Cortical thickness and sub-cortical volumes in post-H1N1 narcolepsy type 1: A brain-wide MRI case-control study

Abstract

AbstractObjectiveThere was an increased incidence of Narcolepsy type 1(NT1) after the H1N1-mass vaccination in 2009/2010 which has been associated with the Pandemrix®-vaccine. We performed the first case-control comparison of MRI-based global and sub-cortical volume and cortical thickness in post-H1N1(largely Pandemrix®-vaccinated) NT1 patients compared with healthy controls.MethodsWe included 54 post-H1N1 NT1 patients (51 with confirmed hypocretin-deficiency; 48 H1N1-vaccinated with Pandemrix®; 39 females, mean age 21.8 ± 11.0 years) and 114 healthy controls (77 females, mean age 23.2 ± 9.0 years). 3T MRI brain scans were obtained, and the T1-weighted MRI data were processed using FreeSurfer. Group differences among three global and 10 sub-cortical volume measures and 34 cortical thickness measures for bilateral brain regions were tested using general linear models with permutation testing. We corrected for multiple testing with the Benjamini-Hochberg procedure with the false discovery rate at 5%.ResultsPatients had significantly thinner brain cortex bilaterally in the temporal poles (Cohen’s d=0.68,p=0.00080), entorhinal cortex (d=0.60,p=0.0018) and superior temporal gyrus (d=0.60,p=0.0020) compared to healthy controls. The analysis revealed no significant group differences for sub-cortical volumes.ConclusionsPost-H1N1(largely Pandemrix®-vaccinated) NT1 patients have significantly thinner cortex in temporal brain regions compared to controls. We speculate that this effect can be partly attributed to the hypothalamic neuronal change in NT1, including loss of function of the widely projecting hypocretin-producing neurons and secondary effects of the abnormal sleep-wake pattern in NT1. Alternatively, the findings could be specific for post-H1N1 (largely Pandemrix®-vaccinated) NT1 patients.