[Presentation of Case]
A 32-year-old man, previously healthy, presented to the emergency departement because of high fever for two days. He reported sleepy, decreased appetite, and general malaise since four days earlier before this presentation. There was headache once, which improved soon after. His family noticed that he had weird talks and responses in these days. But his family denied that he had respiratory, gastrointestinal or genitourinary symptoms. He worked in his farm in Hsin-Chu county, and had not travel outside Hsin-Chu recently. There were no contacts with sick people, but there were farm animals near his house, including pigs. He also fed street dogs and cats in his neighborhood every evening. He did not smoke, consume alcohol or betel nut, or use illicit drug. And there were no hereditary diseases or malignant diseases in his family. On examination, the temperature was 40.5℃, pulse rate 60 per minute, respiratory rate 20 per minute, and blood pressure 117/85 mmHg. He appeared confused with mutism. He had masklike face, with slow eye blinking and movement. There were also neck and back stiffness, right hemiparesis, bradykinesia, hypokinesia, and limb rigidity. Increased deep tendon reflex was observed in the right limbs. The computed tomography of the brain showed no acute hemorrhage or organic lesions. The results of laboratory study, including cerebrospinal fluid analysis, are showed in Table 1. A rapid diagnostic test for influenza reported negative. Ceftriaxone, ampicillin, and acyclovir were administered, and he was admitted. After admission, the magnetic resonance imaging of the brain showed an ill-defined hyperintense area at the left thalamus with mild volume increase as compared to the right side (Figure 1). Japanese encephalitis was suspected. Two days after, detection of IgM and IgG for Japanese encephalitis virus in a serum sample and IgM in a cerebrospinal fluid sample was confirmed by the Centers for Disease Control, Taiwan. Fever gradually resolved 3 days after admission. His cognitive function and muscle power also improved, and he could recognize his family on the 4th day of hospitalization. The EEG reported diffuse slow wave over the bilateral cerebral hemispheres. On the 7th day, he could walk steadily, answer questions, and write his name. He was discharged without further neurogenic sequelae after 2 weeks of hospitalization.
Laboratory studies.
1. CBC and differential count:
WBC
/μl |
RBC
M/μl |
Hb
g/dl |
Plt
K/μl |
Hct
% |
MCV
fL |
Band
% |
Seg
% |
Baso
% |
Eos
% |
Mon
% |
Lym
% |
10200 |
4.7 |
15.4 |
191 |
43.6 |
92.0 |
0 |
81.0 |
0.1 |
0 |
7.2 |
11.7 |
2. Biochemistry:
ALT
U/L |
AST
U/L |
T-bil
mg/dL |
Cre
mg/dL |
Na
mmol/L |
K
mmol/L |
Albumin
g/dL |
CRP
mg/dL |
20 |
11 |
1.1 |
1.3 |
142 |
3.8 |
4.2 |
2.8 |
3.Cerebrospinal fluid analysis:
Appearance |
RBC |
WBC
/μl x11/9 |
L:N |
Glucose,
mg/dL |
Total protein,
mg/dL |
Opening pressure,
cmH2O |
India ink
stain |
Clear |
31 |
268 |
97%:3% |
57 |
104 |
23 |
negative |
Figure 1. Magnetic resonance imaging of the brain. There is an ill-defined hyperintense area at the left thalamus on DWI (1A), T2WI (1B) and FLAIR (1C) images, which is heterogenoeusly hypointense on T1WI with mild volume increase as compared to the right side (1D). There is no obvious increased meningeal enhancement after intravenous administration of gadolinium, but there is subtle corticovascular enhancement.
[討論]
本病例為日本腦炎 (Japanese encephalitis) 個案，並具其典型的臨床症狀及影像表現。日本腦炎病毒 (Japanese encephalitis virus) 為單股RNA病毒，和西尼羅河病毒 (West Nile virus) 和聖路易斯腦炎病毒 (St. Louis encephalitis virus) 同屬於黃病毒屬 (Flavivirida) 中的一員，在全世界每年造成 67,900 人以上感染，並造成 15,000人以上死亡 [1]。在全世界的分布中，北起西伯利亞、日本、韓國，南至中國大陸、台灣、印度、尼泊爾、緬甸、泰國、馬來西亞、菲律賓、印尼、斯里蘭卡、澳大利亞之間的西太平洋諸島嶼......等。在美洲、歐洲、非洲，則除了零星個案外，尚無大規模流行 (Figure 2) [2]。其傳播之媒介為家蚊 (Culex)，在台灣主要由三種家蚊傳播：孳生於水田的三斑家蚊 (Culex tritaeniorhynchus)、環紋家蚊 (Culex annulus)，和孳生於溼地的白頭家蚊(Culex fuscocephal)(Figure 3) [3]。日本腦炎病毒的流行以夏季為主，氣溫越高，其傳播力也越強。台灣主要的流行季為五月到十月，其中又以七月為高峰，而在一天當中，以黎明和黃昏為病媒蚊吸血活動之高峰期。日本腦炎在自然界中的宿主，除了人類之外的其他動物，有豬、鳥類、病媒蚊的成蚊，其中豬是日本腦炎的增幅動物 (amplifying animal)，也就是病毒會在豬隻體內大量繁殖，造成病毒血症 (viremia)，再經由病媒蚊傳播給人類。人類為終端宿主 (dead-end host)，因此不會直接人傳人。
感染日本腦炎後，約有1%的人會進展為疾病，其餘為無症狀至輕微類感冒症狀。中樞神經系統，包括腦、腦膜 (meninges)、脊髓都可能受感染，而大部分以腦炎為主。小孩及老人若發病，較易進展至較嚴重之臨床表現。其潛伏期約5至15 天，而後典型的病況可分為四個時期：(1) 前驅期 (2至3天)：此時期的症狀發作快，主要會出現頭痛、噁心、嘔吐、食慾不振、發燒或輕微呼吸道感染症狀。 (2) 急性期 (3至4天)：高燒、伴隨腦膜刺激現象、頸部僵硬、帕金森氏症候群(Parkinsonian syndrome)之症狀 、面具臉 (masklike face)、四肢僵硬、深部及淺部反射異常、震顫 (tremor)、不語 (mutism)、小腦共濟失調 (cerebellar ataxia)、神智不清、對人時地不能辨別、 甚至昏迷或死亡。 (3) 亞急性期 (7至10天)：中樞神經的侵犯趨緩。 (4) 恢復期 (4至7週)：此時期的病患大部分會有神經功能缺損，包括四肢僵硬、無力、腦神經及錐體外路徑 (extra-pyramidal tract) 的異常 [3]。日本腦炎在腦部的感染，於影像上亦有特殊表現。腦部電腦斷層上，典型的表現是在丘腦 (thalamus)、基底核 (basal ganglia) 有密度降低 (hypodensity) 的表現，或甚至出血。日本腦炎感染患者，約 56% 在腦部電腦斷層上會出現異常。腦部核磁共振比電腦斷層敏感，在丘腦 (thalamus)、基底核 (basal ganglia)、黑質 (substantia nigra)、小腦 (cerebellum)、橋腦 (pons)、大腦皮質 (cerebral cortex)、脊髓 (spinal cord) 都可能發現病灶，其病灶在 T1 影像上為低訊號 (hypointense)，在 T2 影像和 Fluid Attenuation Inversion Recovery (FLAIR) 上為高訊號 (hyperintense)。若在日本腦炎流行區，病患有腦炎之臨床表現，加之腦部核磁共振上出現雙側丘腦 (thalamus)病灶，即可高度懷疑日本腦炎病毒感染 [4]。腦波的表現以diffuse slowing、epileptiform activity、alpha coma 為主，較無特異性 [4]。實驗室診斷多倚賴血清和腦脊髓液的日本腦炎病毒 IgM 抗體，其在症狀開始後 3 至 8 天即可測得，並會在人體內維持 30 到 90 天。因其在人體內可維持較長時間，因此單次 IgM 抗體陽性亦有可能代表過去的感染，最好再與恢復期的 IgM 抗體比較來做確認。目前並沒有任何治療方式對日本腦炎病毒感染有顯著好處，主要還是以支持性療法為主。惟併發腦炎症狀之患者，死亡率仍高，約 20-30%，而存活的病人中，有 30-50% 會有神經學上的後遺症 [4]。
在台灣，於民國二十年開始出現日本腦炎的臨床記載，自此之後每年都有日本腦炎的病例，且遍佈全省各縣市。日本腦炎屬於第三類傳染病，需於一周內通報。當病患有腦膜炎症狀，且出現發燒、意識障礙、嘔吐、頸部僵硬、抽筋、肌張力異常、頭痛、腦膜刺激症狀、精神症狀等其中任一項，或臨床上高度懷疑且與確定病例有流行病學上的相關性時，即需通報。台灣日本腦炎疫苗的接種，每年3至5月為疫苗主要的接種期，兒童共需四劑，建議幼童於出生滿15個月接種第一劑，間隔兩週接種第二劑，隔年接種第三劑，至國小一年級再接種第四劑。而因工作、生活環境有感染之虞之高風險成人亦應自費接種日本腦炎疫苗。台灣使用的疫苗是由鼠腦製作的去活性疫苗 (inactivated vaccine)。根據台灣衛生福利部疾病管制署的統計資料，台灣地區15至90歲人口平均日本腦炎抗體陽性率71%，而24至40歲(1961-1977出生)陽性率最低 (47-61%) [3]。除了疫苗之外，最好的預防方式就是避免病媒蚊的叮咬，如：避免於病媒蚊活動的高峰期，如黃昏，在豬舍、 其他動物畜舍或病媒蚊孳生地點附近活動。
Figure 2. 日本腦炎的全球分布圖，深紅色區域為日本腦炎流行區。 (引用自 http://www.cdc.gov/japaneseencephalitis/maps/index.html )
Figure 3. 日本腦炎的傳播途徑 (取自台灣衛生福利部疾病管制署網站)
參考文獻
- Campbell G, Hills S, Fischer M, et al. Estimated global incidence of Japanese encephalitis:. Bull World Health Org 2011; 89:766–774.
- http://www.cdc.gov/japaneseencephalitis/
- 台灣衛生福利部疾病管制署網站，疾病介紹：日本腦炎
- Misra UK, Kalita J. Overview: Japanese encephalitis. Prog Neurobiol 2010; 91:108-20.
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Case Discussion
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