**4. Role of neuroimaging**

#### **4.1. Germinal Matrix-Intraventricular Hemorrhage (GM-IVH) in preterm infants**

rarely multiple cysts. The evolving cyst(s) are associated with the destruction of motor and associative WM axons and preoligodendrocytes. These infants have a high incidence of hemiplegia later in their life.[23] Asymmetric myelination of the posterior limb of the internal capsule on MRI at term has been suggested as an early predictor of hemiplegia in PVHI. [24]

Intracranial Hemorrhage in the Newborn http://dx.doi.org/10.5772/58476 5

Incidence of ventricular dilatation increases with the severity of GM-IVH. CUS is an ideal tool for monitoring ventricular dilatation in newborns with open fontanelle. Detailed imaging with MRI is usually required prior to shunt surgery and for monitoring the progression or shunt complication after closure of the fontanelle. Posthemorrhagic hydrocephalus (PHH) may be progressive (due to obstruction by blood clot or secondary inflammatory changes which interferes with CSF flow), nonprogressive (due to parenchymal loss secondary to PVHI or PVL) or a combination of the two. PHH survivors with grade III and IV GM-IVH have high risk of significant neurodevelopmental sequelae (e.g. quadriparetic cerebral palsy and/or

A very high association (77%) has been reported between the cerebellar hemorrhagic injury (CHI) and supratentorial GM-IVH. CHI can result from cerebellar GM hemorrhage (subepen‐ dymal or subpial), primary hemorrhage, ischemic hemorrhagic transformation of either arterial or venous origin, or dissection of blood through the fourth ventricle or subarachnoid spaces following massive supratentorial GM-IVH. The location of CHI could be unilateral, vermian, bilateral or a combination of these. Mastoid CUS view helps to detect CHI in 3% of premature infants. MRI detects small petechial cerebellar hemorrhages not visible on CUS. CHI may eventually lead to several types of atrophic changes. 40% of CHI survivors have global developmental (cognitive and social communication disabilities) and functional deficits

A strong association between GM-IVH and periventricular leukomalacia (PVL) has been suggested. GM-IVH and PVL may develop in parallel, the ischemic injury may injure the GM and the periventricular WM leading to both GM-IVH and PVL. The CUS markers of cystic and diffuse PVL include echolucencies, echodensities and nonprogressive ventriculomegaly.[3,27]

Subarachnoid hemorrhage (SAH) is relatively common in premature infants with GM-IVH. The true incidence of SAH is not known as it is difficult to visualize the extra-axial hemorrhage by CUS. MRI is the modality of choice to detect SAH. SAH could be one of the reasons for PHH (obstructive arachnoiditis), neonatal seizure (irritation of cerebral convexity) and cerebral/

Impaired cerebellar and supratentorial gray matter growth has been reported in GM-IVH survivors. The complicated GM-IVH (PVHI and PVL) causes impaired growth and develop‐ ment of the contralateral cerebellar hemisphere due to injury to specific supratentorial projections (crossed cerebellar diaschisis).[28] The uncomplicated GM-IVH (without paren‐ chymal involvement) is associated with impaired growth of the supratentorial gray matter, probably because the GM destruction prevents the neuronal and astrocyte precursor cells from reaching their cortical destination. In addition, SAH (circulating free radical) may directly

profound mental retardation).[3,25]

cerebellar growth impairment.[28,29]

injure the cerebral cortex surface.[29]

(motor deficits).[3,26]

For years neonatal cranial ultrasound (CUS) has been the key diagnostic tool for GM-IVH in premature infants due to its widespread availability, relative low cost, direct bedside scanning and high resolution to detect GM-IVH. CUS is nearly as accurate as CT but much less stressful for an ill premature infant. Diagnostic screening with CUS is recommended in all premature infants (less than 1,500 gm birth weight and less than 32 weeks' gestation) during the second week of life (after which further bleeding is uncommon) or earlier if clinical conditions indicate. [11] Doppler ultrasound can also be used for the imaging and flow velocity measurements of the terminal vein.[12] CT had been used in the original studies to grade the GM-IVH, however, it is no longer recommended for diagnostic purpose due to the adverse effect produce by ionizing radiation on immature brain. MRI is superior to CUS and CT for detection of associ‐ ated white matter (WM) abnormalities and for identifying hemorrhages particularly small petechial hemorrhage, subacute to chronic hemorrhage and for extracerebral or posterior fossa hemorrhage.[13] The severity of GM-IVH has been evaluated by Papile[14] and Volpe's[15] grading system. When bleeding is confined to the subependymal region, it is classified as grade I; grade II is extension of hemorrhage into non distended lateral ventricle(s) where blood fills less than 50% of the ventricular diameter; in grade III, extensive intraventricular hemorrhage fills greater than 50% of the ventricular diameter leading to hydrocephalus; whereas, grade IV is periventricular hemorrhagic infarction (PVHI).[14,15] Most cases have grade I or grade II intraventricular hemorrhage and do not show late sequelae.[16,17] Infants with grade III or IV hemorrhage have high incidence of neurologic sequelae (approx. 30% will have severe cerebral palsy or mental retardation).[18,19]

Once GM-IVH is diagnosed, follow-up CUS examinations are necessary to determine its complications like periventricular hemorrhagic infarction (PVHI) and post-hemorrhagic hydrocephalus (PHH) and associated cerebellar hemorrhagic injury (CHI), periventricular leukomalacia (PVL), and SAH.[1,4]

Periventricular hemorrhagic infarction (PVHI), classified as grade IV GM-IVH, is a complica‐ tion of GM-IVH. As previously thought, it is not due to rupture of ependymal lining and extension of intraventricular hemorrhage into the periventricular white matter; rather it occurs due to compression of the terminal vein by GM-IVH resulting in impaired venous drainage and congestion of the medullary veins, which in turn leads to hypoxia-ischemia, infarction and finally hemorrhagic transformation in the periventricular white matter.[20] PVHI can be associated with all grades of GM-IVH (grade I-III) and may be unilateral (65-75% cases) or bilateral (symmetrical or asymmetrical). The severity of PVHI can be graded based on three CUS parameters: (i) extent, (ii) bilaterality, and (ii) the presence of a midline shift. [21] Decreased flow velocity and displacement of the terminal vein can be seen in surviving infants with PVHI using Doppler flow velocimetry.[22] PVHI is in the distribution of the fan-shaped periventricular medullary veins. Intravascular thrombi within the medullary veins can be demonstrated on T2-weighted MRI as linear abnormalities in the WM of centrum semiovale. [20] In living infants, venous infarction usually evolves to produce a porencephalic cyst and rarely multiple cysts. The evolving cyst(s) are associated with the destruction of motor and associative WM axons and preoligodendrocytes. These infants have a high incidence of hemiplegia later in their life.[23] Asymmetric myelination of the posterior limb of the internal capsule on MRI at term has been suggested as an early predictor of hemiplegia in PVHI. [24]

**4. Role of neuroimaging**

4 Intracerebral Hemorrhage

palsy or mental retardation).[18,19]

leukomalacia (PVL), and SAH.[1,4]

**4.1. Germinal Matrix-Intraventricular Hemorrhage (GM-IVH) in preterm infants**

For years neonatal cranial ultrasound (CUS) has been the key diagnostic tool for GM-IVH in premature infants due to its widespread availability, relative low cost, direct bedside scanning and high resolution to detect GM-IVH. CUS is nearly as accurate as CT but much less stressful for an ill premature infant. Diagnostic screening with CUS is recommended in all premature infants (less than 1,500 gm birth weight and less than 32 weeks' gestation) during the second week of life (after which further bleeding is uncommon) or earlier if clinical conditions indicate. [11] Doppler ultrasound can also be used for the imaging and flow velocity measurements of the terminal vein.[12] CT had been used in the original studies to grade the GM-IVH, however, it is no longer recommended for diagnostic purpose due to the adverse effect produce by ionizing radiation on immature brain. MRI is superior to CUS and CT for detection of associ‐ ated white matter (WM) abnormalities and for identifying hemorrhages particularly small petechial hemorrhage, subacute to chronic hemorrhage and for extracerebral or posterior fossa hemorrhage.[13] The severity of GM-IVH has been evaluated by Papile[14] and Volpe's[15] grading system. When bleeding is confined to the subependymal region, it is classified as grade I; grade II is extension of hemorrhage into non distended lateral ventricle(s) where blood fills less than 50% of the ventricular diameter; in grade III, extensive intraventricular hemorrhage fills greater than 50% of the ventricular diameter leading to hydrocephalus; whereas, grade IV is periventricular hemorrhagic infarction (PVHI).[14,15] Most cases have grade I or grade II intraventricular hemorrhage and do not show late sequelae.[16,17] Infants with grade III or IV hemorrhage have high incidence of neurologic sequelae (approx. 30% will have severe cerebral

Once GM-IVH is diagnosed, follow-up CUS examinations are necessary to determine its complications like periventricular hemorrhagic infarction (PVHI) and post-hemorrhagic hydrocephalus (PHH) and associated cerebellar hemorrhagic injury (CHI), periventricular

Periventricular hemorrhagic infarction (PVHI), classified as grade IV GM-IVH, is a complica‐ tion of GM-IVH. As previously thought, it is not due to rupture of ependymal lining and extension of intraventricular hemorrhage into the periventricular white matter; rather it occurs due to compression of the terminal vein by GM-IVH resulting in impaired venous drainage and congestion of the medullary veins, which in turn leads to hypoxia-ischemia, infarction and finally hemorrhagic transformation in the periventricular white matter.[20] PVHI can be associated with all grades of GM-IVH (grade I-III) and may be unilateral (65-75% cases) or bilateral (symmetrical or asymmetrical). The severity of PVHI can be graded based on three CUS parameters: (i) extent, (ii) bilaterality, and (ii) the presence of a midline shift. [21] Decreased flow velocity and displacement of the terminal vein can be seen in surviving infants with PVHI using Doppler flow velocimetry.[22] PVHI is in the distribution of the fan-shaped periventricular medullary veins. Intravascular thrombi within the medullary veins can be demonstrated on T2-weighted MRI as linear abnormalities in the WM of centrum semiovale. [20] In living infants, venous infarction usually evolves to produce a porencephalic cyst and Incidence of ventricular dilatation increases with the severity of GM-IVH. CUS is an ideal tool for monitoring ventricular dilatation in newborns with open fontanelle. Detailed imaging with MRI is usually required prior to shunt surgery and for monitoring the progression or shunt complication after closure of the fontanelle. Posthemorrhagic hydrocephalus (PHH) may be progressive (due to obstruction by blood clot or secondary inflammatory changes which interferes with CSF flow), nonprogressive (due to parenchymal loss secondary to PVHI or PVL) or a combination of the two. PHH survivors with grade III and IV GM-IVH have high risk of significant neurodevelopmental sequelae (e.g. quadriparetic cerebral palsy and/or profound mental retardation).[3,25]

A very high association (77%) has been reported between the cerebellar hemorrhagic injury (CHI) and supratentorial GM-IVH. CHI can result from cerebellar GM hemorrhage (subepen‐ dymal or subpial), primary hemorrhage, ischemic hemorrhagic transformation of either arterial or venous origin, or dissection of blood through the fourth ventricle or subarachnoid spaces following massive supratentorial GM-IVH. The location of CHI could be unilateral, vermian, bilateral or a combination of these. Mastoid CUS view helps to detect CHI in 3% of premature infants. MRI detects small petechial cerebellar hemorrhages not visible on CUS. CHI may eventually lead to several types of atrophic changes. 40% of CHI survivors have global developmental (cognitive and social communication disabilities) and functional deficits (motor deficits).[3,26]

A strong association between GM-IVH and periventricular leukomalacia (PVL) has been suggested. GM-IVH and PVL may develop in parallel, the ischemic injury may injure the GM and the periventricular WM leading to both GM-IVH and PVL. The CUS markers of cystic and diffuse PVL include echolucencies, echodensities and nonprogressive ventriculomegaly.[3,27]

Subarachnoid hemorrhage (SAH) is relatively common in premature infants with GM-IVH. The true incidence of SAH is not known as it is difficult to visualize the extra-axial hemorrhage by CUS. MRI is the modality of choice to detect SAH. SAH could be one of the reasons for PHH (obstructive arachnoiditis), neonatal seizure (irritation of cerebral convexity) and cerebral/ cerebellar growth impairment.[28,29]

Impaired cerebellar and supratentorial gray matter growth has been reported in GM-IVH survivors. The complicated GM-IVH (PVHI and PVL) causes impaired growth and develop‐ ment of the contralateral cerebellar hemisphere due to injury to specific supratentorial projections (crossed cerebellar diaschisis).[28] The uncomplicated GM-IVH (without paren‐ chymal involvement) is associated with impaired growth of the supratentorial gray matter, probably because the GM destruction prevents the neuronal and astrocyte precursor cells from reaching their cortical destination. In addition, SAH (circulating free radical) may directly injure the cerebral cortex surface.[29]

#### **4.2. Intracranial hemorrhage (ICH) in term newborns**

Subarachnoid hemorrhage (SAH) is the most common type of hemorrhage among the symptomatic term newborns.[6] On FLAIR (fluid attenuated inversion recovery) sequence of MRI, SAH is detected as hyperattenuating fluid in the basal subarachnoid spaces or along the cerebral sulci. Extensive subarachnoid hemorrhage may be difficult to distinguish from subdural hemorrhage and the two may co-exist. [3]

**5. Prevention and management**

for prevention of GM-IVH are still under trial.[25,31,32]

injury to the brain due to neurosurgery or hematoma.[35]

Modern practice should emphasize on (i) prevention of GM-IVH, (ii) halting its progression, and (iii) reducing its complications. Important preventive measures include (i) special obstetric care for high-risk pregnancies, (ii) treatment of bacterial vaginosis for reducing premature delivery, (iii) prevention of imminent premature labor using tocolytic agents, cesarean section delivery in selected cases, and (iv) maternal administration of magnesium sulfate. In addition, optimal ventilation and strict hemodynamic control of the premature infant are the corner‐ stones of preventing GM-IVH and its progression. Several postnatal pharmacological agents

Intracranial Hemorrhage in the Newborn http://dx.doi.org/10.5772/58476 7

PHH, a complication of GM-IVH has a very unpredictable course. 60% of the infants may undergo spontaneous resolution while 40% may require a ventriculoperitoneal shunt, the definitive treatment of progressive PHH.[25] Repeated lumbar puncture may temporarily arrest the progression of PHH, but the long-term benefit of this approach remains unknown.[3]

The single most important primary prevention is successful accomplishment of a vaginal delivery with or without obstetric instrument. However, forceful vaginal delivery should not

Medical interventions should be implemented on the very first clinical suspension of ICH. The goal of medical therapy is to provide adequate ventilation, prevent metabolic acidosis, to keep vital organs well perfused and to control seizure activity. Sick newborns with ICH are managed in the intensive care unit. Any treatable etiological factor (e.g. sepsis, dehydration, thrombo‐ cytopenia, vitamin K deficiency or coagulopathy) should be identified and treated promptly. Most symptomatic newborns with intracranial hemorrhage do not require neurosurgical intervention. Neurosurgical intervention could, however, be lifesaving in a situation in which there is a sudden clinical deterioration primarily due to rise in intracranial pressure as a result of massive ICH and PHH.[34] The secondary prevention is to limit the extent of parenchymal

GM-IVH and its complications have potential impact on morbidity, mortality and long-term neurodevelopmental outcome. The mechanism of GM-IVH is multifactorial and involves a combination of vascular anatomic immaturity and complex hemodynamic factors. Goals are

A strong association between traumatic deliveries especially vacuum extraction/forceps delivery and hemorrhagic lesions has been well established in term newborns. Hemorrhage

prevention of GM-IVH, halting its progression and reducing its complications.

be attempted if either vacuum extraction or forceps delivery has failed.[33]

**5.1. GM-IVH in preterm infants**

**5.2. ICH in term newborns**

**6. Summary**

Subdural hemorrhage (SDH) is the most frequent hemorrhage among asymptomatic term newborns.[5] SDH is usually infratentorial, may result from rupture of the vein of Galen, straight or transverse sinus. On imaging, SDH can be seen as a crescent-shaped hyperattenu‐ ating region conforming to the adjacent brain. Small posterior fossa SDHs are common in infants and are usually of no clinical significance; however, when large, may result in com‐ pression of the brain stem and death. Infratentorial SDH may be difficult to distinguish from transverse sinus thrombosis. The two may co-exist or a SDH may compress the sinus predis‐ posing to thrombosis. Convexity SDH are less common than posterior fossa hemorrhage and the two may co-exist. Rupture of superficial cortical veins gives rise to convexity SDH, which may be accompanied by SAH. Convexity SDH is mainly unilateral. Large convexity hemor‐ rhage may be associated with infarction of the brain either from arterial occlusion or impaired venous drainage. Associated parenchymal hemorrhage either due to hemorrhagic tendency or in association with infarction may also occur.[3]

Large SDH may result in impairment of CSF flow and associated ventricular dilatation or widening of the extracerebral space (external hydrocephalus). The evolution of SDH may result in the formation of a subdural effusion which may remain at the site of a previous SDH for months and may be associated with rebleeding.[3]

Parenchymal hemorrhagic lesions may co-exist with hemorrhage elsewhere in the cranium. Parenchymal hemorrhage may be focal or multifocal and of any size. Multifocal small hemorrhages may be found in term infants presenting with convulsions during the first few days of life. Thalamic hemorrhage is usually unilateral and associated with IVH. Primary thalamic hemorrhage needs to be distinguished from the bilateral thalamic abnormalities seen in HIE. The thalamic lesions in HIE are focal, usually involving the lateral thalamic nuclei and sometimes the medial nuclei, these lesion have high signal intensity on T1-weighted images and low signal intensity on T2-weighted images due to capillary proliferation in region of infarction (not due to hemorrhage). However, infants with HIE may develop large intracranial hemorrhage. Basal ganglia hemorrhage may occur as an isolated event in term newborn, sometimes it is difficult to differentiate it from a hemorrhagic infarction involving a deep branch of middle cerebral artery. Cerebellar hemorrhage may be primary, secondary to venous infarction or may complicate massive intraventricular or subarachnoid hemorrhage. The MR appearance of parenchymal hemorrhage varies with time depending on the oxidation state of hemoglobin.[30]
