An article on emedicine at http://www.emedicine.com/ped/topic1773.htm describes in PVL in more detail:



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"Periventricular Leukomalacia

Article Last Updated: Feb 14, 2008

References Author: Terence Zach, MD, Department Vice-Chair, Professor, Department of Pediatrics, Section of Newborn Medicine, Creighton UniversityTerence Zach is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Nebraska Medical AssociationCoauthor(s): James C Brown, MD, Codirector of Pediatric Radiology, Assistant Professor, Department of Radiology, Creighton University School of MedicineEditors: Scott S MacGilvray, MD, Associate Professor, Department of Pediatrics, East Carolina University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center; Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina; Ted Rosenkrantz, MD, Head, Division of Neonatal-Perinatal Medicine, Professor, Departments of Pediatrics and Obstetrics/Gynecology, University of Connecticut School of Medicine



Synonyms and related keywords: periventricular leukomalacia, PVL, ischemic brain injury, cerebral palsy, CP, hypotension, ischemia, coagulation necrosis, intracranial hemorrhage, ICH, hypocarbia, vasculitis, chorioamnionitis, cytokines, white matter damage, spastic diplegia, quadriplegia, nystagmus, strabismus, blindness, retinopathy of prematurity, maternal chorioamnionitis, respiratory distress syndrome, pneumonia, patent ductus arteriosus, placental vascular anastomoses, twin gestation, antepartum hemorrhage, sepsis

Background
Periventricular leukomalacia (PVL) is the most common ischemic brain injury in premature infants. The ischemia occurs in the border zone at the end of arterial vascular distributions. The ischemia of PVL occurs in the white matter adjacent to the lateral ventricles. The diagnostic hallmarks of PVL are periventricular echodensities or cysts detected by cranial ultrasonography. Diagnosing PVL is important because a significant percentage of surviving premature infants with PVL develop cerebral palsy (CP), intellectual impairment, or visual disturbances.


Pathophysiology
The pathophysiology of PVL is a complex process. PVL may occur because of ischemia-reperfusion injury to the periventricular area of the developing brain or because of cytokine-induced damage following maternal or fetal infection.


PVL is a white matter lesion in premature infants that may result from hypotension, ischemia, and coagulation necrosis at the border or watershed zones of deep penetrating arteries of the middle cerebral artery. Decreased blood flow affects the white matter at the superolateral borders of the lateral ventricles. The site of injury affects the descending corticospinal tracts, visual radiations, and acoustic radiations. In addition to possible ischemic injury, PVL may be the result of edema fluid and hemorrhage that cause compression of arterioles in the white matter. Reperfusion injury by free radicals to developing oligodendrocytes in the fetal or premature infant's brain may play an important role in the pathogenesis of PVL.


Premature infants have impaired cerebrovascular blood flow autoregulation and are susceptible to intracranial hemorrhage (ICH) as well as PVL. Premature infants on mechanical ventilation may develop hypocarbia. Several studies have linked hypocarbia, particularly in the first few days of life, with the development of PVL.1, 2


The relationship of maternal infection, placental inflammation, and vasculitis to the pathogenesis of PVL remains controversial. Some investigators have demonstrated an association of chorioamnionitis and cytokines with PVL although others have not.3


Following the initial insult, whether ischemia-mediated or cytokine-mediated, white matter damage occurs. The white matter damage likely occurs because of selective loss of oligodendrocytes.

Frequency
United States
Incidence of PVL ranges from 4-26% in premature infants in neonatal intensive care units (NICUs).
Incidence of PVL is much higher in reports from autopsy studies of premature infants.
As many as 75% of premature infants have evidence of PVL on postmortem examination.

Mortality/Morbidity
Cerebral palsy: Approximately 60-100% infants with PVL later develop signs of CP. Spastic diplegia is the most common form of CP following mild PVL. Severe PVL is frequently associated with quadriplegia.
Intellectual impairment: Varying degrees of intellectual impairment, developmental impairment, or both have been reported in association with PVL.
Visual dysfunction: Fixation difficulties, nystagmus, strabismus, and blindness have been associated with PVL. Some cases of visual dysfunction in association with PVL occur in the absence of retinopathy of prematurity, suggesting damage to optic radiations as causation.

Age
PVL occurs most commonly in premature infants younger than 32 weeks' gestation at birth.

CLINICAL
History
Periventricular leukomalacia (PVL) occurs most commonly in premature infants born at less than 32 weeks' gestation who have a birth weight of less than 1500 g. Many of these infants have a history of maternal chorioamnionitis. Most affected infants experience cardiorespiratory problems, such as respiratory distress syndrome or pneumonia, in association with hypotension or patent ductus arteriosus during their first days of life. Bacterial infection at birth also appears to be a risk factor.


Physical
Initially, most premature infants are asymptomatic. If symptoms occur, they usually are subtle. Symptoms may include the following:
Decreased tone in lower extremities
Increased tone in neck extensors
Apnea and bradycardia events
Irritability
Pseudobulbar palsy with poor feeding
Clinical seizures (may occur in 10-30% of infants)

Causes
Mechanically ventilated premature infants born at less than 32 weeks' gestation are at greatest risk for PVL.
Hypotension, hypoxemia, and acidosis may result in ischemic brain injury and PVL.
Marked hypocarbia in ventilated premature infants has been associated with increased risk of developing PVL.
Other associated risk factors include the following:
Placental vascular anastomoses, twin gestation, antepartum hemorrhage
Chorioamnionitis and funisitis
Sepsis
Maternal cocaine abuse

DIFFERENTIALS


Other Problems to be Considered
Intraventricular hemorrhagePeriventricular hemorrhagic venous infarction


Imaging Studies
Cranial ultrasonography
Cranial ultrasonography is the modality of choice for the initial evaluation of hypoxic-ischemic damage of the CNS in premature infants. Ultrasonography may be performed in the NICU without the need to transport fragile infants.
The earliest ultrasonographic appearance of periventricular leukomalacia (PVL) is abnormal increased echotexture in the periventricular white matter. This is a nonspecific finding that must be differentiated from the normal periventricular halo and mild periventricular edema that may not result in permanent injury.
The abnormal periventricular echotexture of PVL usually disappears at 2-3 weeks. Approximately 15% of infants experiencing PVL demonstrate periventricular cysts first appearing at 2-3 weeks after the initial increased echodensities.
The severity of PVL is related to the size and distribution of these cysts. Initial cranial ultrasonographic findings may be normal in patients who go on to develop clinical and delayed imaging findings of PVL.
CT scanning: CT scanning is not a first-line modality in evaluating these fragile premature infants in the first weeks of life. CT scanning may be helpful to better evaluate the extent and severity of PVL. Findings include ventriculomegaly involving the lateral ventricles with irregular margins of the ventricles and loss of deep white matter.


MRI: Like CT scanning, MRI does not play a major role in the early evaluation of PVL. MRI is most helpful in monitoring infants with suspected PVL and evaluating infants who develop clinical signs suggestive of PVL. MRI demonstrates the loss of white matter, abnormal signal intensity of the deep white matter, and ventriculomegaly. MRI demonstrates thinning of the posterior body and splenium of the corpus callosum in severe cases of PVL. Volumetric MRI scanning is also helpful in determining the extent of injury to the descending corticospinal tracts. A relationship between the degree of injury to the descending corticospinal tracts as assessed by MRI and the severity of diplegia has been reported.

Other Tests
EEG

Histologic Findings
PVL lesions demonstrate widespread loss of oligodendrocytes and an increase in astrocytes.

TREATMENT


Medical Care
No medical treatment is currently available. Free radical scavengers are being investigated to determine if they have a role in preventing oligodendrocyte injury in periventricular leukomalacia (PVL).
Consultations
Infants with PVL require close neurodevelopmental follow-up after discharge from the hospital. Potential consultants include pediatricians, developmental specialists, neurologists, and occupational and physical therapists.


FOLLOW-UP

Further Outpatient Care
Developmental follow-up: Premature infants with evidence of periventricular leukomalacia (PVL) require close developmental follow-up because of the high association with CP.
Early intervention strategies carried out by occupational therapists or physical therapists may decrease symptoms and may increase the infant's motor function.

Deterrence/Prevention
Prevention of premature birth is the most important means of preventing PVL.
Prior to birth, diagnosing and managing chorioamnionitis may prevent PVL. In 1999, Baud et al reported that betamethasone administered to mothers at 24-31 weeks' gestation, before delivery, significantly reduced the risk of PVL, suggesting the possible effect of steroids on fetal inflammatory response.4, 5
Avoiding maternal cocaine abuse and avoiding maternal-fetal blood flow alterations has been suggested to minimize PVL.
Following delivery of a premature infant, attempts to minimize blood pressure (BP) swings and hypotension may also be beneficial in preventing PVL.
Avoidance of prolonged hypocarbia in the mechanically ventilated premature infant may be useful in the prevention of PVL.

Prognosis
Infants with PVL are at risk for development of neurodevelopmental deficits. Mild PVL is often associated with spastic diplegia. Severe PVL is associated with quadriplegia. Severe PVL is also associated with a higher incidence of intelligence deficiencies and visual disturbances.

MISCELLANEOUS
Medical/Legal Pitfalls
Timing of initial cranial ultrasonography can be useful in determining the timing of the insult. Cystic PVL has been identified on cranial ultrasounds on the first day of life, indicating that the event was prenatal rather than perinatal or postnatal.

MULTIMEDIA
Media file 1: Cranial ultrasound, coronal view, in 1-week-old premature infant. The periventricular echotexture is abnormally increased (greater than or equal to that of the choroid plexus), which is consistent with the early changes of periventricular leukomalacia (PVL). Courtesy of Matthew Omojola, MD.

Media type: Ultrasound
Media file 2: Cranial ultrasound, coronal view, in 1-week-old premature infant without periventricular leukomalacia (PVL). The periventricular echotexture is normal. Compare with Media file 1. Courtesy of Matthew Omojola, MD.

Media type: Ultrasound
Media file 3: Cranial ultrasound, coronal view, in a 3-week-old premature infant. Multiple bilateral periventricular cysts are typical of this stage of periventricular leukomalacia (PVL). Courtesy of Matthew Omojola, MD.

Media type: Ultrasound
Media file 4: Cranial ultrasound, sagittal view, in 3-week-old premature infant. Multiple periventricular cysts are typical of this stage of periventricular leukomalacia (PVL). Courtesy of Matthew Omojola, MD.

Media type: Ultrasound
Media file 5: Cranial CT scan, axial image, in a 5-week-old premature infant with periventricular leukomalacia (PVL). The ventricular margins are irregular, which is consistent with incorporation of the periventricular cysts of PVL. Mild ventriculomegaly and loss of the periventricular white matter is observed. Courtesy of Matthew Omojola, MD.

Media type: CT
Media file 6: Cranial CT scan, axial image, in 14-month-old with periventricular leukomalacia (PVL). Ventriculomegaly is limited to the lateral ventricles secondary to diffuse loss of periventricular white matter. Courtesy of Matthew Omojola, MD.

Media type: CT
Media file 7: Cranial MRI, T1-weighted axial image, in an 18-month-old with periventricular leukomalacia (PVL). The lateral ventricles are enlarged without hydrocephalus. The periventricular white matter is diminished. Courtesy of Matthew Omojola, MD.

Media type: MRI
Media file 8: Cranial MRI, T2-weighted axial image, in an 18-month-old with periventricular leukomalacia (PVL). Again, enlarged ventricles and loss of white matter are demonstrated. Also noted is the abnormal increased signal in the periventricular regions on this T2-weighted image. Courtesy of Matthew Omojola, MD.

Media type: MRI
Media file 9: Cranial MRI, sagittal T1-weighted image in the midline, in an 18-month-old with periventricular leukomalacia (PVL). Hypoplasia of the corpus callosum is present and is most evident, involving the body. Courtesy of Matthew Omojola, MD.

Media type: MRI



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