Dokkyo Journal of Medical Sciences38（2）：161 〜 164，2011161

Case Report

A Fatal Case of Acute Encephalopathy in a 8-year-oldgirl from a Pandemic of Influenza A（H1N1）in 2009
＊George Imataka, Eisei Hoshiyama, Keiko Tsukada, Kenji Miyamoto,
Yoshiyuki Watabe, Yuya Sato, Osamu Arisaka
Department of Pediatrics, Dokkyo Medical University School of Medicine＊Critial care & Medicine, Dokkyo Medical University School of Medicine

SUMMARY
We report on a case in which a child died from acute encephalopathy associated with Influenza A（H1N1）
pdm. The case pertains to an 8-year-old girl, who was diagnosed with influenza A on the previous day andwas prescribed zanamivir hydrate. She experienced abdominal pain and delirium the next morning, so she
was referred to our hospital. Her level of consciousness at the time of consultation was JCS 200. In the brain
CT scan, a swollen brain stem and bilateral middle cerebral artery were depicted. She was in a state of respiratory failure, and was admitted to the intensive care unit. She was diagnosed with acute encephalopathy
caused by Influenza A, and therapeutic brain hypothermia as well as steroid pulse therapy were performed；however, she died on the third day after hospitalization from multiple organ failure.
Key Words：Pandemic, Influenza A（H1N1）,Acute encephalopathy, child, underlying disease

INTRODUCTION
In the year of 2009, there was a pandemic of H1N1
influenza, and there were several mortalities. In Japanalso, this epidemic gradually expanded starting in Mayof the same year. Moreover, there was no detailed in-tic course, even given our concept of acute encephalopathy associated with seasonal influenza, as far as weunderstand it. We herein report on the clinical courseof the present case.

CASE REPORT

formation regarding any serious life threatening com-

An 8-year old girl consulted her local doctor as a re-plications, such as acute encephalopathy and severe

sult of having developed a fever. A quick test for Influ-pneumonia, which thus had a widespread impact onenza A from the nasal cavity identified her as being

Japanese society.

positive, and so she was diagnosed with Influenza A.

We experienced a fatal child case in November ofShe was then prescribed zanamivir hydrate. The next

the same year, which was the middle of the influenza

morning, she was continually in a delirious state fromseason, in which the death was caused by acute en-

the fever and strong abdominal pain, and consulted thecephalopathy associated with Influenza A（ H 1 N 1）.

emergency room of our hospital due to a sudden loss

The course taken by the child was an extremely dras-of consciousness. The level of consciousness of thechild was 2 0 0 on the Japan Coma Scale. A swollen

Received March 1, 2011；accepted March 29, 2011
Reprint requests to：George Imataka M.D., Ph.D.
Department of Pediatrics, Dokkyo Medical
University School of Medicine, Mibu, Tochigi
321-0293 Japan.

brain stem and bilateral middle cerebral arteries wereobserved in the brain CT scan（ Fig. 1）. No signs ofpneumonia were observed in the chest X-rays. Spontaneous respiration was very shallow and she was in astate of respiratory failure, so tracheal intubation was

162

George ImatakaFig. 1

Table 1WBC 9,900/m l
RBC 622×104 /m l
Hb 18.0 g/dl
Ht 52.8％
Plt 10.4×104 /m l

DJMS

Brain CT scan on admission

Blood examination data on admission

AST 369 U/L

Na 136 mEq/l

TP 8.0 g/dl

PT 26.0 sec

Fbg 129 mg/dl

ALT 91 U/L
LDH 1,392 U/L
NH 3 86 mg/dl

K 3.8 mEq/l
Cl 104 mEq/l
Amy 1,826U/l

Alb 4.7 g/dl
CRP 0.82 mg/dl
IgG 1,339 mg/dl

PT-NC 12.2 sec
PT％ 27％
APTT 99.1 sec

Hpt 38％
FDP 80.0 m g/ml（over）
D-Dimer 30.0 m g/ml（over）

Glu 61 mg/dl
CK 572 U/l

IgA 182 mg/dl
IgM 146 mg/dl

APTT-NC 30.4 sec

SFMC negative
AT-Ⅲ 61％

BUN 40 mg/dl
Cre 1.89 mg/dl

required immediately. In a blood test（Table 1）taken

pdm-like symptoms which broke out in Mexico andon admission, various abnormalities were observed insequentially spread in the form of an epidemic to theAST, LDH, CK, as well as coagulation tests, etc. Cere-United States and Canada was H 1 N 1 influenza. Onbral spinal fluid collection revealed normal data as fol-May 9 th of the same year, in Japan also, H1N1 influen-lows, cell count 1 /mm, protein 2 9 mg/dl, Glucouseza was detected in 4 airline passengers from North-

91 mg/dl. In generic testing of the influenza serotype,west of America. Subsequently, the epidemic rapidly

which used nasal secretions taken at the time of ad-

spread throughout the country, and the number of in-

mission, she was diagnosed with an infection of pan-fected patients increased to 3 7 0 people on May 3 0 th

demic Influenza swA（H1N1）. Mild brain hypothermic

and to 1 2 6 6 people by the end of June. On August

therapy as well as steroid pulse therapy by methyl-15 th, one of the first domestic cases of a death due toprednisolone were commenced under the control of ar-

influenza A（ H 1 N 1）pdm was identified in Okinawa

tificial respiration, however, the system vitals remained

prefecture, and by December of the same year, theunstable, and it proved necessary to discontinue thedeaths of 135 people were reported within Japan. Fur-therapeutic brain hypothermia after 3 6 hours. There

thermore, the pace did not even abate by the begin-

was no improvement in the multiple organ failure fromning of 2 0 1 0 , and ultimately, by March 1 5 th, 2 0 1 0 ,the blood test, and the child died on the 3 rd day of hos-when the season came to an end, a total of 198 cases

pitalization.

of influenza-related deaths had been confirmed 1）.

DISCUSSION

Concerning the cases of death by infection during
the influenza A（ H 1 N 1）pdm epidemic period fromIn April 2 0 0 9 , the WHO（ World Health Organiza-

2009 to 2010 published on the web site of the Ministrytion）officially announced that the influenza A（H1N1）

of Health, Labor and Welfare 1）, when the breakdown38（2）（2011）

Acute encephalopathy with Pandemic Influenza A（H1N1）

163

Numberof death18
16
Without
underlying
disease1412With
underlying
disease108642>11䡐45䡐910䡐14

Age (year)

15䡐19

 he Child case of death by infection during the H1N1 influenza epidemic period
Tfrom 2009 to 2010 in Japan

Fig. 2

Table 2The number of death by infection during the H1N1 influenza epidemic period from 2009 to 2010 in Japan

Age（year）

＜1

1～4

5～9

Number ofdeath

317

1353

111431

31

25

23

22198

With
underlying
disease1344

1402223252122138

10～14 15～19 20～29 30～39 40～49 50～59 60～69 70～79 80＜Total
numberby age（ Table 2）is examined, out of all 1 9 8 cases,

early schooling. Moreover, out of all 4 1 cases of childmortalities involving children under 2 0 years old ac-

mortalities, 1 3 children（ 3 1 . 7％ ）had underlying dis-counted for a total of 41 cases. In a breakdown of theeases, and when the ratio of children with underlying

child mortality cases（ Fig. 2）, the number of deaths

diseases within the general population of this age

was greatest, at 1 7 cases, for children over one year

range was considered, this indicated an exceedingly

old to under 4 years old, and out of these, there were 3

high percentage.

cases in which the children had underlying diseases.

In addition, correlation between influenza A（H1N1）

There were 13 cases of death in children over 5 years

pdm and acute encephalopathy was reported on theold to under 9 years old, and out of those, there were 4

web site of the Japan Infectious diseases surveillancecases wherein the children had underlying diseases,center 2）. From the 2 8 th week of 2 0 0 9 until January

which followed the preceding age range. Other than

22 nd, 2010, 120 cases of encephalopathy due to influen-

that, there were 5 cases of death in children over 1 0za A（ H 1 N 1）pdm were reported. The age distribu-years old to under 1 4 years old, 3 cases of death intion was 1 to 70 years of age（median：7 years）, andchildren over 15 years old to under 19 years old, and 3

the cases included 74 males, and 46 females. An under-cases of death in children under one year of age. In

lying disease and previous medical history were ob-view of this data, the number of child mortalities

served in 57 cases out of 119 cases, and there were 24

showed a trend, frequently occurring in nursery schoolcases of febrile convulsion, as well as 16 cases of bron-and kindergarten, from older children to children inchial asthma. The period from the onset of fever untilGeorge Imataka

164

DJMS

the occurrence of an impaired consciousness was：29

hypothermia and steroid pulse treatment, which arecases for 0 days, 6 6 cases for 1 day, 1 4 cases for 2often reported to be useful as treatments for influen-days, 4 cases for 3 days, and 2 cases for 4 days（medi-za-associated encephalopathy, with the patient underan：1 day）. An impaired consciousness was observed

respiratory management 4,5）；however, she did not re-before the onset of fever in 1 case. The duration of im-

spond to any to these treatments and, as a result, shepaired consciousness was, out of 1 1 6 cases：4 0 cases

died. There was no autopsy, and therefore, we cannot

for over 48 hours, 17 cases for 24 to 48 hours, 30 cases

report on the detailed conditions of the disease. How-for 12 to 24 hours, and 29 cases for less than 12 hours.

ever, in the brain CT image taken just before she wasConvulsions were observed in 66 cases（age：1 to 24

admitted to the intensive care unit, the manifestation

years, median：7 years）, and among those, 2 6 casesof a swollen brain stem and bilateral middle cerebral

were observed with status epilepticus. Abnormal be-artery was observed. These are considered to be an

havior and abnormal speech were observed in 81 cases

indication of edema and angiitis. Perhaps this pathog-（age：1 to 70 years old, median：8 years）. Treatment

nomonic image manifestation is specific to influenza-

included steroid pulse treatment（97 cases）, g -globulin

associated encephalopathy caused by pdm.

treatment（49 cases）, hypothermic cerebral protection

Currently, the Ministry of Health, Labor, and Wel-（ 1 2 cases）, high dose antithrombin III treatment（ 5fare is in the process of totaling child mortality casescases）, plasmapheresis（ 2 cases）, and cyclosporinecaused by influenza A（ H 1 N 1）pdm in the 2 0 0 9 totreatment（2 cases）. No treatment was performed for2 0 1 0 season by means of a national consultational in-18 cases（15％）. An artificial respirator was used forvestigation, led by 2 research teams：the Morishima

32 cases. The number of days from the onset of feverteam and the Kondo team. From 2011 onward, reports

to impaired consciousness in the 8 cases of mortalityof acute encephalopathy in children caused by influen-（ age：3 to 3 5 years, median：4 . 5 years）was 1 to 3za A（H1N1）pdm show no signs of decline. Cases ofdays（median：1 day）
, and the number of days fromacute encephalopathy in children caused by A（H1N1）

the onset of fever to death was 1 to 47 days（median：pdm have been accumulated, and along with this, the3.5 days）. Psychoneurotic disorders were observed inoverall picture has thus become clear. We eagerly

13 out of the 14 cases that involved subsequent com-hope for the early establishment of treatment as wellplications, and physical disabilities, such as motor pa-

as precautionary measures, as soon as possible.

ralysis, incontinence, etc., were observed in 8 cases.

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