A 44-year-old woman with a history of migraines and idiopathic intracranial hypertension presented to the emergency room with 1 day of headache and nausea. She had been otherwise healthy with no sick contacts. She was afebrile without nuchal rigidity, rash, or cardiac murmur, and her neurologic examination was normal. Migraine therapy was initiated with IV prochlorperazine, ketorolac, and magnesium. Two hours later, she developed fever (101.4°F) and confusion, continually stating, “It hurts,” but unable to answer questions or follow commands despite an otherwise unremarkable examination. Noncontrast head CT demonstrated mastoid sinus opacification, but no abnormalities of her brain parenchyma or ventricular system.

患者,，女性，44歲,，既往偏頭痛和特發(fā)性顱內高壓病史,，因頭痛、惡心1天就診于急診,。既往體健,。查體：體溫正常，無頸強直、皮疹及心臟雜音,，神經系統(tǒng)查體正常,。偏頭痛起初用靜脈奮乃靜、酮咯酸和鎂劑治療,。兩個小時后,，她出現(xiàn)發(fā)燒（101.4°F）和思維混亂，不斷地說疼,，即使對她進行最簡單的檢查，仍無法回答問題或遵循指令,。非增強頭顱CT顯示乳突小房混濁,，腦實質及腦室系統(tǒng)未見異常。

The patient’s headache, fever, and confusion raise concern for meningitis or encephalitis, and likely sinusitis on CT implicates a potential source for infection. Antibiotics should be initiated immediately when meningitis is considered likely. Until culture results are obtained, therapy should target the most likely pathogens in a given patient population. Vancomycin and a third-generation cephalosporin (e.g., ceftriaxone) are recommended to treat Streptococcus pneumoniae and Neisseria meningiditis, the 2 most common pathogens in immunocompetent children (older than 1 month) and adults up to age 50. Immunocompromise, ·infancy, or advanced age warrant ampicillin therapy against Listeria monocytogenes. A third-generation cephalosporin effective against Pseudomonas (i.e., cefepime, ceftazidime) should be considered in patients with penetrating trauma, ventriculoperitoneal shunt, or following neurosurgery. If there is concern for encephalitis, acyclovir should be empirically initiated while awaiting herpes simplex virus PCR. Antibiotics should be administered prior to lumbar puncture (LP), since CSF cultures do not become sterile until 2 hours from antibiotic administration for meningococcus and 6 hours for pneumococcus, and cellular/biochemical changes last 48–68 hours.

患者頭痛,、發(fā)熱和思維混亂考慮與腦膜炎或腦炎相關,，而且CT表現(xiàn)提示乳突炎可能是感染的潛在來源。當懷疑是腦膜炎時,，應該立即開始使用抗生素,。在獲得培養(yǎng)結果之前，治療應針對特定患者人群中最可能的病原體,。推薦使用萬古霉素和第三代頭孢菌素（如頭孢曲松）治療肺炎鏈球菌和奈瑟氏菌腦膜炎,。在免疫功能正常的兒童（大于1個月）和50歲以下的成人，這是最常見的兩種病原體,。免疫功能低下者,、嬰兒、老年人可以使用氨芐青霉素治療單核細胞增生性李斯特菌,。第三代頭孢菌素（即頭孢吡肟,、頭孢他啶）對合并貫通傷，腦室腹腔分流術,，或即將行神經外科手術的患者防治抗銅綠假單胞菌感染有效,。如果考慮腦炎，在單純皰疹病毒PCR結果出來之前,，應經驗性給予阿昔洛韋治療,。同時，腰椎穿刺（LP）之前應給予抗生素,，因為在抗生素治療腦膜炎雙球菌2小時和治療肺炎球菌6小時之前,，腦脊液培養(yǎng)結果不會呈陰性，細胞學和生化改變會持續(xù)48–68小時。

Dexamethasone is recommended in the treatment of adults with meningitis, based on the results of a randomized trial studying 301 patients. Patients who received dexamethasone (10 mg every 6 hours for 4 days) beginning 15–20 minutes prior to or with the first dose of antibiotics had a significant decrease in unfavorable outcomes and death. This result was driven by patients with pneumococcal meningitis, with no significant benefit to dexamethasone therapy for other organisms, and greatest benefit seen in moderate to severe cases of meningitis.

基于301例患者的隨機對照研究的結果,，推薦使用地塞米松治療成人腦膜炎,。在首劑應用抗生素之前15-20分鐘或者同時給予患者地塞米松（10mg，Q6h,，4天）能明顯減少患者不良預后和死亡,。地塞米松對于肺炎球菌腦膜炎患者有效，對于中重度腦膜炎的患者獲益更大,，對其他病原菌治療無明顯效果,。

In our patient, ceftriaxone, vancomycin, and dexamethasone were initiated. LP revealed opening pressure of 49 cm CSF, protein of 286 mg/dL, glucose less than assay, 117,200 white blood cells (100% polymorphonuclear cells), 30 red blood cells, and moderate Gram-positive cocci in pairs (cultures grew penicillin-sensitive Streptococcus pneumoniae). The patient was admitted to the medical intensive care unit (ICU) where she opened her eyes to voice, tracked, had bilaterally reactive pupils, and moved all 4 extremities equally, but was not following commands. Due to persistent complaints of pain, she received several doses of IV opiates over the 8 succeeding hours. Approximately 12 hours after her initial presentation (6 hours after her LP), her oxygen saturation suddenly fell to 80% and she was found to be apneic.

該患者開始用頭孢曲松，萬古霉素和地塞米松治療,。腰穿結果顯示腦脊液初壓 49厘米,，蛋白286mg/dL，葡萄糖低,，白細胞 117,，200（100%多形核細胞），紅細胞 30,，中等量的革蘭氏陽性雙球菌（培養(yǎng)生長出青霉素敏感的肺炎鏈球菌）,。病人被送往內科重癥監(jiān)護病房（ICU）后，可以睜眼發(fā)音,，視覺追蹤,，雙側瞳孔光反應陽性，四肢遠端均可活動,，但不能遵囑,。因持續(xù)疼痛，在隨后8個多小時給予了不同劑量靜脈阿片類藥物,。約發(fā)病后12小時（腰穿后6小時）,，她的血氧飽和度突然下降到80%，并出現(xiàn)窒息,。

Complications of meningitis that can cause acute deterioration include cerebral edema, hydrocephalus, cerebral infarction, cerebral venous sinus thrombosis, and seizure. The patient received naloxone in the event that recent opiate administration had caused her decline, but she did not improve and was intubated. On examination off sedation, she opened her eyes to voice, tracked, had equal and reactive pupils, full extraocular movements to command with prominent gaze-evoked nystagmus in all directions, corneal reflexes bilaterally, and spontaneous, symmetrical mouth movements. She was unable to protrude her tongue, had no gag reflex, and could not move any extremity spontaneously or to noxious stimuli. She had no spontaneous respirations.

腦膜炎并發(fā)癥可引起病情急性惡化，包括腦水腫,、腦積水,、腦梗死、腦靜脈竇血栓形成和癲癇發(fā)作,?；颊呓邮馨⑵愃幬锖蟪霈F(xiàn)意識下降，給予納洛酮治療癥狀無改善,，隨后行氣管插管,。非鎮(zhèn)靜狀態(tài)下查體,，她可以睜眼、發(fā)聲,、視覺追蹤,，雙瞳孔等大，光反應存在,，眼外肌可遵囑運動,，各個方向注視時均可誘發(fā)眼震，雙側角膜反射存在,，有自發(fā)對稱的口唇運動,。不能伸舌，咽反射陰性,，肢體無任何自發(fā)活動,，對傷害性刺激無躲避。無自主呼吸,。

The patient’s ability to follow commands demonstrates preserved function of the cerebral cortex and its projections from the reticular activating system in the midbrain and thalami. Her preserved eye and mouth movements indicate intact brainstem function above the caudal pons. Prominent nystagmus in all directions of gaze indicates vestibulocerebellar dysfunction. Lack of gag, inability to move the tongue, apnea, and flaccid paralysis also suggest dysfunction at the level of the medulla. Head CT revealed no abnormalities. Brain MRI (obtained 12 hours after her acute decline) demonstrated diffusion restriction consistent with acute infarction in the bilateral cerebellar hemispheres as well as the medulla extending into the cervicomedullary junction (figure). CT angiogram obtained after her MRI did not reveal arterial occlusion, dissection, or venous sinus thrombosis. Echocardiogram was normal, with no valvular abnormalities or vegetations.

病人可遵囑證明大腦皮層和從中腦,、丘腦投射的的網狀激活系統(tǒng)功能保存。她的眼部和口部運動保留表明腦橋尾端以上的腦干功能無受損,。各方向注視時出現(xiàn)明顯的眼球震顫表明前庭小腦功能障礙,。咽反射消失，伸舌不能,，呼吸暫停,，弛緩性麻痹也表明延髓功能受損。頭顱CT未見異常,。頭MRI（在她病情急性惡化后12小時檢查）表明擴散受限符合雙側小腦半球,、延髓及頸髓交界處急性梗死（圖）。之后行CT血管造影,，沒有發(fā)現(xiàn)動脈閉塞,，夾層，或靜脈竇血栓形成,。超聲心動圖正常,，無瓣膜異常或贅生物,。

圖  MRI

(A)軸位DWI和（B）ADC序列顯示雙側小腦半球及延髓梗死。（C）冠狀位和（D）矢狀位T1磁化快速梯度回波序列顯示小腦扁桃體下降到枕骨大孔,，腦干受壓,。

The patient likely developed increased intracranial pressure (ICP) causing transforaminal herniation of the cerebellar tonsils. This led to compression of the arterial supply to structures near the foramen magnum, resulting in infarction of her cerebellum and medulla. To relieve her increased ICP and prevent complications from further cerebral edema, she was treated with hyperosmolar agents (hypertonic saline and mannitol), placement of an external ventricular drain (EVD) for CSF diversion, and decompressive suboccipital craniectomy. Despite these measures and the eradication of her infection, there was no improvement in her quadriplegia, anarthria, or ventilator dependence.

患者可能是逐漸增高的顱內壓（ICP）引起的小腦扁桃體疝,。從而導致枕骨大孔附近的結構供血動脈受壓，引起小腦和延髓梗死,。為減輕高顱壓和預防進一步腦水腫并發(fā)癥,，給予患者高滲性藥物治療（高滲鹽水及甘露醇），置放腦室外引流管（EVD）分流CSF,，及枕骨下開顱減壓,。盡管采取了這些措施，并治愈了感染,，但她的四肢癱瘓,，構音障礙，或呼吸機依賴仍然沒有改善,。

Brain herniation in acute bacterial meningitis has been described in a number of case reports and series, and has been estimated to occur in 5% of cases. Severe inflammation can cause cerebral edema and impairment of CSF flow. The resultant elevated ICP may create a pressure gradient between the skull contents and spinal column. LP may precipitate herniation due to exacerbation of this pressure gradient, though a cause-effect relationship is debated. In a review of 98 reported cases of herniation in acute bacterial meningitis, 11% of herniation events occurred prior to LP, 38% occurred within 3 hours of LP, and 41% occurred between 4 and 12 hours following LP. While imaging findings of midline shift and effacement of the fourth ventricle or cisterns are obvious contraindications to LP, CT is insensitive for predicting elevated ICP in the setting of meningitis, since decreased compliance of inflamed meninges and ventricular walls may counteract the forces of cerebral edema, yielding a falsely reassuring ventricular appearance.

急性細菌性腦膜炎形成的腦疝已在許多病例報告和文獻中被描述過,，它的發(fā)生率約為 5%。嚴重炎癥可引起腦水腫及腦脊液回流受損,。由此導致的ICP升高可能會在顱骨內容物和脊柱之間產生壓力梯度,。LP可能加劇這種壓力梯度，從而促發(fā)腦疝形成,，但二者因果關系仍有爭議,。在對98例急性細菌性腦膜炎的腦疝患者回顧性報道中，11%的腦疝發(fā)生在LP之前,，38%發(fā)生在LP后3小時之內,，41%發(fā)生在LP后4到12小時之間。而中線移位和第四腦室或腦池消失的影像表現(xiàn)是LP明顯禁忌癥,，CT對于預測腦膜炎患者的ICP升高不敏感,，因為炎性腦膜和腦室壁的順應性下降可能抵消了腦水腫的作用，產生一個腦室外觀正常的假象,。

Seizures, focal neurologic deficits, papilledema, and altered consciousness may predict increased ICP in the setting of normal-appearing radiologic images in acute meningitis. While some experts propose that these clinical signs warrant performance of CT prior to LP, others suggest that their presence should lead to deferment of LP.  The potential diagnostic uncertainty if LP is deferred may be mitigated by laboratory testing such as blood cultures (positive in 40%–50% of patients with meningococcal meningitis and 80%–90% with pneumococcal or Hemophilus meningitis). The theoretical risk of inadequately treating an undetermined bacterial pathogen insensitive to typical coverage may be minimal (0.3%) compared to the overall incidence of herniation in meningitis (5%), and the risk of missing alternative diagnoses without LP data could potentially be compensated for by alternative means of data collection (e.g.,signs of tuberculosis on imaging, malaria on blood smear, or CSF cultures obtained via EVD, if one is placed for management of elevated ICP),。

影像學檢查正常的急性腦膜炎患者，癲癇,，局灶性神經功能缺損,、視乳頭水腫和意識改變都能夠預示ICP的升高。一些專家建議應在LP之前出現(xiàn)這些臨床癥狀應行CT檢查,，而其他人認為,，如果有這些癥狀，LP應延期,。如果推遲LP導致的診斷不明確可以通過實驗室檢測彌補,，如血培養(yǎng)（腦膜炎球菌性腦膜炎患者陽性率40%–50%，肺炎鏈球菌或嗜血桿菌腦膜炎患者陽性率80%–90%）,。與所有腦膜炎腦疝的發(fā)生率（5%）相比,，對未明確的,、且對典型藥物不敏感病原菌不適當?shù)闹委熇碚擄L險可能很小（0.3%）,，無LP數(shù)據(jù)的誤診風險能夠被其他的替代手段采集到的數(shù)據(jù)來彌補（可采取其中一種措施處理增高的ICP,，如肺結核影像學，瘧疾血涂片,，或通過EVD行腦脊液培養(yǎng)）,。

Our patient had an initial Glasgow Coma Scale score (GCS) of 13 without focal neurologic deficits or seizures and had a normal head CT, yielding no clear contraindication to LP. Although her fundi were not visualized on presentation, papilledema had been noted during prior evaluation for idiopathic intracranial hypertension, complicating the interpretation of funduscopy in her case. Her opening pressure, however, was 49 cm CSF. In patients with clinical signs concerning for impending herniation (e.g., declining GCS, pupillary dilatation, focal examination findings), the need for urgent management of ICP is evident.

該患者初始格拉斯哥昏迷量表評分（GCS）13分，無局灶性神經功能缺損或癲癇發(fā)作,，頭部CT正常,，LP沒有明顯的禁忌癥。盡管她的眼底沒有直接表現(xiàn),，早期評估特發(fā)性顱內高壓時可見視乳頭水腫,。這使得眼底檢查的結果復雜化?；颊逤SF初壓是49厘米,。患者會有即將發(fā)生腦疝的相關臨床體征（例如,，GCS評分下降,，瞳孔擴大，局部查體體征）,，這時需要緊急處理增高的ICP,。

How should one proceed in a patient such as ours with no clinical or radiographic signs of impending herniation? Her acute change in mental status may have been a clue to intracranial hypertension, though LP is routinely performed in the diagnostic evaluation of altered consciousness. Elevated ICP in acute bacterial meningitis is associated with decreased survival. An elevated opening pressure on LP in this setting reflects an acute process, and requires urgent intervention to reduce the risk of brain herniation. In presumed acute bacterial meningitis, if LP reveals an elevated opening pressure, we recommend immediate cessation of CSF removal, treatment with hyperosmolar therapy, consideration of placement of an ICP monitor and CSF diversion, and close monitoring in an ICU.

在沒有臨床表現(xiàn)或影像學征象時,，我們如何避免出現(xiàn)像該例病人即將發(fā)生的腦疝,？盡管LP常規(guī)用于診斷和評估意識障礙，她急性精神狀態(tài)的變化也可能是顱內高壓的線索,。急性細菌性腦膜炎的ICP升高與生存率降低有關,。本患者LP初壓的升高反映了一個急性過程，需要緊急干預以降低腦疝的風險,。假定是急性細菌性腦膜炎,，如果LP提示初壓升高，建議立即停止腦脊液釋放,，給予高滲治療,，考慮ICP監(jiān)測及腦脊液分流，并在重癥監(jiān)護病房密切監(jiān)測,。

A randomized controlled trial examining use of an osmotic agent (glycerol) in children with meningitis demonstrated a significant decrease in death and severe neurologic sequelae with hyperosmolar therapy. Hyperosmolar therapy is considered safe and effective, and the risk of complications (e.g., renal failure and volume overload or depletion) is balanced by the potential for prevention or reversal of brain herniation. ICP monitoring allows for tailored hyperosmolar therapy and CSF diversion (if an EVD is used), benefits that may outweigh the risks of the procedure (e.g., intracerebral hemorrhage and insertion of a foreign body during active infection) in acute bacterial meningitis with elevated ICP.

一項隨機對照試驗研究顯示對腦膜炎患兒使用滲透劑（甘油果糖）高滲治療后,，死亡率明顯下降，嚴重的神經系統(tǒng)后遺癥顯著降低,。高滲治療被認為是安全和有效的,，其并發(fā)癥的風險（例如,，腎功能衰竭和容量負荷過重或脫水）會被其防止或逆轉腦疝的作用所均衡。在監(jiān)測ICP情況下可以精確的給予高滲性治療和腦脊液分流（如果使用EVD）,，ICP監(jiān)測在ICP升高的急性細菌性腦膜炎患者獲益可能大于風險（比如腦出血及在感染活動期時異物置入）,。

（全文終）

詞句賞析

He who seizes the right moment, is the right man. 

把握機遇的人，才能心想事成,。--歌德