Original Articles

Acute Infantile Encephalopathy Predominantly
Affecting the Frontal Lobes
Hideo Yamanouchi, MD*, Naoko Kawaguchi, MD*, Masato Mori, MD†,
George Imataka, MD*, Takanori Yamagata, MD†, Teisuke Hashimoto, MD‡,
Mariko Y. Momoi, MD†, Mitsuoki Eguchi, MD*, and Masashi Mizuguchi, MD§
To establish a novel subtype of acute infantile encephalopathy, the clinical and radiologic features of nine
infants with acute encephalopathy involving the bilateral frontal lobes were examined. These patients had
convulsive status epilepticus with hyperpyrexia followed by a prolonged impairment of consciousness for
2-20 days. After the recovery of consciousness, all thepatients manifested regression of verbal function andlack of spontaneity. Some of them also exhibited stereotypic movements, instability of mood, or catalepsy.
Transient postictal edema in both frontal lobes was
suggested by diffusion-weighted magnetic resonanceimaging. Attenuated cerebral perfusion in the frontal
lobes was demonstrated by single-photon emission
computed tomography at the tenth day after onset or
subsequently. Serial studies disclosed atrophic changes
in the frontal lobes. All patients manifested regression
or retardation of motor and verbal functions. The
recovery of intellectual deficit was slower and lessprominent than that of motor dysfunction. These
unique features suggest that the frontal lobes are thefocus of this novel subtype of acute encephalopathy,
which we propose to call acute infantile encephalopathy predominantly affecting the frontal lobes. © 2006
by Elsevier Inc. All rights reserved.

Yamanouchi H, Kawaguchi N, Mori M, Imataka G,
Yamagata T, Hashimoto T, Momoi M, Eguchi M, Mizuguchi M. Acute infantile encephalopathy predominantly
affecting the frontal lobes. Pediatr Neurol 2006;34:93-100.

From the Departments of *Pediatrics and ‡Radiology, Dokkyo
University School of Medicine, Tochigi, Japan; †Department ofPediatrics, Jichi Medical School, Tochigi, Japan; §Department ofPediatrics, Graduate School of Medicine, University of Tokyo, Japan.

© 2006 by Elsevier Inc. All rights reserved.
doi:10.1016/j.pediatrneurol.2005.08.002 ● 0887-8994/06/$—see front matter

Introduction
Convulsive status epilepticus with hyperpyrexia andprolonged impairment of consciousness are common clinical features of acute encephalopathies and encephalitides
in childhood. Several subtypes of acute encephalopathy
have been established and classified based on their clinical, radiologic, and laboratory findings: Reye syndrome[1], hemiconvulsion-hemiplegia-epilepsy syndrome [2],acute necrotizing encephalopathy in childhood [3], andhemorrhagic shock and encephalopathy syndrome [4].
Among these, Reye syndrome and hemorrhagic shock andencephalopathy syndrome are presented with diffuse cerebral edema. By contrast, the other syndromes are characterized by the involvement of specific cerebral regions:unilateral cerebral hemispheric lesions in hemiconvulsionhemiplegia-epilepsy syndrome, and bilateral symmetricallesions in the thalamus, cerebral white matter, brainstem,
and cerebellum in acute necrotizing encephalopathy. Focal
cerebral lesions are also encountered in many types ofacute encephalitis: e.g., orbital and medial temporal lesions in herpes simplex type 1 encephalitis, and disseminated multiple lesions in acute disseminated encephalomyelitis [5].
This study describes an acute encephalopathy of childhood characterized by unique clinical and radiologic
features suggesting bilateral involvement of the frontal
lobes. There are at least seven similar cases reported
previously, but the nature of the syndrome has remained
obscure [6,7]. We believe that this syndrome is a novel
subtype of acute encephalopathy in childhood, and propose the term “acute infantile encephalopathy predominantly affecting the frontal lobes (AIEF)”.

Communication should be addressed to:
Dr. Yamanouchi; Department of Pediatrics; Dokkyo University Schoolof Medicine; 880 Kitakobayashi, Mibu; Shimotsuga; Tochigi 3210293, Japan. E-mail: yhideo@dokkyomed.ac.jp
Received April 22, 2005; accepted June 10, 2005.

Yamanouchi et al: Acute Infantile Encephalopathy 93

Patients and Methods
This study focused on nine children (aged 7 months to 3 years at onset,
four males and five females) who were admitted to our hospitals from1999 through 2003 and had the following features: (1) convulsive statusepilepticus with hyperpyrexia and prolonged impairment of consciousness, (2) regression of mental or motor function after the recovery of
consciousness, (3) a cerebrospinal fluid leukocyte count of 8 cells/mm3
or less at onset, (4) neuroradiologic evidence for selective involvement ofboth frontal lobes, and (5) no other reasonable explanation for the
cerebral or metabolic abnormalities. Informed consent for this study was
obtained from all parents.
Magnetic resonance imaging was performed with a 1.0 or 1.5 T
clinical magnetic resonance system. Axial spin-echo T1- and T2-weighted
images as well as fluid-attenuated inversion recovery images with 5 mm
thickness were obtained in all patients. Diffusion-weighted imaging was
performed in two patients. Apparent diffusion coefficient maps were notavailable for this study. Cerebral perfusion was evaluated by singlephoton emission computed tomography using 99mTc-ethyl cysteinate
dimer for seven patients, 99mTc-hexamethyl propylene amine oxime forone patient, and 123I-N-isopropyl-p-iodoamphetamine for one patient.
Single-photon emission computed tomography images were evaluatedwith reference to images of age-matched control cases reported in theliterature [8-10]. Electroencephalograms were recorded every day until
the recovery of consciousness. Subsequently, electroencephalograms
were recorded monthly or bimonthly for the first half year and at 6-monthintervals thereafter.

Results
Clinical Features of Patients
Prenatal and perinatal histories were uneventful in all
patients. They had normal developmental milestones andTable 1.

Clinical features of patients

Age at onset
Sex
Duration of convulsions
Initial feature
Recovery of
consciousness after
onset
Clinical features after
the recovery of
consciousness
Lack of spontaneity
Regression of verbal
function
Instability of mood
Catalepsy
Stereotypic
movements
Recovery or gain offunction after onset
Sitting
Walking
Speaking words
Speaking sentences
Period of observation

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Patient 6

Patient 7

Patient 8

Patient 91 yr 3 momale
100 minCSE

11 mo
female110 minCSE

11 mo
female60 minCSE

2 yr
female40 min
UC

7 mo
male
40 minUC

2 yr 4 mofemale60 minCSE

2 yr 10 mofemale30 minCSE

3 yr 2 momale
30 minCSE

1 yr 1 momale
35 minCSE

7th day

20th day15th day

5th day

14th day2nd day

2nd day

14th day2nd day

yes

yes

yes

yes

yes

yes

yes

yes

yes

yes
no
no

yes
no
no

yes
no
no

yes
yes
no

yes
no
no

yes
yes
yes

yes
yes
no

yes
no
no

yes
no
no

yes

no

yes

no

no

yes

yes

no

no

2nd mo3rd mo22nd mono39 mo

6th mo8th mo14th mo19th mo
43 mo

4th mo10th mo
22nd mo39th mo
54 mo

1st mo2nd mo2nd mo2nd mo24 mo

3rd mo10th mo20th mono24 mo

1st mo1st mo3rd mo8th mo44 mo

1st mo1st monono
28 mo

1st mo1st monono
26 mo

1st mo2nd monono
14 mo

Abbreviations
CSE ⫽ Convulsive status epilepticus
UC ⫽ Unconsciousness

94

no history of remarkable illness. Minor anomalies were
not observed in any patient. None of the patients received
immunization within several weeks before the onset of
encephalopathy. The family history was also unremarkable except that two of the patients’ parents had had febrile
convulsions in childhood. There were neither similar
encephalopathies, other neurologic and metabolic disorders, sudden infantile death syndrome, other forms ofearly unexplained death, nor consanguinity.
All patients had hyperpyrexia, and convulsions appeared within 24 hours after the onset of fever. The initialneurologic symptom was convulsions in seven patientsand unconsciousness in two. The febrile illness was
influenza type A in three patients, exanthema subitum in
two, measles in one, and nonspecified upper respiratory
viral illness in three. Acetaminophen was administered toPatients 1 and 3 before admission; the others received no
antipyretic treatment. Although some patients were administered antibiotics or expectorants, or both, there was no
history of exposure to drugs or chemical substances
known to cause toxic encephalopathies. All patients had
generalized tonic-clonic convulsions lasting for 30 minutes or longer. They were treated with antiepileptics,
including diazepam, midazolam, phenytoin, and pentobarbiturate. All patients fell into a comatose state, reaching ascore of 3 or 4 according to the Glasgow Coma Scale asmodified for children [11]. Two patients were treatedunder mild hypothermia, with an eardrum temperature of

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Vol. 34 No. 2

tenth month from onset, respectively. No patient had
ataxia or paralysis. As compared with the recovery of
motor function, regression and subsequent retardation of
language development were generally striking. Seven
patients could not speak words, even 12 months after
symptom onset. Four patients (Patients 1, 3, 7, and 8)
could not speak two-word sentences even at 3 years of age
or after (Table 1).

34.5°C to 35.5°C. Consciousness recovered between thesecond day and the twentieth day from symptom onset.
Abnormal behavior was noticed after the recovery of
consciousness. Regression of verbal function and lackof spontaneity (marked diminution of active and voluntary behavior) were observed in all patients, although
they had no motor paralysis and could behave in
response to the brief commands by parents or physicians. Loss of spoken words or sentences was evident insix patients, and disappearance of babbling in three.
Instability of mood was observed in three patients.
Patient 6 had catalepsy; once she had her arms lifted by
the examiner, she maintained the fixed posture forseveral minutes. Four patients transiently manifested
various types of stereotypic movements, including tapping on one hand, sucking the hands and then throwing
the arms forward repeatedly, or jumping on the bed.
Such movements appeared at the second or third weekfrom onset, persisted through the waking hours, andlasted for 1 to 4 weeks (Table 1).

Laboratory Findings
In most patients, laboratory tests indicated mildly tomoderately increased levels of lactate dehydrogenase andcreatine kinase, reaching peak levels on the third to theseventh day from symptom onset. In Patient 5, lactate
dehydrogenase and creatine kinase rose strikingly to 4680
U/L and 63,400 U/L, respectively. No patient had hyperammonemia or hypoglycemia. The results of carnitine andamino acid analyses were normal. Cerebrospinal fluid
samples obtained on the first or second day revealed
normal protein levels in all patients but Patient 5, who had
an elevated cerebrospinal fluid protein level of 52 mg/dL.
Interleukin-6 was measured in three patients, and waselevated up to 157 pg/mL and 180 pg/mL in cerebrospinal

Clinical Features on Follow-up Study
Motor functions regressed in all patients. The patients
could sit and walk without support by the sixth month andTable 2.

Laboratory and radiologic findings

Blood tests
AST (U/L) (onset¡peak)
LD (U/L) (onset¡peak)
CK (U/L) (onset¡peak)ammonia (␮g/dL)
glucose (mg/dL)
CSF
Cell count (/␮L)
Protein (mg/dL)
Glucose (mg/dL)
MRI
Atrophy in FLs(the period of detection)
HI on FLAIR in FLs
SPECT
Decreased perfusion in
FLs(the period of detection)
Follow-up studies(the period of thefindings)

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Patient 6

Patient 7

Patient 8

Patient 911¡13565¡1046
72¡59832
235

39¡104834¡1376
803¡3345
1
181

21¡19
764¡1502
285¡458
11
93

12¡22
636¡91758¡1015140

6¡58702¡4680
319¡63,400
22
121

14¡14
614¡116468¡121
51
128

13¡32
335¡62284¡153
53
253

16¡22
576¡969
96¡132
113
239

13¡63
375¡529112¡765
5
92

7
21
ND

8
24
ND

7
26
56

2
10
102

1
52
114

1
12
53

3
27
71

2
13
83

1
10
60

yes
(29th day)noyes
(23rd day)yes

yes
(22nd day)yes

yes
(40th day)noyes
(20th day)yes

yes
(21st day)yes

yes
(23rd day)yes

yes
(31st day)noyes
(42nd day)noyes
(10th day)improved(21st mo)yes
(23rd day)normalized(20th mo)yes
(21st day)normalized(38th mo)yes
(42nd day)normalized(7th mo)yes(19th day)normalized(16th mo)yes
(19th day)normalized(7th mo)yes
yes(13th day) (40th day)unchanged NA(20th mo)yes
(30th day)improved(7th mo)Abbreviations
AST⫽ Aspartate aminotransferase
CK⫽ Creatine kinase
CSF⫽ Cerebrospinal fluid
FLAIR ⫽ Fluid-attenuated inversion recovery
FLs⫽ Frontal lobes
HI⫽ High intensity
LD⫽ Lactate dehydrogenase
MRI⫽ Magnetic resonance image
NA⫽ Not available
ND⫽ Not done
SPECT ⫽ Single-photon emission computed tomography

Yamanouchi et al: Acute Infantile Encephalopathy 95

Figure 1. Diffusion-weighted magnetic resonance imaging (TR/TE ⫽ 3300 ms/123 ms, b ⫽ 1000 s/mm2). (A) High signal intensity (arrowheads) in thecortex of both frontal lobes at the sixth day from onset in Patient 5. (B) High signal intensity (arrows) in the cortex and white matter of both frontal lobes
at the sixth day from onset in Patient 9.

fluid of Patients 4 and 5, respectively. In these twopatients, interleukin-6 in the serum was 3.1 and 16.9
pg/mL, respectively (Table 2).
Electroencephalography
Electroencephalograms were obtained at symptom onset in six patients and indicated slow background activity
waves. Two patients presented with high-amplitude delta
activity predominantly in both frontal areas. Follow-up
electroencephalograms obtained 1 year after onset revealed focal spike or spike-and-wave discharge in threepatients. Epilepsy developed in one patient (Patient 6),
who had several episodes of staring with unconsciousness
lasting for more than 5 minutes. This patient was given adiagnosis of localization-related epilepsy.
Neuroradiologic Findings
Initial magnetic resonance imaging was performed between the sixth and ninth days from symptom onset in six
patients (Table 2). Two patients (Patients 5 and 9) who
underwent diffusion-weighted magnetic resonance imaging on the sixth day had high signal intensity in the cortex
and white matter of both frontal lobes on diffusionweighted images, but not on spin echo T2-weighted
images (Figs 1A, 1B). One patient (Patient 7) had diffusely increased signal intensity in the cortex and subcor-

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tical white matter of both frontal lobes on T2-weighted
magnetic resonance imaging on the sixth day from symptom onset (Figs 2A, 2B). Diffusion-weighted images were
not obtained in this patient. The other patients disclosed noabnormal findings on the initial T1, T2, and fluid-attenuated inversion recovery magnetic resonance imaging studies. On serial magnetic resonance imaging studies performed between the 20th day and 42nd day from onset,
atrophic changes were observed in both frontal lobes of all
patients; fluid-attenuated inversion recovery images documented mildly increased intensity in the white matter ofboth frontal lobes in five patients (Figs 3 and 4). Follow-up magnetic resonance imaging studies were performed in eight patients between the seventh month andfiftieth month from symptom onset. Atrophic changes had
improved or resolved in seven patients, but progressive
atrophic changes were present in the frontal cortex andinsular cortex in one patient (Patient 7, Fig 2C).
On single-photon emission computed tomography
studies, decreased perfusion in both frontal lobes was
detected in all patients between the tenth day and the42nd day after onset (Figs 2D, 3D-3F, 4E, 4F). Follow-up single-photon emission computed tomography
studies were performed in eight patients. In five patients, normalized cerebral perfusion was observed
between the seventh month and the 38th month after
symptom onset (Figs 4G, 4H). Two patients demonstrated improved perfusion between the seventh monthFigure 2. Axial (A) and sagittal (B) views of
T2-weighted magnetic resonance imaging (TR/TE ⫽4600 ms/110 ms) at the sixth day from onset inPatient 7, depicting high intensity in the cortex andsubcortical white matter of both frontal lobes (arrowheads in (A) and small arrows in (B)). (C)Fluid-attenuated inversion recovery image (TR/TE/TI ⫽ 6744 ms/110 ms/1588 ms) at the 20thmonth after onset in Patient 7, revealing atrophic
cortical changes and high intensity of both frontal
lobes and insulae. (D) Single-photon emission computed tomography study (99mTc-ethyl cysteinate
dimer) at the 20th month in the same patient,revealing decreased perfusion in the bilateral frontal lobes and left temporal lobe (arrow).

and the 21st month from onset. In one patient (Patient7), decreased perfusion in the frontal lobes was observed even at the twentieth month after symptom
onset. In this patient, decreased perfusion was also
observed in the left temporal lobe (Fig 2D).
Discussion
All patients in our series manifested convulsive statusepilepticus within 24 hours after the onset of hyperpyrexia.
Although initially suspected, the diagnosis of prolonged
febrile seizures was eventually ruled out based on theirsubsequent neurologic and imaging findings. They had
prolonged impairment of consciousness after the prolonged convulsions, and lack of spontaneity and regressionof verbal function were observed after the recovery of
consciousness. As compared with the relatively good
recovery of motor functions, acquisition or restoration ofverbal function was delayed in most patients. In addition,some of the patients subsequently exhibited abnormal
behaviors: stereotypic movements and catalepsy. Magnetic resonance imaging suggested postictal edematouschanges in the white matter and cortex of both frontal
lobes. Single-photon emission computed tomography
studies revealed decreased perfusion predominantly in thefrontal lobes, which improved or normalized over thecourse of months or years in most patients. Rarely,
decreased perfusion persisted and was associated with

progressive bilateral atrophic changes with sustained highsignal intensity on T2-weighted image in the frontal lobes.
These unique features differ distinctly from those observed in previously established types of acute encephalopathy in childhood. None of the patients in the present
study had the metabolic abnormalities typically observedin Reye syndrome, such as hyperammonemia, hypoglycemia, or abnormal amino acid analyses [1]. Other congenital metabolic disorders, such as aminoaciduria, urea cycle
disorders, or disorders of ␤-oxidation of fatty acids, arealso ruled out on the same grounds [12]. The biochemical
abnormalities of our patients’ serum were mostly mild andnonspecific. The high serum level of creatine kinase isascribed to the prolonged convulsions, whereas that oflactate dehydrogenase may have resulted from the underlying viral infections, or from the effect of cytokines, suchas interleukin-6, as discussed later.
In our patients, the clinical picture consisted of multiple
focal neurologic signs, and the radiologic picture wascharacterized by multiple localized lesions in the cerebral
cortex. These features are reminiscent of acute disseminated encephalomyelitis. This encephalitis is caused by anautoimmune response, and is usually observed several
days or more after the viral illness. Imaging studies inacute disseminated encephalomyelitis commonly reveal
multiple areas of T2 prolongation in the white matter, andto a lesser extent in the cortical and deep gray matter. They
are moderate to large in size, and disseminated randomly

Yamanouchi et al: Acute Infantile Encephalopathy 97

Figure 3. Serial magnetic resonance imaging (A, B, C: fluid-attenuated inversion recovery images, TR/TE/TI ⫽ 6744 ms/110 ms/1588 ms andsingle-photon emission computed tomography (D, E, F: 99mTc-ethyl cysteinate dimer) studies in Patient 1, which were performed at the tenth day (A, D),
the seventh month (B, E), and the 21st month (C, F) from onset. Decreased cerebral perfusion in the frontal lobes was evident at the tenth day (D).
Progressively decreased perfusion as well as atrophic change in the frontal lobes was observed at the seventh month. Improvement of perfusion andatrophy in the frontal lobes appeared at the 21st month.

in various regions of the brain [5,13]. However, neurologic
symptoms in the patients in the present study developed
within 24 hours after the development of viral infection.
Lesions detected by magnetic resonance imaging studies
were symmetric and localized exclusively in the frontal
lobes. These findings differentiate our patients’ condition
from acute disseminated encephalomyelitis.
On diffusion-weighted or T2-weighted magnetic resonance imaging, increased intensity in both frontal lobes
was found in three of the six patients who underwent
magnetic resonance imaging between the sixth day and theninth day from onset. Transient signal changes on magnetic resonance imaging in patients with status epilepticus
have been reported, suggesting focal episodes of transientcerebral cytotoxic or vasogenic edema caused by epileptic
seizures [14,15]. Diffusion-weighted magnetic resonanceimaging is useful for detecting periictal edematous lesionsof the cerebrum after seizures, as demonstrated by studies
in which initial magnetic resonance was generally done
within 3 days from symptom onset [14,15]. Earlier diffusion-weighted images might consistently reveal postictal
edematous changes in the white matter and cortex of thefrontal lobes.

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One of the cardinal features of our patients was decreased perfusion predominantly in the frontal lobes on
single-photon emission computed tomography, appearing
on the tenth day or subsequently. Decreased perfusion
normalized or improved between the seventh month andthe 38th month from onset in seven patients, but persisted
in one patient who had progressive atrophy of both frontal
lobes found on magnetic resonance imaging. These characteristics of cerebral perfusion, including the distribution
and chronologic changes of suspected lesions, are notobserved in other subtypes of acute encephalopathy. Evidence of restoration of cerebral perfusion in the frontal
lobes suggests that this syndrome is associated with neuraldysfunction or hypofunction in the cortex of the frontal
lobes, which gradually resolves with the passage of time inmost cases.
The frontal lobe is thought to have crucial roles ininitiation, planning, designing, and sequencing [16,17].
Dysfunction of the frontal lobe and its connections produces a wide array of signs and symptoms, such as
cognitive impairment, disturbance of behavioral planning,
and loss of working memory, i.e., temporary storing of
information used to guide future actions [16,17]. Func-

Figure 4. Serial magnetic resonance imaging (A, B, C, D: fluid-attenuated inversion recovery image, 6744 ms/110 ms/1588 ms) and single-photon
emission computed tomography (E, F, G, H: 99mTc-ethyl cysteinate dimer) studies in Patient 3, which were performed at the 21st day (A, E), the twelfth
month (B, F), the 38th month (C, G), and the 52nd month (D, H) from the onset. Markedly decreased perfusion and atrophic changes were observed in
the frontal lobes at the 21st day (A, E). The decreased perfusion was improved at the 12th month, and then normalized at the 38th month or subsequently.
High signal intensities in the white matter of the frontal lobes were observed between the 21st day and the 38th month, and disappeared at the 52nd month.

tional magnetic resonance imaging studies have demonstrated activation of the dorsolateral prefrontal cortex inawake infants processing normal speech, suggesting that
precursors of adult cortical language areas are alreadyactive in infants, well before the onset of speech production [18]. Psychologic testing, using the A not B task, has
documented the emergence of working memory from 7 to
12 months of age [19]. Frontal lobe dysfunction may occur
even during infancy, during which bursts of functional
development emerge in the premotor and prefrontal cortex. The regression of verbal function and lack of spontaneity as well as the various stereotypic movements in ourpatients are considered signs of dysfunction of the frontal
lobes and related areas [20]. Defective social and moral
behaviors are suspected to occur in adults with a history of
prefrontal cortex lesions developing before the age of 16months [21]. Children with AIEF should therefore be
carefully observed for the potential development of psychopathy.
The etiology and pathogenesis of AIEF are unknown.
In an attempt to explore the possible involvement of
immunologic mechanisms, we assayed cytokines in the
blood and cerebrospinal fluid of three patients, andfound that the concentration of interleukin-6 in cerebrospinal fluid was much higher than that in serum in twoof them. Although the number of patients examined waslimited, this evidence suggests that interleukin-6 was, atleast in part, actively produced in the central nervous
system in this illness. A high cerebrospinal fluid levelof interleukin-6 is also present in other types of acuteencephalopathy in childhood, but not in prolonged
febrile seizure [22].
The mechanisms and contributions of overexpressedinterleukin-6 in patients with acute encephalopathy
remain controversial: both destructive and protectiveroles of interleukin-6 in the central nervous system havebeen suggested. Transgenic mice in which interleukin-6
is expressed under the control of the glial fibrillary
acidic protein promoter manifest neurodegeneration anddisruption of the blood– brain barrier [23]. Phenotypically, these mice exhibit impaired learning as well as
tremor, ataxia, and seizures [24]. In contrast, increased
levels of interleukin-6 might have a neuroprotectiverole, acting against insults such as against excitotoxic
brain injury [25]. Prolonged convulsions could provoke
oxidative stress and accumulation of calcium in neurons, resulting in the release of cytochrome c frommitochondria, activating caspase-3 and caspase-7.
These series of events could lead to apoptotic neuronalcell death. Apoptotic processes have been demonstrated
in status epilepticus [26] as well as in acute encephalopathy in childhood [27]. Interleukin-6 is produced inneurons in response to excitatory receptor activationand protects against excitotoxic effects potentially leading to apoptosis [28]. Measurement of cytochrome c andcytokines including interleukin-6 in cerebrospinal fluid
may be helpful when evaluating brain insults in AIEF
and other acute encephalopathies in children.
In conclusion, this study describes a unique subtype ofacute encephalopathy in infancy, characterized by pro-

Yamanouchi et al: Acute Infantile Encephalopathy 99

longed impairment of consciousness after convulsive status epilepticus with hyperpyrexia, regression and subsequent retardation of language development, lack ofspontaneity, periictal edematous changes, and subsequent
decreased perfusion in the frontal lobes. We believe that
this syndrome is a novel subtype of acute encephalopathy
in infancy, and we propose to call it acute infantile
encephalopathy predominantly affecting the frontal lobes(AIEF).
We thank Dr. Takashi Ichiyama (Yamaguchi University School of
Medicine) for cytokine assay. Dr. Hideo Yamanouchi was funded by
grants (H14-shoni-004 and 15A-4) from the Ministry of Health, Labor,and Welfare, Japan. Dr. Masashi Mizuguchi was funded by a grant from
the Ministry of Health, Labor, and Welfare (H15-shinko-4), Japan.

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