兒科學(xué)：化膿性腦膜炎

1、化膿性腦膜炎purulent meningitis,Abbreviations PM purulent meningitis CSF cerebrospinal fluid CNS central nervous system ICP intracranial pressure BBB blood-brain barrier WBC white blood cell NC neutrocyte,INTRODUCTION Purulent Meningitis (PM) is one of serious bacterial infection. PM is associated with a

2、high rate of acute complications and risk of chronic sequelae. PM is quite common CNS disorders in childhood, and it should be included in the differential diagnosis of altered mental status.,概念,由化膿性細(xì)菌引起的 中樞神經(jīng)系統(tǒng)急性感 染性疾病,病原學(xué)(1),常見(jiàn)病原 腦膜炎球菌 (meningococcus) 肺炎鏈球菌 (pneumococcus) 流感嗜血桿菌 (haemophilus influ

3、enzae) 金黃色葡萄球菌（staphylococcus aureus） 大腸桿菌（escherichia coli）,腦膜炎球菌,肺 炎 球 菌,Common bacteria The first 2 month: escherichia coli ; staphylococcus aureus; 2 month12 yr: Pneumococcus; Meningococcus; Hemophilus influenzae type b.,病原學(xué)(2),病原菌與年齡的關(guān)系 新生兒 大腸桿菌、綠膿桿菌、金黃色葡萄球菌 兒童 腦膜炎球菌、肺炎球菌、流感嗜血桿菌,發(fā)病機(jī)制(1),The ris

4、k factors 1. Lack of immunity: young age, defects of T-lymphocyte, defects of immunoglobulin, defects of the complement system or properdin system 2. Environment Congenital or acquired CSF leak: such as cranial defect or middle ear fistulas, basal skull fracture, lumbosacral dermal sinus, penetratin

5、g cranial trauma,Meningocele Sinus, 回顧 中樞神經(jīng)系統(tǒng)腦膜的解剖及腦脊液的循環(huán),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 infi

6、ltration, which produce TNF, IL-1, PG-2 and other cytokines.,致病菌入侵途徑,致病菌,軟腦膜,蛛網(wǎng)膜,表層腦,血流途徑,直接通道,臨近感染,發(fā)病機(jī)制(2),決定入侵中樞神經(jīng)系統(tǒng)的因素 細(xì)菌數(shù)量 毒力 機(jī)體免疫狀態(tài) 多種細(xì)胞因子參與發(fā)病 TNF，IL1等,PATHOLOGY Meningeal exudation and varying thickness Vascular changes: vasculitis , thrombosis, necrosis or occlusion of small vascules Cerebral

7、 infarction Increased ICP Ventriculitis Hydrocephalus, communicating Damage of the cerebral cortex,輕癥化腦的病理變化 軟腦膜及蛛網(wǎng)膜炎、表層腦組織為主的炎 癥反應(yīng)，炎癥滲出物主要在大腦頂部表面。 重癥化腦的病理變化 除輕癥的改變外，還出現(xiàn)血管病變、腦實(shí)質(zhì)損害，腦室管膜炎、顱神經(jīng)受累。,CLINICAL MANIFESTATIONS,(1) Nonspecific finding: fever; anorexia or poor feeding; symptoms of URI, myalgias

8、, arthralgias, tachycardia, hypotension, various cutaneous signs,(2) cerebral dysfunction: Seizures: focal or generalized due to cerebritis, infarction, or electrolyte disturbances. After 4 days, persisting seizures are associated with a poor prognosis. Alternations of mental status and reduced leve

9、l 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

10、 nerve paralysis), signs of herniation (tachycardia or bradycardia, apnea or hyperventilation),(4) Meningeal irritation: Nuchal rigidity Back pain Kernig sign Brudrinski sign,臨床表現(xiàn)(1),年長(zhǎng)兒及成人典型表現(xiàn),（）感染中毒及急性腦功能障礙癥狀,興奮：煩躁、驚厥 抑制：嗜睡、昏睡、淺昏迷、深昏迷,（2）顱高壓表現(xiàn) 頭痛、嘔吐、視乳頭水腫,顱高壓三聯(lián)征,頸項(xiàng)強(qiáng)直 （3）體征 ：腦膜刺激征 克氏征陽(yáng)性 布氏征陽(yáng)性,4歲女孩患

11、腦膜炎 表現(xiàn)為神志淡漠,4歲女孩患腦膜炎 頸項(xiàng)強(qiáng)直、布氏征陽(yáng)性,4,4歲女孩患腦膜炎 克氏征陽(yáng)性,臨床表現(xiàn)(),年齡小于3個(gè)月的幼嬰和新生兒化腦的特點(diǎn)： 1、體溫可高可低 2、顱壓增高不明顯 3、驚厥可不典型 4、腦膜刺激征不明顯,COMPLICATIONS,1. 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 c

12、ases occur in infants. Manifestations: After treating and getting a good effect by antibiotic, then the patients manifest the symptoms and signs of PM again:,fever, seizures, alternation of mental status, bulging fontanel, diastasis of sutures, enlarging head circumference, emesis, positive cranial

13、transillumination, etc. CT or MRI of brain can make the definite diagnosis.,并發(fā)癥及后遺癥(1),硬膜下積液 2ml，蛋白定量 400 mg/L,2. 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,并發(fā)癥及后遺癥(2),腦室管膜炎(見(jiàn)

14、于新生兒、小嬰兒) 治療被延誤 強(qiáng)力治療后仍持續(xù)發(fā)熱、反復(fù)抽搐、呼吸衰竭且進(jìn)行性加重 腦脊液始終不正常 頭顱B超、CT可助診，確診依靠側(cè)腦室穿刺腦室液,3. 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 exacerb

15、ate cerebral edema or directly produce hyponatremic seizures.,并發(fā)癥及后遺癥(3),抗利尿激素異常分泌綜合征 病因 炎癥累及下丘腦及垂體后葉，引起抗利尿激素過(guò)量分泌。 表現(xiàn) 低鈉及血漿滲透壓降低,others Cranial nerve palsies: such as deafness, blindness Cerebral or cerebellar herniation hydrocephalus,其他并發(fā)癥及后遺癥 腦積水 各種顱神經(jīng)功能障礙 癲癇,EXAMINATION OF EXPERIMENT,(1) CSF: Whe

16、n PM is suspected, lumbar puncture (LP) should be performed to get CSF. It should be found in CSF: Turbid or purulent High ICP,Elevated leukocyte count: greater than 1000/mm3 (3002000/mm3) and neutrophilic predominance (7595%) elevated protein (100500mg/dl) reduced glucose and chloride concentration

17、s Gram stain may be positive with bacteria Bacteria culture may be positive,(2) Other potentially valuable diagnostic tests CT or MRI of brain: Maybe normal except of complication，When the cases are difficult to diagnosis, the examinations are necessary. Blood cultures Bacteria on the smear of cutan

18、eous petechiae Peripheral blood: WBC, NC,實(shí)驗(yàn)室檢查(1),腦脊液檢查 是確診本病的主要依據(jù),腦脊液(CSF)正常值,外觀清亮 壓力 新生兒 0.29-0.78（30-80） 兒童 0.69-1.96（70-200） 白細(xì)胞數(shù) 嬰兒 0-20 兒童 0-10 蛋白質(zhì) 新生兒 20-120mg/dl 兒童 40mg/dl 糖 嬰兒 3.9-4.9(70-90) 兒童 2.8-4.4(50-80) 氯化物 嬰兒 111-123 兒童 118-128(650-750),化膿性腦膜炎的腦脊液改變： 壓力升高，外觀渾濁似米湯，白細(xì)胞顯著增多，以中性粒細(xì)胞為主，糖含

19、量降低，蛋白增高。,實(shí)驗(yàn)室檢查(2),腦脊液涂片 腦脊液細(xì)菌培養(yǎng) 血培養(yǎng) 皮膚瘀點(diǎn)、瘀斑涂片 外周血象：白細(xì)胞增多，中性粒細(xì)胞為主 降鈣素原,診斷與鑒別診斷(1),早期診斷是治療成功與否的關(guān)鍵 臨床癥狀、體征及腦脊液檢查 不規(guī)則抗生素治療后,腦脊液檢查結(jié)果可不典型 起病24小時(shí)內(nèi)腦脊液檢查結(jié)果可不典型,診斷與鑒別診斷(2),病毒性腦膜炎 結(jié)核性腦膜炎 真菌性腦膜炎,幾種常見(jiàn)腦膜炎的腦脊液比較,項(xiàng)目壓力外觀白細(xì)胞數(shù) 蛋白質(zhì) 糖氯化物 化膿性 混濁1000以中 腦膜炎 膿樣 性粒為主 結(jié)核性 毛玻 200-500 腦膜炎 璃樣 淋巴為主 病毒性 輕度 清亮 0-數(shù)百 輕度 正常 正常 腦膜炎 淋巴

20、為主 ,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 antibiot

21、ics 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.,治療原則(1),選擇抗生素原則 早期足量 有效殺菌劑 易通過(guò)血腦屏障 療程足,治療原則(2),抗生素治療 肺炎球菌 青霉素、氯霉素、三代頭孢菌素 腦膜炎球菌 青霉素、三代頭孢菌素 流感桿菌 氨芐西林、三代頭孢菌素、氯霉素 療程10-14天 金黃色葡萄球菌 耐酶青霉素、萬(wàn)古霉素、利福平 大腸桿菌腦膜炎 三代頭孢、哌拉西林、氨基甙類(lèi) 療程21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, pupil