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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岁，既往偏头痛和特发性颅内高压病史，因头痛、恶心1天就诊于急诊。既往体健。查体：体温正常，无颈强直、皮疹及心脏杂音，神经系统查体正常。偏头痛起初用静脉奋乃静、酮咯酸和镁剂治疗。两个小时后，她出现发烧（101.4°F）和思维混乱，不断地说疼，即使对她进行最简单的检查，仍无法回答问题或遵循指令。非增强头颅CT显示乳突小房混浊，脑实质及脑室系统未见异常。 Question for consideration: 1、How should one evaluate and manage the patient?
思考的问题： 1、该患者如何评估和处理？ 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.
患者头痛、发热和思维混乱考虑与脑膜炎或脑炎相关，而且CT表现提示乳突炎可能是感染的潜在来源。当怀疑是脑膜炎时，应该立即开始使用抗生素。在获得培养结果之前，治疗应针对特定患者人群中最可能的病原体。推荐使用万古霉素和第三代头孢菌素（如头孢曲松）治疗肺炎链球菌和奈瑟氏菌脑膜炎。在免疫功能正常的儿童（大于1个月）和50岁以下的成人，这是最常见的两种病原体。免疫功能低下者、婴儿、老年人可以使用氨苄青霉素治疗单核细胞增生性李斯特菌。第三代头孢菌素（即头孢吡肟、头孢他啶）对合并贯通伤，脑室腹腔分流术，或即将行神经外科手术的患者防治抗铜绿假单胞菌感染有效。如果考虑脑炎，在单纯疱疹病毒PCR结果出来之前，应经验性给予阿昔洛韦治疗。同时，腰椎穿刺（LP）之前应给予抗生素，因为在抗生素治疗脑膜炎双球菌2小时和治疗肺炎球菌6小时之前，脑脊液培养结果不会呈阴性，细胞学和生化改变会持续48–68小时。
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例患者的随机对照研究的结果，推荐使用地塞米松治疗成人脑膜炎。在首剂应用抗生素之前15-20分钟或者同时给予患者地塞米松（10mg，Q6h，4天）能明显减少患者不良预后和死亡。地塞米松对于肺炎球菌脑膜炎患者有效，对于中重度脑膜炎的患者获益更大，对其他病原菌治疗无明显效果。
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.
该患者开始用头孢曲松，万古霉素和地塞米松治疗。腰穿结果显示脑脊液初压 49厘米，蛋白286mg/dL，葡萄糖低，白细胞 117，200（100%多形核细胞），红细胞 30，中等量的革兰氏阳性双球菌（培养生长出青霉素敏感的肺炎链球菌）。病人被送往内科重症监护病房（ICU）后，可以睁眼发音，视觉追踪，双侧瞳孔光反应阳性，四肢远端均可活动，但不能遵嘱。因持续疼痛，在随后8个多小时给予了不同剂量静脉阿片类药物。约发病后12小时（腰穿后6小时），她的血氧饱和度突然下降到80%，并出现窒息。 Question for consideration: 1. What is the differential diagnosis for her sudden respiratory arrest?
思考的问题： 1. 导致她突然呼吸抑制的鉴别诊断是什么？ 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.
脑膜炎并发症可引起病情急性恶化，包括脑水肿、脑积水、脑梗死、脑静脉窦血栓形成和癫痫发作。患者接受阿片类药物后出现意识下降，给予纳洛酮治疗症状无改善，随后行气管插管。非镇静状态下查体，她可以睁眼、发声、视觉追踪，双瞳孔等大，光反应存在，眼外肌可遵嘱运动，各个方向注视时均可诱发眼震，双侧角膜反射存在，有自发对称的口唇运动。不能伸舌，咽反射阴性，肢体无任何自发活动，对伤害性刺激无躲避。无自主呼吸。 Question for consideration: What is the localization of her examination findings?
思考的问题： 根据患者的体格检查，定位在哪里？ 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.
病人可遵嘱证明大脑皮层和从中脑、丘脑投射的的网状激活系统功能保存。她的眼部和口部运动保留表明脑桥尾端以上的脑干功能无受损。各方向注视时出现明显的眼球震颤表明前庭小脑功能障碍。咽反射消失，伸舌不能，呼吸暂停，弛缓性麻痹也表明延髓功能受损。头颅CT未见异常。头MRI（在她病情急性恶化后12小时检查）表明扩散受限符合双侧小脑半球、延髓及颈髓交界处急性梗死（图）。之后行CT血管造影，没有发现动脉闭塞，夹层，或静脉窦血栓形成。超声心动图正常，无瓣膜异常或赘生物。
Question for consideration: 1. What is the cause and management of her condition?
思考的问题： 1. 引起患者疾病的原因是什么？如何治疗? 图 MRI (A)轴位DWI和（B）ADC序列显示双侧小脑半球及延髓梗死。（C）冠状位和（D）矢状位T1磁化快速梯度回波序列显示小脑扁桃体下降到枕骨大孔，脑干受压。 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.
患者可能是逐渐增高的颅内压（ICP）引起的小脑扁桃体疝。从而导致枕骨大孔附近的结构供血动脉受压，引起小脑和延髓梗死。为减轻高颅压和预防进一步脑水肿并发症，给予患者高渗性药物治疗（高渗盐水及甘露醇），置放脑室外引流管（EVD）分流CSF，及枕骨下开颅减压。尽管采取了这些措施，并治愈了感染，但她的四肢瘫痪，构音障碍，或呼吸机依赖仍然没有改善。 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.
急性细菌性脑膜炎形成的脑疝已在许多病例报告和文献中被描述过，它的发生率约为 5%。严重炎症可引起脑水肿及脑脊液回流受损。由此导致的ICP升高可能会在颅骨内容物和脊柱之间产生压力梯度。LP可能加剧这种压力梯度，从而促发脑疝形成，但二者因果关系仍有争议。在对98例急性细菌性脑膜炎的脑疝患者回顾性报道中，11%的脑疝发生在LP之前，38%发生在LP后3小时之内，41%发生在LP后4到12小时之间。而中线移位和第四脑室或脑池消失的影像表现是LP明显禁忌症，CT对于预测脑膜炎患者的ICP升高不敏感，因为炎性脑膜和脑室壁的顺应性下降可能抵消了脑水肿的作用，产生一个脑室外观正常的假象。
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)。
影像学检查正常的急性脑膜炎患者，癫痫，局灶性神经功能缺损、视乳头水肿和意识改变都能够预示ICP的升高。一些专家建议应在LP之前出现这些临床症状应行CT检查，而其他人认为，如果有这些症状，LP应延期。如果推迟LP导致的诊断不明确可以通过实验室检测弥补，如血培养（脑膜炎球菌性脑膜炎患者阳性率40%–50%，肺炎链球菌或嗜血杆菌脑膜炎患者阳性率80%–90%）。与所有脑膜炎脑疝的发生率（5%）相比，对未明确的、且对典型药物不敏感病原菌不适当的治疗理论风险可能很小（0.3%），无LP数据的误诊风险能够被其他的替代手段采集到的数据来弥补（可采取其中一种措施处理增高的ICP，如肺结核影像学，疟疾血涂片，或通过EVD行脑脊液培养）。
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.
该患者初始格拉斯哥昏迷量表评分（GCS）13分，无局灶性神经功能缺损或癫痫发作，头部CT正常，LP没有明显的禁忌症。尽管她的眼底没有直接表现，早期评估特发性颅内高压时可见视乳头水肿。这使得眼底检查的结果复杂化。患者CSF初压是49厘米。患者会有即将发生脑疝的相关临床体征（例如，GCS评分下降，瞳孔扩大，局部查体体征），这时需要紧急处理增高的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.
在没有临床表现或影像学征象时，我们如何避免出现像该例病人即将发生的脑疝？尽管LP常规用于诊断和评估意识障碍，她急性精神状态的变化也可能是颅内高压的线索。急性细菌性脑膜炎的ICP升高与生存率降低有关。本患者LP初压的升高反映了一个急性过程，需要紧急干预以降低脑疝的风险。假定是急性细菌性脑膜炎，如果LP提示初压升高，建议立即停止脑脊液释放，给予高渗治疗，考虑ICP监测及脑脊液分流，并在重症监护病房密切监测。
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.
一项随机对照试验研究显示对脑膜炎患儿使用渗透剂（甘油果糖）高渗治疗后，死亡率明显下降，严重的神经系统后遗症显著降低。高渗治疗被认为是安全和有效的，其并发症的风险（例如，肾功能衰竭和容量负荷过重或脱水）会被其防止或逆转脑疝的作用所均衡。在监测ICP情况下可以精确的给予高渗性治疗和脑脊液分流（如果使用EVD），ICP监测在ICP升高的急性细菌性脑膜炎患者获益可能大于风险（比如脑出血及在感染活动期时异物置入）。 （全文终） 词句赏析 He who seizes the right moment, is the right man. 把握机遇的人，才能心想事成。--歌德 编辑：李会琪 |
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