2026年03月09日发布 | 3943阅读

《新英格兰医学杂志》发布特发性正常压力脑积水(iNPH)重磅研究进展

徐昊

安徽省立医院

达人收藏


2025年9月,国际成人脑积水临床研究组公布了特发性正常压力脑积水分流有效性研究Efficacy in iNPH Shunting Trial(PENS)的初步结论。本研究为双盲随机对照试验,纳入99例经脑脊液引流的特发性正常压力脑积水患者,随机分开放分流组(阀门压110mmH2O)与安慰剂组(>400mmH2O),评估术后3个月疗效。结果显示,开放分流组步态速度改善显著优于安慰剂组(治疗差异0.21m/s,P<0.001)。



2025年12月《新英格兰医学杂志》再次发表iNPH的综述,总结了近年来iNPH的研究进展。


iNPH是多见于60岁以上人群的综合征,核心表现为步态与平衡障碍、排尿障碍、认知功能受损及脑室扩大(图1)。60年前,《新英格兰医学杂志》首次发表了对正常压力脑积水的描述,目前临床仍存在四大认知困惑:误认为疾病罕见、诊断性检查无价值、分流手术风险大于获益、术后改善无长期临床意义。


图1. 正常压力脑积水患者三主征


iNPH发病与高脂血症、高血压、糖尿病等危险因素相关,发病机制并非单纯脑室牵拉,还涉及颅内压力脉冲幅度增加、白质病变、脑类淋巴通路脑脊液流动减少,且CFAP43基因突变可能与其相关1-13。该病患病率远高于临床诊疗率,美国、瑞典、日本老年人群患病率分别为1.3%16、1.5%17、7.7%18,记忆障碍门诊就诊患者及养老院人群患病率更高,分别达到15%21和14%21,但美国每年接受分流手术的患者不足万人,漏诊问题突出19-20


Evans比率>0.3、胼胝体角<90°为仅为筛查工具,但无法可靠预测手术效果23。脑顶部沟回消失伴其他部位局灶性沟回扩张,对分流反应的阳性预测值为77%26。需通过CT或MRI排除脑脊液流动梗阻,脑脊液电影可清晰显示脑脊液流动情况,放射性核素脑池造影已不被临床指南推荐用于诊断14、15


iNPH核心症状中,步态与平衡障碍发生率超90%32,表现为小步幅拖曳步态,腿部肌力等无异常,易与帕金森病混淆;认知障碍以额-皮质下功能受损为主,短期记忆下降但远期记忆保留,与阿尔茨海默病存在特征性差异;排尿障碍主要为尿急、排尿抑制困难,大便失禁罕见,需排查其他病因36。部分仅影像学异常而无症状者,3年内约52%会出现症状,需定期随访38


指南推荐通过脑脊液循环生理学检查或脑脊液引流临床反应测试判断分流术获益可能性14-15,39-40。其中,腰椎穿刺引流30-50ml脑脊液对分流反应的阳性预测值约90%,腰大池引流特异性与敏感性均约90%,但是引发颅内感染的几率是1%-2%20、24、44各类测试均需结合步态的定量评估。脑脊液分析结果多正常,相关生物标志物仅能辅助识别合并的阿尔茨海默病,无法单独诊断iNPH或预测手术效果。合并阿尔茨海默病的患者,分流手术仅能改善步态和排尿障碍,需充分沟通手术获益与风险。


分流手术是iNPH最有效的治疗方式,脑室-腹腔、脑室-心房、腰-腹腔分流术疗效相近,内镜下第三脑室造口术有效性尚无定论。分流术可使步态速度平均提高30%47。手术严重并发症主要为感染、颅内出血等,专业治疗中心术后1年无并发症率达91%,约90%患者术后症状可持续缓解,75%以上患者术后4年仍有改善,且治疗具备成本效益。证实为iNPH的患者,手术延迟超过6个月会导致症状加重、术后疗效变差,6年死亡率升高2.6倍,尽早诊疗对预后至关重要。若术后症状复发,需调整分流阀、排查分流管功能障碍及新发共存疾病。约90%的患者术后症状可持续缓解,80岁以上患者易出现功能衰退45。诊断和治疗延迟不利,手术延迟超过6个月的患者症状恶化更明显,6年死亡率是及时手术者的2.6倍52-53








总之,特发性正常压力脑积水是一种常见但常被漏诊的疾病,严重影响老年人的生存质量的疾病。对脑类淋巴循环、脉络丛功能、脑脊液运输和疾病遗传倾向的研究可能有助于阐明病因和病理生理学55-57。研发通过减少脑脊液生成或增加脑脊液引流来缩小脑室体积的新手术方法和药物58-59,有利于更好的服务此类患者。



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专家简介

徐昊 副主任医师

● 中国科学技术大学附属第一医院(安徽省立医院)神经外科,医学博士、博士后,硕士生导师,国家公派留学归国人员。曾先后在美国加州大学旧金山分校、德州大学西南医学中心等国际著名医学院交流学习,具备深厚的专业理论功底与前沿的诊疗视野

● 社会任职:国际脑积水协会委员,中国研究型神经科学学会青年委员,《Frontier neurology脑积水专栏责任编辑,“安徽省脑积水诊疗联盟” 常务副理事长,《临床与病理》青年编委,《中华神经外科疾病研究杂志》审稿专家,《神经损伤与功能重建》审稿专家,《中国循证医学杂志》青年审稿人

● 长期深耕神经系统疾病诊疗领域,擅长:1. 脑积水相关:脑室腹腔分流术、腰大池腹腔分流术、脑积水和蛛网膜囊肿的内镜微创手术、脑积水各种短程长程引流术、颅内感染手术和综合治疗;以及全类型分流泵测压调压。2. 其他神经外科疾病:脑内出血内镜手术和综合治疗,脑干出血微创治疗,重症颅脑创伤救治,脑膜转移癌的(Ommaya)囊植入术、复杂颅骨缺损的修补手术等。3. 各类神经系统疾病:颅脑损伤、昏迷促醒、颅内肿瘤、神经重症、头痛、头晕等病症的诊治

● 科研与科普成果:主持及参与多项国家自然科学基金项目,以第一作者或通讯作者发表 SCI论文30篇;深耕医学科普与学术传播,撰写医学科普作品7部,翻译医学专著1部

● 出诊时间:每周一下午(中区)、周六上午(南区)、周三下午(南区-脑积水调压门诊)


END

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