Study ObjectivesNarcolepsy type 1(NT1) is associated with loss of functioning hypocretin-producing neurons and an increase in histaminergic neuron numbers in the hypothalamus. These cell groups have largely overlapping projections to other brain regions, and may be associated with distributed patterns of secondary affection of sub-cortical and cortical gray matter. We performed a case-control comparison of MRI-based global and sub-cortical volume and cortical thickness in NT1 patients compared with healthy controls.MethodsWe processed T1-weighted brain MRI data from 54 NT1 patients (51 with confirmed hypocretin-deficiency; 39 females, mean age 21.8 ± 11.0 years) and 114 healthy controls (77 females, mean age 23.2 ± 9.0 years) 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%.ResultsNT1 patients 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.ConclusionsNT1 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.Statement of SignificanceNarcolepsy type 1 (NT1) patients have loss/dysfunction of hypocretin-producing neurons and increased histaminergic neurons number – cell groups which project widely to other brain regions. It is therefore plausible that other brain regions may be affected by the hypothalamic changes in NT1 patients. Compared to healthy controls, we show that NT1 patients have thinner cortex bilaterally in the entorhinal cortex, temporal poles and superior temporal gyrus (STG). STG play a role in hallucinations and entorhinal cortex and temporal poles in memory functions. Thinner cortex in these regions have been implicated in diseases sharing common features with NT1, like schizophrenia and obstructive sleep apnea. Further studies are needed to establish the clinical relevance and investigate possible causal effects using a longitudinal design.
