Periventricular Leukomalacia, by Dr. Anne Hansen.
Hello. My name is Anne Hansen, and I'm going to talk to you today about a common neurologic
complication of preterm babies-- namely periventricular leukomalacia. I will refer to it by its abbreviation,
PVL. In this lesson, we're going to cover incidence, pathology, risk factors, diagnosis,
presentation, and outcome of babies who develop PVL.
Incidence.
First, we'll start with the incidence of PVL. PVL occurs in the patient population of newborns
with birth weight less than 1,500 grams or gestational age less than 32 weeks. If you
look at patients who are diagnosed with PVL by autopsy, about one quarter of patients
in this population will be diagnosed with PVL. However, if you look at survivors, who
are typically diagnosed by head ultrasound, 15% will have the early presentation of echodensities
on head ultrasound, and about a third of those, or 5%, will develop echolucencies by head
ultrasound.
The discrepancy between the autopsy numbers of 25% and the head ultrasound numbers of
5-15%, are, of course, partially explained by the fact that the patients diagnosed by
autopsy had a higher severity of illness than the survivors. But there also has been a large
number of head ultrasounds that have missed the diagnosis of PVL, especially in earlier
machines that were less sensitive. Now that machines are more sensitive to diagnose PVL,
the number of cases that are missed and would need an MRI for diagnosis is becoming smaller.
Looking at Vermont Oxford data from 2009, patients less than 1,500 grams, 3% developed
cystic PVL. That's the echolucent form.
Pathology.
Understanding the pathogenesis of PVL. It's helpful to look at the diagram on the left,
in which we see the cerebral vascular supply of the newborn, and compare it to the pathological
specimen on the right that shows PVL. The picture on the left shows the system by which
newborns receive blood supply to their brain. There's a system of short penetrating arteries
that's very redundant, that provides blood to the cerebral cortex. And then, you can
see long penetrating arteries that provide blood supply into the deep periventricular
white matter. It's easy to look at these two pictures together and imagine that the problem
with PVL is that there's inadequate blood perfusion to the long penetrating arteries,
in a kind of watershed distribution theory, like adult stroke.
Another piece of the pathogenesis of PVL is related to the pressure and passive circulation
of some premature infants. If you look at this graph that has cerebral blood flow on
the y-axis, and mean arterial pressure on the x-axis, most of us live on the flat portion
of this graph, in which our mean arterial pressure can go up or down, but our cerebral
blood flow stays very constant. There are many preterm infants who live on the sloped
portion of this curve, such that any variation in mean arterial pressure converts immediately
to a decrease in cerebral blood flow. This is a very dangerous situation for the perfusion
of the brain, because as the blood pressure drops the cerebral blood flow will drop accordingly.
The pathogenesis of PVL also includes intrinsic vulnerability of cerebral white matter of
premature infants, the high metabolic demand of early differentiating oligodendroglial
cells, the sensitivity of free radical mediated cell death, or apoptosis, and is also closely
connected with infection and inflammation, especially involving cytokines.
Risk Factors.
The risk factors for PVL include in utero, perinatal, or postnatal hypoxia/ischemia,
and infection. Again, either pre- or postnatal.
Diagnosis.
The diagnosis of PVL is largely made by head ultrasound. We know that many cases of PVL
can be missed by head ultrasound. And so MRIs are especially helpful for detection of delayed
or decreased myelination.
Presentation, Management, and Prevention.
Now let's talk about PVL presentation and management. PVL presents silently. It typically
evolves over weeks. It can be diagnosed by cranial ultrasound or by MRI prior to the
development of any symptoms. Spasticity may be picked up as early as term, but typically
not until later. There is currently no treatment options for peri-ventricular leukomalacia.
Management consists of early identification and treatment of cognitive, motor, or sensory
impairments.
In terms of prevention of PVL there are not specific preventive approaches that we have
at this point. We try in general to maintain stable cerebral perfusion, maintain normal
intravascular volume, stable oxygenation and ventilation, and avoid large swings in systemic
hemodynamics. We also try to avoid an environment of infection or inflammation, including prompt
delivery if there are obstetric concerns for chorioamnionitis and postnatal treatment of
infections.
Outcome.
Now let's talk about the outcome for PVL. Large cystic lesions and ventricular dilation
strongly predict a neurologic deficit in the 60% to 90% range. Generally, motor function
is more impaired than cognitive and language function, and spastic diplegia is the most
common motor sequelae. Why do you think that might be?
If you look back to Mr. Homunculus-- or a slightly easier way to think through it is
in cross section-- the long fibers to the leg, trunk, arm, face, and mouth, track right
along this periventricular region that's affected by periventricular leukomalacia. If you have
relatively mild periventricular leukomalacia, it will affect the leg fibers and cause spastic
diplegia.
The more severe the PVL, the more fibers will be involved. At its most severe, it can involve
all the way up to the function of the mouth. PVL, less commonly, can cause global developmental
delay, mental retardation, and damage to visual, auditory, and somesthetic fibers.
Learning about PVL, it's hard not to realize the responsibility that we have in caring
for the brains of these preterm infants. To the degree that it's possible to provide stable
hemodynamics and aggressively treat infections, it is possible to improve the outcome of these
fragile infants. Your attention to these details over a short period of time really can improve
the neurologic outcome of these patients for the rest of their lives. Thank you.
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