Periventricular leukomalacia
Encyclopedia
Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis (more often coagulation) of white matter
near the lateral ventricles
. It can affect newborns and (less commonly) fetuses; premature infants are at the greatest risk of the disorder. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy
or epilepsy
later in life.
This pathology of the brain was described under various names ("encephalodystrophy", "ischemic necrosis," "periventricular infarction", "coagulation necrosis", "leukomalacia," "softening of the brain," "infarct periventricular white matter", "necrosis of white matter", "diffuse symmetrical periventricular leukoencephalopathy”), and more often by German scientists, but the worldwide dissemination was the term «periventricular leukomalacia», introduced in 1962 B.A.Banker and J.C.Larroche. The term is not clear, since there are no softening of PVL, and more dense than surrounding areas of the brain foci of coagulation necrosis. V.V. Vlasyuk and V.P. Tumanov in 1985 published the world's first monograph devoted to PVL. The most comprehensive study of PVL in the world at the largest section material held V.V. Vlasyuk (1981) (frequency, etiopathogenesis, topography, degree of damage different parts of the brain, developmental stage lesions, histoneurology, the role of microglia, electron microscopy, histochemistry, and others), who first revealed the high incidence of optic radiation lesions and demonstrated that PVL - a persistent process that the old necrosis can join a new, foci of PVL may be at different stages of development.
In the process of morphogenesis focuses PVL pass through three stages: 1) necrosis, 2) resorption, and 3) the formation gliosis scars or cysts. Cysts occur when large and confluent focuses of PVL, with mixed necrosis (kollikvacia in the center and coagulation rim at the periphery). Around the foci is generally defined area of other lesions of the brain white matter - the death of prooligodendrocytes, proliferation mikrogliocytes and astrocytes, swelling, bleeding, loss of capillaries, and others (the so-called "diffuse component PVL"). However, diffuse lesions without necrosis are not PVL.
The initial hypoxia (decreased oxygen flow) or ischemia (decreased blood flow) can occur for a number of reasons. Fetal blood vessels are thin-walled structures, and it is likely that the vessels providing nutrients to the periventricular region cannot maintain a sufficient blood flow during episodes of decreased oxygenation during development. Additionally, hypotension
resulting from fetal distress
or cesarean section births can lead to decreased blood and oxygen flow to the developing brain. These hypoxic-ischemic incidents can cause damage to the blood brain barrier (BBB), a system of endothelial cells and glial cells that regulates the flow of nutrients to the brain. A damaged BBB can contribute to even greater levels of hypoxia. Alternatively, damage to the BBB can occur due to maternal infection during fetal development, fetal infections, or infection of the newly delivered infant. Because their cardiovascular and immune systems are not fully developed, premature infants are especially at risk for these initial insults.
Damage caused to the BBB by hypoxic-ischemic injury or infection sets off a sequence of responses called the inflammatory response. Immediately after an injury, the nervous system generates “pro-inflammatory” cytokines, which are molecules used to coordinate a response to the insult. These cytokines are toxic to the developing brain, and their activity in an effort to respond to specific areas of damaged tissue is believed to cause “bystander damage” to nearby areas that were not affected by the original insult. Further damage is believed to be caused by free radicals, compounds produced during ischemic episodes. The processes affecting neurons also cause damage to glial cells, leaving nearby neurons with little or no support system.
It is thought that other factors might lead to PVL, and researchers are studying other potential pathways. A recent article by Miller, et al., provides evidence that white-matter injury is not a condition limited to premature infants: full-term infants with congenital heart diseases also exhibit a "strikingly high incidence of white-matter injury." In a study described by Miller, of 41 full-term newborns with congenital heart disease, 13 infants (32%) exhibited white matter injury.
The extent of signs is strongly dependent on the extent of white matter damage: minor damage leads to only minor deficits or delays, while significant white matter damage can cause severe problems with motor coordination or organ
function. Some of the most frequent signs include: delayed motor developments, vision deficits, apnea
s, low heart rates
, and seizure
s.
, and refractive error
.
. The preliminary diagnosis of PVL is often made using imaging technologies. In most hospitals, premature infants are examined with ultrasound
soon after birth to check for brain damage. Severe white matter injury can be seen with a head ultrasound; however, the low sensitivity of this technology allows for some white matter damage to be missed. Magnetic resonance imaging (MRI) is much more effective at identifying PVL, but it is unusual for preterm infants to receive an MRI unless they have had a particularly difficult course of development (including repeated or severe infection, or known hypoxic events during or immediately after birth). No agencies or regulatory bodies have established protocols or guidelines for screening of at-risk populations, so each hospital or doctor generally makes decisions regarding which patients should be screened with a more sensitive MRI instead of the basic head ultrasound.
Currently, there is overdiagnosis of PVL by neuroimaging studies reassessment data and underestimating the other white matter lesions of the brain. PVL is necessary to differentiate from the following major white matter lesions in the cerebral hemispheres: edematous hemorrhagic leukoencephalopathy (OGL), telentsefalny gliosis (TG), diffuse leukomalacia (DFL), subcortical leukomalacia (SL), periventricular hemorrhagic infarction (PHI), intracerebral hemorrhage ( ICH), multicystic encephalomalacia (ME), subendymal pseudocyst. Diffuse white matter lesions of the cerebral hemispheres of the brain, accompanied by softening and spreading to the central and subcortical areas are more likely DFL, PHI and ME.
An emphasis on prenatal health and regular medical examinations of the mother can also notably decrease the risk of PVL. Prompt diagnosis and treatment of maternal infection during gestation reduces the likelihood of large inflammatory responses. Additionally, treatment of infection with steroids (especially in the 24–31 weeks of gestation) have been indicated in decreasing the risk of PVL.
It has also been suggested that avoiding maternal cocaine
usage and any maternal-fetal blood flow alterations can decrease the risk of PVL. Episodes of hypotension or decreased blood flow to the infant can cause white matter damage.
Patients are typically treated with an individualized treatment. It is crucial for doctors to observe and maintain organ function: visceral organ failure can potentially occur in untreated patients. Additionally, motor deficits and increased muscle tone
are often treated with individualized physical and occupational therapy treatments.
to minimize the amount of lesioning in patients exposed to ischemic conditions.
of patients with PVL is dependent on the severity and extent of white matter damage. Some children exhibit relatively minor deficits, while others have significant deficits and disabilities.
, a condition characterized by increased muscle tone and spasticity
in the lower body. The gait of PVL patients with spastic diplegia exhibits an unusual pattern of flexing during walking.
, exhibiting a loss of function or paralysis of all four limbs.
. The percentage of individuals with PVL who develop cerebral palsy is generally reported with significant variability from study to study, with estimates ranging from 20% to more than 60%. One of the reasons for this discrepancy is the large variability in severity of cerebral palsy. This range corresponds to the severity of PVL, which can also be quite variable. More white matter damage leads to more severe cerebral palsy; different subtypes are identified and diagnosed by a neurologist.
Despite the varying grades of PVL and cerebral palsy, affected infants typically begin to exhibit signs of cerebral palsy in a predictable manner. Typically, some abnormal neurological signs (such as those previously mentioned) are visible by the third trimester of pregnancy (28 to 40 weeks after conception), and definitive signs of cerebral palsy are visible by six to nine months of age.
. The link between the two is not entirely clear; however, it appears that both genetic and early environmental factors are involved. One study estimated that 47% of children with PVL also have epilepsy, with 78% of those patients having a form of epilepsy not easily managed by medication. Many of these affected patients exhibit some seizures, as well as spastic diplegia or more severe forms of cerebral palsy, before a diagnosis of epilepsy is made.
Other ongoing clinical studies are aimed at the prevention and treatment of PVL: clinical trials testing neuroprotectants, prevention of premature births, and examining potential medications for the attenuation of white matter damage are all currently supported by NIH funding.
White matter
White matter is one of the two components of the central nervous system and consists mostly of myelinated axons. White matter tissue of the freshly cut brain appears pinkish white to the naked eye because myelin is composed largely of lipid tissue veined with capillaries. Its white color is due to...
near the lateral ventricles
Lateral ventricles
The lateral ventricles are part of the ventricular system of the brain. Classified as part of the telencephalon, they are the largest of the ventricles....
. It can affect newborns and (less commonly) fetuses; premature infants are at the greatest risk of the disorder. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
or epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
later in life.
This pathology of the brain was described under various names ("encephalodystrophy", "ischemic necrosis," "periventricular infarction", "coagulation necrosis", "leukomalacia," "softening of the brain," "infarct periventricular white matter", "necrosis of white matter", "diffuse symmetrical periventricular leukoencephalopathy”), and more often by German scientists, but the worldwide dissemination was the term «periventricular leukomalacia», introduced in 1962 B.A.Banker and J.C.Larroche. The term is not clear, since there are no softening of PVL, and more dense than surrounding areas of the brain foci of coagulation necrosis. V.V. Vlasyuk and V.P. Tumanov in 1985 published the world's first monograph devoted to PVL. The most comprehensive study of PVL in the world at the largest section material held V.V. Vlasyuk (1981) (frequency, etiopathogenesis, topography, degree of damage different parts of the brain, developmental stage lesions, histoneurology, the role of microglia, electron microscopy, histochemistry, and others), who first revealed the high incidence of optic radiation lesions and demonstrated that PVL - a persistent process that the old necrosis can join a new, foci of PVL may be at different stages of development.
In the process of morphogenesis focuses PVL pass through three stages: 1) necrosis, 2) resorption, and 3) the formation gliosis scars or cysts. Cysts occur when large and confluent focuses of PVL, with mixed necrosis (kollikvacia in the center and coagulation rim at the periphery). Around the foci is generally defined area of other lesions of the brain white matter - the death of prooligodendrocytes, proliferation mikrogliocytes and astrocytes, swelling, bleeding, loss of capillaries, and others (the so-called "diffuse component PVL"). However, diffuse lesions without necrosis are not PVL.
Predisposing Factors
Those generally considered to be at greatest risk for PVL are premature, very low birth-weight infants. It is estimated that approximately 3-4% of infants who weigh less than 1500 g (3.3 lb) have PVL, and 4-10% of those born prior to 33 weeks of gestation (but who survive more than three days postpartum) have the disorder.Injury Pathway
Two major factors appear to be involved in the development of PVL: (1) decreased blood or oxygen flow to the periventricular region (the white matter near the cerebral ventricles) and (2) damage to glial cells, the cells that support neurons throughout the nervous system. These factors are especially likely to interact in premature infants, resulting in a sequence of events that leads to the development of white matter lesions.The initial hypoxia (decreased oxygen flow) or ischemia (decreased blood flow) can occur for a number of reasons. Fetal blood vessels are thin-walled structures, and it is likely that the vessels providing nutrients to the periventricular region cannot maintain a sufficient blood flow during episodes of decreased oxygenation during development. Additionally, hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
resulting from fetal distress
Fetal distress
In medicine , the term fetal distress refers to the presence of signs in a pregnant woman—before or during childbirth—that suggest that the fetus may not be well...
or cesarean section births can lead to decreased blood and oxygen flow to the developing brain. These hypoxic-ischemic incidents can cause damage to the blood brain barrier (BBB), a system of endothelial cells and glial cells that regulates the flow of nutrients to the brain. A damaged BBB can contribute to even greater levels of hypoxia. Alternatively, damage to the BBB can occur due to maternal infection during fetal development, fetal infections, or infection of the newly delivered infant. Because their cardiovascular and immune systems are not fully developed, premature infants are especially at risk for these initial insults.
Damage caused to the BBB by hypoxic-ischemic injury or infection sets off a sequence of responses called the inflammatory response. Immediately after an injury, the nervous system generates “pro-inflammatory” cytokines, which are molecules used to coordinate a response to the insult. These cytokines are toxic to the developing brain, and their activity in an effort to respond to specific areas of damaged tissue is believed to cause “bystander damage” to nearby areas that were not affected by the original insult. Further damage is believed to be caused by free radicals, compounds produced during ischemic episodes. The processes affecting neurons also cause damage to glial cells, leaving nearby neurons with little or no support system.
It is thought that other factors might lead to PVL, and researchers are studying other potential pathways. A recent article by Miller, et al., provides evidence that white-matter injury is not a condition limited to premature infants: full-term infants with congenital heart diseases also exhibit a "strikingly high incidence of white-matter injury." In a study described by Miller, of 41 full-term newborns with congenital heart disease, 13 infants (32%) exhibited white matter injury.
Presentation
It is often impossible to identify PVL based on the patient’s physical or behavioral characteristics. The white matter in the periventricular regions is involved heavily in motor control, and so individuals with PVL often exhibit motor problems. However, since healthy newborns (especially premature infants) can perform very few specific motor tasks, early deficits are very difficult to identify. As the individual develops, the areas and extent of problems caused by PVL can begin to be identified; however, these problems are usually found after an initial diagnosis has been made.The extent of signs is strongly dependent on the extent of white matter damage: minor damage leads to only minor deficits or delays, while significant white matter damage can cause severe problems with motor coordination or organ
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
function. Some of the most frequent signs include: delayed motor developments, vision deficits, apnea
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
s, low heart rates
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
, and seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s.
Delayed Motor Development
Delayed motor development of infants affected by PVL has been demonstrated in multiple studies. One of the earliest markers of developmental delays can be seen in the leg movements of affected infants, as early as one month of age. Those with white matter injury often exhibit “tight coupling” of leg joints (all extending or all flexing) much longer than other infants (premature and full-term). Additionally, infants with PVL may not be able to assume the same positions for sleeping, playing, and feeding as premature or full-term children of the same age. These developmental delays can continue throughout infancy, childhood, and adulthood.Vision Deficits
Premature infants often exhibit visual impairment and motor deficits in eye control immediately after birth. However, the correction of these deficits occurs “in a predictable pattern” in healthy premature infants, and infants have vision comparable to full-term infants by 36 to 40 weeks after conception. Infants with PVL often exhibit decreased abilities to maintain a steady gaze on a fixed object and create coordinated eye movements. Additionally, children with PVL often exhibit nystagmus, strabismusStrabismus
Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...
, and refractive error
Refractive error
A refractive error, or refraction error, is an error in the focusing of light by the eye and a frequent reason for reduced visual acuity.-Classification:...
.
Seizures
Occurrence of seizures is often reported in children with PVL. In an Israel-based study of infants born between 1995 and 2002, seizures occurred in 102 of 541, or 18.7%, of PVL patients. Seizures are typically seen in more severe cases of PVL, affecting patients with greater amounts of lesions and those born at lower gestational ages and birth weights.Diagnosis
As previously noted, there are often few signs of white matter injury in newborns. Occasionally, physicians can make the initial observations of extreme stiffness or poor ability to suckleBreastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
. The preliminary diagnosis of PVL is often made using imaging technologies. In most hospitals, premature infants are examined with ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
soon after birth to check for brain damage. Severe white matter injury can be seen with a head ultrasound; however, the low sensitivity of this technology allows for some white matter damage to be missed. Magnetic resonance imaging (MRI) is much more effective at identifying PVL, but it is unusual for preterm infants to receive an MRI unless they have had a particularly difficult course of development (including repeated or severe infection, or known hypoxic events during or immediately after birth). No agencies or regulatory bodies have established protocols or guidelines for screening of at-risk populations, so each hospital or doctor generally makes decisions regarding which patients should be screened with a more sensitive MRI instead of the basic head ultrasound.
Currently, there is overdiagnosis of PVL by neuroimaging studies reassessment data and underestimating the other white matter lesions of the brain. PVL is necessary to differentiate from the following major white matter lesions in the cerebral hemispheres: edematous hemorrhagic leukoencephalopathy (OGL), telentsefalny gliosis (TG), diffuse leukomalacia (DFL), subcortical leukomalacia (SL), periventricular hemorrhagic infarction (PHI), intracerebral hemorrhage ( ICH), multicystic encephalomalacia (ME), subendymal pseudocyst. Diffuse white matter lesions of the cerebral hemispheres of the brain, accompanied by softening and spreading to the central and subcortical areas are more likely DFL, PHI and ME.
Prevention
Preventing or delaying premature birth is considered the most important step in decreasing the risk of PVL. Common methods for preventing a premature birth include self-care techniques (dietary and lifestyle decisions), bed rest, and prescribed anti-contraction medications. Avoiding premature birth allows the fetus to develop further, strengthening the systems affected during the development of PVL.An emphasis on prenatal health and regular medical examinations of the mother can also notably decrease the risk of PVL. Prompt diagnosis and treatment of maternal infection during gestation reduces the likelihood of large inflammatory responses. Additionally, treatment of infection with steroids (especially in the 24–31 weeks of gestation) have been indicated in decreasing the risk of PVL.
It has also been suggested that avoiding maternal cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
usage and any maternal-fetal blood flow alterations can decrease the risk of PVL. Episodes of hypotension or decreased blood flow to the infant can cause white matter damage.
Current Treatments
Currently, there are no treatments prescribed for PVL. All treatments administered are in response to secondary pathologies that develop as a consequence of the PVL. Because white matter injury in the periventricular region can result in a variety of deficits, neurologists must closely monitor infants diagnosed with PVL in order to determine the severity and extent of their conditions.Patients are typically treated with an individualized treatment. It is crucial for doctors to observe and maintain organ function: visceral organ failure can potentially occur in untreated patients. Additionally, motor deficits and increased muscle tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
are often treated with individualized physical and occupational therapy treatments.
Treatment Challenges
The fetal and neonatal brain is a rapidly changing, developing structure. Because neural structures are still developing and connections are still being formed at birth, many medications that are successful for treatment and protection in the adult central nervous system (CNS) are ineffective in infants. Moreover, some adult treatments have actually been shown to be toxic to developing brains.Future Treatments
Although no treatments have been approved for use in human PVL patients, a significant amount of research is occurring in developing treatments for protection of the nervous system. Researchers have begun to examine the potential of synthetic neuroprotectionNeuroprotection
Neuroprotection within the nervous system protects neurons from apoptosis or degeneration, for example following a brain injury or as a result of chronic neurodegenerative diseases....
to minimize the amount of lesioning in patients exposed to ischemic conditions.
Prognosis
The prognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
of patients with PVL is dependent on the severity and extent of white matter damage. Some children exhibit relatively minor deficits, while others have significant deficits and disabilities.
Minor Tissue Damage
Minor white matter damage usually is exhibited through slight developmental delays and deficits in posture, vision systems, and motor skills. Many patients exhibit spastic diplegiaSpastic diplegia
Spastic diplegia, historically known as Little's Disease, is a form of cerebral palsy that is a neuromuscular condition of hypertonia and spasticity in the muscles of the lower extremities of the human body, usually those of the legs, hips and pelvis...
, a condition characterized by increased muscle tone and spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
in the lower body. The gait of PVL patients with spastic diplegia exhibits an unusual pattern of flexing during walking.
Progression to More Serious Conditions
Those patients with severe white matter injury typically exhibit more extensive signs of brain damage. Infants with severe PVL suffer from extremely high levels of muscle tone and frequent seizures. Children and adults may be quadriplegicQuadriplegia
Tetraplegia, also known as quadriplegia, is paralysis caused by illness or injury to a human that results in the partial or total loss of use of all their limbs and torso; paraplegia is similar but does not affect the arms...
, exhibiting a loss of function or paralysis of all four limbs.
Cerebral Palsy
Many infants with PVL eventually develop cerebral palsyCerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
. The percentage of individuals with PVL who develop cerebral palsy is generally reported with significant variability from study to study, with estimates ranging from 20% to more than 60%. One of the reasons for this discrepancy is the large variability in severity of cerebral palsy. This range corresponds to the severity of PVL, which can also be quite variable. More white matter damage leads to more severe cerebral palsy; different subtypes are identified and diagnosed by a neurologist.
Despite the varying grades of PVL and cerebral palsy, affected infants typically begin to exhibit signs of cerebral palsy in a predictable manner. Typically, some abnormal neurological signs (such as those previously mentioned) are visible by the third trimester of pregnancy (28 to 40 weeks after conception), and definitive signs of cerebral palsy are visible by six to nine months of age.
Epilepsy
Another common but severe outcome of PVL patients is the development of epilepsyEpilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
. The link between the two is not entirely clear; however, it appears that both genetic and early environmental factors are involved. One study estimated that 47% of children with PVL also have epilepsy, with 78% of those patients having a form of epilepsy not easily managed by medication. Many of these affected patients exhibit some seizures, as well as spastic diplegia or more severe forms of cerebral palsy, before a diagnosis of epilepsy is made.
Frequency
Unfortunately, there are very few population-based studies on the frequency of PVL. As previously described, the highest frequency of PVL is seen in premature, very low birth weight infants. These infants are typically seen in the NICU in a hospital, with approximately 4-20% of patients in the NICU being affected by PVL. On a large autopsy material without selecting the most frequently detected PVL in male children with birth weight was 1500-2500 g., dying at 6–8 days of life. Diffuse brain damage with softening (diffus leucomalacia, DFL) are found more frequently in children weighing less than 1500 g. However, PVL is not a DFL.Animal Research
Animal models are frequently used to develop improved treatments for and a more complete understanding of PVL. A rat model that has white matter lesions and experiences seizures has been developed, as well as other rodents used in the study of PVL. These animal models can be used to examine the potential efficacy of new medications in the prevention and treatment of PVL.Clinical Research
Current clinical research ranges from studies aimed at understanding the progression and pathology of PVL to developing protocols for the prevention of PVL development. Many studies examine the trends in outcomes of individuals with PVL: a recent study by Hamrick, et al., considered the role of cystic periventricular leukomalacia (a particularly severe form of PVL, involving development of cysts) in the developmental outcome of the infant.Other ongoing clinical studies are aimed at the prevention and treatment of PVL: clinical trials testing neuroprotectants, prevention of premature births, and examining potential medications for the attenuation of white matter damage are all currently supported by NIH funding.