化脓性脑膜炎 purulent meningitisAbbreviationsl lPM purulent meningitis l lCSF cerebrospinal fluidl lCNS central nervous systeml lICP intracranial pressurel lBBB blood-brain barrierl lWBC white blood celll lNC neutrocyte INTRODUCTION Purulent Meningitis (PM) is one of serious Purulent Meningitis (PM) is one of serious bacterial infection. PM is associated with a high bacterial infection. PM is associated with a high rate of acute complications and risk of chronic rate of acute complications and risk of chronic sequelae. PM is quite common CNS disorders in sequelae. PM is quite common CNS disorders in childhood, and it should be included in the childhood, and it should be included in the differential diagnosis of altered mental status.differential diagnosis of altered mental status.概念l 由化脓性细菌引起的 中枢神经系统急性感 染性疾病病原学(1)常见病原 脑膜炎球菌脑膜炎球菌 (meningococcus)肺炎肺炎链链球菌球菌 ( (pneumococcus)流感嗜血杆菌流感嗜血杆菌 ( (haemophilus influenzae) )金黄色葡萄球菌金黄色葡萄球菌（staphylococcus aureus）大肠杆菌大肠杆菌（escherichia coli） 脑膜炎球菌脑膜炎球菌肺肺 炎炎 球球 菌菌 Common bacterial lThe first 2 month: escherichia coli ; staphylococcus aureus;l l2 month12 yr: Pneumococcus; Meningococcus; Hemophilus influenzae type b.病原学(2) 病原菌与年龄的关系 新生儿 大肠杆菌、绿脓杆菌、金黄色葡萄球菌 儿童 脑膜炎球菌、肺炎球菌、流感嗜血杆菌发病机制(1) The risk factors1. Lack of immunity: young age, defects of T-lymphocyte, defects of immunoglobulin, defects of the complement system or properdin system 2. Environment3. 3.Congenital or acquired CSF leak: such as cranial defect or middle ear fistulas, basal skull fracture, lumbosacral dermal sinus, penetrating cranial traumaMeningocele Sinus 回顾回顾 中枢神经系统脑膜的解剖及脑脊液的循环中枢神经系统脑膜的解剖及脑脊液的循环 PATHOGENESIS Bacteria attack to the mucosal epithelial cell receptors by pili, enter the circulation, penetrate the BBB (blood-brain barrier) to the CSF, colonize and multiply, then incite inflammatory response and polymorphonuclear cell infiltration, which produce TNF, IL-1, PG-2 and other cytokines.致病菌入侵途径致病菌入侵途径致病菌致病菌软脑膜软脑膜蛛网膜蛛网膜表层脑表层脑血流途径血流途径直接通道直接通道临近感染临近感染发病机制(2)l l决定入侵中枢神经系统的因素决定入侵中枢神经系统的因素 细菌数量细菌数量 毒力毒力 机体免疫状态机体免疫状态l l多种细胞因子参与发病多种细胞因子参与发病 TNFTNF，ILIL1 1等等 PATHOLOGY Meningeal exudation and varying thickness Vascular changes: vasculitis , thrombosis, necrosis or occlusion of small vascules Cerebral infarction Increased ICP Ventriculitis Hydrocephalus, communicating Damage of the cerebral cortex 轻症化脑的病理变化 软脑膜及蛛网膜炎、表层脑组织为主的炎软脑膜及蛛网膜炎、表层脑组织为主的炎症反应，炎症渗出物主要在大脑顶部表面。症反应，炎症渗出物主要在大脑顶部表面。 重症化脑的病理变化 除轻症的改变外，还出现血管病变、脑除轻症的改变外，还出现血管病变、脑实质损害，脑室管膜炎、颅神经受累。实质损害，脑室管膜炎、颅神经受累。 CLINICAL MANIFESTATIONSl(1) Nonspecific finding: fever; anorexia or poor feeding; symptoms of URI, myalgias, arthralgias, tachycardia, hypotension, various cutaneous signs(2) cerebral dysfunction:l lSeizures: focal or generalized due to cerebritis, infarction, or electrolyte disturbances. After 4 days, persisting seizures are associated with a poor prognosis.l lAlternations of mental status and reduced level of consciounes: irritality, lethargy, stupor, obtundation, coma. Comatose ones have a poor prognosis(3) Increased ICP: headache, emesis, papilledema (more chronic process). bulging fontanel and widening of the sutures, cranial neurologic paralysis (such as facial, oculomotor, abducens or auditory nerve paralysis), signs of herniation (tachycardia or bradycardia, apnea or hyperventilation) (4) Meningeal irritation: Nuchal rigidity Back pain Kernig sign Brudrinski sign临床表现临床表现(1)(1)年长儿及成人典型表现年长儿及成人典型表现（）（）感染中毒及急性脑功能障碍症状感染中毒及急性脑功能障碍症状兴奋：烦躁、惊厥兴奋：烦躁、惊厥抑制：嗜睡、昏睡、浅昏迷、深昏迷抑制：嗜睡、昏睡、浅昏迷、深昏迷 （2 2）颅高压表现）颅高压表现 头痛、呕吐、视乳头水肿头痛、呕吐、视乳头水肿颅高压三联征颅高压三联征 颈项强直颈项强直 （3 3）体征）体征 ：脑膜刺激征：脑膜刺激征 克氏征阳性克氏征阳性 布氏征阳性布氏征阳性4 4岁女孩患脑膜炎岁女孩患脑膜炎 表现为神志淡漠表现为神志淡漠4 4岁女孩患脑膜炎岁女孩患脑膜炎 颈项强直、布氏征阳性颈项强直、布氏征阳性44 4岁女孩患脑膜炎岁女孩患脑膜炎 克氏征阳性克氏征阳性临床表现临床表现()年龄小于年龄小于3 3个月的幼婴和新生儿化脑的特点：个月的幼婴和新生儿化脑的特点：1 1、体温可高可低、体温可高可低2 2、颅压增高不明显、颅压增高不明显3 3、惊厥可不典型、惊厥可不典型4 4、脑膜刺激征不明显、脑膜刺激征不明显COMPLICATIONSl1. Subdural effusion It is the most common complication of PM in childhood. Its incidence is around 3060%, and adding asymptomatic ones, the incidence is 8590%. Most of cases occur in infants. l lManifestations: After treating and getting a good effect by antibiotic, then the patients manifest the symptoms and signs of PM again:l lfever, seizures, alternation of mental status, bulging fontanel, diastasis of sutures, enlarging head circumference, emesis, positive cranial transillumination, etc. l lCT or MRI of brain can make the definite diagnosis.并发症及后遗症(1)硬膜下积液硬膜下积液硬膜下积液硬膜下积液l l 12ml2ml，蛋白定量，蛋白定量 400 mg/L400 mg/L2. Ventriculitis It is occurred in the patients who are not treated in time. The symptoms and signs of PM are not improved and even progressed using effective antibiotics并发症及后遗症(2)脑室管膜炎脑室管膜炎( (见于新生儿、小婴儿见于新生儿、小婴儿) )l l治疗被延误治疗被延误治疗被延误治疗被延误l l强力治疗后仍持续发热、反复抽搐、呼吸衰竭且进行强力治疗后仍持续发热、反复抽搐、呼吸衰竭且进行强力治疗后仍持续发热、反复抽搐、呼吸衰竭且进行强力治疗后仍持续发热、反复抽搐、呼吸衰竭且进行性加重性加重性加重性加重l l脑脊液始终不正常脑脊液始终不正常脑脊液始终不正常脑脊液始终不正常l l头颅头颅头颅头颅B B B B超、超、超、超、CTCTCTCT可助诊，确诊依靠侧脑室穿刺脑室液可助诊，确诊依靠侧脑室穿刺脑室液可助诊，确诊依靠侧脑室穿刺脑室液可助诊，确诊依靠侧脑室穿刺脑室液l l3. SIADH (syndrome of inappropriation ADH-secretion) Occurring in the majority of patients with PM. It is a result of hypothalamic or pituitary dysfunction. Resulting in hyponatremia and reduced serum osmolarity, and exacerbate cerebral edema or directly produce hyponatremic seizures.并发症及后遗症(3)抗利尿激素异常分泌综合征抗利尿激素异常分泌综合征病因病因 炎症累及下丘脑及垂体后叶，引起抗炎症累及下丘脑及垂体后叶，引起抗利尿激素过量分泌。利尿激素过量分泌。表现表现 低钠及血浆渗透压降低低钠及血浆渗透压降低 othersl lCranial nerve palsies: such as deafness, blindnessl lCerebral or cerebellar herniationl lhydrocephalus其他并发症及后遗症其他并发症及后遗症l l脑积水脑积水l l各种颅神经功能障碍各种颅神经功能障碍l l 癫痫癫痫lEXAMINATION OF EXPERIMENT(1) CSF: When PM is suspected, lumbar puncture (LP) should be performed to get CSF. It should be found in CSF:l lTurbid or purulent l lHigh ICP l lElevated leukocyte count: greater than 1000/mm3 (3002000/mm3) and neutrophilic predominance (7595%)l l elevated protein (100500mg/dl)l l reduced glucose and chloride concentrationsl lGram stain may be positive with bacterial lBacteria culture may be positive(2) Other potentially valuable diagnostic testsl CT or MRI of brain: Maybe normal except of complication，When the cases are difficult to diagnosis, the examinations are necessary. l Blood culturesl Bacteria on the smear of cutaneous petechiael Peripheral blood: WBC, NC实验室检查(1)脑脊液检查 是确诊本病的主要依据是确诊本病的主要依据脑脊液脑脊液(CSF)正常值正常值外观清亮外观清亮压力压力 新生儿新生儿 0.29-0.78（30-80） 儿童儿童 0.69-1.96（70-200）白细胞数白细胞数 婴儿婴儿 0-20 儿童儿童 0-10蛋白质蛋白质 新生儿新生儿 20-120mg/dl 儿童儿童 10001000以中以中 脑膜炎脑膜炎 脓样脓样 性粒为主性粒为主结核性结核性 毛玻毛玻 200-500 200-500 脑膜炎脑膜炎 璃样璃样 淋巴为主淋巴为主病毒性病毒性 轻度轻度 清亮清亮 0-数百数百 轻度轻度 正常正常 正常正常 脑膜炎脑膜炎 淋巴为主淋巴为主 TREATMENT Antibiotics In order to raise curing rate, reduce the complications, improve the prognosis, the earlier diagnosis and the earlier treatment are very important. A child with rapidly progressing disease of less than 24 hr duration, in the absence of increased ICP, should receive antibiotics at once after an LP is performed. If there are signs of increased ICP or focal neurologic findings, antibiotics should be given without performing an LP. Increased ICP should be treated simultaneously.治疗原则(1)选择抗生素原则l l早期足量l l有效杀菌剂l l易通过血脑屏障l l疗程足 治疗原则(2)抗生素治疗l l肺炎球菌肺炎球菌 青霉素、氯霉素、三代头孢菌素青霉素、氯霉素、三代头孢菌素l l脑膜炎球菌脑膜炎球菌 青霉素、三代头孢菌素青霉素、三代头孢菌素 l l流感杆菌流感杆菌 氨苄西林、三代头孢菌素、氯霉素氨苄西林、三代头孢菌素、氯霉素 疗程疗程10-1410-14天天l l金黄色葡萄球菌金黄色葡萄球菌 耐酶青霉素、万古霉素、利福平耐酶青霉素、万古霉素、利福平l l大肠杆菌脑膜炎大肠杆菌脑膜炎 三代头孢、哌拉西林、氨基甙类三代头孢、哌拉西林、氨基甙类 疗程疗程2121天天 Supportive care Repeated medical assessments of patients with PM are essential to identify early signs of cardiovascular, CNS, and metabolic complications, such as pulse rate, blood pressure, respiratory rate, pupillary reflexes, level of consciousness, motor strength, cranial nerve signs, and evaluation for seizures. Maintain the balances of fluids, electrolytes, and plasma osomotic pressure. Corticosteroids Rapid killing of bacteria releases toxic cell products after cell lysis that precipitates the cytokine-mediated inflammatory response result in edema formation and neurologic injury. Protein and fibrous effusion may result in fibrosis and Hydrocephalus due to interfering absorption of CSF. The corticosteroids can limit production of inflammatory mediators and fibrosis.治疗原则(3)l肾上腺皮质激素l对症治疗、支持治疗 降温 降颅压 20甘露醇、速尿 止惊 鲁米那、安定治疗原则(4)l并发症治疗硬膜下积液 穿刺放液、外科脑室炎 引流、脑室内局部抗生素应用 小结 1、小儿化脑常见致病菌。 2、小儿化脑临床特点。 3、化脑脑脊液变化特点。 4、选用敏感抗生素，掌握好剂量及给 药方式。