瑞氏综合征的诊断治疗

瑞氏综合征的诊断治疗 瑞氏综合征(Reye综合症)也称为脑病合并脂肪变性(encephalopathy with fatty degeneration of the viscera)，是因多脏器脂肪浸润所引起的以脑水肿和肝功能障碍为现的一组症候群。澳大利亚病理学家Reye及其同事于1963年首次报道此综合征。本病的临床特点:病毒感染后出现脑病的症状(意识障碍、惊厥)，肝功能异常及代谢紊乱。多发生于6个月至4岁的婴幼儿和儿童，亦可见于任何年龄段。 一、病因 本病的发病原因目前尚未完全清楚。认为与下列因素有关: 1)感染:多数患儿病前1-7天常有病毒感染的表现，如呼吸道感染、消化道感染，也曾从Reye综合征病人身上分离出流感病毒、副流感病毒、柯萨奇病毒、疱疹病毒、EB病毒、水痘病毒等。除此之外部分细菌感染后也可出现Reye综合征如化脓性脑膜炎，细菌性痢疾等。但是目前尚无证据证明本病是由于直接感染所致。 2)药物:大量临床报道发现患儿病毒感染时服用水杨酸盐(阿司匹林)，发生本病的可能性大。鉴于此英、美等国家减少或停止儿童应用水杨酸制剂的应用。2000年Casteels-Van Daele M等报道美国密歇根州Reye综合征的发病率随阿司匹林的应用减少而下降。研究发现系统性红斑狼疮、类风湿性关节炎等长期应用阿司匹林的患儿易患Reye综合征，减少使用后发生率明显下降。以上研究均提示阿司匹林与此病相关，但是目前尚不明确阿司匹林与Reye的关系。此外，loan management (post) review: 1, approval criteria have been implemented; 2, the contract is correct; 3, in line with the contract, payment; 4, no other major cases against loan security;、Reviewed by: date of record form 9: qilu bank borrowing by single years of maximum amount a maximum no-loan borrowers: borrowers: ... Borrower name number, line of credit expiry date year month day to year month day maximum number of years in the loan contract are the top line opened, the borrowed and requested your bank opened credit lines above, is hereby requested. Borrower signature: date agreed to open credit lines. Customer Manager signature: date agreed to open credit lines. Loan review signature: date line cancellation-I did not use the loan amount, your bank credit lines to be cancelled. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-unused credit lines, agree to write off loans. -Credit loan principal repayment, agree to write off loans. Customer Manager signature: date case, agree to write off loans. Loan review signature: date of record form 16: qilu self credit for credit card cancellation application form name of borrower ID number and credit limit expiration date year month day to year month day year contract number self-service card-I do not use credit, your bank credit lines to be cancelled. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-unused credit lines, agree to write off loans. -Credit loan principal repayment, agree to write off loans. Customer Manager signature: 其他药物的应用也可引起与Reye综合征相同的症状如抗癫痫药物丙戊酸钠。 3)毒素:黄曲霉素、有机农药等中毒者可出现与Reye综合征相同的临床表型。 4)遗传代谢:部分患儿有家族史，提示此病可能与遗传因素有关。 二、发病机制 前驱表现:患儿发病前2周内常有呼吸道或消化道感染的前驱症状，如发热、流涕、咳嗽、呕吐、腹痛、腹泻等。 中枢神经系统受累的表现:在病程中突然出现剧烈的头痛、频繁呕吐及烦躁不安的表现，之后神经系统症状快速进展，由开始时兴奋烦躁、精神错乱、嗜睡，转为惊厥、昏迷，甚至出现去大脑强直状态。随着病情的发展，部分病人病情逐渐恶化，意识障碍和颅内压增高进行性加重，最后可因发生脑疝和脑干功能障碍死亡。查体多无神经系统的局灶体征。根据中枢神经系统的症状分为5期。?期:频繁呕吐，精神淡漠，嗜睡;?期:随着病情的加重，患者出现定向力丧失、谵妄、呼吸深快及肝功能异常等表现。?、?期代表脑水肿逐渐加重及肝功能出现异常的过程。随着病情的进展，出现颅内压增高及脑疝的表现。?期:意识模糊或昏迷，去大脑强直，过度换气，瞳孔对光反射存在，肝功能异常;?期:昏迷，抽搐，呼吸不整，查体:瞳孔散大，对光反射消失，视乳头水肿;?期:昏迷，肌张力低，腱反射不能引出，心率慢，血压低，甚至出现呼吸停止。 unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-cancelled. I did not use the loan amount, your bank credit lines to be -ed to open credit lines. Loan review signature: date line cancellationnes above, is hereby requested. Borrower signature: date agreed to open credit lines. Customer Manager signature: date agreer of years in the loan contract are the top line opened, the borrowed and requested your bank opened credit liloan borrowers: borrowers: ... Borrower name number, line of credit expiry date year month day to year month day maximum numb-amount a maximum noReviewed by: date of record form 9: qilu bank borrowing by single years of maximum 、4, no other major cases against loan security; (post) review: 1, approval criteria have been implemented; 2, the contract is correct; 3, in line with the contract, payment;loan management 2, agree to write off loans. Customer Manager signature:Credit loan principal repayment-unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-I do not use credit, your bank credit lines to be cancelled. -service card-fer sellication form name of borrower ID number and credit limit expiration date year month day to year month day year contract numbe, agree to write off loans. Loan review signature: date of record form 16: qilu self credit for credit card cancellation appCredit loan principal repayment, agree to write off loans. Customer Manager signature: date cas- 肝脏受累的症状:是Reye综合征特征性的临床表现，由于Reye综合征病理改变主要在细胞内的线粒体(并不影响胆红素的代谢(故临床上通常表现为肝功能异常而无黄疽。查体:肝脏轻度-中度增大。 代谢紊乱:多数患儿出现低血糖和高血氨的症状，少数伴有脱水和代谢性酸中毒等。 Reye综合征轻重不同，轻者可在病情的早期停止发展并逐渐恢复而重者或治疗不及时着可在数日或24小时内死亡。 三、辅助检查 血常规:白细胞总数大多明显增高，分类以中性粒细胞增高为主; 肝功能:肝功能检查多有转氨酶的明显升高，且多数患者为进行性加重，反复检查肝功，有助于确诊，但病程中无胆红素的升高。肝功能多在1—2周恢复正常，少数患者在4周内恢复正常。除转氨酶升高外，高玉兴等发现心肌酶常伴同肝功异常同时出现，并进行性加重; 血氨、血糖:血氨在疾病早期就有升高，升高通常为本病特异性诊断之一，需早期检查，常常较早恢复;血糖大多降低，尤其是婴儿明显，也有少部分患儿血糖正常; 脑脊液检查:脑脊液除压力升高外，脑脊液细胞数、糖、蛋白、氯化物多正常; 脑脊液检查:脑脊液除压力升高外，脑脊液细胞数、糖、蛋白、氯化物多正常; 脑电图检查:脑病的改变，背景呈现广泛高波幅慢波; 头颅影像:头颅CT和MRI示弥漫性或局部性水肿表现; principal repayment, agree to write off loans. Customer Manager signature: date case, agree to write off loans. Loan review Credit loan -unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-I did not use the loan amount, your bank credit lines to be cancelled. -date line cancellation ture:signature: date agreed to open credit lines. Customer Manager signature: date agreed to open credit lines. Loan review signa tract are the top line opened, the borrowed and requested your bank opened credit lines above, is hereby requested. Borrowerer of years in the loan conloan borrowers: borrowers: ... Borrower name number, line of credit expiry date year month day to year month day maximum numb-Reviewed by: date of record form 9: qilu bank borrowing by single years of maximum amount a maximum no、ntract, payment; 4, no other major cases against loan security;loan management (post) review: 1, approval criteria have been implemented; 2, the contract is correct; 3, in line with the co3Credit loan principal repayment, agree to write off loans. Customer Manager signature:-unused credit lines, agree to write off loans. -ateCredit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: d-I do not use credit, your bank credit lines to be cancelled. -service card-edit limit expiration date year month day to year month day year contract number selfand crsignature: date of record form 16: qilu self credit for credit card cancellation application form name of borrower ID number 肝脏活检:本病的确诊依赖于肝脏的活体组织检查，可见肝细胞内有大量脂肪滴，电镜下观察可见线粒体膨大以及致密体的减少或消失等特征性改变。 四、诊断 Reye综合征涉及一组由不同原因包括感染、 中毒及药物诱导等引起的疾病。目前被国际接受的Reye综合征的定义为:1)16岁以下的急性非炎性脑病:2)急性肝病(血清转氨酶或血氨升高，超出上限3倍(或呈典型的肝脂肪变性病理改变。但是这一定义缺乏特异性，仅适用于临床调查。目前诊断尚无统一，主要是根据临床表现，辅助检查及组织病理学三个方面做出诊断。 临床表现:患儿病前有前驱病毒感染，之后出现急性进行性脑部症状，如呕吐、惊厥、意识障碍等，但没有神经系统受累的局灶体征。 辅助检查:1)脑脊液压力升高，但常规、生化正常; 2)血清转氨酶升高、血胆红素不高，血氨高、血糖低、 凝血酶原时间延长; 3)头颅影像:弥漫性或局部性水肿表现。 组织病理学:肝细胞内有大量脂肪滴，电镜下观察可见线粒体膨大以及致密体的减少或消失等特征性改变。 若患儿病前有前驱病毒感染，之后出现急性进行性脑部症状，如呕吐、惊厥、意识障碍等，脑脊液压力升高但无炎症改变的表现，同时伴有血氨、转氨酶升高要考虑Reye综合征的可能性，给予积极治疗。因为早期诊断、早期治疗对于此病的预后具有重要意义。 e, agree to write off loans. Loan review signature: date of record form 16: qilu self credit for credit card cancellation appCredit loan principal repayment, agree to write off loans. Customer Manager signature: date cas-unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-cancelled. I did not use the loan amount, your bank credit lines to be -ed to open credit lines. Loan review signature: date line cancellationnes above, is hereby requested. Borrower signature: date agreed to open credit lines. Customer Manager signature: date agreer of years in the loan contract are the top line opened, the borrowed and requested your bank opened credit liloan borrowers: borrowers: ... Borrower name number, line of credit expiry date year month day to year month day maximum numb-amount a maximum noReviewed by: date of record form 9: qilu bank borrowing by single years of maximum 、4, no other major cases against loan security; (post) review: 1, approval criteria have been implemented; 2, the contract is correct; 3, in line with the contract, payment;loan management 4, agree to write off loans. Customer Manager signature:Credit loan principal repayment-unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-I do not use credit, your bank credit lines to be cancelled. -service card-fer sellication form name of borrower ID number and credit limit expiration date year month day to year month day year contract numb 五、鉴别诊断 中枢神经系统感染疾病:病毒性脑炎、化脓性脑膜炎等，这些疾病与Reye综合征的主要区别是其脑脊液伴有炎症改变，不伴有肝功能异常、血氨升高及肝脏脂肪变性。 急性中毒性脑病:与Reye综合征的共同点:伴有全身性感染和脑病的表现:惊厥和意识障碍等。脑脊液与Reye综合征类似压力升高无炎症改变。但是急性中毒性脑病没有线粒体病变，所以不伴内脏脂肪变性，若治疗及时病程较瑞氏综合征为轻。 病毒性肝炎:当病毒性肝炎出现脑症状时注意与Reye综合征相鉴别。病毒性肝炎是有黄疸和持续性肝功能损害。 遗传代谢病:部分遗传代谢性疾病影响线粒体的功能，所以其临床表现与瑞氏综合征相似。如尿素循环障碍、Leigh综合征、中链和长链脂肪酸酰基辅酶缺陷等。这些遗传代谢病多起病较早且有相同症状的反复发生，体格及智力发育落后。遗传代谢病的确诊要靠血尿代谢筛查、酶活性测定及基因等。 六、治疗 1、纠正代谢紊乱，维持水电解质及酸碱平衡: 1)低血糖要积极纠正，当血糖稍高于正常水平时，可给予胰岛素以减少游离脂肪酸。 2)维持电解质正常，注意防止地血钙。 3)维持酸碱平衡，纠正代谢性酸中毒及呼吸性碱中毒。 2、控制脑水肿、降低颅内压: Credit loan -unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-I did not use the loan amount, your bank credit lines to be cancelled. -date line cancellation ture:signature: date agreed to open credit lines. Customer Manager signature: date agreed to open credit lines. Loan review signa tract are the top line opened, the borrowed and requested your bank opened credit lines above, is hereby requested. Borrowerer of years in the loan conloan borrowers: borrowers: ... Borrower name number, line of credit expiry date year month day to year month day maximum numb-Reviewed by: date of record form 9: qilu bank borrowing by single years of maximum amount a maximum no、ntract, payment; 4, no other major cases against loan security;loan management (post) review: 1, approval criteria have been implemented; 2, the contract is correct; 3, in line with the co5Credit loan principal repayment, agree to write off loans. Customer Manager signature:-unused credit lines, agree to write off loans. -ateCredit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: d-I do not use credit, your bank credit lines to be cancelled. -service card-edit limit expiration date year month day to year month day year contract number selfand crsignature: date of record form 16: qilu self credit for credit card cancellation application form name of borrower ID number principal repayment, agree to write off loans. Customer Manager signature: date case, agree to write off loans. Loan review 1)20%甘露醇每次2.5—5ml/kg静注，每4—6小时一次。速尿和地塞米松可同时应用。 2)监测血气:防止低氧血症和高碳酸血症，避免加重脑水肿。 3)维持正常血压:保证脑内灌注压在50mmHg以上。脑灌注压=平均动脉压—颅内压，如果脑灌注压过低，则引起脑缺氧，加重脑水肿。脑水肿时须限制液体入量，但要检测血压，以免出现低血容量性低血压加重脑水肿。 3、降低血氨、保肝治疗。 4、防治出血可给予维生素K有助于凝血酶原的合成，也可输注凝血因子或新鲜血浆等。 5、Reye综合征的病情重、进展快，不同的患者可能会出现不同脏器受损。应及时针对患者具体的情况给予必要的对症和支持治疗。 七、疾病预后 Reye综合征病死率10%—40%，存活者中可遗留智力障碍、癫痫、瘫痪及行为异常等后遗症。Reye综合征的预后与以下因素有关:发病年龄、病情轻重、进展速度以及治疗早晚。早期昏迷、去大脑强直、反复惊厥、血氨在176umol/L以上、高血钾及空腹血糖在2(2mmol/L以下者，预后不良。 八、预防 虽然导致Reye综合征的原因不清楚，但研究表明阿司匹林或含阿司匹林的药物会引发这种病症。目前能做到的最好的预防方法是不要给孩子服用阿司匹林。 service card-fer sellication form name of borrower ID number and credit limit expiration date year month day to year month day year contract numbe, agree to write off loans. Loan review signature: date of record form 16: qilu self credit for credit card cancellation appCredit loan principal repayment, agree to write off loans. Customer Manager signature: date cas-unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-cancelled. I did not use the loan amount, your bank credit lines to be -ed to open credit lines. Loan review signature: date line cancellationnes above, is hereby requested. Borrower signature: date agreed to open credit lines. Customer Manager signature: date agreer of years in the loan contract are the top line opened, the borrowed and requested your bank opened credit liloan borrowers: borrowers: ... Borrower name number, line of credit expiry date year month day to year month day maximum numb-amount a maximum noReviewed by: date of record form 9: qilu bank borrowing by single years of maximum 、4, no other major cases against loan security; (post) review: 1, approval criteria have been implemented; 2, the contract is correct; 3, in line with the contract, payment;loan management 6, agree to write off loans. Customer Manager signature:Credit loan principal repayment-unused credit lines, agree to write off loans. -Credit loan principal repayment, your bank credit lines to be cancelled. Borrower signature: date-I do not use credit, your bank credit lines to be cancelled. -