukocyte count of 30/mm3 (mono-/polynucear cell = 5/ 11, and CSF glucose and protein concentrations were within normal ranges. Other data in the CFS was not available. A computed tomography (CT) showed no abnormalities. Her clinical symptoms improved gradually, and she was able to walk on day 24. MRI performed on day 46 revealed widespread lesions of the white matter and basal ganglia, consistent with typical ADEM. Follow-up MRI was performed monthly, and the brain lesions were completely resolved within 6 months. The findings in this patient have been reported previously [6]. Patient 3: a 7-year-old boy with herpes encephalitis (day 1) showed a good recovery after 7 days in the intensive care unit. The leukocyte count in the CSF was 120/mm3 (most were mononuclear cells). CSF protein and glucose concentrations were within normal ranges. MRI showed no abnormalities during the acute phase. However, MRI performed on day 18 showed symmetrical external capsule lesions (Fig. 21, which were almost completely resolved on day 30. CSF analysis on day 20 including cell count, and the values of total protein, gluocse, MBP, and NSE were within normal ranges. Oligoclonal IgG band was negative. The patient’s clinical details have been reported previously [7]. Patient 4: a 14-year-old boy developed a fever and headache on January 31st and was admitted to our hospital on February 5th. Analysis of a lumbar puncture specimen showed 317 cells/mm3 (mono-/polynuclear cell = 3/2). His fever persisted for 2 weeks. MRI performed on February 13th showed no lesions
1996: 18: 461-46s
MRI on day 12. b: the cerebellar
white matter lesions had almost
abnormalities. Treatment with PSL (1 mg/kg/day) was initiated on February 14th, and his fever was resolved within 2 days. He was discharged after 2 weeks of therapy with PSL. A partial motor seizure of the left hand developed on March 7th, and so he
Fig. 2. Patient 3. Symmetrical high signal lesions were seen in the external capsules on T2-weighted imaging, which were resolved almost completely within 12 days. Reproduced from [7] with permission of the publisher.
463
S. Kimura et al./ Brain & Deaelopment 1996: 18: 461-465
Fig. 3. Patient 4. Right: a round, high signal lesion was observed in the right thalamus frontal cortex is indicated by an arrow. These lesions were resolved within 13 days.
was readmitted. Dressing apraxia was present. MRI revealed no abnormalities. The leukocyte count in CSF was 33/mm3 (mono/polynuclear cells = 5/l). and the CSF glucose and protein
on T2-weighted
imaging.
Left: gadolinium
enhancement
in the
concentration were within normal ranges. The value of NSE was normal, and the oligoclonal IgG band was negative. MBE concentration in the serum was 10 ng/ml (normal < 4). MRI per-
Fig. 4. Patient 6. a: a CT scan showed symmetrical but right-dominant low-intensity lesions in the caudate and putamen MRI performed when the girl was 13 years old showed small high-signal lesions in the right caudate and putamen.
(7 months old). b: T2-weighted
464
S. Kimura et al. /Brain
& Development 1996; 18: 461-465
formed on March 14th revealed a high signal intensity lesion in the right thalamus on a T2-weighted imaging. Small gadoliniumenhanced lesions were observed in the right thalamus and the cortex of the right frontal lobe (Fig. 3). PSL therapy was initiated on March 15th. MRI performed 13 days later showed resolution of the lesions. Influenza B HI antibodies were significantly increased. Patient 5: a 13-year-old girl developed a fever and headache on January 20th. On February 10th (20 days after onset of the fever), she had a focal motor seizure and so was admitted to our hospital. She was alert, and a CT scan showed no abnormalities. She developed a fever and headache 10 days after admission. CSF analysis showed 318/mm3 leukocytes (mono-/polynuclear cell = 3/l). CSF glucose and protein concentrations were within normal ranges. Other examinations in the CSF were not avairable. MRI performed on February 25th revealed high signal intensity lesions on T2-weighted imaging in the right parietal cortex and the corticomedullary junction, that showed linear gadolinium enhancement. MRI performed 10 days later showed resolution of the lesions. Influenza B hemagglutinin inhibition (HI) antibody titers were significantly increased. The clinical details of Patients 4 and 5 have already been reported [8]. Patient 6: a 7-month-old girl developed anorexia and hypotonia (day 1) 6 days after resolution of a 5-day episode of vomiting and fever. On admission, she could not hold her head up. A CT scanning of the brain performed on day 11 revealed areas of hypodensity in the bilateral putamen and caudate (Fig. 4a). A CT scan performed on day 36 showed resolution of the lesions. The patient showed a complete recovery. Electroencephalography and CSF analysis including cell count, and protein and glucse concen-
Fig. 6. Patient 8. MRI showed a well-demarcated T2-weighted imaging in the brainstem.
high signal lesion on
trations showed no abnormalities. She is now 13 years old. Although a CT scan showed no abnormalities, small lesions in the basal ganglia were still observed on MRI (Fig. 4b). Patient 7: a 1 year and 6-months-old male exhibited a fever from December 19th to 21st. He developed ataxia and anorexia the day the fever disappeared (day 1). His symptoms improved rapidly; he was able to sit by day 6 and walk by day 7. but his gait was unsteady. By day 14 he was able to walk normally. CSF was not evaluated. MRI performed on day 29 showed high- and low signal cerebellar lesions on T2- and Tl-weighted imaging, respectively (Fig. 5). These lesions became smaller but were found to persist on MRI performed approximately 6 months later. Patient 8: a 3-year-old boy had a fever from July 27th to 30th. His respiration became weak and ataxic on August 1st (day 1). He was admitted to our hospital on day 2 because of drowsiness caused by CO, narcosis. He became alert immediately after being placed on assisted ventilation. MRI revealed a well demarcated brainstem lesion that extended from the pons to the medulla oblongata (Fig. 6). His respiratory disorder gradually improved, and he was able to breathe spontaneously 10 days after admission. He was alert during hospitalization. CSF analysis including cell count and concentrations of protein, glucose, and NSE were within normal range, and oligoclonal IgG band was negative. The value of MBE was normal. CT scan with/without contrast enhancement showed no abnormality. The MRI lesion gradually became smaller but was not resolved completely 6 months later.
4. DISCUSSION
Fig. 5. Patient 7. MRI showed two cerebellar white matter lesions. Top: high signals on T2-weighted imaging. Bottom: low signals on Tl-weighted imaging.
PIE is thought to be an allergic demyelinating disorder, and the term ‘PIE’ is used interchangeably with ADEM [l-5]. However, the diagnosis of demyelinating allergic encephalitis is based on autopsy findings or experimental models of allergic encephalitis, while PIE is diagnosed clinically. Thus it has not been established if PIE is really identical to allergic encephalitis or ADEM.
S. Kimura et al. /Brain
4.1. MRI findings
& Development
in PIE
We classified the MRI findings in the present study as follows. Categorj~ I (ADEM; Patients l-3): multifocal lesions in the white matter with/without basal ganglia consistent with ADEM. Patients 1 and 2 were typical ADEM on MRI, having multifocal lesions in the white matter and basal ganglia, which were dominant in T2-weighted images, but Tl-weighted MRI and CT scans were usually unremarkable. Some of the lesions migrated or were resolved rapidly (within 10 days in Patient 1). All lesions resolved completely within 54 days in Patient 1 and within 6 months in Patient 2. Patient 3 (atypical ADEM?) showed only external capsular lesions, which were almost completely resolved within 12 days. Although these were very small lesions, they looked similar to those in ADEM because they were localized only in the white matter. Category 2 (Postinfectious focal encephalitis: Patients 4 and 5): these patients had characteristic lesions localized only in the gray matter. Linear or small, spotty, gadolinium-enhanced lesions were also observed in both patients. These lesions were resolved rapidly, i.e., within 13 days in both patients. This condition can be more accurately classified as Cutegov 3 (Localized enpostinfectious focal encephalitis. cephalitis of unknown origin; Patients 6-8): these patients had localized lesions in the basal ganglia. brain stem or cerebellum. Long-term follow-up MRI showed that their lesions became smaller, but were not resolved completely.
4.2. Is PIE an allergic demyelinating identical to ADEM?
disorder,
and is it
ADEM has been characterized as an allergic demyelinating disorder involving only the white matter based on autopsy findings including mononuclear cell infiltration and demyelination around small vessels [3], which are similar to the findings in experimental allergic encephalomyelitis in animals. ADEM is usually diagnosed in patients who show characteristic multifocal and widespread white matter lesions on MRI. The term ‘ADEM’ is usually used synonymously with PIE [l-.5]. However, it is controversial whether the widespread lesions of the white matter detected on MRI are truly demyelinated lesions, and it is doubtful if PIE is identical to ADEM. In the present study, typical ADEM was found in only two (Patients 1 and 2) of eight patients with a clinical diagnosis of PIE, suggesting that PIE is not identical to ADEM. Only gray matter lesions were present in two of the five patients in Categories 1 and 2, and the lesions in these five patients, including those with typical ADEM, were resolved rapidly. In Patient 1 with typical ADEM, the cerebellar lesions
465
1996; 18: 461-465
observed on MRI were almost completely resolved within 10 days. Linear or spotty gadolinium enhancement of lesions was observed in Patients 4 and 5. These findings suggest that the lesions in patients in Categories 1 and 2 are caused by angiopathy, not demyelination. The high-intensity T2-weighted images may have been caused by molecules leaking from blood vessels as a result of an increase in vascular permeability. The severe lesions observed in autopsy-proven cases of ADEM are thought to be caused by such angiopathy. The MRI lesions in patents in Categories 1 and 2 were transient and became apparent in the middle or late stage of the CNS manifestations, suggesting that serial MRI may be required for diagnosis and may be useful for elucidating the pathogenesis of this disorder. The pathogenesis of the disorder in the patients in Category 3 is not clear. Although, MRI lesions such as those seen in the patients in Category 3 have been attributed to an immune-mediated event [9], it has not been proved yet. The lesions were not resolved completely in patients in Category 3.
4.3. Is predonisolone
therapy necessary
for PIE?
Only one patient (Patient 4) received PSL. The lesions in all patients having no PSL therapy diminished gradually, suggesting that PIE is a self-limiting disorder.
REFERENCES 1. Perdue Z, Bale JF, Dunn VD, Bell WE. Magnetic resonance imaging in childhood disseminated encephalitis, Pediatr Neural 1985; 1: 3704. 2. Dunn V, Bale JF, Zimmerman RA, Perdue Z, Bell W. MRI in children with postinfectious disseminated encephalomyelitis. Magn Reson Imaging 1986; 4: 25-32. 3. Johnson RT. The pathogeneses of acute viral encephalitis and postinfectious encephalomyelitis. J Infect Dis 1987: 155: 359-64. 4. Whitley RJ. Viral encephalitis. N Engl J Med 1990; 233: 242-50. 5. Kesselring J, Miller DH, Robb SA. et al. Acute disseminated encephalomyelitis. Brain 1990: 113: 291-302. 6. Kimura S. Unayama T. Mori T. The natural history of acute disseminated leukoencephalitis. A serial magnetic resonance imaging study. Neuropediatrics 1992; 23: 192-5. 7. Kimura S, Nezu A. Osaka H, Saitou K. Symmetrical external capsule lesions in a patient with herpes simplex encephalitis. Neuropediatrics 1994; 25: 162-4. 8. Kimura S, Kobayashi T, Osaka H, Shimizu C, Uehara S, Ohtuki N. Serial magnetic resonance imaging in post-infectious focal encephalitis due to influenza virus. J Neural Sci 1995; 131: 74-7. 9. Donovan MK, Lenn NJ. Postinfectious encephalomyelitis with localized basal ganglia involvement. Pediatr Neural 1989; 5: 31 l-3.
Orginal article
Serial magnetic resonance imaging in children with postinfectious encephalitis Seiji Kimura
*,
Atsuo Nezu, Noriyuki Ohtsuki, Takuya Kobayashi, Saori Uehara
Hitoshi Osaka,
Yokohama City Uniuersity, Urafune Hospital, Deparrment of Pediatn’cs, 3-46, Urafune-cho, Minami-ku, Yokohama, 232 Kanagawa, Japan
Received 27 December 1995; accepted 27 April 1996
We analyzed follow-up magnetic resonance images (MRI) in eight children with clinical postinfectious encephalitis (PIE), and discussed their pathogeneses. Three categories of MRI findings were apparent: (1) multifocal lesions in the white matter with/without basal ganglia involvement consistent with acute disseminated encephalomyelitis (ADEM) (three patients); (2) single or multifocal lesions localized only in the gray matter (two patients); and (3) localized lesions in the brain stem, basal ganglia or cerebellum. Some lesions in the patients in Categories 1 and 2 migrated or were resolved quickly, sometimes within 10 days. Gadolinium caused linear or spotty enhancement in the patients in Category 2. These findings suggest that Categories 1 and 2 are a self-limiting allergic angiopathy without demyelination. In contrast, the lesions in the patients in Category 3 were fixed, and not resolved within 6 months (three patients). The pathogenesis of Category 3 is not known. All except one patient had no prednisolone (PSL) therapy, however; all lesions were resolved completely or markedly reduced in size, which indicates PSL therapy is not always necessary in patients with PIE. Keywords: Encephalitis; Postinfectious encephalomyelitis; acute disseminated encephalomyelitis; Allergic encephalitis; Angiopathy
1. INTRODUCTION Postinfectious encephalomyelitis (PIE) is believed to be an allergic phenomenon initiated by a viral pathogen, and has been considered to be synonymous with acute disseminated encephalomyelitis (ADEM) [l--S]. However, the magnetic resonance imaging (MRI) findings in PIE vary, and features typical of ADEM are not common. Although PIE is commonly considered to be a demyelinating disorder, lesions are sometimes located in the gray matter. In addition, the lesions in the white and gray matter were usually resolved rapidly, which is not typical of demyelinating lesions. The purpose of this study is to clarify the pathogenesis of PIE by analyzing follow-up MRI findings in eight patients.
2. MATERIALS
AND METHODS
We analyzed MRI findings in eight Japanese children with PIE who had preceding infections and who showed MRI evi-
* Corresponding author. Fax: (81) (45) 243-3886. 0387.7604/96/$15.00
dence of lesions in the central nervous system (CNS). There were four females and four males aged 7 months to 14 years. Each child exhibited normal development and the family history was not contributory. Prednisolone (PSL) was not administered except to Patient 4. We now present each case in brief.
3. CASE REPORTS Patient 1: an 11 -month-old boy developed a fever 6 days after receiving the 1st oral poliomyelitis vaccination. He developed ataxia and intention tremor one day after reduction of the fever (day 1). On admission (day 81, he exhibited truncal ataxia, tremor and dysmetria. CSF analysis showed 28/mm3 leukocytes, and CSF protein and glucose concentrations were within normal ranges. Oligoclonal IgG band, myelin-basic protein (MBP) and neuron specific enolase (NSE) were not evaluated. Viral culture was negative. MRI showed widespread lesions in the white matter of the cerebrum and cerebellum, and basal ganglia lesions; high signals on T2-weighted images and mildly low signals on Tl-weighted images. His symptoms had resolved by day 12. Follow-up MRI performed on day 12 showed more expanded
Copyright 0 1996 Elsevier Science B.V. All rights reserved.
PIZ SO387-7604(96)00046-O
462
Fig. 1. Patient 1. a: diffuse high-signal been resolved by day 23.
S. Kimura et al. /Brain
& Development
white matter lesions were seen on T2-weighted
than the first MRI. The third MRI performed on day 23 showed improvement of the lesions; the cerebellar white matter lesions had almost been resolved (Fig. 1). MRI performed on day 54 showed disappearance of the white matter lesions. Patient 2: a 3-year-old girl had a persistent fever for about 1 month. She then developed a static and an intention tremor, and was admitted to our hospital (day 1). She was unable to sit or eat because of the severity of the tremor. CSF analysis showed a leukocyte count of 30/mm3 (mono-/polynucear cell = 5/ 11, and CSF glucose and protein concentrations were within normal ranges. Other data in the CFS was not available. A computed tomography (CT) showed no abnormalities. Her clinical symptoms improved gradually, and she was able to walk on day 24. MRI performed on day 46 revealed widespread lesions of the white matter and basal ganglia, consistent with typical ADEM. Follow-up MRI was performed monthly, and the brain lesions were completely resolved within 6 months. The findings in this patient have been reported previously [6]. Patient 3: a 7-year-old boy with herpes encephalitis (day 1) showed a good recovery after 7 days in the intensive care unit. The leukocyte count in the CSF was 120/mm3 (most were mononuclear cells). CSF protein and glucose concentrations were within normal ranges. MRI showed no abnormalities during the acute phase. However, MRI performed on day 18 showed symmetrical external capsule lesions (Fig. 21, which were almost completely resolved on day 30. CSF analysis on day 20 including cell count, and the values of total protein, gluocse, MBP, and NSE were within normal ranges. Oligoclonal IgG band was negative. The patient’s clinical details have been reported previously [7]. Patient 4: a 14-year-old boy developed a fever and headache on January 31st and was admitted to our hospital on February 5th. Analysis of a lumbar puncture specimen showed 317 cells/mm3 (mono-/polynuclear cell = 3/2). His fever persisted for 2 weeks. MRI performed on February 13th showed no lesions
1996: 18: 461-46s
MRI on day 12. b: the cerebellar
white matter lesions had almost
abnormalities. Treatment with PSL (1 mg/kg/day) was initiated on February 14th, and his fever was resolved within 2 days. He was discharged after 2 weeks of therapy with PSL. A partial motor seizure of the left hand developed on March 7th, and so he
Fig. 2. Patient 3. Symmetrical high signal lesions were seen in the external capsules on T2-weighted imaging, which were resolved almost completely within 12 days. Reproduced from [7] with permission of the publisher.
463
S. Kimura et al./ Brain & Deaelopment 1996: 18: 461-465
Fig. 3. Patient 4. Right: a round, high signal lesion was observed in the right thalamus frontal cortex is indicated by an arrow. These lesions were resolved within 13 days.
was readmitted. Dressing apraxia was present. MRI revealed no abnormalities. The leukocyte count in CSF was 33/mm3 (mono/polynuclear cells = 5/l). and the CSF glucose and protein
on T2-weighted
imaging.
Left: gadolinium
enhancement
in the
concentration were within normal ranges. The value of NSE was normal, and the oligoclonal IgG band was negative. MBE concentration in the serum was 10 ng/ml (normal < 4). MRI per-
Fig. 4. Patient 6. a: a CT scan showed symmetrical but right-dominant low-intensity lesions in the caudate and putamen MRI performed when the girl was 13 years old showed small high-signal lesions in the right caudate and putamen.
(7 months old). b: T2-weighted
464
S. Kimura et al. /Brain
& Development 1996; 18: 461-465
formed on March 14th revealed a high signal intensity lesion in the right thalamus on a T2-weighted imaging. Small gadoliniumenhanced lesions were observed in the right thalamus and the cortex of the right frontal lobe (Fig. 3). PSL therapy was initiated on March 15th. MRI performed 13 days later showed resolution of the lesions. Influenza B HI antibodies were significantly increased. Patient 5: a 13-year-old girl developed a fever and headache on January 20th. On February 10th (20 days after onset of the fever), she had a focal motor seizure and so was admitted to our hospital. She was alert, and a CT scan showed no abnormalities. She developed a fever and headache 10 days after admission. CSF analysis showed 318/mm3 leukocytes (mono-/polynuclear cell = 3/l). CSF glucose and protein concentrations were within normal ranges. Other examinations in the CSF were not avairable. MRI performed on February 25th revealed high signal intensity lesions on T2-weighted imaging in the right parietal cortex and the corticomedullary junction, that showed linear gadolinium enhancement. MRI performed 10 days later showed resolution of the lesions. Influenza B hemagglutinin inhibition (HI) antibody titers were significantly increased. The clinical details of Patients 4 and 5 have already been reported [8]. Patient 6: a 7-month-old girl developed anorexia and hypotonia (day 1) 6 days after resolution of a 5-day episode of vomiting and fever. On admission, she could not hold her head up. A CT scanning of the brain performed on day 11 revealed areas of hypodensity in the bilateral putamen and caudate (Fig. 4a). A CT scan performed on day 36 showed resolution of the lesions. The patient showed a complete recovery. Electroencephalography and CSF analysis including cell count, and protein and glucse concen-
Fig. 6. Patient 8. MRI showed a well-demarcated T2-weighted imaging in the brainstem.
high signal lesion on
trations showed no abnormalities. She is now 13 years old. Although a CT scan showed no abnormalities, small lesions in the basal ganglia were still observed on MRI (Fig. 4b). Patient 7: a 1 year and 6-months-old male exhibited a fever from December 19th to 21st. He developed ataxia and anorexia the day the fever disappeared (day 1). His symptoms improved rapidly; he was able to sit by day 6 and walk by day 7. but his gait was unsteady. By day 14 he was able to walk normally. CSF was not evaluated. MRI performed on day 29 showed high- and low signal cerebellar lesions on T2- and Tl-weighted imaging, respectively (Fig. 5). These lesions became smaller but were found to persist on MRI performed approximately 6 months later. Patient 8: a 3-year-old boy had a fever from July 27th to 30th. His respiration became weak and ataxic on August 1st (day 1). He was admitted to our hospital on day 2 because of drowsiness caused by CO, narcosis. He became alert immediately after being placed on assisted ventilation. MRI revealed a well demarcated brainstem lesion that extended from the pons to the medulla oblongata (Fig. 6). His respiratory disorder gradually improved, and he was able to breathe spontaneously 10 days after admission. He was alert during hospitalization. CSF analysis including cell count and concentrations of protein, glucose, and NSE were within normal range, and oligoclonal IgG band was negative. The value of MBE was normal. CT scan with/without contrast enhancement showed no abnormality. The MRI lesion gradually became smaller but was not resolved completely 6 months later.
4. DISCUSSION
Fig. 5. Patient 7. MRI showed two cerebellar white matter lesions. Top: high signals on T2-weighted imaging. Bottom: low signals on Tl-weighted imaging.
PIE is thought to be an allergic demyelinating disorder, and the term ‘PIE’ is used interchangeably with ADEM [l-5]. However, the diagnosis of demyelinating allergic encephalitis is based on autopsy findings or experimental models of allergic encephalitis, while PIE is diagnosed clinically. Thus it has not been established if PIE is really identical to allergic encephalitis or ADEM.
S. Kimura et al. /Brain
4.1. MRI findings
& Development
in PIE
We classified the MRI findings in the present study as follows. Categorj~ I (ADEM; Patients l-3): multifocal lesions in the white matter with/without basal ganglia consistent with ADEM. Patients 1 and 2 were typical ADEM on MRI, having multifocal lesions in the white matter and basal ganglia, which were dominant in T2-weighted images, but Tl-weighted MRI and CT scans were usually unremarkable. Some of the lesions migrated or were resolved rapidly (within 10 days in Patient 1). All lesions resolved completely within 54 days in Patient 1 and within 6 months in Patient 2. Patient 3 (atypical ADEM?) showed only external capsular lesions, which were almost completely resolved within 12 days. Although these were very small lesions, they looked similar to those in ADEM because they were localized only in the white matter. Category 2 (Postinfectious focal encephalitis: Patients 4 and 5): these patients had characteristic lesions localized only in the gray matter. Linear or small, spotty, gadolinium-enhanced lesions were also observed in both patients. These lesions were resolved rapidly, i.e., within 13 days in both patients. This condition can be more accurately classified as Cutegov 3 (Localized enpostinfectious focal encephalitis. cephalitis of unknown origin; Patients 6-8): these patients had localized lesions in the basal ganglia. brain stem or cerebellum. Long-term follow-up MRI showed that their lesions became smaller, but were not resolved completely.
4.2. Is PIE an allergic demyelinating identical to ADEM?
disorder,
and is it
ADEM has been characterized as an allergic demyelinating disorder involving only the white matter based on autopsy findings including mononuclear cell infiltration and demyelination around small vessels [3], which are similar to the findings in experimental allergic encephalomyelitis in animals. ADEM is usually diagnosed in patients who show characteristic multifocal and widespread white matter lesions on MRI. The term ‘ADEM’ is usually used synonymously with PIE [l-.5]. However, it is controversial whether the widespread lesions of the white matter detected on MRI are truly demyelinated lesions, and it is doubtful if PIE is identical to ADEM. In the present study, typical ADEM was found in only two (Patients 1 and 2) of eight patients with a clinical diagnosis of PIE, suggesting that PIE is not identical to ADEM. Only gray matter lesions were present in two of the five patients in Categories 1 and 2, and the lesions in these five patients, including those with typical ADEM, were resolved rapidly. In Patient 1 with typical ADEM, the cerebellar lesions
465
1996; 18: 461-465
observed on MRI were almost completely resolved within 10 days. Linear or spotty gadolinium enhancement of lesions was observed in Patients 4 and 5. These findings suggest that the lesions in patients in Categories 1 and 2 are caused by angiopathy, not demyelination. The high-intensity T2-weighted images may have been caused by molecules leaking from blood vessels as a result of an increase in vascular permeability. The severe lesions observed in autopsy-proven cases of ADEM are thought to be caused by such angiopathy. The MRI lesions in patents in Categories 1 and 2 were transient and became apparent in the middle or late stage of the CNS manifestations, suggesting that serial MRI may be required for diagnosis and may be useful for elucidating the pathogenesis of this disorder. The pathogenesis of the disorder in the patients in Category 3 is not clear. Although, MRI lesions such as those seen in the patients in Category 3 have been attributed to an immune-mediated event [9], it has not been proved yet. The lesions were not resolved completely in patients in Category 3.
4.3. Is predonisolone
therapy necessary
for PIE?
Only one patient (Patient 4) received PSL. The lesions in all patients having no PSL therapy diminished gradually, suggesting that PIE is a self-limiting disorder.
REFERENCES 1. Perdue Z, Bale JF, Dunn VD, Bell WE. Magnetic resonance imaging in childhood disseminated encephalitis, Pediatr Neural 1985; 1: 3704. 2. Dunn V, Bale JF, Zimmerman RA, Perdue Z, Bell W. MRI in children with postinfectious disseminated encephalomyelitis. Magn Reson Imaging 1986; 4: 25-32. 3. Johnson RT. The pathogeneses of acute viral encephalitis and postinfectious encephalomyelitis. J Infect Dis 1987: 155: 359-64. 4. Whitley RJ. Viral encephalitis. N Engl J Med 1990; 233: 242-50. 5. Kesselring J, Miller DH, Robb SA. et al. Acute disseminated encephalomyelitis. Brain 1990: 113: 291-302. 6. Kimura S. Unayama T. Mori T. The natural history of acute disseminated leukoencephalitis. A serial magnetic resonance imaging study. Neuropediatrics 1992; 23: 192-5. 7. Kimura S, Nezu A. Osaka H, Saitou K. Symmetrical external capsule lesions in a patient with herpes simplex encephalitis. Neuropediatrics 1994; 25: 162-4. 8. Kimura S, Kobayashi T, Osaka H, Shimizu C, Uehara S, Ohtuki N. Serial magnetic resonance imaging in post-infectious focal encephalitis due to influenza virus. J Neural Sci 1995; 131: 74-7. 9. Donovan MK, Lenn NJ. Postinfectious encephalomyelitis with localized basal ganglia involvement. Pediatr Neural 1989; 5: 31 l-3.