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New evidence from St. Jude investigators strengthens the link between a rare, devastating complication of brain tumor surgery and disruption of a pathway that functions like a fiber optic cable connecting important structures in the brain.
The complication is posterior fossa syndrome (PFS). Named for the region of the brain at the base of the skull, the syndrome strikes about 25 percent of young patients who undergo surgery to remove malignant brain tumors there, primarily a type of tumor called a medulloblastoma. A day or two into an apparently normal recovery, affected patients abruptly stop talking and become increasingly irritable and emotionally unstable. In severe cases, they must rely on feeding tubes for nutrition and tracheostomies for breathing support. Rehabilitation usually takes weeks or months, and patients are often left with lingering physical and intellectual problems.
Despite more than two decades of research, PFS remains a puzzling problem.
“Posterior fossa syndrome is an extreme example of how brain function is altered in this population,” said Robert Ogg, PhD, Radiological Sciences, and the study’s senior author. “We have no clear idea why this happens.”
This St. Jude study, published in the November issue of Brain, adds to growing evidence that disruption of the proximal dentatothalamocortical tracts in the brain plays a key role in PFS. These tracts are located on both sides of the brainstem, close to where medulloblastomas and certain other tumors develop.
Dentatothalamocortical tracts are the primary communication link between the cerebellum and the cerebral hemispheres, which house regions of the brain charged with advanced functions like language, thought and emotional regulation. Other investigators have proposed disruption of the dentatothalamocortical tracts as a risk factor for PFS.
This study marks the first time a tool known as diffusion tensor imaging (DTI) was combined with standard magnetic resonance imaging (MRI) to compare changes in the brains of patients who did and did not develop PFS. DTI is an advanced neuro-imaging technique that measures water diffusion in brain tissue, particularly in the nerve fibers that brain cells rely on for communication. The direction and magnitude of water movement along these fibers can provide clues about the health of nerve fibers and how they are functioning. This research focused on 13 patients with PFS and 13 without. All underwent MRI and DTI shortly after the surgery and again several weeks later.
In patients with PFS, DTI revealed bilateral abnormalities of the proximal dentatothalamocortical tracts as they course through the superior cerebellar peduncles. The superior cerebellar peduncles are part of the dentatothalamocortical tracts that connect the cerebellum to the midbrain. They are thought to be vulnerable to injury from the tumor itself or the surgery to remove it.
“There is strong evidence to suggest disruption of the axons traveling through the superior cerebellar peduncles is associated with posterior fossa syndrome,” said the study’s lead author, E. Brannon Morris, MD, Oncology.
DTI also picked up abnormalities in the cerebral hemispheres, although those regions are not close to the surgery site. The finding suggests injury near the brainstem may affect cerebral hemisphere function via the dentatothalamocortical pathway. The injury might also play a role in the behavioral and cognitive deficits seen in PFS.
Exactly what causes the disruption remains unclear, Morris said, adding that sometimes there is no apparent direct surgical injury. “The cerebellum is essentially a timing instrument, so there may be an upstream timing mechanism that has been perturbed leading to disruption of higher cognitive and behavioral function,” he said. Although results of the study suggest specific involved structures, until the syndrome’s cause is better understood, prevention and treatment will remain difficult, Morris said.
Other St. Jude authors of this paper are Nicholas Phillips, MD, PhD, and Zoltan Patay, MD, PhD, both of Radiological Sciences; Amar Gajjar, MD, Oncology co-chair; Dana Wallace, Biostatistics; Frederick Boop, MD, and Robert Sanford, MD, both of Surgery; and Kirsten Ness, PhD, Epidemiology and Cancer Control.
The research was supported in part by grants from the National Institutes of Health Cancer Center Support Grant, the National Institute of Child Health and Human Development and ALSAC.