Introduction
Axial nonenhanced computed tomography scan. The image shows bilateral grade 2 subependymal and intraventricular germinal matrix hemorrhage without hydrocephalus.
Sagittal sonogram. The image demonstrates a grade 3 germinal matrix hemorrhage and shows a subependymal focus of hyperechogenicity (arrow) that represents hemorrhage, as well as intraventricular hemorrhage and hydrocephalus.
Background
Germinal matrix hemorrhage (GMH) and intraventricular hemorrhage (IVH) are the most common and most important neurologic injuries in preterm neonates.
The brain of a premature infant lacks the ability to autoregulate cerebral blood pressure. Fluctuations in cerebral blood pressure and flow can rupture the primitive germinal matrix vessels or lead to infarction of the metabolically active germinal matrix. The damage can extend into the periventricular white matter, resulting in significant neurologic sequelae, including cerebral palsy, mental retardation, and seizures. Injury to the germinal matrix has substantial mortality and morbidity rates.
Ultrasonography (US) is the primary imaging modality for the screening and diagnosis of GMH/IVH, and computed tomography (CT) scanning and magnetic resonance imaging (MRI) are used as supplementary tools.
Related eMedicine topics:
Brain, MRI Appearance of Hemorrhage
Intracranial Hemorrhage
Brain, Hypertensive Hemorrhage
Cerebellar Hemorrhage
Subarachnoid Hemorrhage
Pathophysiology
A common lesion that characterizes the neuropathology of germinal matrix hemorrhage and intraventricular hemorrhage (GMH/IVH) is bleeding into the subependymal germinal matrix, with or without subsequent rupture into the lateral ventricle.
The pathogenesis of GMH is multifactorial. For simplification, the influences can be divided into intravascular, vascular, and extravascular factors. The autoregulation of blood flow and blood pressure in the germinal matrix circulation is primitive in premature infants, and the thin microvasculature of the germinal matrix is susceptible to rupture. The primitive mesenchymal and glial supportive tissues influence the extent of GMH.
Large fluctuations in blood flow and blood pressure can result, leading to injury to the germinal matrix vessels and subsequent hemorrhage. Alternatively, hypotension or hypoperfusion can lead to focal or diffuse infarction; the metabolically active germinal matrix is particularly vulnerable. Hemorrhage can occur in infarcted regions after reperfusion, but hemorrhage from any cause can be confined to the subependymal layer, or it can extend into the ventricles or brain parenchyma.
Sequelae of GMH/IVH include germinal matrix destruction, periventricular hemorrhagic infarction with subsequent encephalomalacia, and posthemorrhagic hydrocephalus.1,2,3,4
Frequency
United States
Frequency of GMH is inversely related to the neonate's gestational age and birth weight.5 Improvements in obstetric and perinatal care have markedly decreased the incidence and severity of GMH/IVH, which was reported to be as high as 50% in 1977.6 Incidence is now 8-56% in infants; most nurseries report rates of 20-30%. The severity of germinal matrix hemorrhage and intraventricular hemorrhage (GMH/IVH) has decreased along with the incidence. Sheth et al observed that the rate for severe grade 3 or 4 IVH decreased from 70% in 1986 to 23% in 1995 and that the associated mortality rate decreased by 30% in the same period.6,7
International
The incidence of germinal matrix hemorrhage (GMH) varies throughout the world. Rates of GMH are most dependent on the birth rates of premature infants.
Mortality/Morbidity
The extent of intracranial hemorrhage and any associated parenchymal injury or hydrocephalus are the most important factors in predicting mortality and morbidity.
- In 1983, Papile et al found major neurologic deficits in 10% of premature infants without germinal matrix hemorrhage (GMH) and intraventricular hemorrhage (IVH) and in 28% of infants with GMH/IVH.8 Major deficits were present in 9% of infants with grade 1 GMH, in 11% with grade 2 injury, in 36% with grade 3 injury, and in 76% with grade 4 GMH/IVH. Cerebral palsy occurs in as many as 15% of these children.
- The mortality rate in infants with GMH/IVH has been reported as high as 35%, compared with 13% in premature infants without GMH/IVH.9
Race
No significant racial predilection is known.
Sex
Germinal matrix hemorrhage affects the 2 sexes equally.
Age
Because maturation of the germinal matrix vasculature occurs in the perinatal period for premature infants, most cases of germinal matrix hemorrhage (GMH) and intraventricular hemorrhage (IVH) occur in the first week of life for these infants. Approximately 50% of cases of GMH/IVH occur in the first day of life, and about 65% occur in the first week.
- Neonates born at 32 weeks' gestation or earlier and those born with birth weights less than 1500 g are at particular risk.
- It is unusual to find GMH/IVH in infants born after 34 weeks' gestation.
Anatomy
The germinal matrix is located in the subependyma of the ventricular walls and initially extends along the ventricles. At 8-28 weeks' gestation, the germinal matrix produces neurons and glial cells, which migrate to populate the cerebral cortex. Neurons are produced earlier in gestation, and glial cells are produced later. Involution of the germinal matrix toward the caudothalamic groove begins late in the second trimester and is nearly complete by 32 weeks' gestation.
The germinal matrix is metabolically active with a rich supply of blood via a thin, fragile capillary network. Arterial supply of the germinal matrix is provided by branches of the anterior cerebral artery: the arterioles from the recurrent artery of Heubner at the level of the foramen of Monro and the terminal branches of the lateral striate arteries, located more superiorly. Venous blood flows through the terminal vein, which drains via the internal cerebral vein into the vein of Galen.
Presentation
The major risk factors for germinal matrix hemorrhage (GMH) include a young gestational age, low birth weight, acute amnionitis, and exposure to antenatal steroids for less than 48 hours. Other risk factors include the use of general anesthesia for cesarean delivery; Apgar scores that are less than 4 in the first minute or are less than 8 by 5 minutes; respiratory distress; persistent ductus arteriosus; anemia; and arterial catheterization.The grading system created by Burstein et al in 1979 relies on the detection of blood in the subependymal germinal matrix and the ventricles as follows10 :
- Grade 1: Hemorrhage that is confined to the germinal matrix
- Grade 2: Extension of the hemorrhage into the lateral ventricles without hydrocephalus
- Grade 3: Ventricular hemorrhage with the presence of associated hydrocephalus
- Grade 4: Parenchymal hemorrhage
Preferred Examination
US is the preferred screening and diagnostic tool for germinal matrix hemorrhage (GMH). The portability of US allows imaging in the nursery with minimal disturbance of the infant. US also depicts GMHs that are larger than 5 mm, with a sensitivity of nearly 100% and specificity of 91%. Smaller GMHs, however, are more difficult to identify.
Power and pulsed-wave Doppler US can be used to identify preterm neonates who are at risk for GMH and intraventricular hemorrhage (IVH) during their first week of life. Using this modality, clinicians can detect autoregulatory fluctuations in the preterm neonate's cerebral blood flow with examination of the lenticulostriate arteries; measurements of the peak velocity, resistive index, and coronal vascular cross-sectional area; and product of the peak velocity and vascular cross-sectional area.
CT scanning and MRI are also used and have better interobserver agreement. Because these modalities more readily depict small GMHs, CT scanning and MRI have a higher sensitivity than that of US. However, these imaging modalities require that the infant be moved from the nursery; there is also the possibility that sedation would be required.
Limitations of Techniques
All imaging modalities have relatively low negative predictive values (NPVs). In a 2000 study, Blankenberg et al found NPVs of 53% and 59% (irrespective of the modality) at 2-month and at 2-year follow-up, respectively.11 However, the absence of neuroimaging abnormalities in the infant does not exclude the possibility of later neurodevelopmental problems.
Differential Diagnoses
More on Germinal Matrix Hemorrhage |
 Overview: Germinal Matrix Hemorrhage |
| Imaging: Germinal Matrix Hemorrhage |
| Follow-up: Germinal Matrix Hemorrhage |
| Multimedia: Germinal Matrix Hemorrhage |
| References |
| Further Reading |
| Next Page » |
References
Simard JM, Castellani RJ, Ivanova S, Koltz MT, Gerzanich V. Sulfonylurea receptor 1 in the germinal matrix of premature infants. Pediatr Res. Dec 2008;64(6):648-52. [Medline].
Roze E, Kerstjens JM, Maathuis CG, ter Horst HJ, Bos AF. Risk factors for adverse outcome in preterm infants with periventricular hemorrhagic infarction. Pediatrics. Jul 2008;122(1):e46-52. [Medline].
Xu H, Hu F, Sado Y, Ninomiya Y, Borza DB, Ungvari Z, et al. Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone. J Neurosci Res. May 15 2008;86(7):1482-500. [Medline].
Yang LT, Li WY, Kaartinen V. Tissue-specific expression of Cre recombinase from the Tgfb3 locus. Genesis. Feb 2008;46(2):112-8. [Medline].
Kadri H, Mawla AA, Kazah J. The incidence, timing, and predisposing factors of germinal matrix and intraventricular hemorrhage (GMH/IVH) in preterm neonates. Childs Nerv Syst. Sep 2006;22(9):1086-90. [Medline].
Sheth RD. Trends in incidence and severity of intraventricular hemorrhage. J Child Neurol. Jun 1998;13(6):261-4. [Medline].
Morioka T, Hashiguchi K, Nagata S, et al. Fetal germinal matrix and intraventricular hemorrhage. Pediatr Neurosurg. 2006;42(6):354-61. [Medline]. [Full Text].
Papile LA, Munsick-Bruno G, Schaefer A. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr. Aug 1983;103(2):273-7. [Medline].
Hawgood S, Spong J, Yu VY. Intraventricular hemorrhage. Incidence and outcome in a population of very-low-birth-weight infants. Am J Dis Child. Feb 1984;138(2):136-9. [Medline].
Burstein J, Papile LA, Burstein R. Intraventricular hemorrhage and hydrocephalus in premature newborns: a prospective study with CT. AJR Am J Roentgenol. Apr 1979;132(4):631-5. [Medline].
Blankenberg FG, Loh NN, Bracci P, et al. Sonography, CT, and MR imaging: a prospective comparison of neonates with suspected intracranial ischemia and hemorrhage. AJNR Am J Neuroradiol. Jan 2000;21(1):213-8. [Medline]. [Full Text].
Yikilmaz A, Taylor GA. Cranial sonography in term and near-term infants. Pediatr Radiol. Jun 2008;38(6):605-16; qiuz 718-9. [Medline].
Antoniuk S, da Silva RV. [Periventricular and intraventricular hemorrhage in the premature infants] [Spanish]. Rev Neurol. Aug 1-15 2000;31(3):238-43. [Medline].
Balasubramaniam J, Del Bigio MR. Animal models of germinal matrix hemorrhage. J Child Neurol. May 2006;21(5):365-71. [Medline].
Batton DG, Holtrop P, DeWitte D, Pryce C, Roberts C. Current gestational age-related incidence of major intraventricular hemorrhage. J Pediatr. Oct 1994;125(4):623-5. [Medline].
Blankenberg FG, Norbash AM, Lane B, et al. Neonatal intracranial ischemia and hemorrhage: diagnosis with US, CT, and MR imaging. Radiology. Apr 1996;199(1):253-9. [Medline].
Boal DK, Watterberg KL, Miles S, Gifford KL. Optimal cost-effective timing of cranial ultrasound screening in low-birth-weight infants. Pediatr Radiol. 1995;25(6):425-8. [Medline].
Carson SC, Hertzberg BS, Bowie JD, Burger PC. Value of sonography in the diagnosis of intracranial hemorrhage and periventricular leukomalacia: a postmortem study of 35 cases. AJNR Am J Neuroradiol. Jul-Aug 1990;11(4):677-83. [Medline].
Duncan CC, Ment LR. Intraventricular hemorrhage and prematurity. Neurosurg Clin N Am. Oct 1993;4(4):727-34. [Medline].
Ghazi-Birry HS, Brown WR, Moody DM, et al. Human germinal matrix: venous origin of hemorrhage and vascular characteristics. AJNR Am J Neuroradiol. Feb 1997;18(2):219-29. [Medline]. [Full Text].
Levy ML, Masri LS, McComb JG. Outcome for preterm infants with germinal matrix hemorrhage and progressive hydrocephalus. Neurosurgery. Nov 1997;41(5):1111-7; discussion 1117-8. [Medline].
Ment LR, Oh W, Philip AG, et al. Risk factors for early intraventricular hemorrhage in low birth weight infants. J Pediatr. Nov 1992;121(5 Pt 1):776-83. [Medline].
Paneth N, Pinto-Martin J, Gardiner J, et al. Incidence and timing of germinal matrix/intraventricular hemorrhage in low birth weight infants. Am J Epidemiol. Jun 1 1993;137(11):1167-76. [Medline].
Pinto-Martin JA, Riolo S, Cnaan A, et al. Cranial ultrasound prediction of disabling and nondisabling cerebral palsy at age two in a low birth weight population. Pediatrics. Feb 1995;95(2):249-54. [Medline].
Salafia CM, Minior VK, Rosenkrantz TS, et al. Maternal, placental, and neonatal associations with early germinal matrix/intraventricular hemorrhage in infants born before 32 weeks' gestation. Am J Perinatol. Nov 1995;12(6):429-36. [Medline].
Tarby TJ, Volpe JJ. Intraventricular hemorrhage in the premature infant. Pediatr Clin North Am. Oct 1982;29(5):1077-104. [Medline].
Taylor GA. New concepts in the pathogenesis of germinal matrix intraparenchymal hemorrhage in premature infants. AJNR Am J Neuroradiol. Feb 1997;18(2):231-2. [Medline]. [Full Text].
Townsend SF, Rumack CM, Thilo EH, Merenstein GB, Rosenberg AA. Late neurosonographic screening is important to the diagnosis of periventricular leukomalacia and ventricular enlargement in preterm infants. Pediatr Radiol. May 1999;29(5):347-52. [Medline].
Volpe JJ. Intraventricular hemorrhage in the premature infant--current concepts. Part I. Ann Neurol. Jan 1989;25(1):3-11. [Medline].
Further Reading
Related eMedicine topics:
Brain, MRI Appearance of Hemorrhage
Intracranial Hemorrhage
Brain, Hypertensive Hemorrhage
Cerebellar Hemorrhage
Subarachnoid Hemorrhage
Keywords
germinal matrix hemorrhage, periventricular/intraventricular/subependymal hemorrhage, hypoxic-ischemic injury, persistent ventricular enlargement, PVH, IVH, HII, PVE, GM/IVH, GMH, neonatal/fetal cerebral hemorrhage
