Dr. Maynard’s presentation on the description of the types of brain injuries in pre-term infants (presented on 3/24/11).

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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6. Incidence: Grade 3 & 4 IVH
Vermont Oxford Network Children’s Minneapolis
25
% Occurrence
20 21
1994-2002
15 16
10 11
9 9 8
5 6
4
3 3
No. Patients 38,576 465 46,183 483 50,253 516 59,403 617 194,415 2,081
0
501-750 751-1000 1001-1250 1251-1500 501-1500
Birth Weight (501-1500 grams)
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7. Incidence: PVL
Vermont Oxford Network Children’s Minneapolis
10
% Occurrence
9
1994-2002
8
7
6
5
5 5
4
4
3
3 3 3
2
2 2 2
1
1
No. Patients 38,576 465 46,183 483 50,253 516 59,403 617 194,415 2,081
0
501-750 751-1000 1001-1250 1251-1500 501-1500
Birth Weight (501-1500 grams)
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8. 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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9. Germinal Matrix
(Primary site of IVH/PVH)
Arachnoid Villi
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th
Magendie
Germinal Matrix
Choroid Plexus
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10. Germinal Matrix
• Primitive cellular region ventrolateral to LV
– prominent: 26-32 weeks
– involuted: term
• Contains pluripotential migrating cells
– neurons, astrocytes, oligodendroglia
• Contains immature blood vessels:
– thin walls (lack muscularis layer)
– immature cell junctions & basal laminae
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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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18. Normal Anatomy
Arachnoid Villi
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th
Magendie
Germinal Matrix
Choroid Plexus
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19. Grade 1 IVH
(Blood in GM only)
Arachnoid Villi
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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20. Grade 2 IVH
(Blood in LV without ventriculomegaly)
Arachnoid Villi
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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21. Grade 3 IVH
(Blood in LV with ventriculomegaly)
Lateral Ventricle Blood on
Arachnoid
Ventriculomegaly
Villi
GM
Occipital
CP Horn
Monro OBLITERATIVE
3rd
ARACHNOIDITIS
Luschka
4th Germinal Matrix
Magendie
Slowly
Evolving Choroid
Plexus
Hydrocephalus Blood
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22. Grade 3 IVH
(Blood in LV with ventriculomegaly)
Lateral Ventricle
Arachnoid Villi
Ventriculomegaly
GM
Occipital
Obstruction CP Horn
Monro
at Foramen
3rd
of Monro
Luschka
4th Germinal Matrix
Magendie
Rapidly
Progressive Choroid
Plexus
Hydrocephalus Blood
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23. Grade 4 IVH
(Periventricular Hemorrhagic Infarction)
PVHI Arachnoid Villi
v
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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24. PV Hemorrhagic Infarction
Pathogenesis
Germinal Matrix/IVH
↓
PV Venous Congestion
↓
PV Ischemia
↓
PV Hemorrhagic Infarction
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25. Begins as Grade 1-2 IVH
IVH
in right
lateral
ventricle
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26. May Evolve to Grade 3 IVH
Massive IVH on right
• obstruction at
foramen of Monro
• unilateral
ventricular
dilatation
Coronal Section 26 of 74

27. Periventricular Hemorrhagic Infarction
IVH
IVH
Early
Evolving
PVHI
Coronal Section 27 of 74

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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31. Normal Cranial Ultrasound
Lateral
3rd Ventricle
Ventricle
Coronal View 31 of 74

32. Normal Cranial Ultrasound
Lateral
3rd Ventricle
Ventricle
Coronal View 32 of 74

33. Normal Cranial Ultrasound
3rd
Ventricle
Lateral
Choroid Ventricle
Plexus
Coronal View 33 of 74

34. Grade 1 Intraventricular Hemorrhage
(Blood in GM only)
Arachnoid Villi
GM Occipital
CP
Horn
Monro
3rd
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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35. Grade 1 IVH
SEH
parasagittal view
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36. Acute Subependymal Hemorrhage
Bilateral Grade 1 IVH
SEH
Coronal View 36 of 74

37. Acute Subependymal Hemorrhage
Grade 1 IVH
SEH
CP
Left Parasagittal View 37 of 74

38. Grade 2 IVH
(Blood in LV without ventriculomegaly)
Arachnoid Villi
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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39. Grade 2 IVH
Echogenic
blood fills
< 50% of
ventricle
Parasagittal View 39 of 74

40. Grade 2 IVH
Clot in posterior
right horn
Posterior Coronal View
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41. Grade II IVH
Grade 2 IVH
SEH
Clot in
Posterior
Horn on R
parasagittal view
Parasagittal View 41 of 74

42. Grade 3 IVH
(Blood in LV with ventriculomegaly)
Lateral Ventricle
Arachnoid Villi
Ventriculomegaly
GM
Occipital
Obstruction CP Horn
Monro
at Foramen
3rd
of Monro
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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43. Grade 3 IVH
Large blood clot filling
and distending LV
Parasagittal View
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44. Grade 3 IVH
(Blood in LV with ventriculomegaly)
Lateral Ventricle Blood on
Arachnoid
Ventriculomegaly
Villi
GM
Occipital
CP Horn
Monro OBLITERATIVE
3rd
ARACHNOIDITIS
Luschka
4th Germinal Matrix
Magendie
Slowly
Evolving Choroid
Plexus
Hydrocephalus Blood
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45. Posthemorrhagic Hydrocephalus
Extraventricular Obstruction of CSF
From Obliterative Arachnoiditis
LV LV
LV LV
Coronal View 45 of 74

46. Grade III IVH
Grade 3 IVH
Dilated,
Dilated,
blood-filled
blood-filled
frontal horn
frontal horns
Coronal View
Coronal view 46 of 74

47. Grade 3 IVH
Dilated lateral ventricle
Hemorrhage in
Lateral Ventricle
Parasagittal View
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48. Evolution of Grade 3 IVH
Hemorrhage
filling lateral
ventricle
body
occipital
temporal
Parasagittal View
Initial scan
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49. Evolution of Grade 3 IVH
Retraction Ventricular
of IVH clot Dilatation
coronal view
Coronal View
F/U scan weeks later
F/U scan weeks later 49 of 74

50. Evolution of Grade 3 IVH
Coronal View
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F/U scan weeks later

51. Grade 4 IVH
(Periventricular Hemorrhagic Infarction)
PVHI Arachnoid Villi
v
GM
Occipital
CP Horn
Monro
3rd
Luschka
4th Germinal Matrix
Magendie
Choroid
Plexus
Blood
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52. Evolution of Periventricular
Hemorrhagic Infarction
Bulging
SEH
coronal view
Coronal View
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Day 7 (scan #1)
Day 7 (scan #1)

53. Evolution of Periventricular
Hemorrhagic Infarction
Increasing size
of crescentic
PVED  PVHI
Bulging
SEH
coronal view
Coronal View
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Day 7 (scan #2)

54. Evolution of Periventricular
Hemorrhagic Infarction
Increasing size
of crescentic
PVED  PVHI
coronal view
Coronal View
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Day 7 (scan #3)
Day 7 (scan #3)

55. Evolution of Periventricular
Hemorrhagic Infarction
Large
Porencephalic
Cyst
Coronal view
coronal View
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2 Months Later
2 months later

56. Periventricular Hemorrhagic Infarction
(9 days)
PED
Ventricular
dilatation
IVH
Parasagittal View 56 of 74

57. Periventricular Hemorrhagic Infarction
(3 weeks of age)
Cyst Formation
• tissue necrosis
• clot retraction
Parasagittal View 57 of 74

58. Periventricular Hemorrhagic Infarction
(2 months of age)
Porencephalic
cyst
Parasagittal View 58 of 74

59. Periventricular Leukomalacia
Periventricular Leukomalacia (PVL)
PVL has emerged as the prinicipal
form of brain injury in the
premature infant
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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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65. Clinical Correlates of PVL
Diagnostic Methods Clinical Correlates
MRI/DWI
• Diffuse Cognitive/Behavioral
Pre-Oligo Injury Deficits
Cranial Spastic
Ultrasound diplegia
• Focal
Necrosis
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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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72. Neurodevelopmental Outcome
Classification
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73. Neurodevelopmental Outcome
23-26 weeks GA (552 infants: 1986-1998) -- Mean Age: 48.6 months
Normal Mild-Mod. Impaired Severely Impaired
% Occurrence
80
79
70
70
66
60 64
50
40
39
30 31 31
20 21
17 18 18
10 12 13 11 11
0
Normal U/S Grade 1&2 IVH Grade 3 IVH Grade 4 IVH PVL
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74. Q&A
Thank you for attending!
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