Case Discussion      A 58-year-old woman was admitted to the hospital because of left limbs focal tonic seizure and marked confusion.      The patient had been well until nine years ago, when diabetes mellitus developed. It was managed with insulin. The dosage of the insulin had not changed recently. She suffered from general malaise on 12/23. Fever, chills, nausea, vomits, and headache developed on 12/25. The patient was admitted to local hospital where laboratory tests revealed leukocytosis (WBC: 11,820/uL with 74% seg.) and pyuria (WBC: 15-20/HPF). A urine culture yielded methicillin-resistant Staphylococcus aureus. Intravenous cefazolin and gentamicin were administered. But she became disoriented (self-talking and change of sleep pattern) on 12/27. Haloperidaol was given under the impression of delirium. The WBC was 9140/uL on 12/31. Antibiotics were shifted to oral form on 1/1, but fever up to 38.5℃ was noted on 1/2 morning. Left focal seizure with left limbs tonic movement with mouth angle deviation and neck stiffness was noted. The patient was transferred to this hospital on 1/2.      On examination, the temperature was 38.5℃ , the pulse rate was 110/min, and the respiration rate was 24/min. The blood pressure was 105/60 mm Hg. On neurologic examination, the patient was confused and could be aroused to speak a few words. She could not know her name, location, or date. Pupils were isocoric, rounded and reactive to light. Facial expression was symmetric. Neck was stiff. Muscle strength by observation was 3 in the left arm and 4 in the right arm and legs. Muscle bulk and tone were normal. There were no hyperreflexia and plantar reflex.      Laboratory tests revealed that WBC was 30,060/uL with 7% band form and 76% segment, hemoglobin 15.5 g/dL, platelets 263K/uL, serum glucose 350 mg/dL, serum sodium 145 mmol/L, potassium 3.67 mmol/L, chloride 99 mmol/L, calcium 2.15 mmol/L, albumin 3.4 g/dL and ammonia 29 umol/L. Her renal function was BUN 19.5 mg/dL and Cre 0.93 mg/dL. A specimen of arterial blood revealed that pO2 was 126mm Hg, pCO2 28.4mm Hg, HCO3- 15.5mmol/L, pH 7.35, base excess -8.4 mEq/L, and anion gap 26 mEq/L. The urine was positive for glucose (>= 1.0g/dL) and ketones (3+). Urine sediment was normal. A lumbar puncture revealed that WBC was 10/uL with L:N= 9:1,RBC 2/uL, protein 69 mg/dL, and glucose 188 mg/dL. A CT of the head with and without contrast showed no definite focal mass or abnormal enhancement and the ventricles were normal in size. Phenytoin was prescribed. Shock developed and conscious level deteriorated at general ward. The patient entered the intensive care unit. Confusion and disorientation persisted after serum glucose, pH and hemodynamic status were corrected. Antibiotics with acyclovir, ceftriaxone and penicillin G were given for treatment of meningoencephalitis. On 1/4, EEG revealed one episode of subclinical seizure, periodic generalized epileptic form discharge and moderate diffuse cortical dysfunction. Brain MRI examination showed increased hyperintense signal in the bilateral medial temporal areas and insulas. The patient's conscious level improved in the following days. After the condition improved, the patient was transferred back to general ward on 1/10. Ceftriaxone and penicillin G were discontinued because there was no evidence of bacterial infection. The blood sugar was under control by insulin injection. We kept acyclovir use for 14 days and her conscious recovered gradually. Then he was discharged with mild sequela on 91/01/21. 病案分析       本病例是一單純(ㄆㄠˋ)疹病毒所致之腦膜腦炎(Herpes simplex meningoencephalitis)。Herpes simplex meningoencephalitis常易被誤診，而延誤治療。主要是臨床的表現並無特一性，病人一開始可能發燒、頭痛、噁心，而被誤為其他感染症。在給予抗生素下，病人持續惡化，產生精神方面的症狀 (psychotic symptoms)；譬如：性格改變，甚至被誤認為acute psychosis。然後可能發生抽搐，以及 focal neurological signs，此時大家一定會做電腦斷層，但結果可能如本病例般，電腦斷層沒有發現異常。此時須高度懷疑meningoencephalitis，需要做CSF 的檢查，Herpes simplex meningoencephalitis CSF中淋巴球稍微增加、有紅血球、蛋白質稍微增高、sugar可能正常。此時高度懷疑是herpes simplex meningoencephalitis，給予intravenous acyclovir。進一步安排EEG，有典型的periodic lateralized epileptiform discharge，以及MRI有localized temporal abnormalities。       CSF之HSV DNA PCR具有高度sensitivity及specificity幾乎可以取代brain biopsy。而CSF之HSV culture在成年病患中較少培養出來。       當懷疑herpes simplex meningoencephalitis時就必須即早使用acyclovir。延遲使用acyclovir將使病人預後非常差(死亡或有嚴重的neurological deficits)。 繼續教育考題 1. (B) 下列何者最可能是 Herpes simplex meningoencephalitis 的表現? A A 24 year old woman with two months of fatigue and arthralgias, presenting with mild fever, and a facial rash B A 50 year old woman with fever and headache developing after diagnosis of acute psychosis, and EEG revealing periodic epileptiform discharges from the left temporal region. C A 20 year old woman with three days of fever, night sweats, conscious disturbance and a heart murmur D A 20 year old woman with sudden onset of severe headache, vomiting and loss of consciousness 2. (D) Herpes simplex virus (HSV) meningoencephalitis can be excluded by: A Psychotic symptoms B Normal or near-normal CSF studies C Absence of focal findings on CT D None of the above 3. (C) HSV meningoencephalitis 可以下列哪些檢查來確定，除了何者以外？ A Culture of HSV from CSF B CSF PCR to detect HSV DNA C Active herpes labialis associated with clinical meningoencephalitis D Culture of HSV from brain tissue. 4. (A) 下列何者為真？ A There are no pathognomonic clinical findings of HSV meningoencephalitis. B HSV meningoencephalitis is a seasonal epidemic infection with peaks of incidence in the winter. C Herpes labialis is noted in the majority of patients with HSV meningoencephalitis. D There is no effective treatment for viral meningoencephalitis. 5. (B) 下列何者為真？ A Acyclovir should be administrated with rapid infusion to reach effective concentration. B Nephrotoxicity of acyclovir may result from renal tubular precipitation during excessive dosage or dehydration C Gancyclovir is the first line of treatment for HSV meningoencephalitis. D Acyclovir does not cause phlebitis at the IV site. 6. (D) 當懷疑一位36歲男病患得了 HSV meningoencephalitis，下列何者是對的？ A 最可能引起此病人HSV meningoencephalitis的病毒是HSV-2 B 此病人需盡快作brain biopsy 以確定診斷 C 與此病人接觸之家屬及醫護人員，需服用acyclovir 以預防感染 D 需盡快給予此病人注射acyclovir 7. (D) 關於HSV meningoencephalitis adult的CSF findings，下列何者是錯的？ A 一開始時，CSF 檢查可能是正常 B CSF之HSV DNA PCR 檢查，在發病一星期後可能轉為 negative C 在non-traumatic tapping，CSF中可以有相當數量的 RBC D CSF 培養出 HSV-1 的比率 > 70% 8. (D) HSV meningoencephalitis 病人在下列何者情況下，其neurological sequelae 較嚴重 ? A Delayed treatment B Age>30 years old C Coma D All of the above 9. (D) 治療HSV meningoencephalitis 病人，需給予下列何治療 A Anticonvulsant regimens to treat seizure B Fluid restriction and avoidance of hypotonic intravenous solution to prevent IICP C Intravenous acyclovir 10 mg/kg every 8 hours for at least 14 days D All of the above 10. (D) HSV encephalitis should be considered in a febrile patient with which of the following clinical features? A Bizarre hehavior or personality alteration B Memory disturbance C Olfactory or gustatory hallucination D All of the above