Abstract Details

Title Decreased Cerebrospinal Fluid (CSF) Hypocretin 1 (Orexin A) Levels after Whole Brain Radiotherapy: A Candidate Biomarker for Radiation Encephalopathy

Topic Neuro-oncology

Presentation(s) P02 - (-)

Poster/Presentation
Number 164

Objective

Background BACKGROUND: Radiation encephalopathy is a side effect of whole brain radiation and can include clinically significant hypersomnia, the mechanism of which is unknown. Low CSF hypocretin levels are associated with clinical hypersomnia and narcolepsy, with very low levels associated with cataplexy. Low CSF hypocretin levels are found in alpha-synucleinopathies and after head injury, with hypocretin neurons appearing especially vulnerable to injury.

Design/Methods DESIGN/METHODS: We compared CSF hypocretin 1 levels from breast cancer patients who had received whole brain radiation and the levels from individuals without cerebral malignancy and radiation. None of the patients had tumors or MRI evidence of injury in the hypocretin neuronal field, ascending inputs to this region or in the region of the ascending arousal pathways. The CSF hypocretin levels were compared using a two-tailed Wilcoxon rank sum test and examined correlations between CSF hypocretin level and clinical parameters.

Results RESULTS: CSF hypocretin 1 (mean±SD) was significantly lower in patients after whole brain radiation (261.5±63.3 pg/ml, n=16) versus controls (321.4±41.1 pg/ml, n=14) (P=0.004). There was no correlation with age (range 35-81 years) (Pearson [sigma]=0.1137, P=0.5498), circadian time of CSF collection (range 09:00-18:12) (Pearson [sigma]=-0.3026, P=0.2546), and time from radiation therapy (range 0.1-55.4 months) (Pearson [sigma]=0.1832, P=0.4971).

Conclusions CONCLUSIONS: There is a significant reduction of CSF hypocretin after whole brain radiation. This is the first study to address the pathophysiology of post-radiation hypersomnolence. These findings may be important in determining the risk for specific patients and identifying therapies.

Authors/Disclosures
Nigel P. Pedersen, MBBS (University of California, Davis) PRESENTER	No disclosure on file
	No disclosure on file
Eric T. Wong, MD, FAAN (Rhode Island Hospital)	Dr. Wong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novocure. Dr. Wong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ZaiLab. Dr. Wong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Turning Point Therapeutics. Dr. Wong has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imvax. The institution of Dr. Wong has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novocure. The institution of Dr. Wong has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Turning Point Therapeutics. The institution of Dr. Wong has received research support from Novocure. Dr. Wong has received intellectual property interests from a discovery or technology relating to health care. Dr. Wong has received publishing royalties from a publication relating to health care.
	No disclosure on file

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