Neonatal
Neurological Diseases
陈 超
Children’s Hospital,Fudan University
Neonatal Hypoxic-Ischemic
Encephalopathy
新生儿缺氧缺血性脑病
（ HIE）
Hypoxia
Perinatal asphyxia,apnea,respiratory failure,
right to left shunt
Ischemia
Heart arrest,Heart failure,Shock
1,Causes
Onset of HIE
Timing of Insults Percentage
Antepartum 20
Intrapartum 35
Antepartum ? antepartum 35
Postnatal 10
1,Cerebral hemodynamic alteration：
脑血流重分布
Initial changes,redistribution of circulation
(diving reflex) ? cerebral blood flow↑
Continue insult,loss of vascular
autoregulation,systemic hypotension,cerebral
blood flow↓ cerebral ischemia
Pathogenesis
Pathogenesis (Cont’s)
2,Effects of Hypoxic-Ischemic Insults
on Energy Metabolism（ 能力代谢）
(1) Brain glucose ?
(2) Lactate production ?
(3) ATP ?
(4) Energy failure
(5) Neuronal death
Pathogenesis (Cont’s)
3,Role of Free Radicals (自由基 )
(1) Perioxidation (过氧化 ) of membrane
phospholipids
(2) Damage to DNA
(3) Activation of proapoptotic (促凋亡 ) genes
Pathogenesis (Cont’s)
4,Calcium Reflux（ 钙内流）
(1) Activate phospholipases (磷脂酶 )
(2) Activate proteases (蛋白酶 )
(3) Activate nucleases (核酸酶 )
(4) ? neurotransmitter release
(5) 钙内流，导致细胞死亡
Pathogenesis (Cont’s)
5,Neurotoxicity of Excitatory Amino Acids
(兴奋性氨基酸 )
(1) Na+ entry,with H2O cell swelling and lysis
(2) Ca+ entry,Ca+-mediated events to cell death
Pathogenesis (Cont’s)
6,Delayed Cell Death (迟发性神经元死亡 )
(1) Cell death,Necrosis (坏死 ) and Apoptosis (凋亡 )
(2) Necrosis,occurs in minutes
(3) Apoptosis,delayed cell death occurs over hours
or days,or months
神经细胞凋亡的机制
MAPK激活
Fos
Jun
效应阶段
caspase级联
bcl-2家族
线粒体功能下降
自由基生成
细胞钙稳态失衡
细胞色素 c释放
扩展阶段
内切酶、蛋白酶激活
巨噬细胞活化
交介点 细胞凋亡
降解阶段 。 。
apoptosis in neurobiology
启动阶段
Neuropathology（ 神经病理）
1,Selective neuronal necrosis
2,Parasagittal cerebral injury（ 矢状旁区）
3,Periventricular leukomalacia （ PVL）
脑室周围白质软化
4,Periventricular-intraventricular hemorrhage
5,Focal ischemic brain necrosis（ 局灶缺血性）
Clinical Aspects
1,consciousness（ 意识）
Hyperalertness (兴奋 ),irritability (激惹 ),
lethargy(嗜睡 ),stupor or coma
2,Seizure (Jitteriness 抖动 )
3,Muscle tone（ 肌张力）
Hypertonia,weakness,hypotonia
Clinical Aspects
4,Primitive reflex（ 原始反射）
Hyperactive,depress,absence
5,Brain stem disfunction
Respiratory disturbance
abnormal pupillary response to light
Severity of HIE in Full-term Neonate
Mild Moderate severe
consciousness Hyperalertness Lethargy Coma
Seizure -,Jitteriness Variable +
Primitive reflexes Exaggerated Suppressed Absent
Muscle tone Hypertonia Weakness Floppy
Normal
Brain stem _ _ +
Diagnosis
1,History of hypoxia or ischemia
2,Clinical features
3,Neuroimaging
4,Electrodiagnostic techniques
5,Neuronal biochemistry
Neuroimaging（ 神经影像）
1,Cranial Ultrasound (头颅超声 )
（ 1） Diffuse increased echogenicity of
parenchyma
（ 2） Effacement of cortical sulci
（ 3） Increased periventricular echoes
Neuroimaging
2,Computed Tomography (CT)
（ 1） Focal or generalized low tissue
attenuation (低密度 )
（ 2） Focal or generalized cerebral atrophy
（ 3） Multicystic encephalomelacia (多囊脑软化 )
（ 4） Limited value for early assessment in
preterm neonate
脑萎缩和脑软化
脑萎缩和脑软化
重度 HIE
脑萎缩和基底节区软化
Neuroimaging
3,Magnetic Resonance Imaging (MRI)
（ 1） Demonstrate specific patterns of injury
（ 2） Early diagnosis
（ 3） Assessment neurodevelopment after injury
（ 3） Limited application in acute HIE
Electrodiagnostic techniques
Electroencephalogram (EEG)
Voltage suppression (低电压 )
burst suppression (爆发抑制 )
isoelectric EEG (电静息 ),slow wave,
focal lateralized epileptiform discharge (痫样放电 )
Neuronal biochemistry
Markers in blood or cerebrospinal fluid
Neuron-specific enolase (NSE)
(神经元烯醇化酶 )
Creatine kinase brain-specific（ CK）
S-100 protein (S-100 蛋白 )
Management
1,Monitoring of vital signs
NICU,CNS,respiration,
cardiovascular,renal,GI,fluid ……
Management
2,Maintenance of Adequate
Ventilation and Perfusion
? Respiratory support,blood gas
? Avoidance of systemic hypotension or
hypertension
? Avoidance of hyperviscosity
Management
3,Maintenance of Adequate Glucose Levels
Normal level,3.9-6,6 mmol/L
4,Control of Seizure
Phenobarbital (苯巴比妥 )
5,Control of Brain swelling
Prevention of fluid overload
Mannitol (甘露醇 ) 20％ 0.25 ~ 0.5 /kg 次
Management
6,Other Therapeutic Approaches
Mild hypothemia
Neuronal growth factor
7,Follow-up and Rehibitation
Intracranial Hemorrhage
新生儿颅内出血
2,Prematurity and hypoxia
Primarily in premature neonate
2,Birth trauma（ 产伤）
Primarily in term neonate
3,Others
Rapid volume expansion (扩容 )
alteration in cerebral blood flow
mechanical ventilation,coagulation defect
Causes
Cerebral Venous System
Type of Hemorrhage
1,Periventricular-intraventricular
Hemorrhage (PIVH)
脑室周围 -脑室内出血
2,Germinal Matrix Hemorrhage (GMH)
室管膜下生发层基质出血
脑室内出血
脑室内出血
脑室内出血
3,Subdural Hemorrhage (SDH)
硬膜下出血
Full term > premature
Uncommon
Clinically serious
Type of Hemorrhage (Cont’d)
Type of Hemorrhage (Cont’d)
4,Subarachnoid Hemorrhage (SAH)
（ 蛛网膜下腔出血）
Usually self-limited
Venous origin
Trauma or hypoxia
Rarely develop hydrocephalus
5,Intracerebellar Hemorrhage 小脑出血
蛛网膜下腔出血
蛛网膜下腔出血
蛛网膜下腔出血
脑池和脑室内出血
? 鞍上池、右侧裂池和环
池内出血（蓝箭）
? 第四脑室出血（红箭）
? 枕大池内出血（黄箭）
Grading of Severity of IVH
Grade I,Germinal matrix hemorrhage
Grade II,Intraventricular hemorrhage
Grade III,Intraventricular hemorrhage with
dilated ventricle
Separate notation,
periventricular posthemorrhage infarction
脑室周围出血后梗塞
Clinical Features
Common in premeture
Mild,asymptomatic state
Moderate to severe,neurological
deterioration (apnea,brainstem
dysfunction,floppy,coma,hypotension,
bradycardia)
May develop hydrocephylus (脑积水 )
Clinical Features
兴奋型,激惹，脑性尖叫，两眼凝视，
惊厥,四肢强直
抑制型,意识障碍、昏迷、呼吸不规则、
抽泣样呼吸、四肢肌张力下降
1,Clinical features
2,Neuroimaging
Ultrasound Scan,CT,MRI
3,Lumbar puncture (LP)
Many RBCs,elevated protein,
xanthochromia (变黄色 )
Diagnosis
Management
1,Correction of major hemodynamic
disturbance and coagulation defect
2,Control seizure
3,Control intracranial pressure
Management
4,Supportive care
5,Surgical intervention
6,Post-hemorrhagic hydrocephalus,
V-P shunt
Neonatal Infections
新生儿感染
features of neonatal infection
1、免疫功能不完善
屏障功能差，白细胞杀菌力差, IgM,IgA低，
T细胞功能差
2、环境因素,接触者、奶瓶、医疗器械、各种操作
3、感染途径,宫内感染、出生时感染、出生后感染
4、临床表现,不典型
感染途径,皮肤、脐部、呼吸道、消化道、
泌尿道
病原菌
金葡菌、大肠杆菌、克雷白杆菌、绿脓杆菌
新生儿败血症
临 床 表 现
?不典型、非特异性
?不哭、不吃、体温不升
?黄疸、呕吐、腹胀、呼吸困难、
呼吸暂停、酸中毒
?易并发化脓性脑膜炎
注 意 皮 肤 呈 明 显 大 理 石 花 纹
诊 断
临床表现,仔细观察才能发现
病原检查：细菌培养、涂片
其他检查：白细胞、血小板、血气分析
治 疗
抗菌治疗：合理治疗
免疫治疗：免疫球蛋白、粒细胞
支持疗法：保证营养供给
化脓性脑膜炎
一、临床特点：反应差，注意前囟饱满
二、诊 断：临床表现为线索，及时做腰穿
三、治 疗：选用易通过血脑屏障的药物
宫内感染
1、巨细胞病毒感染
2、弓形虫感染
3、先天性梅毒
4,病毒性肝炎
5,HIV感染
宫内感染
TORCH 综合征
T,弓形虫 ( Toxoplasma )
O,其它 ( Others )
R,风疹病毒 ( Rubella )
C,巨细胞病毒 ( cytomegalovirus )
H,疱疹病毒 ( Herpes )
Neurological Diseases
陈 超
Children’s Hospital,Fudan University
Neonatal Hypoxic-Ischemic
Encephalopathy
新生儿缺氧缺血性脑病
（ HIE）
Hypoxia
Perinatal asphyxia,apnea,respiratory failure,
right to left shunt
Ischemia
Heart arrest,Heart failure,Shock
1,Causes
Onset of HIE
Timing of Insults Percentage
Antepartum 20
Intrapartum 35
Antepartum ? antepartum 35
Postnatal 10
1,Cerebral hemodynamic alteration：
脑血流重分布
Initial changes,redistribution of circulation
(diving reflex) ? cerebral blood flow↑
Continue insult,loss of vascular
autoregulation,systemic hypotension,cerebral
blood flow↓ cerebral ischemia
Pathogenesis
Pathogenesis (Cont’s)
2,Effects of Hypoxic-Ischemic Insults
on Energy Metabolism（ 能力代谢）
(1) Brain glucose ?
(2) Lactate production ?
(3) ATP ?
(4) Energy failure
(5) Neuronal death
Pathogenesis (Cont’s)
3,Role of Free Radicals (自由基 )
(1) Perioxidation (过氧化 ) of membrane
phospholipids
(2) Damage to DNA
(3) Activation of proapoptotic (促凋亡 ) genes
Pathogenesis (Cont’s)
4,Calcium Reflux（ 钙内流）
(1) Activate phospholipases (磷脂酶 )
(2) Activate proteases (蛋白酶 )
(3) Activate nucleases (核酸酶 )
(4) ? neurotransmitter release
(5) 钙内流，导致细胞死亡
Pathogenesis (Cont’s)
5,Neurotoxicity of Excitatory Amino Acids
(兴奋性氨基酸 )
(1) Na+ entry,with H2O cell swelling and lysis
(2) Ca+ entry,Ca+-mediated events to cell death
Pathogenesis (Cont’s)
6,Delayed Cell Death (迟发性神经元死亡 )
(1) Cell death,Necrosis (坏死 ) and Apoptosis (凋亡 )
(2) Necrosis,occurs in minutes
(3) Apoptosis,delayed cell death occurs over hours
or days,or months
神经细胞凋亡的机制
MAPK激活
Fos
Jun
效应阶段
caspase级联
bcl-2家族
线粒体功能下降
自由基生成
细胞钙稳态失衡
细胞色素 c释放
扩展阶段
内切酶、蛋白酶激活
巨噬细胞活化
交介点 细胞凋亡
降解阶段 。 。
apoptosis in neurobiology
启动阶段
Neuropathology（ 神经病理）
1,Selective neuronal necrosis
2,Parasagittal cerebral injury（ 矢状旁区）
3,Periventricular leukomalacia （ PVL）
脑室周围白质软化
4,Periventricular-intraventricular hemorrhage
5,Focal ischemic brain necrosis（ 局灶缺血性）
Clinical Aspects
1,consciousness（ 意识）
Hyperalertness (兴奋 ),irritability (激惹 ),
lethargy(嗜睡 ),stupor or coma
2,Seizure (Jitteriness 抖动 )
3,Muscle tone（ 肌张力）
Hypertonia,weakness,hypotonia
Clinical Aspects
4,Primitive reflex（ 原始反射）
Hyperactive,depress,absence
5,Brain stem disfunction
Respiratory disturbance
abnormal pupillary response to light
Severity of HIE in Full-term Neonate
Mild Moderate severe
consciousness Hyperalertness Lethargy Coma
Seizure -,Jitteriness Variable +
Primitive reflexes Exaggerated Suppressed Absent
Muscle tone Hypertonia Weakness Floppy
Normal
Brain stem _ _ +
Diagnosis
1,History of hypoxia or ischemia
2,Clinical features
3,Neuroimaging
4,Electrodiagnostic techniques
5,Neuronal biochemistry
Neuroimaging（ 神经影像）
1,Cranial Ultrasound (头颅超声 )
（ 1） Diffuse increased echogenicity of
parenchyma
（ 2） Effacement of cortical sulci
（ 3） Increased periventricular echoes
Neuroimaging
2,Computed Tomography (CT)
（ 1） Focal or generalized low tissue
attenuation (低密度 )
（ 2） Focal or generalized cerebral atrophy
（ 3） Multicystic encephalomelacia (多囊脑软化 )
（ 4） Limited value for early assessment in
preterm neonate
脑萎缩和脑软化
脑萎缩和脑软化
重度 HIE
脑萎缩和基底节区软化
Neuroimaging
3,Magnetic Resonance Imaging (MRI)
（ 1） Demonstrate specific patterns of injury
（ 2） Early diagnosis
（ 3） Assessment neurodevelopment after injury
（ 3） Limited application in acute HIE
Electrodiagnostic techniques
Electroencephalogram (EEG)
Voltage suppression (低电压 )
burst suppression (爆发抑制 )
isoelectric EEG (电静息 ),slow wave,
focal lateralized epileptiform discharge (痫样放电 )
Neuronal biochemistry
Markers in blood or cerebrospinal fluid
Neuron-specific enolase (NSE)
(神经元烯醇化酶 )
Creatine kinase brain-specific（ CK）
S-100 protein (S-100 蛋白 )
Management
1,Monitoring of vital signs
NICU,CNS,respiration,
cardiovascular,renal,GI,fluid ……
Management
2,Maintenance of Adequate
Ventilation and Perfusion
? Respiratory support,blood gas
? Avoidance of systemic hypotension or
hypertension
? Avoidance of hyperviscosity
Management
3,Maintenance of Adequate Glucose Levels
Normal level,3.9-6,6 mmol/L
4,Control of Seizure
Phenobarbital (苯巴比妥 )
5,Control of Brain swelling
Prevention of fluid overload
Mannitol (甘露醇 ) 20％ 0.25 ~ 0.5 /kg 次
Management
6,Other Therapeutic Approaches
Mild hypothemia
Neuronal growth factor
7,Follow-up and Rehibitation
Intracranial Hemorrhage
新生儿颅内出血
2,Prematurity and hypoxia
Primarily in premature neonate
2,Birth trauma（ 产伤）
Primarily in term neonate
3,Others
Rapid volume expansion (扩容 )
alteration in cerebral blood flow
mechanical ventilation,coagulation defect
Causes
Cerebral Venous System
Type of Hemorrhage
1,Periventricular-intraventricular
Hemorrhage (PIVH)
脑室周围 -脑室内出血
2,Germinal Matrix Hemorrhage (GMH)
室管膜下生发层基质出血
脑室内出血
脑室内出血
脑室内出血
3,Subdural Hemorrhage (SDH)
硬膜下出血
Full term > premature
Uncommon
Clinically serious
Type of Hemorrhage (Cont’d)
Type of Hemorrhage (Cont’d)
4,Subarachnoid Hemorrhage (SAH)
（ 蛛网膜下腔出血）
Usually self-limited
Venous origin
Trauma or hypoxia
Rarely develop hydrocephalus
5,Intracerebellar Hemorrhage 小脑出血
蛛网膜下腔出血
蛛网膜下腔出血
蛛网膜下腔出血
脑池和脑室内出血
? 鞍上池、右侧裂池和环
池内出血（蓝箭）
? 第四脑室出血（红箭）
? 枕大池内出血（黄箭）
Grading of Severity of IVH
Grade I,Germinal matrix hemorrhage
Grade II,Intraventricular hemorrhage
Grade III,Intraventricular hemorrhage with
dilated ventricle
Separate notation,
periventricular posthemorrhage infarction
脑室周围出血后梗塞
Clinical Features
Common in premeture
Mild,asymptomatic state
Moderate to severe,neurological
deterioration (apnea,brainstem
dysfunction,floppy,coma,hypotension,
bradycardia)
May develop hydrocephylus (脑积水 )
Clinical Features
兴奋型,激惹，脑性尖叫，两眼凝视，
惊厥,四肢强直
抑制型,意识障碍、昏迷、呼吸不规则、
抽泣样呼吸、四肢肌张力下降
1,Clinical features
2,Neuroimaging
Ultrasound Scan,CT,MRI
3,Lumbar puncture (LP)
Many RBCs,elevated protein,
xanthochromia (变黄色 )
Diagnosis
Management
1,Correction of major hemodynamic
disturbance and coagulation defect
2,Control seizure
3,Control intracranial pressure
Management
4,Supportive care
5,Surgical intervention
6,Post-hemorrhagic hydrocephalus,
V-P shunt
Neonatal Infections
新生儿感染
features of neonatal infection
1、免疫功能不完善
屏障功能差，白细胞杀菌力差, IgM,IgA低，
T细胞功能差
2、环境因素,接触者、奶瓶、医疗器械、各种操作
3、感染途径,宫内感染、出生时感染、出生后感染
4、临床表现,不典型
感染途径,皮肤、脐部、呼吸道、消化道、
泌尿道
病原菌
金葡菌、大肠杆菌、克雷白杆菌、绿脓杆菌
新生儿败血症
临 床 表 现
?不典型、非特异性
?不哭、不吃、体温不升
?黄疸、呕吐、腹胀、呼吸困难、
呼吸暂停、酸中毒
?易并发化脓性脑膜炎
注 意 皮 肤 呈 明 显 大 理 石 花 纹
诊 断
临床表现,仔细观察才能发现
病原检查：细菌培养、涂片
其他检查：白细胞、血小板、血气分析
治 疗
抗菌治疗：合理治疗
免疫治疗：免疫球蛋白、粒细胞
支持疗法：保证营养供给
化脓性脑膜炎
一、临床特点：反应差，注意前囟饱满
二、诊 断：临床表现为线索，及时做腰穿
三、治 疗：选用易通过血脑屏障的药物
宫内感染
1、巨细胞病毒感染
2、弓形虫感染
3、先天性梅毒
4,病毒性肝炎
5,HIV感染
宫内感染
TORCH 综合征
T,弓形虫 ( Toxoplasma )
O,其它 ( Others )
R,风疹病毒 ( Rubella )
C,巨细胞病毒 ( cytomegalovirus )
H,疱疹病毒 ( Herpes )
