Wednesday, February 13, 2013

A Primer on Perinatal Telencephalic Leukoencephalopathy

In my last post, it was correctly pointed out by two astute readers that the Netter figure demonstrating brain malformations included an entity which is NOT a brain malformation: perinatal telencephalic leukoencephalopathy (PTL). PTL results from a perinatal hypoxic insult and is not a malformation per se, as the term "malformation" should really be reserved for anatomic abnormalities resulting from developmental defects. The cerebral white matter in the fetus and neonate is particularly susceptible to injury as it is metabolically highly active. Ischemia of the germinal matrix, subependymal region, and periventricular white matter can lead to periventricular leukomalacia that may even calcify and result in periventricular mineralization (1). At its most extreme, PTL may take the form of hemispheric multicystic leukomalacia in which the cerebral hemispheric white matter is replaced by multiloculated cysts separated by strands of fibroglial tissue.(2)

1. Fuller, Gregory N. and Goodman, J. Clay. Practical Review of Neuropathology. Lippincott 2001. Page 315.
2. Haberland, Catherine. Clinical Neuropathology: Text and Atlas. Demos Publishing 2007. Page 303.


shipcolldoc said...

There are several terms out there with overlapping meaning, such as "periventricular leukomalacia". Perinatal Telencephalic Leukoencephalopathy as a term or as a diagnosis was coined by Floyd Gilles and described in a series of papers with an animal model as well as human autopsy tissues. PTL was strongly associated with exposure to Gram-negative endotoxins, secondary to infection in the mother (who might even be asymptomatic, as with a mild cystitis), in the placenta, or in the fetus itself. The endotoxin crosses the placental barriers, and probably has vasoconstrictive actions so that ultimately the damage is ischemic. Becky Folkerth has done nice follow-up studies on the original Gilles et alia work.

Floyd's original descriptions were of white matter that was more soft than surrounding gray matter, such that it "sank" on cut surfaces of formalin-fixed brain (if you use an alcohol-based fixative you lose this gross change). Histologically there was gliosis with hypertrophic astrocytes, glial cell damage which was termed "acutely damaged glia" and which in modern terms might be thought of as apoptosis, and deposits of what I think has been shown to be mostly carbohydrate as "amphophilic globules" (because they were in-between eosinophilic and basophilic). The globules are sometimes mistaken for calcifications but are not mineral.

I'm indebted for my understanding of this not only to Floyd himself for his papers and books on the subject, but also to Tessa Hedley-Whyte, who worked with Floyd at Boston Children's before eventually moving across town to MGH where she was one of my teachers in my residency.

Brian E. Moore, MD said...

Thank you, shipcolldoc. Ellison and Love has a picture of these "amphophilic globules" in the second edition of their text.