Case Discussion <Presentation of a case> This 67 year-old man, an aborigines and a retired fisher living in the countryside of Taitung, had been well until 25 August, 2006 when he began to experience generalized headache, general myalgia, and arthralgia over multiple joints that continued for one month prior to this admission. He had no history of head injury, fever, night sweats or weight loss. Gradual onset of ptosis of the right eye was found by his family at the same time. The symptoms progressed and he sought medical attention at the Emergency Department of Tzu-Chi Hospital in Hua-Lien on 24 September, 2006, where computed tomography of the brain did not reveal any specific lesion. Two days later, he was brought to our outpatient department on 26 September, 2006 for second opinion because his movement became retarded. He was admitted to our ward for further evaluation and treatment. According to his statement, he did not raise pets, but he fed chicken in the court. He had no recent travel. He used to eat cooked snails several times a week since he was young. He denied a history of tuberculosis or use of Chinese herb remedies or over-the-counter medicines. On admission, his consciousness was clear but speech was sluggish. The body temperature 37.2℃, pulse rate was 76 beats per minute, and respiratory rate was 20 breaths per minute and the blood pressure was 104/60 mmHg. His conjunctiva was pink and sclera was not icteric. The pupils were isocoric with prompt reaction to light. Right eye was ptotic but the eye movement was intact. There was no oral thrush or oral ulcers in the oral cavity. The neck was supple without lymphadenopathy, engorged jugular veins, palpable thyroid gland or carotid bruits. The chest wall expansion was symmetric, and breath sounds were bilaterally clear. The heart beats were regular without audible murmur. The abdomen was soft. Bowel sounds were normoactive and liver and spleen were impalpable. His extremities were freely movable without edema. There was no cyanosis, petechiae, purpura or pigmentation. The genitalia were free of ulcers and discharge. <Laboratory data> 1. Hemogram CBC+PLT WBC K/μL HB g/dL HCT % MCV fL  PLT K/μL Band % Segment % Eos % 950925 4.41 14.2 41.6F 94.3 151 3 26 40 951002 9.41 14.2 42.9 96.6 154 0 62.1 0.7 951018 3.66 14.1 43.6 98.4 132 0 39.6 16.7 2. Biochemistry (BCS) and electrolytes BCS T-Bil U/L GOT U/L ALP U/L r-GT U/L LDH U/L BUN mg/dl Cre mg/dl Uric Acid mg/dl 950925 0.89 28 168 36 405 11.2 0.7 5.7 BCS Na mmole/l K mmole/l Cl mmole/l  Ca mmole/l Mg mmole/l 950925 140 3.7 106 2.24 405 3. Stool examination         Egg concentration (III sets): no parasite ova were identified. 4. Cerebrospinal fluid (CSF) study CSF Appearance Opening pressure (mmH2O) Closing Pressure (mmH2O) Protein g/dl glucose mg/dl  WBC cells/ul L:N:Eos RBC /ul 950925 Clear 165 120 0.104 47 150 62:2:86 0 CSF AFS TB culture Virology Bacterial Fungus Weil- Felix  Widal 950925 Negative Negative Negative Negative Negative Negative Negative CSF India ink smear Cryptococcal Antigen VDRL Cytology 950925 Negative Negative Negative Negative <Course and treatment> After admission, a lumbar puncture was performed. The CSF was clear; however, it showed pleocytosis with eosinophil predominance (Lymphocyte/Neutrophil/Eosinophil: 62/2/86). No parasite was seen by microscopy. Praziquantel was prescribed for six doses and ivermectin 12mg was given. Magnetic resonance imaging (MRI) of the brain showed mild nonspecific white mater change. The follow-up eosinophil count showed decreasing, and he felt improvement. Steriods were tapered. However, the eosinophil count increased to about 600 cells/μL. Another dose of ivermectin was given on 11 October 2007. Bone marrow biopsy to search for other causes of hypereosinophilia showed erythroid hyperplasia with an increased number of eosinophils. We sent the CSF specimens to Professor Huang Kao-Pin's (黃高彬) laboratory where a positive antigen test for Angiostrongylus cantonensis was found. <Discussion> Eosinophilia is defined as the presence of more than 500 eosinophils per microliter of peripheral blood. The common etiologies are infection, inflammation, iatrogenic agent and malignancy. Eosinophilic meningitis is defined as the presence of 10 or more eosinophils/uL in the CSF specimen or eosinophilia of at least 10% of the total CSF leukocyte count. The common etiologies of eosinophilic meningitis are infections with parasites, fungi, bacteria, rickettsiae, and viruses and malignancy. A. cantonensis is the leading etiology of eosinophilic meningitis caused by parasites. Reaction to 31KD monoclonal antibody of A. cantonensis is found to be diagnostic, with sensitivity of more than 90% and specificity of nearly about 100%. The pumping lumbar puncture method has been found to increase the recovery rate of the A. cantonensis larva. Larva recovery rate ranges from 24% to 50%. The incubation period was 2 to 35 days. Headache, nuchal rigidity, and visual disturbance are common clinical manifestations. Fever is seen in less than half of the patients with eosinophilic meningitis due to A. cantonensis. Paresthesia and hyperesthesia of the extremities, trunk or face are the most distinctive neurological findings. Paralysis of the extraocular or facial nerve, delirium, seizures, and persistent cognitive dysfunction have been reported. Most of the symptoms were self-limiting. Steroids and larvicidal agents could help improve the symptoms. Most of the cases were reported from southern and eastern Taiwan. <References> 1. Am J Med. 2003;114:217-23. 2. Southeast Asia J Trop Med Public Health 2003;34;1-6. 3. Clin Infect Dis 2001;33:112-5. 4. Southeast Asian J Trop Med Public Health 1991;22:194-9. 繼續教育考題 1. (E) Eosinophilia 是指每microliter超過多少顆噬酸性白血球?  A 100 B 200 C 300 D 400 E 500 2. (A) 造成急性嗜酸性腦膜炎(eosinophilic meningitis)最常見的寄生蟲？  A Angiostrongylus cantonensis 廣東住血線蟲 B Gnathostoma spinigerum 棘頷口線蟲 C Paragonimus westermani 衛氏肺吸蟲 D Schistosoma japonicum 血吸蟲 E Taenia solium (neurocysticercosis) 豬肉絛蟲 3. (B) 下列敘述何者為是？ A 如果檢體中沒有看到蟲卵，就沒辦法證實病人感染廣東住血線蟲 B 如果檢體中沒有看到蟲卵，還可以用31KD monoclonal antibody to Angiostrongylus cantonensis 佐證我們的想法 C 31KD monoclonal antibody敏感性很低 D 31KD monoclonal antibody 特異性很低 E 從CSF中可以看到蟲卵的機會很高 4. (A) 有關Angiostrongylus cantonensis 感染造成臨床表現的敘述，何者有誤？ A 一半以上的人會出現發燒 B 潛伏期約為 2 to 35 days. C 常見頭痛 D 常見頸部僵硬 E 常見視覺障礙 5. (B) 台灣Angiostrongylus cantonensis 感染較常見在哪些區域？ 1. 東部 2. 西部 3. 南部 4. 北部 5. 中部      A 1 + 2 B 1 + 3 C 1 + 4 D 1 + 5 E 3 + 5 6. (A) 有關Angiostrongylus cantonensis 的治療敘述那個有誤？ A 一定要用抗寄生蟲藥物 　 B Acetaminophen可以緩解症狀 C 類固醇可以減少頭痛與使用止痛藥的次數 D 大部分的病症會自行緩解 E 少部分的病人會進展到coma status 答案解說 【E】 Eosinophilia 的定義是每microliter 的血液中有超過500顆噬酸性白血球 The definition of eosinophilia is defined as the presence of more than 500 eosinophils per microliter of blood. Harrison's Principles of Internal Medicine, 16 th Edition 【A】 最常造成急性嗜酸性腦膜炎的寄生蟲是廣東住血線蟲 The most common parasitic etiology of acute eosinophilic meningitis is Angiostrongylus cantonensis. Am J Med 2003;114:217-23. 【B】 如果檢體中沒有看到蟲卵,還可以用31KD monoclonal antibody to Angiostrongylus cantonensis 佐證我們的想法。它的敏感性高達90%，特異性接近100%。一般的腰椎穿刺可以看到蟲卵的比列約24%。 Courtesy: Prof. Kao-Pin Hwuang (黃高彬), Kaoshiung CGMH Southeast Asia J Trop Med Public Health 2003;34;1-6. 【A】 廣東住血線蟲感染的潛伏期約2至35天。常見的症狀有頸部僵直和視力模糊；少於一半的人會有發燒的症狀；一些神經感覺異常的症狀也曾經被報導過。 The incubation period was 2 to 35 days. Headache, nuchal rigidity, and visual disturbance are common clinical manifestations. Fever is seen in less than half of the patients with eosinophilic meningitis due to A. cantonensis. Paresthesia and hyperesthesia of the extremities, trunk or face are the most distinctive neurological findings. Paralysis of the extraocular or facial nerve, delirium, seizures, persistent cognitive dysfunction have been reported. Am J Med 2003;114;217-23 【B 】 台灣東部與南部地區於民國75年的嗜尹紅性腦炎年發生率，每十萬人大於15人，其他區域都是小於15人。 疫情報導 民國75年 期刊 黃高彬 【A 】 大部份的症狀不需藥物治療就會自行緩解. 類固醇與抗寄生蟲的藥物可以改善不舒服的症狀 Most of the symptoms were self-limited. Steroids and larvicidal agents could help improve the symptoms. Clin Infect Dis 2001;33:112-5.