Periventricular Leukomalacia
Periventricular Leukomalacia Overview
- Pathophysiologic events (eg, hypoxia, ischemia, infection, trauma), especially during a period of white matter vulnerability at ~ 24 - 34 weeks gestation, result in chronic, persistent white matter damage in the periventricular region, called periventricular leukomalacia.
- Periventricular leukomalacia is the leading cause of cerebral palsy, which is a common childhood onset movement disorder that affects:
- Movement: weakness, tone (spasticity or flaccidity), tremor, involuntary movements
- Coordination: ataxia (lack of muscle coordination), fine motor skills (eg, writing)
- Gait: eg, toe-walking, "scissored gait"
- Note that additional neurological domains may be affected (eg, cognitive, sensory, language) and additional pathologies can occur, such as seizures.
Diagnosis
- Ultrasound or MRI is used to identify necrotic and cystic lesions and periventricular gliosis.
Pathophysiology
- In preterm infants, neurological damage leads to white matter injury (periventricular leukomalacia); whereas, in term infants, the cerebral cortex is more susceptible to injury (leading to stroke-like distributions of injury).
- Periventricular leukomalacia comprises periventricular necrosis and diffuse gliosis (astrogliosis and microgliosis) with/without cystic formation.
- Large areas of focal necrosis lead to cyst formation: macroscopic necrosis is > 1 mm and evolves (over several weeks) into a cyst.
- Tiny areas of focal necrosis lead to gliosis: microscopic necrosis < 1 mm and evolves (over several weeks) into gliosis.
- Neurologic injury triggers activated microglia to release toxic byproducts. These byproducts can injure the robust population of premyelinating oligodendroglia that are present between weeks ~ 24 - 34 weeks gestation. The periventricular region of premyelinating oligodendroglia appear to be especially vulnerable to this injury.
References
- Back, Stephen A., Ning Ling Luo, Natalya S. Borenstein, Joel M. Levine, Joseph J. Volpe, and Hannah C. Kinney. “Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury.” Journal of Neuroscience 21, no. 4 (February 15, 2001): 1302–12. https://doi.org/10.1523/JNEUROSCI.21-04-01302.2001.
- “Cerebral Palsy: Hope Through Research | National Institute of Neurological Disorders and Stroke.” Accessed May 28, 2018. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Hope-Through-Research/Cerebral-Palsy-Hope-Through-Research.
- Deng, Wenbin, Jeanette Pleasure, and David Pleasure. “Progress in Periventricular Leukomalacia.” Archives of Neurology 65, no. 10 (October 2008): 1291–95. https://doi.org/10.1001/archneur.65.10.1291.
- Kinney, Hannah C., Robin L. Haynes, Gang Xu, Sarah E. Andiman, Rebecca D. Folkerth, Lynn A Sleeper, and Joseph J.
- Volpe. “Neuron Deficit in the White Matter and Subplate in Periventricular Leukomalacia.” Annals of Neurology 71, no. 3 (March 2012): 397–406. https://doi.org/10.1002/ana.22612.
- Zaghloul, Nahla, Hardik Patel, and Mohamed Nagy Ahmed. “A Model of Periventricular Leukomalacia (PVL) in Neonate Mice with Histopathological and Neurodevelopmental Outcomes Mimicking Human PVL in Neonates.” PLoS ONE 12, no. 4 (April 13, 2017). https://doi.org/10.1371/journal.pone.0175438.