Prematurity is Most Strongly Associated with Periventricular Leukomalacia
The correct answer is C: Prematurity is the most strongly associated factor with periventricular leukomalacia (PVL), representing the primary risk factor and underlying pathophysiological mechanism for developing this condition. 1
Understanding the Clinical Context
The patient described exhibits scissoring of the legs (bilateral lower limb spasticity) with MRI-confirmed periventricular leukomalacia. While all the answer choices are related to PVL, the question asks what is most strongly associated with the diagnosis itself.
Why Prematurity is the Primary Association
Prematurity is the fundamental risk factor that creates the pathophysiological vulnerability for PVL to develop, with the incidence of severe periventricular hemorrhagic infarction reaching 30% in infants born at 22 weeks and decreasing to 3% at 28 weeks gestational age. 1
The immature cerebrovasculature of preterm infants lacks appropriate autoregulation of cerebral blood flow in response to hypoxic-ischemic insults, making the periventricular white matter particularly vulnerable during mid-to-late gestation. 2
PVL occurs predominantly in premature infants and represents a major precursor for neurological and intellectual impairment in this population. 2
Why the Other Options Are Consequences, Not Associations
Bilateral lower limb spasticity (Option B) is a characteristic clinical manifestation and consequence of PVL, not an associated risk factor. 1 It represents the motor outcome of the white matter injury, particularly when bilateral cystic PVL is present, which specifically predicts nonambulant cerebral palsy with severe motor impairment. 1
Static motor delay (Option A) is an outcome of PVL rather than an association with its development—it is a broad category that could result from many conditions. 1
Periventricular white matter changes on MRI (Option D) is the diagnostic finding itself, not an associated factor. This is what defines PVL radiologically.
Clinical Reasoning Algorithm
When evaluating what is "most strongly associated" with a diagnosis:
- Distinguish between cause/risk factors versus consequences/manifestations: Prematurity creates the vulnerability → PVL develops → Motor deficits result
- Identify the primary pathophysiological driver: The immature brain of preterm infants is the fundamental issue 2
- Recognize that diagnostic findings are not associations: MRI changes define the diagnosis but don't associate with it
Important Clinical Considerations
43% of infants with cystic PVL also have intraventricular hemorrhage (IVH), requiring monitoring for both conditions. 1
Serial imaging is essential as early changes may be subtle or absent initially. 1, 3
Cerebellar hemorrhage co-occurs in 10% of preterm infants with PVL and increases the risk of abnormal neurological outcomes 5-fold. 1, 3
Additional risk factors beyond prematurity include maternal obesity and chorioamnionitis, which increase PVL risk beyond that expected from prematurity alone. 4
The incidence of cerebral palsy in preterm infants has decreased 3-fold from the early 1990s to early 2000s, largely due to a 93% reduction in cystic periventricular leukomalacia. 5