新生儿缺氧缺血性脑损伤MRI研究与脑成熟度、围产因素的关系
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摘要
前言
新生儿缺氧缺血性脑损伤(HIBD)是由于围产期缺氧窒息而导致的脑部缺氧缺血性损害。本病不仅可造成围产儿死亡，而且是新生儿期后遗留神经系统后遗症的常见原因之一。然而新生儿缺氧缺血性脑损伤后，准确地预知其临床预后是困难的。随着MRI技术的广泛应用于临床，早期诊断和评价缺氧缺血性脑损伤变得容易。本研究旨在阐述围产期缺氧缺血性脑损伤早产儿、足月儿MRI表现的差异，阐明其与脑成熟度，血生化指标及围产因素的关系。
方法
选择缺氧缺血性脑损伤患儿足月儿、早产儿共108例，年龄为生后10分钟～7天，均为适于胎龄儿，临床分度：轻度22例，中度56例，重度13例，早产儿17例，于生后4～10天进行MRI检查，观察和评价脑水肿、脑实质、基底节丘脑区、蛛网膜下腔及脑室内病变，比较HIBD患儿轻、中、重度组及早产儿组间差异，入院后开始治疗前采血检查血气分析和血肌酸磷酸激酶CPK，比较HIBD轻、中、重度组血气及血生化指标的差异，以及围产因素与HIBD分度、MRI表现的关系。
结果
HIBD患儿的MBI检查，在基底节、丘脑部位损伤中，轻、中、重
度组间差异显著，且足月儿多见，早产儿与重度HIBD患儿差异显
著；广泛脑水肿改变轻、中度组间差异显著h＜0．05八似RI表现
为丘脑基底节区损伤的仅见于中、重度HIBD患儿；广泛脑水肿、
蛛网膜下腔脑室内出血，多见于中、重度HIBD患儿。在蛛网膜下
腔脑室内出血患儿中，中重度组间差异显著，重度明显多于中度
组；脑实质“出血”，可见于轻、中、重度组HIBD患儿，以深部脑白
质“出血”为主。人院时血气和血肌酸磷酸激酶CPK的检查示重
度HIBD患儿血pH值＊E值和CPK明显重于轻、中度HIBD患
儿。HIBD分度与围产因素的关系，5分钟 APgar评分低者（＜5
分）发生中、重度 HIBD者明显多于 Apgar评分高者（3 5分人差
异显著 p＜0．05。在 MRI表现为丘脑基底节区损伤者，宫内窘迫
所致 HIBD患儿重于产时窒息所致者，差异显著 P＜0．05；APgP
评分低者发生率，多于 APgar评分高者，但差异不显著 P＞0．05；
足月儿基底节丘脑区损伤发生率 27．5％，多于早产儿发生率 11．
8％，差异不显著P＞O．05。
讨 论
早期识别IllBD尽早医疗干预，准确地判断产时缺氧缺血性
脑损伤对于减少患病率、死亡率是相当重要的。
本研究MRI检查显示，脑实质“出血”，轻、中、重度组间无显
著差异；蛛网膜下腔脑室内出血中、重度组间差异显著；而广泛的
脑水肿，基底节丘脑部位损伤，中、重度组明显高于轻度组，表明广
泛脑水肿及基底节丘脑区损伤是HIBD患儿脑损伤程度严重的表
现，尤其基底节丘脑区损伤在HIBD患儿轻、中、重度组间差异显
著。广泛性脑水肿反映HIBD的严重程度，生后第一周内作为严
重脑损伤的标志’与缺血、缺氧时血管调节功能紊乱，脑组织代谢
·2·
连锁反应所致脑组织直接受损有关。
足月儿HIBD的脑实质“出血”主要表现为深部白质内“出
血”；基底节丘脑区损伤一般多见于足月儿，但在较严重缺氧缺血
时，早产儿也可发生基底节丘脑区损伤。基底节损伤与严重的痉
挛性四肢瘫、喂养困难、持续性惊厥密切相关。在新生儿缺氧缺血
性脑损伤的 MRI表现基底节丘脑部位 T；人短信号，一些学者把
这些信号异常归结为出血，其他学者推测由于钙盐沉积或髓鞘崩
解产物；足月儿蛛网膜下腔出血以后纵裂池、矢状窦旁、横窦J脑
幕和窦汇处最常见，少量出血常位于窦汇附近，后纵裂池。早产儿
的＊＊D患儿，脑实质出血以生发层出血即侧脑室额角、枕角、三
角区多见，早产儿容易有皮层下及脑室旁白质梗塞伴点状、斑点状
出血，且容易合并脑室内出血。早产儿HIBD患儿，脑室旁白质代
谢特点，脑室旁胶质细胞分化的内在易损性，以及血管因素三者构
成了脑室旁白质软化（PVL）的基本病因，在早期MM检查中，PVL
不易诊断。BarkoyiCh报导在基底节丘脑病变中早产儿很少受损，
即使受累多表现为形成空洞和萎缩而不是足月儿中的胶质过度增
生所致的癫痕形成。
通过本研究我们发现脑损伤类型与HIBD的临床严重程度密
切相关。足月儿重度HIBD主要表现为基底节、丘脑部位损伤，而
轻、中度HIBD主要表现为深部脑白质损伤。此外，HIBD导致脑
损伤与脑成熟度密切相关，早产儿HIBD主要表现为深部脑白质
及皮层下的白质损伤，而丘脑基底节部位损伤在足月儿中多见，另
外，白质区损伤亦是足月儿HIBD最常见类型，机理可能为缺血性
损伤所致。
通过本研究人院时血气分析的检查我们还发现，脑在缺氧情
况下，糖酵解作用增加 5J 倍，大量丙酮酸被还原成乳酸，乳酸
在脑组织内堆积，细胞内酸中毒发展快且严重，因此在本研究中
iBD患儿其临床表现越重，其酸中毒也越重。而血肌酸磷酸激
·3·
酶（CPK）在中、重度组间差异显著，当缺氧持续时，由于呼吸循环
功能的继续恶化，导致脑、心等组织器官缺氧缺血，此时，上述脏器
Hypoxic-iischemic brain damage ( HIBD) in neonates is due to perinatal asphyxia. It can not only lead to the death of neonates but also is one of the frequent causes to leave sequelae of nerve system. However, it's difficult to accuratelly predict the clinical outcomes of HIBD. With MRI applied to the clinical practice extensively, it has become easier to evaluate and diagnose the HIBD. Our present study is to elucidate the difference between preterm infants and term neonates with HIBD, find the relationship between the maturation of brain, blood biochemical indexes and factors during perinatal period, and compare these findings with the clinical evaluation.
Materials and Methods
108 newborn infants with HIBD were selected, including preterm infants (n = 17) and term neonates (n =91). The subjects were between the ages of 10 minutes and seven days all appropriated for their gestational age. The term neonates were divided into three groups, the mild (n =28) , moderate (n =56) and severe (n = 13) group, based
on their clinical symptoms. They were scaned by MRI at the age from 4 days to 10 days after birth. We observed and evaluated brain edema , brain parenchymal hemorrhage, basal ganglia and thalamus, sub-arachnoid hemorrhage and intraventricular hemorrhage. Find the differences between the mild, moderate, severe group and preterm infants.
After they entered the hospital, we examined the blood gas analysis and the creatine phosphokinase in every neonates. Detect the differences between groups and elucidate the relationship between perinatal factors, classifications of HIBD and the patterns of MRI.
Result
The rates of extensive brain edema was significantly lower in the mild group than in the moderate group. Subarachnoid hemorrhage and introventricular hemorrhage could be seen more frequently in the severe group than in the moderate group ( p < 0. 05 ). Brain parenchymal hemmorrhage, mainly in the white matter, could be found in each group of term HIBD. The blood creatine phosphokinase and cord PH in the moderate and severe group was significantly higher than in the mild group ( p < 0.05 ).
As to the relationship between perinatal factors, groups of HIBD and neonates with low Apgar scores at 5 minutes suffered from severe HIBD much more frequently than those with high Apgar scores at 5 minutes ( p < 0.05 ). HIBD caused by asphyxia in uterus was significantly more severe than that caused by asphyxia during perinatal period ( p < 0. 05 ). The injury of basal ganglia and thalamus was more
common in the neonates with low Apgar scores (27. 3%) than in those with high Apgar scores (25. 3% ) , but the difference was not significant. The morbidity of the damage in basal ganglia and thalamus in term neonates (27. 5%) was more than that in preterm neonates (11.8%), but the difference was not significant.
Discussion
It is very important to identify and intervene neonatal HIBD as early as possible in order to reduce the morbidity and mortality.
The present study of MRI, demonstrated the rates of the brain parenchyma! hemorrhage wasnt significant in the mild, moderate and severe group. Its suggested that extensive brain edema and the damage in basal ganglia and thalamus, especially the latter, was the symbol of severe brain damage, since the morbidity was significant higher in the moderate and severe group than in the mild group. The extensive brain edema reflected the severity of HIBD, functions as the symbol of severe brain damage during the first week after birth and was associated with the direct damage of brain tissue caused by impaired vascular regulation and brain metabolism under hypoxic and/or ischemic state. Brain parenchyma! hemorrhage in term HIBD was mainly focused on the deep white matter; Injury of basal ganglia and thalamus was mostly seen in term neonates, however, under severe hypoxic and ischemic state, it could also be seen in preterm neonates.
Under hypoxic state, glycolysis increased by 5 - 10 times. And by producing and accumulating large amount of lactate, acidosis develope
新生儿缺氧缺血性脑损伤(HIBD)是由于围产期缺氧窒息而导致的脑部缺氧缺血性损害。本病不仅可造成围产儿死亡，而且是新生儿期后遗留神经系统后遗症的常见原因之一。然而新生儿缺氧缺血性脑损伤后，准确地预知其临床预后是困难的。随着MRI技术的广泛应用于临床，早期诊断和评价缺氧缺血性脑损伤变得容易。本研究旨在阐述围产期缺氧缺血性脑损伤早产儿、足月儿MRI表现的差异，阐明其与脑成熟度，血生化指标及围产因素的关系。
方法
选择缺氧缺血性脑损伤患儿足月儿、早产儿共108例，年龄为生后10分钟～7天，均为适于胎龄儿，临床分度：轻度22例，中度56例，重度13例，早产儿17例，于生后4～10天进行MRI检查，观察和评价脑水肿、脑实质、基底节丘脑区、蛛网膜下腔及脑室内病变，比较HIBD患儿轻、中、重度组及早产儿组间差异，入院后开始治疗前采血检查血气分析和血肌酸磷酸激酶CPK，比较HIBD轻、中、重度组血气及血生化指标的差异，以及围产因素与HIBD分度、MRI表现的关系。
结果
HIBD患儿的MBI检查，在基底节、丘脑部位损伤中，轻、中、重
度组间差异显著，且足月儿多见，早产儿与重度HIBD患儿差异显
著；广泛脑水肿改变轻、中度组间差异显著h＜0．05八似RI表现
为丘脑基底节区损伤的仅见于中、重度HIBD患儿；广泛脑水肿、
蛛网膜下腔脑室内出血，多见于中、重度HIBD患儿。在蛛网膜下
腔脑室内出血患儿中，中重度组间差异显著，重度明显多于中度
组；脑实质“出血”，可见于轻、中、重度组HIBD患儿，以深部脑白
质“出血”为主。人院时血气和血肌酸磷酸激酶CPK的检查示重
度HIBD患儿血pH值＊E值和CPK明显重于轻、中度HIBD患
儿。HIBD分度与围产因素的关系，5分钟 APgar评分低者（＜5
分）发生中、重度 HIBD者明显多于 Apgar评分高者（3 5分人差
异显著 p＜0．05。在 MRI表现为丘脑基底节区损伤者，宫内窘迫
所致 HIBD患儿重于产时窒息所致者，差异显著 P＜0．05；APgP
评分低者发生率，多于 APgar评分高者，但差异不显著 P＞0．05；
足月儿基底节丘脑区损伤发生率 27．5％，多于早产儿发生率 11．
8％，差异不显著P＞O．05。
讨 论
早期识别IllBD尽早医疗干预，准确地判断产时缺氧缺血性
脑损伤对于减少患病率、死亡率是相当重要的。
本研究MRI检查显示，脑实质“出血”，轻、中、重度组间无显
著差异；蛛网膜下腔脑室内出血中、重度组间差异显著；而广泛的
脑水肿，基底节丘脑部位损伤，中、重度组明显高于轻度组，表明广
泛脑水肿及基底节丘脑区损伤是HIBD患儿脑损伤程度严重的表
现，尤其基底节丘脑区损伤在HIBD患儿轻、中、重度组间差异显
著。广泛性脑水肿反映HIBD的严重程度，生后第一周内作为严
重脑损伤的标志’与缺血、缺氧时血管调节功能紊乱，脑组织代谢
·2·
连锁反应所致脑组织直接受损有关。
足月儿HIBD的脑实质“出血”主要表现为深部白质内“出
血”；基底节丘脑区损伤一般多见于足月儿，但在较严重缺氧缺血
时，早产儿也可发生基底节丘脑区损伤。基底节损伤与严重的痉
挛性四肢瘫、喂养困难、持续性惊厥密切相关。在新生儿缺氧缺血
性脑损伤的 MRI表现基底节丘脑部位 T；人短信号，一些学者把
这些信号异常归结为出血，其他学者推测由于钙盐沉积或髓鞘崩
解产物；足月儿蛛网膜下腔出血以后纵裂池、矢状窦旁、横窦J脑
幕和窦汇处最常见，少量出血常位于窦汇附近，后纵裂池。早产儿
的＊＊D患儿，脑实质出血以生发层出血即侧脑室额角、枕角、三
角区多见，早产儿容易有皮层下及脑室旁白质梗塞伴点状、斑点状
出血，且容易合并脑室内出血。早产儿HIBD患儿，脑室旁白质代
谢特点，脑室旁胶质细胞分化的内在易损性，以及血管因素三者构
成了脑室旁白质软化（PVL）的基本病因，在早期MM检查中，PVL
不易诊断。BarkoyiCh报导在基底节丘脑病变中早产儿很少受损，
即使受累多表现为形成空洞和萎缩而不是足月儿中的胶质过度增
生所致的癫痕形成。
通过本研究我们发现脑损伤类型与HIBD的临床严重程度密
切相关。足月儿重度HIBD主要表现为基底节、丘脑部位损伤，而
轻、中度HIBD主要表现为深部脑白质损伤。此外，HIBD导致脑
损伤与脑成熟度密切相关，早产儿HIBD主要表现为深部脑白质
及皮层下的白质损伤，而丘脑基底节部位损伤在足月儿中多见，另
外，白质区损伤亦是足月儿HIBD最常见类型，机理可能为缺血性
损伤所致。
通过本研究人院时血气分析的检查我们还发现，脑在缺氧情
况下，糖酵解作用增加 5J 倍，大量丙酮酸被还原成乳酸，乳酸
在脑组织内堆积，细胞内酸中毒发展快且严重，因此在本研究中
iBD患儿其临床表现越重，其酸中毒也越重。而血肌酸磷酸激
·3·
酶（CPK）在中、重度组间差异显著，当缺氧持续时，由于呼吸循环
功能的继续恶化，导致脑、心等组织器官缺氧缺血，此时，上述脏器
Hypoxic-iischemic brain damage ( HIBD) in neonates is due to perinatal asphyxia. It can not only lead to the death of neonates but also is one of the frequent causes to leave sequelae of nerve system. However, it's difficult to accuratelly predict the clinical outcomes of HIBD. With MRI applied to the clinical practice extensively, it has become easier to evaluate and diagnose the HIBD. Our present study is to elucidate the difference between preterm infants and term neonates with HIBD, find the relationship between the maturation of brain, blood biochemical indexes and factors during perinatal period, and compare these findings with the clinical evaluation.
Materials and Methods
108 newborn infants with HIBD were selected, including preterm infants (n = 17) and term neonates (n =91). The subjects were between the ages of 10 minutes and seven days all appropriated for their gestational age. The term neonates were divided into three groups, the mild (n =28) , moderate (n =56) and severe (n = 13) group, based
on their clinical symptoms. They were scaned by MRI at the age from 4 days to 10 days after birth. We observed and evaluated brain edema , brain parenchymal hemorrhage, basal ganglia and thalamus, sub-arachnoid hemorrhage and intraventricular hemorrhage. Find the differences between the mild, moderate, severe group and preterm infants.
After they entered the hospital, we examined the blood gas analysis and the creatine phosphokinase in every neonates. Detect the differences between groups and elucidate the relationship between perinatal factors, classifications of HIBD and the patterns of MRI.
Result
The rates of extensive brain edema was significantly lower in the mild group than in the moderate group. Subarachnoid hemorrhage and introventricular hemorrhage could be seen more frequently in the severe group than in the moderate group ( p < 0. 05 ). Brain parenchymal hemmorrhage, mainly in the white matter, could be found in each group of term HIBD. The blood creatine phosphokinase and cord PH in the moderate and severe group was significantly higher than in the mild group ( p < 0.05 ).
As to the relationship between perinatal factors, groups of HIBD and neonates with low Apgar scores at 5 minutes suffered from severe HIBD much more frequently than those with high Apgar scores at 5 minutes ( p < 0.05 ). HIBD caused by asphyxia in uterus was significantly more severe than that caused by asphyxia during perinatal period ( p < 0. 05 ). The injury of basal ganglia and thalamus was more
common in the neonates with low Apgar scores (27. 3%) than in those with high Apgar scores (25. 3% ) , but the difference was not significant. The morbidity of the damage in basal ganglia and thalamus in term neonates (27. 5%) was more than that in preterm neonates (11.8%), but the difference was not significant.
Discussion
It is very important to identify and intervene neonatal HIBD as early as possible in order to reduce the morbidity and mortality.
The present study of MRI, demonstrated the rates of the brain parenchyma! hemorrhage wasnt significant in the mild, moderate and severe group. Its suggested that extensive brain edema and the damage in basal ganglia and thalamus, especially the latter, was the symbol of severe brain damage, since the morbidity was significant higher in the moderate and severe group than in the mild group. The extensive brain edema reflected the severity of HIBD, functions as the symbol of severe brain damage during the first week after birth and was associated with the direct damage of brain tissue caused by impaired vascular regulation and brain metabolism under hypoxic and/or ischemic state. Brain parenchyma! hemorrhage in term HIBD was mainly focused on the deep white matter; Injury of basal ganglia and thalamus was mostly seen in term neonates, however, under severe hypoxic and ischemic state, it could also be seen in preterm neonates.
Under hypoxic state, glycolysis increased by 5 - 10 times. And by producing and accumulating large amount of lactate, acidosis develope
引文
1．韩玉昆．新生儿缺氧缺血性脑病诊断依据和临床分度．中华儿科杂志 1997，35：99-100．
2. Noriko Aida, Gen Nisbimar, Yuriko Hachiya, et al. MR imaging of perinatal brain damage: comparison of clinical outcome with initial and follow-up MR findigs. AJNR 1998, 19:1909-1921
3．曾超美．新生儿缺氧缺血性脑病MRI和~1HMRS检查的临床意义．中华儿科杂志 1999，37：69-72．
4. Rutherford MA. Hypoxic-ischemic encephalopathy: early and late magnetic resonance of disease in childhood. Arch Dis Child 1996, 75:F145-151.
5. Janes Barkovich, Profound asphyxia in the preterm infants: imaging findings. AJNR 1995,16:1837-1846.
6. Keeney SE, Adcock EW. Prospective observations of 100 high-risk neonates by high field (1.5 tesla) magnetic resonance imaging of the central nervous system: Ⅰ, intraventricular and extracerebral lesions. Pediatrics 1991,87:421-430.
7. Keeney SE, Adcock EW. Prospective observations of 100 high-risk neonates by high field (1.5 tesla) magnetic resonance imaging of the central nervous system:Ⅱ, lesions associated with hypoxic-ischemic encephalopathy. Pediatrics 1991,87:431-438.
8. Schonman-Clays E, Henry-Feugeas M-C, Roset F, et al. Periventricular leakomalacia: correlation between MR imaging and autopsy findings during the first 2 months of life. Radiology 1993, 189:59-64.
9. Barkovich AJ, Truwit CL. Brain damage for perinatal asphyxia: correlation of MR findings with gestational age. AJNR 1990, 11:
1087-1096.
10. Dienel GA. Regional accumulation of calcium in postischemie rat brain. J Neurochem 1984,43:913.
11．沈惟堂．新生儿缺氧缺血性脑病发病机理的研究．中国实用儿科杂志 1995，10(2)：69．
12．左思奇等．新生儿缺氧缺血性脑病时血浆内皮素、心钠素、血钙血钠动态变化及临床意义探讨．新生儿科杂志 1997，12(4)：158．
13. Matsuo Y, Hasegama K, Doi Y, et al. Erythrocyte sodiumpotassium transport in hyperkalaermic and normokalaemic infants. Eur J Pediatr 1995,154(7):571-576.
14. Markers of asphyxia and neonatal brain injury. the new England Joural of Medicine 1999, 341:364-365.
2. Noriko Aida, Gen Nisbimar, Yuriko Hachiya, et al. MR imaging of perinatal brain damage: comparison of clinical outcome with initial and follow-up MR findigs. AJNR 1998, 19:1909-1921
3．曾超美．新生儿缺氧缺血性脑病MRI和~1HMRS检查的临床意义．中华儿科杂志 1999，37：69-72．
4. Rutherford MA. Hypoxic-ischemic encephalopathy: early and late magnetic resonance of disease in childhood. Arch Dis Child 1996, 75:F145-151.
5. Janes Barkovich, Profound asphyxia in the preterm infants: imaging findings. AJNR 1995,16:1837-1846.
6. Keeney SE, Adcock EW. Prospective observations of 100 high-risk neonates by high field (1.5 tesla) magnetic resonance imaging of the central nervous system: Ⅰ, intraventricular and extracerebral lesions. Pediatrics 1991,87:421-430.
7. Keeney SE, Adcock EW. Prospective observations of 100 high-risk neonates by high field (1.5 tesla) magnetic resonance imaging of the central nervous system:Ⅱ, lesions associated with hypoxic-ischemic encephalopathy. Pediatrics 1991,87:431-438.
8. Schonman-Clays E, Henry-Feugeas M-C, Roset F, et al. Periventricular leakomalacia: correlation between MR imaging and autopsy findings during the first 2 months of life. Radiology 1993, 189:59-64.
9. Barkovich AJ, Truwit CL. Brain damage for perinatal asphyxia: correlation of MR findings with gestational age. AJNR 1990, 11:
1087-1096.
10. Dienel GA. Regional accumulation of calcium in postischemie rat brain. J Neurochem 1984,43:913.
11．沈惟堂．新生儿缺氧缺血性脑病发病机理的研究．中国实用儿科杂志 1995，10(2)：69．
12．左思奇等．新生儿缺氧缺血性脑病时血浆内皮素、心钠素、血钙血钠动态变化及临床意义探讨．新生儿科杂志 1997，12(4)：158．
13. Matsuo Y, Hasegama K, Doi Y, et al. Erythrocyte sodiumpotassium transport in hyperkalaermic and normokalaemic infants. Eur J Pediatr 1995,154(7):571-576.
14. Markers of asphyxia and neonatal brain injury. the new England Joural of Medicine 1999, 341:364-365.