新生儿缺氧缺血性脑病磁共振诊断与损伤类型的分类建议

新生儿缺氧缺血性脑病(HIE)有比较统一的临床诊断与分度标准,但是符合相同诊断标准的窒息所致HIE的临床表现、神经病理损伤类型有很大差异。磁共振成像(MRI)能很好地呈现HIE损伤类型、损伤进程,且与其远期神经发育结局密切相关,但不同MRI检查序列所反映的损伤表现可能不尽相同。弥散加权序列适宜的检查时间为出生后2~4 d,常规序列为出生后的4~8 d。HIE的MRI主要损伤类型有丘脑基底节+内囊后肢损伤、分水岭样损伤累及皮层和皮层下白质、局灶-多灶性微小性白质损伤,以及广泛全脑性损伤。严重的急性产时窒息易导致深部灰质损伤(丘脑基底节),也可累及脑干,锥体束是最易受累的白质纤维束,而反复间断性缺氧缺血以及伴有感染、低血糖等易导致分水岭区和深部白质损伤。但上述损伤类型有时很难明确区分,而是以某一类型为主,并非所有HIE都有特征性的MRI表现。     

高危晚期早产儿脑损伤病因学及其磁共振发现

目的 探讨以弥散加权成像(DWI)结合常规磁共振成像(T1WI-T2WI)诊断的高危晚期早产儿脑损伤的相关危险因素及临床特点,并分析不同时间MRI序列的信号特点及DWI的早期诊断价值。方法 首先对符合纳入标准的649例晚期早产儿的MRI片重新阅片,按照脑损伤评估标准得出诊断,其次收集相关的临床资料,分析不同类型脑损伤的危险因素和临床特点,并对其中271例确诊脑白质损伤（CWMD）的MRI序列进行分析,探讨不同类型CWMD的信号特点、损伤部位及结局。结果 ①晚期早产儿发生脑损伤332例（51.2%）,其中CWMD 271例（41.8%）,以局灶性CWMD为主（62.7％,170例）;颅内出血112例（17.3%）,主要为蛛网膜下腔出血55.4%（62/112）。②非出血性脑损伤的危险因素是男性（OR=1.510,95％CI：1.067～2.136,P=0.020）、阴道分娩（OR=2.367,95％CI：0.251～22.294 ,P=0.000）、早发型败血症（OR=2.194,95％CI：1.159～4.155,P=0.016）及抢救复苏史（OR=3.784,95％CI：1.908～7.506,P=0.000）。出血性脑损伤的危险因素是阴道分娩（OR=7.195,95％CI：4.249～12.184 ,P=0.000）和早发型败血症（OR=2.692,95％CI：1.185～6.117,P=0.018）。低钙血症（OR=2.593,95％CI：1.343～5.005,P=0.005）、晚发型败血症（OR=1.533,95％CI：1.012～2.323,P=0.044）和抽搐（OR=4.006,95％CI：1.790～8.970,P=0.001）是非出血性脑损伤组的主要临床特点。出血性脑损伤组主要表现为高血糖和抽搐。③局灶性CWMD 65.3％仅累及一处损伤,主要集中在侧脑室后脚（53.5%）,有97.1%病灶消失或病灶范围减少;广泛性CWMD 79.2%累及胼胝体和内囊;弥漫性CWMD 50％合并灰质损伤,全部发生软化。④生后2周内,DWI具有较高的敏感性,98.0%表现为高信号,T1WI信号无变化或稍高信号,伴或不伴T2WI低信号。局灶性CWMD DWI高信号持续时间长达3周以上,弥漫性CWMD DWI高信号持续时间2周以内。结论 晚期早产儿仍然容易受产前产时因素影响而发生不同类型的脑损伤。对有高危因素,或早期出现临床表现或电解质紊乱的患儿应选择生后2周内（1周内最佳）进行DWI和常规MRI检查,以早期发现病变。局灶性CWMD预后较好,合并有灰质损伤或弥漫性CWMD预后极差,需要动态随访,并进行早期康复训练。     

Brain damage in preterm newborns: biological response modification as a strategy to reduce disabilities

Substances that promote the growth and maturation of oligodendrocytes and their precursors might protect against white matter injury. We suggest that neuroprotection can also be provided by such modulators of fetal and neonatal inflammatory responses as antiinflammatory cytokines, cytokine-binding proteins, and cytokine-receptor blockers. We briefly describe inflammatory responses in the fetus and newborn and show how they might contribute to brain damage. We conclude with the possibility that so-called biological response modifiers, which are drugs that modulate these inflammatory responses, might reduce the risk of brain damage and disabilities.     

Fetal and neonatal origins of altered brain development

Abnormal development of the brain during fetal life is now thought to contribute to the aetiology of many neurological disorders that manifest throughout life. Many factors are likely to underlie such abnormal development including genetic makeup and an adverse intrauterine environment. This review will focus on prenatal hypoxic/ischaemic injury, inflammatory/infective insults and preterm birth. A range of experimental models have been used to characterize lesions formed in response to these insults and to determine mechanisms of damage resulting from such events. Relatively brief periods of fetal hypoxia result in neuronal death (cerebellum, hippocampus, and cerebral cortex), white matter damage and reduced growth of neural processes. These effects are more profound at mid than late gestation. Chronic mild placental insufficiency can result in fetal growth restriction and deficits in neural connectivity and myelination. Exposure of the preterm fetus to inflammatory agents causes brain damage particularly in the white matter and this is exacerbated by hypoxia. Premature birth without potentiating factors can result in subtle neuropathologies including cerebral white matter gliosis, hippocampal sclerosis and subarachnoid haemorrhage; the extent of the damage appears to be related to the regimen of ventilatory support. These studies show that the timing, severity and nature of specific insults are critical in determining the pattern of injury and thus the extent to which neurological function will be affected postnatally. Defining the causes, patterns and mechanisms of brain injury is crucial if we are to develop rational neuroprotective strategies to reduce the burden of altered brain growth and poor functional and behavioural outcomes.     

Early detection of periventricular leukomalacia by diffusion-weighted magnetic resonance imaging techniques

Periventricular leukomalacia (PVL), the principal form of brain injury in the premature infant, is characterized by overt focal necrotic lesions in periventricular white matter and less prominent, more diffuse cerebral white matter injury. The early detection of the latter, diffuse component of PVL is not consistently possible with conventional brain imaging techniques. We demonstrate the early detection of the diffuse component of PVL by diffusion-weighted magnetic resonance imaging (DWI). In a premature infant with no definite cerebral abnormality detectable by cranial ultrasonography or conventional magnetic resonance imaging, DWI showed a striking bilateral decrease in water diffusion in cerebral white matter. The DWI abnormality (ie, decreased apparent diffusion coefficient) was similar to that observed with acute cerebral ischemic lesions in adults. At 10 weeks of age, conventional magnetic resonance imaging and ultrasonography showed striking changes consistent with PVL, including the presence of small cysts. The observations indicate the importance of DWI in the early identification of the diffuse component of PVL and also perhaps the role of ischemia in the pathogenesis of the lesion.     

Glycine antagonist and NO synthase inhibitor protect the developing mouse brain against neonatal excitotoxic lesions

The prevention of cerebral palsy and neuroprotection of the immature brain continue to be health care priorities. The pathophysiology of perinatal brain lesions associated with cerebral palsy seems to be multifactorial and includes pre- and perinatal factors such as preconceptional events, hormone and growth factors deficiencies, maternal infections with production of cytokines, and hypoxic/ischemic perfusion failures. Excitotoxic cascade could represent a common pathway that leads to neural cell death and subsequent brain damage. Brain injuries induced by ibotenate, a glutamatergic analog, which are essentially mediated through the N-methyl-D-aspartate receptor, mimic some aspects of the white matter cysts and transcortical necrosis observed in human perinatal brain damage. The purpose of the present study was to assess the protective role of several pharmacological agents, administered in conjunction with ibotenate, against induced excitotoxic lesions. We injected ibotenate in the developing mouse brain 5 d postnatally, after the full settlement of neuronal layers. Co-treatment with kynurenic acid, an antagonist of the facilitating glycine site of the N-methyl-D-aspartate receptor, or with N(G)-nitro-L-arginine, an inhibitor of nitric oxide synthesis, induced a dose-dependent neuroprotective effect. Conversely, zinc gluconate, a blocking agent of the channel linked to the N-methyl-D-aspartate receptor, and a free radical scavenger (U74389F), were unable to protect the developing brain against excitotoxic attack. These data help to clarify some molecular mechanisms involved in excitotoxic lesions of the developing mouse brain and permit us to envision new strategies in the prevention of cerebral palsy.     

Head circumference and brain and hippocampal volume after severe traumatic brain injury in childhood

Vulnerability of the hippocampus to traumatic brain injury (TBI) in adults is related to severity of injury and white matter atrophy. The objectives of this study were to determine features of anthropometry and cerebral morphometry late after TBI in childhood and to assess whether hippocampal volume is related to severity of initial ictus and changes in white matter at follow-up. Thirty-three patients underwent magnetic resonance imaging 4.9 y after severe TBI that necessitated intensive care; 23 had mechanical ventilation and intracranial pressure monitoring longer than 3 d. Magnetic resonance imaging analyses included volume of brain, hemisphere, ventricles, and hippocampal and perihippocampal regions; spatial distribution of voxel-based morphometry differences in white matter; and eigenvalues of diffusion tensor imaging diffusivity. Patients with longer intensive care ictus had smaller-than-expected occipitofrontal head circumference. Eight of these, identified by voxel-based morphometry, had periventricular white matter loss and smaller-than-expected brain volume for OFC, suggesting "atrophy"; the remainder had expected volume for a smaller OFC, suggesting "growth disturbance." Ninety-three percent of the variation in right hippocampal volume was accounted for by factors related to severity of injury and white matter atrophy. It is concluded that anthropometry and cerebral morphometric measurements late after severe TBI in childhood provides useful outcome data and indicate that, despite adequate growth in stature, effects of TBI on brain growth and hippocampal volume may extend into adulthood.     

Diffusion-weighted MRI in shaken baby syndrome

We present the characteristic CT and MRI findings of a 2-month-old girl with shaken baby syndrome. Diffusion-weighted MR imaging performed 8 days after the insult established the presence of injury to the white matter in the corpus callosum and subcortical white matter in the temporo-occipito-parietal region. Diffusion-weighted MR imaging is valuable in the diagnostic work-up of suspected shaken baby syndrome, as injury to the white matter can be demonstrated days after the injury.     

早产儿脑室旁白质损伤发病机制的研究进展

脑室旁白质损伤是早产儿特征性脑损伤,也是早产儿最重要的脑病类型之一。其病理变化主要包括脑白质的凝固性坏死、少突胶质细胞损伤、髓鞘损害、轴突损伤以及坏死部位出现反应性胶质化和小胶质细胞浸润等,这些病变与新生儿期后的神经系统后遗症密切相关。早产儿脑室旁白质软化的发病机制主要是与脑血管发育未成熟和少突胶质细胞前体细胞损伤易感性有关。本文通过文献复习对早产儿脑室旁白质损伤发病机制的研究进展进行概述,为临床预防和诊治提供理论依据。     

Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury.     

Long-term follow up of children with head injuries-classified as “good recovery” using the Glasgow Outcome Scale: neurological, neuropsychological and magnetic resonance imaging results

The primary issues addressed in this study were: (1) determination of the significance of the classification “good outcome” utilizing the Glasgow Outcome Scale (GOS) in children at least 1 year after brain injury; (2) detection of residual lesions of brain parenchyma in these children upon follow up MRI scans; and (3) detection of relationships between neuropsychological test performance and MRI results. Selection criteria included children 6–15 years of age at the time of testing who received an initial CT scan at the time of their head injury and who had been injured at least 12 months prior to the follow up test. Only children who did not demonstrate neurological disability at the time of follow up examination were selected. The children showed a status of “good outcome” as defined by the GOS. Neurological examination, neuropsychological tests and an MRI were done. The test results of 59 patients were compared to those of a matched control group. Children, after receiving head injuries, showed significantly poorer results with respect to cognitive, motor and fine motor skills. Of all MRI-scans 66% revealed pathological findings. Cortical lesions were detected on MRI in 14% of cases; subcortical injuries were detected in 12% and, deep white matter lesions in 31%. Furthermore, corpus callosum damage was observed in 26% of cases. Pathological MRI findings were also observed in children with mild head injuries. All of the children with normal MRI findings showed abilities comparable to those of children in the control group. Patients with cortical lesions exhibited only motor deficits, whereas motor and cognitive deficits were seen in patients with deep white matter lesions. Children with multiple lesions demonstrated test results in all variables 1 to 2 standard deviations below those of the control group. Conclusions Children suffering a brain injury who 1 year later are classified within the “good outcome” group according to the Glasgow Outcome Scale often have significant morphological and functional brain deficits. Received: 6 January 1996 /  Accepted: 10 August 1996     

新生儿低血糖脑损伤临床特征与磁共振成像动态变化

目的：探讨新生儿低血糖性脑损伤的影像特征与临床及预后关系，为低血糖性脑损伤的诊断及预防提供依据。方法：16例低血糖性脑损伤新生儿于入院24~48小时（n=16），生后2周左右（n=11），1~5月(n=3)进行了常规的MRI 与MRI-DWI动态观察与临床随访。结果：惊厥、嗜睡、肌张力减低为常见的症状和体征，昏迷和呼吸衰竭5例。低血糖脑损伤时最低血糖值为0.98±0.43 mmol/L,5例重者血糖为0.72±0.42 mmol/L。脑电图提示轻者为间断低电压，重者电压平坦，甚至电静息。16例均有顶枕部皮层受累，合并脑室周围白质损伤2例，弥漫性皮层受累5例，其中1例合并广泛的脑白质损伤，2例合并丘脑基底节受累。弥漫性皮层受累5例和顶枕部合并脑白质损伤2例血糖明显低于仅有顶枕部受累者（0.71±0.35 mmol/L vs 1.19±0.42 mmol/L，t=2.4124,P<0.05）。早期信号改变在DWI表现最明显为高信号。4例弥漫性脑水肿者再次检查已发生广泛性脑萎缩和多发脑软化；顶枕部受累者7例接受了再次检查，5例T1WI与T2WI信号异常，而DWI信号异常3例。临床表现轻者以顶枕部皮层受累为主，重者弥漫性皮层受累为主。顶枕部受累1例随访发现髓鞘发育落后；合并白质受累1例发生双下肢痉挛性瘫痪；弥漫性皮层受累1例发生广泛脑软化。结论：新生儿低血糖性脑损伤与低血糖的严重程度密切相关，顶枕部皮层是易损区，但重度的损伤可表现为弥漫性皮层受累甚至合并广泛的白质或基底节丘脑受损，DWI可以早期反映脑损伤情况。     

Protecting the brain of the micropreemie

Advances in perinatal care have seen substantial improvements in survival without disability for extremely preterm infants. Protecting the developing brain and reducing neurodevelopmental sequelae of extremely preterm birth are strategic priorities for both research and clinical care. A number of evidence-based interventions exist for neuroprotection in micropreemies, inclusive of prevention of preterm birth and multiple births with implantation of only one embryo during in vitro fertilisation, as well as antenatal care to optimize fetal wellbeing, strategies for supporting neonatal transition, and neuroprotective developmental care. Avoidance of complications that trigger ischemia and inflammation is vital for minimizing brain dysmaturation and injury, particularly of the white matter. Neurodevelopmental surveillance, early diagnosis of cerebral palsy and early intervention are essential for optimizing long-term outcomes and quality of life. Research priorities include further evaluation of putative neuroprotective agents, and investigation of common neonatal interventions in trials adequately powered to assess neurodevelopmental outcome.     

早产儿脑病的研究进展

随着低出生体重儿存活率的提高,早产儿脑损伤成为热点问题,损伤部位不仅局限于脑白质,灰质区域也有受累,故提出了“早产儿脑病”的概念。早产儿脑病包括脑白质损伤和神经元轴突病变。在缺血缺氧、围生期感染等致病因素作用下,脑组织发生直接或间接的神经细胞死亡或者是成熟障碍,最终导致脑性瘫痪、认知、语言、行为等能力障碍。该文总结了早产儿脑病的病理、发病机制、治疗及预后等情况。     

Update on mechanisms of the pathophysiology of neonatal encephalopathy

Therapeutic hypothermia is now well established to significantly improve survival without disability after neonatal encephalopathy (NE). To further improve outcomes, we need to better understand the mechanisms of brain injury. The central finding, which offers the potential for neuroprotective and neurorestorative interventions, is that brain damage after perinatal hypoxia-ischemia evolves slowly over time. Although brain cells may die during profound hypoxia-ischemia, even after surprisingly severe insults many cells show transient recovery of oxidative metabolism during a “latent” phase characterized by actively suppressed neural metabolism and activity. Critically, after moderate to severe hypoxia-ischemia, this transient recovery is followed after ~6 h by a phase of secondary deterioration, with delayed seizures, failure of mitochondrial function, cytotoxic edema, and cell death over ~72 h. This is followed by a tertiary phase of remodeling and recovery. This review discusses the mechanisms of injury that occur during the primary, latent, secondary and tertiary phases of injury and potential treatments that target one or more of these phases. By analogy with therapeutic hypothermia, treatment as early as possible in the latent phase is likely to have the greatest potential to prevent injury (“neuroprotection”). In the secondary phase of injury, anticonvulsants can attenuate seizures, but show limited neuroprotection. Encouragingly, there is now increasing preclinical evidence that late, neurorestorative interventions have potential to improve long-term outcomes.     

早产儿脑白质损伤程度与早期脑电生理变化关系的研究

目的通过振幅整合脑电图(amplitude-integrated EEG,aEEG)及原始脑电抑制性电活动持续时间的研究,探讨早产儿脑白质损伤程度与早期脑功能变化的关系。方法 38例小于32周的脑白质损伤早产儿(轻度脑白质损伤20例,重度脑白质损伤18例)及42例无脑白质损伤的早产儿纳入研究。自生后开始每周进行一次aEEG监测和颅脑超声检查,直至生后4周或矫正胎龄32周。比较各组aEEG图形及振幅变化趋势及原始脑电爆发抑制比的变化。结果脑白质损伤组和对照组aEEG均呈高度不连续图形,无成熟的睡眠周期。重度脑白质损伤组下边界振幅明显低于轻度脑白质损伤组和对照组。脑白质损伤组和对照组的原始脑电图形均为爆发性电活动-抑制性电活动交替出现,重度脑白质损伤组抑制段时间及爆发抑制比明显大于轻度脑白质损伤组及对照组。结论脑白质损伤早产儿早期动态进行脑功能监测有助于早期发现严重脑白质损伤。     

磁敏感加权成像在早产儿伴脑室旁白质损伤中的应用研究

目的脑室旁白质损伤是早产儿围生期窒息后常见的脑损伤类型之一,其MRI表现具有特征性,但常规序列难以区分病灶内是否合并出血,而出血与否可能影响治疗和预后。该研究应用磁敏感加权成像(SWAN)来检测存在白质损伤的早产儿脑内的出血性病变。方法对临床怀疑围生期窒息后脑损伤的75例早产儿行头颅GE HDx Twin Speed 3.0T MRI检查,扫描序列包括T1FLAIR、T2FLAIR、DWI和SWAN。结果44例(58.7%)早产儿存在脑室旁白质损伤,其中4例(9.1%)存在出血性白质损伤。在这4例中有3例合并生发基质出血-脑室内出血;4例合并小脑出血;1例合并蛛网膜下隙出血。结论脑室旁白质损伤中绝大多数为非出血性损伤,当伴有生发基质出血或脑室内出血时,脑室周围白质损伤病灶中常存在出血。     

Cerebral white matter damage in the preterm infant: pathophysiology and risk factors

Based on clinical, epidemiologic, and experimental studies, the aetiology of white matter damage, specifically periventricular leukomalacia (PVL), is multifactorial and involves pre- and perinatal factors possibly including genetic factors, hypoxic-ischaemic insults, infection, excess cytokines, free radical production, increased excitatory amino acid release, and trophic factor deficiencies. The article summarizes research findings about the aetiology of white matter damage and cerebral palsy in preterm infants. The information is organized according to specific antecedents, for which we present epidemiological and neurobiological data. The most important prenatal factor appears to be intrauterine infection. We discuss the evidence supporting the hypothesis that the foetal inflammatory response contributes to neonatal brain injury and later developmental disability. We recently established an animal model of excitotoxic lesions in the developing mouse brain. Brain damage was induced by intra-cortical injections of ibotenate, a glutamatergic agonist. When administered on post-natal day 5 ibotenate induced the formation of white matter cysts. Our animal model could be used to further explore the mechanisms involved in the formation of PVL. Potentially preventive strategies will be discussed.     

Diffusion tensor imaging of brain development

Understanding early human brain development is of great clinical importance, as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral organization and maturation. Diffusion tensor imaging (DTI), a recent magnetic resonance (MR) modality which assesses water diffusion in biological tissues at a microstructural level, has revealed a powerful technique to explore the structural basis of normal brain development. In fact, the tissue organization can be probed non-invasively, and the age-related changes of diffusion parameters (mean diffusivity, anisotropy) reveal crucial maturational processes, such as white matter myelination. Nevertheless, the developing human brain presents several challenges for DTI applications compared with the adult brain. DTI may further be used to detect brain injury well before conventional MRI, as water diffusion changes are an early indicator of cellular injury. This is particularly critical in infants in the context of administration of neuroprotective therapies. Changes in diffusion characteristics further provide early evidence of both focal and diffuse white matter injury in association with periventricular leukomalacia in the preterm infant. Finally, with the development of 3D fiber tractography, the maturation of white matter connectivity can be followed throughout infant development into adulthood with the potential to study correlations between abnormalities on DTI and ultimate neurologic/cognitive outcome.