How are resting-state networks and cognitive performance affected following treatment for singular brain metastasis?
27th October 2021
Martin Kocher, Christiane Jockwitz, Christoph Lerche, Michael Sabel, Philipp Lohmann, Gabriele Stoffels, Christian Filss, Felix M. Mottaghy, Maximilian I. Ruge, Gereon R. Fink, Nadim J. Shah, Norbert Galldiks, Svenja Caspers and Karl-Josef Langen
It is known that long-term survivors of whole brain radiation (WBRT) are at significant risk
for developing cognitive deficits. However, our understanding of the underlying pathophysiological mechanisms causing this is limited.
This case report used resting-state functional MRI to investigate the integrity of brain networks following resection of a brain metastasis and WBRT in a female patient who survived for more than 10 years after treatment.
The patient suffered from a left frontal non-small cell lung cancer (NSCLC) brain metastasis, was treated with resection and postoperative WBRT (30.0 in 3.0Gy fractions) in 2008, and stayed free from recurrence in- and outside the brain for a follow-up period of 11 years.
During the 11 years, structural magnetic resonance imaging (MRI) and amino acid [O-(2-[18F]fluoroethyl)-L-tyrosine] positron emission tomography (FET PET) were repeatedly acquired. At the last follow up, neurocognitive functions and resting-state functional connectivity (RSFC) using resting-state fMRI were additionally assessed. Within-network and inter-network connectivity of seven resting-state networks were computed from a connectivity matrix. All measures were compared to a group of 10 healthy female subjects closely matched for age and education level.
At the 11-year follow up, T2/FLAIR MR images of the patient showed extended regions of hyper-intensities that mainly covered the white mater of the bilateral dorsal frontal and parietal lobes, while sparing most of the temporal lobes. Furthermore, compared to the healthy subjects, the patient performed significantly worse in all cognitive domains that included executive function, attention and processing speed. However, verbal working memory, verbal episodic memory and visual working memory were left mostly unaffected.
The connectivity matrix showed a heavily disturbed pattern with a widely distributed, scattered loss of RSFC. The within-network RSFC revealed a significant loss of connectivity within all seven networks, with the dorsal attention and fronto-parietal control networks being most severely affected. In addition, the inter-network RSFC was found to be significantly reduced for the visual, somato-motor, and dorsal and ventral attention networks.
This report supports the observation that treatment with WBRT may lead to extended white matter damage and cause severe disruption of the RSFC in multiple resting-state networks. Furthermore, executive functioning, which is assumed to depend on the interaction of several networks, may be severely impaired following WBRT, along with the well-recognised deficits in memory function.
Although this case report assumes that the presented patient suffered the typical course of image changes and side effects induced by WBRT, more studies are needed to confirm these findings.
Origional publication