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Brain Injury in Pre-Term Infants
1. Brain Injury in Pre-Term Infants
Roy Maynard, M.D.
March 24, 2011
2. Objectives for Brain Injury in Pre-Term Infants
• Identify types of brain injury in pre-term
infants.
• Appreciate the incidence of Grade 1-IV
intraventricular hemorrhages in very low birth
weight infants.
• Understand the neurodevelopmental
implications of Periventricular Leukomalacia
in very low birth weight infants.
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3. Types of Brain Injury
• Periventricular Leukomalacia (PVL)
• Severe Intraventricular/Periventricular
Hemorrhage (IVH/PVH)
• Posthemorrhagic Hydrocephalus
• Other patterns of neuronal injury
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4. IVH/PVH of the Pre-Term Infant
• Epidemiology
• Pathogenesis
– germinal matrix anatomy
– factors:
• intravascular
• vascular
• extravascular
– spread of IVH
• Diagnosis and Management
• Neurodevelopmental Outcomes
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5. What is the magnitude of brain injury
in pre-term infants?
Pre-Term Infants (BW<1500g)
No. born in U.S. ………………………..55,000/yr.
Survival…………………………………..90%
Incidence of:
IVH (Grade 3&4)………………………3-21%
PVL ……………………………………. 2-5%
Morbidity in survivors:
Spastic/motor deficits…………………10%
Cognitive/behavioral…………………..25-50%
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11. IVH/PVH of the Pre-Term Infant
• Epidemiology
• Pathogenesis
– germinal matrix anatomy
– factors:
• intravascular
• vascular
• extravascular
– spread of IVH
• Diagnosis and Management
• Neurodevelopmental Outcomes
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12. Pathogenesis of IVH/PVH
Factors
• Intravascular
– regulation of CBF, BP, Blood volume
– platelet-capillary function
– blood-clotting function
• Vascular
• Extravascular
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13. Intravascular Factors
• Pressure-passive cerebral circulation factors:
↑ blood pressure will increase cerebral blood
flow
• Increase in central venous pressure will
increase cerebral venous pressure
• Increase pressure within the brain’s blood
vessels may lead to rupture of fragile blood
vessel(s) and bleeding
– Tracheal suctioning
– Pneumothorax
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14. Vascular Factors
Intrinsic properties of GM vessels
• Immature vascular structures
– Larger and lack muscle/collagen
– Incomplete basal laminae
– More susceptible to rupture
• More susceptible to hypoxic/ischemic insult
– Vascular border zone in GM
– Endothelium contain ↑ mitochondria
– ↑ need for oxidative metabolism
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15. Spread of IVH/PVH
• 40% stays in GM (Grade 1 IVH)
• 60% enters ventricles (Grade 2 & 3 IVH)
– Large IVH → obstructs CSF flow
• Aqueduct of Sylvius, Luschka, Magendie
• Rapidly progressive hydrocephalus
– Small IVH → retards CSF absorption
• Obliterative arachnoiditis of basilar cisterns
• Slow evolving hydrocephalus
• PV Hemorrhagic Infarction (Grade 4 IVH)
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16. IVH/PVH of the Pre-Term Infant
• Epidemiology
• Pathogenesis
– germinal matrix anatomy
– factors:
• intravascular
• vascular
• extravascular
– spread of IVH
• Diagnosis and Management
• Neurodevelopmental Outcomes
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17. Diagnosis and Management
Grading IVH/PVH (Papile)
• Grade 1: GM hemorrhage only
• Grade 2: GM hemorrhage extending into LV
without ventriculomegaly
• Grade 3: IVH with ventriculomegaly
• Grade 4: Intraparenchymal hemorrhage vs.
Periventricular hemorrhagic infarction
J Pediatr 1978; 92: 529-34
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28. Diagnosis and Management
Timing of IVH/PVH
• 90% occur within first 72H
– 50%: <24H
– 25%: >24H & <48H
– 15%: >48H & <72H
• 20-40% progress further
– Maximal extension occurs 3-5 days after
initial insult
Volpe: Neurology of the Newborn: 1995 Saunders
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29. Conclusions
• Most intracranial pathology in sick pre-term
infants is clinically silent.
• Severe lesions most often occur in tiniest of
pre-term neonates.
• Shift toward a delayed presentation of the
clinically significant lesions.
Arch Pediatr Adolesc Med 2000; 154: 822-826
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30. Diagnosis and Management
Cranial Imaging of IVH/PVH
Ultrasonography
• Preferred diagnostic technique
equivalent resolution
portable, practical
CT Scan • Subdural hemorrhage
MRI Scan • Posterior fossa lesions
PET Scan • Complicated cerebral lesions
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60. What is PVL?
1. Death of white matter (WM) in the
brain’s Periventricular (PV) region
2. Caused by decrease in O2 or blood
flow to PV WM area of brain
Periventricular white matter contains
nerve fibers that carry messages from
the brain to the body’s muscles
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61. What is PVL?
3. Most common Ischemic injury in
pre-term infants
4. Occurs in Border Vascular Zone
• end of arterial distributions
5. Diagnostic hallmarks include:
• Initial: PV echodensities
• Later: PV cystic changes
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62. Importance of Diagnosis?
Surviving pre-term infants with PVL
are at risk for the following:
• Cerebral Palsy (CP),
• intellectual impairment
• visual/hearing disturbances
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63. Periventricular Leukomalacia
Pathogenesis (3 interacting factors)
1. Periventricular vascular
anatomic physiologic factors
2. Cerebral Ischemia and pressure-
passive cerebral circulation
3. Maturation-dependent vulnerability of
cerebral white matter
Oligodendroglial precursors
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64. Periventricular Leukomalacia
Periventricular Vascular Anatomic
Physiologic Factors
Short Penetrator Vessels
•
Basal Penetrator Vessels
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66. Periventricular Leukomalacia
Pathogenesis (3 interacting factors)
1. Periventricular vascular anatomic
physiologic factors
2. Cerebral Ischemia and
pressure-passive cerebral
circulation
3. Maturation-dependent vulnerability of
cerebral white matter
Oligodendroglial precursors
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67. Periventricular Leukomalacia
CBF Autoregulation with Maturation
180
Narrow Regulatory
160 Control Window
Normal Regulatory
CBF (% of normal)
140 Control Window
120
100
80
60
40 Premature Child
Newborn
20
0
0 10 20 30 40 50 60 70 80
MABP (mmHg)
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68. PVL: Diagnosis & Management
Coronal View Coronal View
1-week-old pre-term infant without 1-week-old pre-term infant. Peri-
PVL. The periventricular echo- ventricular echotexture is increased,
texture is normal. consistent with early changes of PVL.
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69. PVL: Diagnosis & Management
Parasagittal View PVL Coronal View
Cysts
3-week-old pre-term infant. Multiple periventricular cysts
typical of established periventricular leukomalacia.
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70. Diagnosis and Management
Postnatal Treatment
• Postnatal resuscitation (NICU)
• Maximize risk for fluctuation CBF & BP
– avoid unnecessary BP, suctioning, rapid
infusions, pneumothorax
– avoid ventilator asynchrony
• Correct coagulation disturbances
• Indomethacin
• Antioxidants (SOD)
• Management of post-hemorrhagic
hydrocephalus
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71. IVH/PVH of the Pre-Term Infant
• Epidemiology
• Pathogenesis
– germinal matrix anatomy
– factors:
• intravascular
• vascular
• extravascular
– spread of IVH
• Diagnosis and Management
• Neurodevelopmental Outcomes
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