Case Discussion <Brief History> The 43-year-old man had fever, headache for about one week and loss of consciousness for one day. He had been in good health before until 1 week before admission when he had fever, headache, generalized malaise and myalgia. There were no rhinorrhea, no cough, no sorethroat or cutaneous exanthems. The headache was over the fronto-temporal area without photophobia or visual disturbance. He visited LMD where acute tonsillitis was told. However, the headache and fever did not subside after medication. He loss his consciousness four days after the initial presentation. He was taken to local hospital where high fever and neck stiffness were noted. Brain CT scan did not reveal abnormal findings. He was then referred to our hospital. At our hospital, fever, leukocytosis, neck stiffness and impaired consciousness were noted. A recent travel history to Thailand one month ago was told. Lumbar puncture revealed pleocytosis with neutrophil predominant (WBC 63/ul L/N 3/60, open/close pressure 165/140cmH2 O, protein 86 mg/dl, glucose 77 mg/dl). Brain MRI study revealed meningitis with brain parenchymal change. However, prolonged and repeated generalized tonic-clonic seizure without regain of consciousness developed on the next day. He was put on antibiotics with ceftriaxone, and acyclovir for meningitis and phenytoin for generalized tonic-clonic seizures. Under the impression of meningoencephalitis with status epilepticus without defined pathogens, he was admitted to ICU for further care. <Physical Examination> Consciousness:comatous, vital sign:BP 124/80 mmHg, T/P/R: 36.8/92/20,HEENT: grossly normal ,Conjunctiva not pale, sclera not icteric, pupils isocoric, light reflex: +/+, Neck: stiff, no lymphadenopathy, no jugular vein engorgement, Chest: symmetric expansion, breathing sound clear, Heart: regular heart beat, no murmur Extremities: freely movable, no cyanosis, no pitting edema, Kernig's sign (+), Brudzinski's sign (+) <Laboratory> [ CBC+PLT ] WBC RBC HB HCT MCV MCH MCHC PLT K/μL M/μL g/dL  %  fL  pg g/Dl K/μL 17.93  5.16 11.8 35.1 68.0 22.9 33.6 127.0 Seg Eos Baso Mono  Lym % % % % % 76.1 0.1 0.4 9.6 13.8 [ Coagulation Rout ] PT PT Cont INR  PTT  PTT Cont sec sec   sec sec 12.4 11.4 1.0 38.3 31.5 [ Biochemistry ] GLU UN CRE T-BIL AST mg/dl mg/dl  mg/dl mg/dl U/l 105.0  6.0 0.8  0.5  23.0 Na  K Cl Ca Mg mmmole/l mmole/l mmole/l mmole/l mmole/l 135.0 3.7 100.0 1.97 0.8 檢 體 : C.S.F Count (L:N:M&H) TP GLU AC  AFS GS Indian Ink Cytology /ul g/dL mg/dl         63 ( 3:60:0) 0.086 77 (-) (-)  (-) (-) 15 (13:2:0) 0.044 70 (-) (-) (-) (-) Blood Culture & Sensitivity test: No aerobic&anaerobic pathogens C.S.F. HSV-PCR : positive C.S.F: No aerobic&anaerobic pathogens C.S.F Fungus: No fungus 項 目 檢驗值 Anti-HIV Non-Reactive 項 目 檢驗值 Virus isolation: Blood Negative 項 目 檢驗值 Virus isolation: C.S.F. Negative [ Blood pH/Gas ] PH PCO2 PO2  HCO3 BaseExc mmHg mmHg mEq/l mEq/l   7.41 37.5 93.0 23.0 -0.9 <Course and Treatment> After admission, repeated generalized tonic-clonic seizures without regain of consciousness still persisted. HSV-PCR was strong positive and HSV meningoencephalitis was diagnosed. He was treated with phenytoin and intermittent intravenous diazepam. Repeated cerebrospinal study 3 days later showed pleocytosis with lymphocyte predominant ( WBC 15/ul, L:N 13/2). Due to prolonged seizures under anti-epileptic medications with unstable oxygenation and hemodynamics, he was intubated and transferred to ICU. Acyclovir (10 mg/kg q8h) was given for 14 days. Thiopental with titration from 50mg to 125 mg/hr for 21 days, lamotrigine with titration from 200 mg to 400 mg/day and midazolam continuous infusion with 0.2 mg/kg/hr to 0.8 mg/kg/hr were used to control seizure activity. Serial EEG study revealed gradual improvement without frequent seizure spikes. The attack of generalized tonic-clonic seizure decreased but not totally subsided. He underwent tracheostomy for airway protection and off-ventilatory support smoothly. Intermittent generalized tonic-clonic seizure which lasted for about 1 minute persisted. His consciousness was clear during interictal periods with labile moods and some impairment of higher cortical function. Rhabdomyolysis due to repeated generalized tonic-clonic seizure gradually imporved after hydration and urine alkalization. He was transferred to neurologic general ward on for further care. <病歷分析> 本病例為一中年男性發燒頭痛數日後，出現頸部僵硬和意識障礙，而進入昏迷狀態。腰椎穿刺腦脊髓液中出現噬中性白血球、蛋白增加等發炎現象。三天後之腦脊髓液檢查發現發炎細胞變成淋巴球為主，腦部MRI檢查顯示腦膜和腦實質有發炎反應，診斷為急性腦膜腦炎。後續腦脊髓液之炮疹病毒PCR呈陽性反應，因此確診為炮疹病毒造成之腦膜腦炎。病人在住院期間出現癲癇之重積狀態，因為對一般抗癲癇藥物反應不佳，因此病人被轉送至加護病房治療。隨後病人接受thiopental, lamotrigine, midazolam等藥物治療，其癲癇之重積狀態才被控制。病人之後恢復意識，但殘存部分神經之損傷。 炮疹病毒性腦膜腦炎，男女的發生率相近，其發生並無地域或季節之區別。臨床表現以發燒頭痛（frontal, retrobulbar, with photophobia or pain on moving the eyes），和腦膜刺激之症狀。腦脊髓液內之發炎反應，以淋巴球增多為主，蛋白質的含量稍增加，而葡萄糖的含量正常。當有腦炎發生時，會出現意識狀態改變，人格改變，50％之嚴重腦炎會出現癲癇的現象。診斷此疾病主要是由腦脊髓液檢查發現淋巴球為主的發炎現象，同時利用CSF nucleic acid amplification的方法（PCR）偵測炮疹病毒的核酸存在來診斷，CSF的病毒培養常常並無結果。此病之治療，主要是給予acyclovir 10 mg/kg q8h for 14 days，加上支持療法。 癲癇的重積狀態，其定義為二次以上次第的癲癇發作，其間病人的意識狀態無法恢復，或者是持續的癲癇發作超過30分鐘（有人定義5分鐘）以上。其原因可分成急性原因：代謝障礙（電解質異常、腎衰竭、敗血症等）、中樞神經系統感染、中風、頭部外傷、藥物中毒和組織缺氧。慢性原因：本來就存在的癲癇症因停藥而發作，酒精成癮等。癲癇的重積狀態其原因是多重的，主要是因為使癲癇停止的機轉失常。如興奮性的神經傳導物過多或抑制性的神經傳導機制失常等。臨床上，處理的原則第一是要保持呼吸道的暢通，必要時需氣管插管。當有體溫升高時要降溫。當病人使用長效之肌肉麻痺劑或長期使用抗癲癇藥物而效果不佳時，需監測腦電圖。 藥物的治療：當診斷確立後就要馬上開始使用抗癲癇藥物，80％的病人在30分鐘內使用第一線藥物（diazepam followed by phenytoin）後癲癇可被控制。當使用benzodiazepine, phenytoin或phenobarbital後癲癇的重積狀態無法被控制，稱為refractory status epilepticus，此時須要更積極的治療。持續的靜脈滴注midazolam, propofol或barbiturate等麻醉劑最有效。midazolam的劑量為 0.2 mg/kg slowly IV，然後 0.75∼10μg/kg/min；propofol 1-2 mg/kg IV，然後 2-10 mg/kg/hr持續12至24小時，若臨床或EEG監測，癲癇不再發作再慢慢減量。 繼續教育考題 1. (C) Concerning HSV meningoencephalitis, which is wrong in the following statements? A HSV accounts for 10 to 20% of all causes of sporadic viral encephalitis in U.S. B HSV encephalitis may be caused by reactivation of latent HSV infection or reinfection C HSV meningitis is not usually seen in association with primary genital HSV infection D HSV is the most commonly identified cause of recurrent lymphocytic meningitis 2. (B) Concerning HSV meningoencephalitis, which is wrong in the following statements? A CSF study showed mild to moderate pleocytosis with lymphocyte predominance, normal sugar level B EEG showed paroxysmal sharp waves of triphasic complexes with a temporal predominance which is a pathognomonic pattern for HSV encephalitis C Primary diagnostic test is CSF nucleic acid amplification for HSV D Encephalitis is commonly associated with HSV-1 infection 3. (A) Concerning status epilepticus, which is wrong in the following statements? A Status epilepticus of generalized onset accounts for the majority of episodes B The incidence of status epilepticus was bimodally distributed, occurring most frequently during the first year of life and after the age of 60 years C In adults, the major causes were low levels of antiepileptic drugs D The mortality rate among children was only 3 % 4. (C) The causes of status epilepticus that had the highest mortality rate are (is)? A alcohol withdrawal B low levels of antiepileptic drugs C anoxia and stroke D electrolyte abnormalities 5. (B) Which is not the systemic complication of generalized convulsive status epilepticus? A lactic acidosis B hypothermia C hypoglycemia D arrhythmia 6. (B) Concerning the management of status epilepticus, which is wrong in the following statements? A Physician first should assess the patient's airway and oxygenation B Immediate intubation is mandatory C A screening neurologic examinations should be performed to check for signs of a focal intracranial lesion D In patients with history of seizures, an survey should be made to determined the compliance of antiepileptic medications 7. (C) Concerning the management of status epilepticus, which is wrong in the following statements? A Initially, acidosis, hyperpyrexia and hypertension need not be treated B Because hypoglycemia may precipitate status epilepticus, 50 ml of 50% glucose should be given if hypoglycemia is suspected C Pyridoxine (vitamin B6) should be given along with the glucose in patients with the risk of Wernicke's encephalopathy D If CT imaging of brain is negative, lumbar puncture is required to rule out infection etiologies 8. (D) Concerning the role of EEG in the management of status epilepticus, which is wrong in the following statements? A EEG is extremely useful but under-utilized B EEG can establish the diagnosis in patients with altered consciousness whose diagnosis was unclear and with no clinical signs of status epilepticus C EEG can help to confirm that an episode of status epilepticus has ended D EEG monitoring after presumed control of status epilepticus is not necessary 9. (D) Concerning the pharmacologic management of status epilepticus, which is wrong in the following statements? A The benzodiazepines most commonly used to treat status epilepticus are diazepam, lorazepam and midazolam B Benzodiazepin worked by enhancing the inhibition of GABA system C Diazepam enter the brain rapidly because of its high lipid solubility, after 15 to 20 minutes it redistributed to other area of body and reducing its clinical effect D Lorazepam is less lipid soluble than diazepam, with the same distribution half-life as diazepam 10. (A) Concerning status epilepticus, which is wrong in the following statements? A Patients who have electrographic status epilepticus with little or no motor activity are at low risk for CNS injury B The primary determinants of mortality in patients with status epilepticus were duration of seizures, age at onset, and etiology C The serious adverse effects of phenytoin are arrhythmia and hypotension D Patients with subtle status epilepticus had significantly lower response rates to all treatments 答案解說 (C)  HSV meningitis is usually seen in association with primary genital HSV infection (B) EEG showed paroxysmal sharp waves of triphasic complexes with a temporal predominance which is not a pathognomonic pattern for HSV encephalitis (A )  Status epilepticus of partial onset accounts for the majority of episodes. One epidemiologic study on status epilepticus found 69 percent of episodes in adults and 64 percent of episodes in childrens were partial onset. (C )  Patients with anoxia and stroke had a very high mortality rate that was independent of other variables (B) Hperthermia developed due to the massive catecholamine discharge associated with continuous generalized seizure (B )  Physician first should assess the patient's airway and oxygenation. If the airway is clear and intubation is not immediately required. (C)  Thiamine (100 mg)should be given along with the glucose in patients with the risk of Wernicke's encephalopathy (D )  EEG monitoring after presumed control of status epilepticus is necessary (D ) Lorazepam is less lipid soluble than diazepam, with the distribution half-life two to three hours versus 15 minutes for diazepam (A)  Patients who have electrographic status epilepticus with little or no motor activity are still at high risk for CNS injury