1、徐州医学院附属医院王永DAI诊断中的主要问题诊断中的主要问题早期诊断困难早期诊断困难DAI诊断中的主要问题诊断中的主要问题-昏迷昏迷n 弥漫性轴索损伤(diffuse axonal injury，DAI)是指头部在加速度，尤其是减速运动时，在成角旋转的剪应力作用下，造成深部脑白质广泛神经轴索肿胀断裂而引起的脑损伤。n弥漫性轴索损伤在重型颅脑损伤中占20%左右，在脑外伤死亡病例中占29%43%。nDAI是颅脑外伤致死致残最常见、医疗纠纷最多的一类损伤。DAI的发生机制n多为交通事故伤n少数为坠落伤、打击伤抛鞭样损伤抛鞭样损伤植物状态的主要原因（剪力，DAI弥漫性轴索损伤）脑脊液冲击作用使胼胝体向
2、外伸展脑脊液冲击作用使胼胝体向外伸展资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head injuries EMERGENCY RADIOLOGY 12: 12371252猪猪DAI模型中观察到脑组织移位模型中观察到脑组织移位(冠状位冠状位)左左:静止静止 中中: 加速加速 右右:减速减速资料来源资料来源: :Douglas H.(2003) Diffuse Axonal Injury in Head Trauma. J Head Trauma Rehabil Vol. 18: 307316n在大脑灰白质交界处、胼胝体、内
3、囊、基底节、脑干及小脑等脑中轴部位可见组织的损伤、出血或水肿。脑震荡属于脑震荡属于弥漫性轴索损伤的轻型弥漫性轴索损伤的轻型n急性期急性期(1(1周内周内) )n病变区域弥漫或成簇的小针尖样出血病变区域弥漫或成簇的小针尖样出血灶灶, ,部分成融合状态部分成融合状态n病变区域轴索扭曲、肿胀、断裂和轴病变区域轴索扭曲、肿胀、断裂和轴索收缩球索收缩球(axonal retraction ball, (axonal retraction ball, ARB)ARB)形成形成n轴索损伤时间窗轴索损伤时间窗n伤后伤后2h 2h 轴索明显肿胀轴索明显肿胀n伤后伤后16h 16h 出现出现ARBARBn伤后伤后
4、72h ARB72h ARB发展到高峰发展到高峰n轴索损伤区和小出血灶周条带样水肿轴索损伤区和小出血灶周条带样水肿n吸收期吸收期( (第第2 2周周8 8周周) )n弥漫的小针尖样出血灶被吸收弥漫的小针尖样出血灶被吸收n较大的小出血灶囊性变较大的小出血灶囊性变, ,小疤痕形成小疤痕形成n损伤的轴索周大量小胶质细胞成簇增生损伤的轴索周大量小胶质细胞成簇增生 n恢复期恢复期(8(8周后周后) )n脑白质萎缩脑白质萎缩n脑室扩大脑室扩大n髓鞘变性髓鞘变性 胼胝体出血胼胝体出血DAI. Lesions of the corpus callosum. The pathology illustrates
5、vascular rupture but the key lesion is axonal damage.Demonstration of macroscopic alterations accompanying b-APP-reactive axons: Focal hemorrhages in the corpus callosum脑干出血脑干出血晚期晚期DAIDAI:胼胝体萎缩,变性的白质 因陈旧性出血而变成棕色Severe white matter degeneration and atrophy of the corpus callosum in old DAI. Brownish
6、color of the degenerated white matter due to old hemorrhages. n脑组织轴索断裂、肿胀、轴浆溢出，断裂处形成圆形轴索球；n出血处红细胞溶解后遗留含铁血黄素。轴缩球轴缩球（ PAP染色，取自胼胝体）染色，取自胼胝体）资料来源资料来源:Jos Eymard Homem Pittella1,(2004),The conformation of the brain plays an important role in the distribution of diffuse axonal injury in fatal road traffic
7、 accident . Arq Neuropsiquiatr 62(2-B):406-413轴突病理切片轴突病理切片取材部位（左取材部位（左: :皮质下白质皮质下白质 右右: :脑干）脑干）资料来源资料来源: : Douglas H.(2003) Diffuse Axonal Injury in Head Trauma. J Head Trauma Rehabil Vol. 18: 307316Photomicrographs demonstrating traumatic axonal pathology revealed by immunoreactivity of accumulatin
8、g neurofilament protein. Darkly stained profiles show axonal pathology in the subcortical white matter (left) and brainstem (right), represented by elongated varicose swellings and axonal bulbs that form at the terminal stump of disconnected axons.Neuronal cultures at 21 days in vitro had formed lar
9、ge clusters, interconnected by fasciculated bundles of axons. shown by bright-field microscopy (A), immunocytochemical neurofilament staining (B), and scanning electron microscopy (C). Bar 10 m (A,C), 20 m (B).电镜下：无菌空气吹打轴突致轴突牵张损伤电镜下：无菌空气吹打轴突致轴突牵张损伤箭头示轴突原先位置箭头示轴突原先位置资料来源资料来源: R. S. Chung ,(2005), Mil
10、d Axonal Stretch Injury In Vitro Induces a Progressive Series of Neurofilament Alterations Ultimately Leading to Delayed Axotomy. JOURNAL OF NEUROTRAUMA Volume 22, Number 10:10811091An individual bundle of axons was targeted with a single blast of sterile air, and the resultant deflection was captur
11、ed by video camera. In the selected series of frames (AD), the axon bundle is rapidly stretched, before recovering to its original position (indicated by arrowheads). For reference, frame B displays an increase in original axon length of 3%. Bar 25 m.电镜下：伤后电镜下：伤后48h48h在损伤位点可见轴突逐渐裂解在损伤位点可见轴突逐渐裂解(C),(
12、C),并并出现神经微丝环状结构出现神经微丝环状结构(D); (D); 伤后伤后72h72h：轴突完全裂解，神经微丝环状结构增多：轴突完全裂解，神经微丝环状结构增多(F)(F)资料来源资料来源: R. S. Chung ,(2005), Mild Axonal Stretch Injury In Vitro Induces a Progressive Series of Neurofilament Alterations Ultimately Leading to Delayed Axotomy. JOURNAL OF NEUROTRAUMA Volume 22, Number 10:10811
13、091电镜下：伤后电镜下：伤后48h48h轴突三维重建，在损伤位点轴突三维重建，在损伤位点可见许多成球状的肿胀神经微丝可见许多成球状的肿胀神经微丝(B(B箭头箭头) ) 资料来源资料来源: R. S. Chung ,(2005), Mild Axonal Stretch Injury In Vitro Induces a Progressive Series of Neurofilament Alterations Ultimately Leading to Delayed Axotomy. JOURNAL OF NEUROTRAUMA Volume 22, Number 10:1081109
14、11、有确切的颅脑外伤史；2、伤后立即昏迷或无昏迷；3、可能有瞳孔、眼球位置改变。4、CT、MRI发现胼胝体、脑干、基底节、大脑半球皮质髓质交界区、小脑、脑室等部位有出血灶；或弥漫性脑肿胀。5、颅内压增高症状、体征不明 显，CT、MRI可无明显改变。6、病检发现轴缩球。7、病情恢复后CT、MRI出现弥漫 性脑萎缩，伴有严重的神经 系统后遗症。8、可合并其他类型的颅脑损伤。1、意识障碍： 绝大部分患者头部受伤后立即出 现昏迷， 入院时GCS 计分： 70%80% 的病人8分， 15%25% 的病人912分， 73 的病人1315分 昏迷时间长 24小时病人占2030。 24小时病人占7080。2
15、、脑干损伤脑干损伤 ： 34%51%的病人可有 一侧或双侧瞳孔散大， 或双瞳针尖样缩小， 对光反应消失， 眼球分离运动 或同向凝视。 2、脑干损伤脑干损伤 ： 双侧锥体束征阳性 去大脑、去皮层状态等。 一般无颅内压增高3、生命体征： 7090病人有呼吸、心率、 血压及体温改变； 约4%32%的病人有中间清期，神志 好转后，可因继发性脑水肿很快进入 再次昏迷。易引发医疗纠纷。易引发医疗纠纷。n颅脑外伤后长时间的原发昏迷颅脑外伤后长时间的原发昏迷n该昏迷系该昏迷系DAIDAI累及脑内广泛纵、累及脑内广泛纵、横轴索导致上行激活系统和或皮横轴索导致上行激活系统和或皮层广泛抑制所致层广泛抑制所致 n定位
16、体征：可出现程度不同的偏瘫定位体征：可出现程度不同的偏瘫, , 而而CTCT却很少有相应部位局灶性改变却很少有相应部位局灶性改变n颅内压：多无明显颅内压增高颅内压：多无明显颅内压增高 1、CTCT： 可见大脑皮质与髓质交界处、 胼胝体、内囊区或第三脑室周 围、脑干等有多个点状或小片 状出血灶。 可见脑室系统变小； 脑池，如外侧裂池变小，尤其 是环池变小或消失； 脑干肿胀； 晚期脑室系统扩大。患者患者26岁，伤后岁，伤后2月月CT资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head injuries EMERGENCY RA
17、DIOLOGY 12: 12371252Patient, 26 years of age, with persistent vegetative state CT scan 2 months after injury shows an extensive lesion within the frontal periventricular white matter and at the gray matter/white matter junction (long arrow). A hypodense lesion in the right putamen (thin arrow). Mild
18、 dilatation患者患者33岁持续性植物生存岁持续性植物生存资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head injuries EMERGENCY RADIOLOGY 12: 12371252Patient, 33 years of age, who suffered DAI with persistent vegetative state. Non-enhanced CT shows marked dilatation of the ventricles with diffuse brain atrophy2、
19、MRI： 可精确反映出早期脑组织缺血灶、 轴索损伤、脑室、脑池及脑等 结构改变的情况。 nT1WI呈等、稍低信号，部分不均匀，少数为低信号；合并出血者有小点状高信号；nT2WI均为高信号，合并出血者有等、稍低信号；n可以合并脑室内出血；n均无占位效应。MRI obtained 14 days after the accident. Multifocal lesions of the white matter and lesions of the posterior parts of corpus callosum.7979岁男性岁男性, ,伤后伤后5 5天天MRIMRI资料来源资料来源: A.
20、 Uchino,(2006), Acquired lesions of the corpus callosum: MR imaging. Eur Radiol 16: 905914Diffuse axonal injury in a 79-year-old man. a, b FLAIR axial and midsagittal images (TR/TI/TE=10,000/2,200/125, 1.5 T) obtained 5 days after head injury show lesions in the posterior half of the corpus callosum
21、. The midbrain, cingulate gyrus and both frontal lobes are also involvedMRI:右海马旁回继发于正铁血红蛋白的异常右海马旁回继发于正铁血红蛋白的异常稍高信号及中脑背侧脑桥损伤信号稍高信号及中脑背侧脑桥损伤信号资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head injuries EMERGENCY RADIOLOGY 12: 12371252Slightly abnormal increase of signal on T1-weighted spin
22、 echo secondary to methemoglobin in the right parahipoccampal gyrus (thick arrow) and a small lesion within the midbrain and dorsal part of the pons (thin arrow). T2WI 示颞上回表面小脑挫伤灶示颞上回表面小脑挫伤灶,周围水肿周围水肿. 右右侧丘脑和胼胝体压部亦有小损伤灶侧丘脑和胼胝体压部亦有小损伤灶资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head inju
23、ries EMERGENCY RADIOLOGY 12: 12371252T2-weighted imaging shows very small cortical contusion along the superior temporal gyral surface surrounded by high-signal edema (long thin arrow). The right thalamic lesion (small thin arrow) and a small lesion within the splenium of corpus callosum (thick arro
24、w) due to shearing injury is also seenA midsagittal T2-weighted fast spin-echo image clearly shows high-signal lesions in the body of the corpus callosum27岁男性岁男性 伤后伤后48h48h内内 FLAIR及T2WI成像 资料来源资料来源:K. Paterakis,(2000); Outcome of Patients with Diffuse Axonal Injury The Significance and Prognostic Val
25、ue of MRI in the Acute Phase.J Trauma.Vol 49 :1071-1075A 27-year-old man with a GOS score consistent with moderate disability. (A) Turbo FLAIR (cerebrospinal fluid 5 0) shows hemorrhagic DAI in the subcortical white matter. (B) T2-weighted turbo spin echo sequence shows edematous DAI in the posterio
26、r half corpus callosum.TurboFLAIR25岁男性岁男性 伤后伤后48h48h内内 FLAIR及T2WI成像 资料来源资料来源:K. Paterakis,(2000); Outcome of Patients with Diffuse Axonal Injury The Significance and Prognostic Value of MRI .Trauma.Vol 49 :1071-1075 A 25-year-old man with severe disability. (A) Turbo FLAIR shows hemorrhagic DAI in t
27、he right dorsolateral midbrain, cortical hemorrhagic contusion in the right temporal lobe, and subarachnoid hemorrhage. (B) T2WI shows edematous DAI in the posterior half of the corpus callosum and hemorrhagic DAI in the midbrain.Turbo FLAIR示右颞叶皮质下、中脑背外侧出血（箭头示）T2WI示胼胝体后部水肿及中脑出血（箭头示）胼胝体损伤胼胝体损伤左左:T2WI
28、 中、右：快速梯度回波序列（中、右：快速梯度回波序列（GRE）资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head injuries EMERGENCY RADIOLOGY 12: 12371252Lesions of corpus callosum (corpus, splenium) demonstrated by a T2-weighted imaging(arrow) and b, c GRE sequences show the course of the traumatic force within splen
29、ium (b, arrow) and corpus callosum (c, arrow). Note that lesions are better seen on the GRE sequencesGRE-MR(快速梯度回波序列快速梯度回波序列) 资料来源资料来源: N. Beenski,(2002) Traumatic injuries imaging of head injuries EMERGENCY RADIOLOGY 12: 12371252Multifocal low signal on GRE T2* sequences caused by shearing injury c
30、orrespond to a small foci of former hemorrhage within the periventricular white matter (arrow), basal ganglia, and b deep parasagittal subcortical hemispheric white matter (arrows) Reconstruction of white matter fibres of the brain superimposed over DTI b0 images. The fibres are colour-coded for dir
31、ection: blue fibres are cranio-caudal, green fibres are anteroposterior and red fibres are transverse. Normal pattern of the white matter fibres inside the genu (anterior) and splenium (posterior) part of the corpus callosum, with anterior efferent forceps fibres. Note that the cortico-spinal tract
32、appears in blue on the posterior part of the internal capsula1919岁男性岁男性, ,入院时入院时GCS 7GCS 7分分, ,治疗一周出院预后良好治疗一周出院预后良好. .伤后伤后2 2天天 FLAIR-MRFLAIR-MR 资料来源：资料来源：D. Ducreux,( (2005) Brain MR diffusion tensor imaging and fibre tracking to differentiate between two diffuse axonal injuries, Neuroradiology 47:
33、 604608Patient 1: axial FLAIR (a) and coronal T2 (b) images centred on the corpus callosum. Hyperintense area in T2 and FLAIR on the splenium without T2 hypointense area (no magnetic susceptibility effect) that suggests the presence of oedema脑白质纤维重构示：脑白质纤维重构示：胼胝体压部纤维轻度弯曲并增宽胼胝体压部纤维轻度弯曲并增宽( (箭头示箭头示) )
34、reconstruction of brain white matter fibres superimposed over DTI b0 images. The fibres are colour-coded for direction: blue fibres are cranio-caudal, green fibres are anteroposterior and red fibres are transverse. Splenium fibres are slightly warped in the superior part and widened (arrow). There a
35、re no broken fibres1919岁男性患者入院时岁男性患者入院时GCS 4GCS 4分分, ,预后差植物生存预后差植物生存. . 伤后伤后1 1天天 FLAIR-MRFLAIR-MR 资料来源：资料来源：D. Ducreux,( (2005) Brain MR diffusion tensor imaging and fibre tracking to differentiate between two diffuse axonal injuries, Neuroradiology 47: 604608Patient 2: axial FLAIR (a) and T2* (b)
36、images centred on the corpus callosum. The FLAIR hyperintense areas that are hypointense on T2* and FLAIR on the genu and splenium suggest the presence of magnetic susceptibility effect脑白质纤维重构示胼胝体膝、压部左侧纤维脑白质纤维重构示胼胝体膝、压部左侧纤维增宽增宽( (如箭头如箭头) )，右侧损坏，右侧损坏reconstruction of brain white matter fibres superim
37、posed over DTI b0 images. The fibres are colour-coded for direction: blue fibres are cranio-caudal, green fibres are anteroposterior and red fibres are transverse. Splenium and genu fibres are widened and warped in the left segment and broken in the right segmentn 2月后MRI复查： 大部分较小的病灶消失、吸收、变小 较大的病灶缩小、
38、边界较前清晰； T1WI信号更低；T2WI信号更高； 脑萎缩伤后伤后1212天天 T2WI及弥散加权成像及弥散加权成像资料来源资料来源:H Takayama,(2000), Diffusion-weighted imaging demonstrates transient cytotoxic edema involving the corpus callosum in a patient with diffuse brain injury.Clinical Neurology and Neurosurgery 102:135139(a) Axial T2-weighted image on 1
39、2 days postinjury reveals an area of yperintensity (brightness) in the trunk and splenium of the corpus callosum. (b) Diffusion-weighted image shows extensive yperintensity in the same region. Note signal of the splenium is more remarkable than that of the trunk.与上张幻灯片同一个病人伤后与上张幻灯片同一个病人伤后20天，天，T2WI及
40、及DWI成像成像资料来源资料来源:H Takayama,(2000), Diffusion-weighted imaging demonstrates transient cytotoxic edema involving the corpus callosum in a patient with diffuse brain injury.Clinical Neurology and Neurosurgery 102:135139(a) A sagittal T2-weighted image obtained 20 days post injury shows restricted hype
41、rintense lesion in the trunk and the splenium of the corpus callosum. (b) A repeated axial T2-weighted image on the same day demonstrates decrease in the extent of hyperintensity. Diffusion-weighted images (c) on the same day reveals resolution of abnormally decreased diffusion.nCTCT与常规与常规MRIMRI均不能直
42、接显示轴均不能直接显示轴索本身的病变索本身的病变, , 只能借助于一些只能借助于一些间接征象判断间接征象判断DAI,DAI,因此有其一定因此有其一定的局限性的局限性n部分部分DAIDAI病例在病例在CTCT与与MRIMRI上可均无上可均无异常表现异常表现n急性期急性期n脑白质区水肿脑白质区水肿, ,多叶同时受累多叶同时受累nCTCT表现：脑白质内弥漫性片状低密度区表现：脑白质内弥漫性片状低密度区nMRIMRI表现：脑白质内有深在的较小的卵圆形、表现：脑白质内有深在的较小的卵圆形、片状及片索状异常信号区，片状及片索状异常信号区，T1WIT1WI上低信上低信号号,T2WI,T2WI上高信号上高信号
43、n脑白质内单发或多发无占位效应的小出血脑白质内单发或多发无占位效应的小出血n弥漫性脑肿胀弥漫性脑肿胀(DBS)(DBS)n脑室内出血脑室内出血n其他其他n蛛网膜下腔出血蛛网膜下腔出血(SAH)(SAH)n硬膜下血肿硬膜下血肿n硬膜外血肿硬膜外血肿n颅骨骨折颅骨骨折 左顶叶白质弥漫性轴索损伤左顶叶白质弥漫性轴索损伤横轴位T1WI斑点状长T1信号横轴位T2WI斑点状长T2信号灶横轴位FLAIR斑片状不均质高信号T1WI正中矢状位胼胝体周围斑片状出血灶n恢复期影像学表现恢复期影像学表现n脑白质区出现小囊状脑软化灶；随着时脑白质区出现小囊状脑软化灶；随着时间的推移，较小的病灶趋于消失，较大间的推移，较
44、小的病灶趋于消失，较大的病灶呈卵圆形，边界清晰的病灶呈卵圆形，边界清晰n脑白质萎缩脑白质萎缩n脑室扩大脑室扩大 n磁共振波谱分析磁共振波谱分析-MRS-MRS检查检查nMRSMRS是无创性研究活体器官的组织代谢、生化是无创性研究活体器官的组织代谢、生化 改变及化学物定量分析的方法改变及化学物定量分析的方法, ,被誉为被誉为“无无创活检创活检” ” nNAA/Cr NAA/Cr 和和Cho/Cr Cho/Cr 分别反映神经元及神经胶质分别反映神经元及神经胶质 细胞的变化细胞的变化nDAI DAI 损伤后损伤后4h NAA/Cr 4h NAA/Cr 显著下降，显著下降，Cho/Cr Cho/Cr
45、无无 明显差异明显差异 nCTCT诊断优势诊断优势: :显示超急性期少量的蛛网膜下显示超急性期少量的蛛网膜下腔出血腔出血nMRIMRI诊断优势诊断优势n显示非出血性剪切伤病变显示非出血性剪切伤病变n显示脑水肿、实质内小病灶或挫伤方面显示脑水肿、实质内小病灶或挫伤方面, ,特别是对特别是对脑干、胼胝体、小脑、透明隔和穹窿损伤的观察脑干、胼胝体、小脑、透明隔和穹窿损伤的观察均较均较CTCT敏感敏感nMRI 90% ;CT 15%-28%MRI 90% ;CT 15%-28%CTT2WICTT1WI右额顶叶多发小灶状出血n 对重型DAI患者原则上按脑挫裂伤治疗，包括传统的开颅手术、脱水、防治继发感染
46、等综合治疗方法。1对于单纯对于单纯DAIDAI病病人人, ,不强调进行不强调进行颅内压监测颅内压监测3根据血糖水平调根据血糖水平调整胰岛素用量越整胰岛素用量越来越被神经外科来越被神经外科医师所重视医师所重视2美国神经外科学美国神经外科学会已建议在会已建议在DAIDAI的治疗中不再使的治疗中不再使用糖皮质激素用糖皮质激素如无癫痫发作如无癫痫发作, ,则不必使用抗则不必使用抗癫痫药癫痫药44576DAI DAI 病人的营养已引起病人的营养已引起足够的重视，并认为静足够的重视，并认为静脉营养和鼻饲营养无明脉营养和鼻饲营养无明显差异显差异神经轴索生长抑制物神经轴索生长抑制物NI235NI235和和NI
47、2250 NI2250 单单克隆抗体克隆抗体 对颅内高压明显对颅内高压明显,CT ,CT 提示第三提示第三脑室和基底池严重受压或消脑室和基底池严重受压或消失失, ,中线结构移位的患者可采中线结构移位的患者可采取手术治疗去骨瓣减压取手术治疗去骨瓣减压56DAI DAI 病人的营养已引起病人的营养已引起足够的重视，并认为静足够的重视，并认为静脉营养和鼻饲营养无明脉营养和鼻饲营养无明显差异显差异神经轴索生长抑制物神经轴索生长抑制物NI235NI235和和NI2250 NI2250 单单克隆抗体克隆抗体 对颅内高压明显对颅内高压明显,CT ,CT 提示第三提示第三脑室和基底池严重受压或消脑室和基底池严
48、重受压或消失失, ,中线结构移位的患者可采中线结构移位的患者可采取手术治疗去骨瓣减压取手术治疗去骨瓣减压56DAI DAI 病人的营养已引起病人的营养已引起足够的重视，并认为静足够的重视，并认为静脉营养和鼻饲营养无明脉营养和鼻饲营养无明显差异显差异神经轴索生长抑制物神经轴索生长抑制物NI235NI235和和NI2250 NI2250 单单克隆抗体克隆抗体 对颅内高压明显对颅内高压明显,CT ,CT 提示第三提示第三脑室和基底池严重受压或消脑室和基底池严重受压或消失失, ,中线结构移位的患者可采中线结构移位的患者可采取手术治疗去骨瓣减压取手术治疗去骨瓣减压56DAI DAI 病人的营养已引起病人的营养已引起足够的重视，并认为静足够的重视，并认为静脉营养和鼻饲营养无明脉营养和鼻饲营养无明显差异显差异神经轴索生长抑制神经轴索生长抑制物物NI235NI235和和NI2250 NI2250 单克隆抗体单克隆抗体 对颅内高压明显对颅内高压明显,CT ,CT 提示第三提示第三脑室和基底池严重受压或消脑室和基底池严重受压或消失的患者可采取手术治疗去失的患者可采取手术治疗去骨瓣减压骨瓣减压5
