Age dependence of macro-and microstructural modulation of hypothalamic nuclei in Narcolepsy Type 1 - an in vivo 7T MRI study
Abstract
Study objectives: Previous imaging studies have produced conflicting results regarding structural changes to the hypothalamus in patients with narcolepsy type 1 (NT1). Our aim was to investigate volumetric and microstructural alterations across hypothalamic nuclei using ultrahigh-field magnetic resonance imaging (MRI). Methods: Fifteen NT1 patients (cerebrospinal fluid orexin ≥ 110 pg/mL) and 30 age-and sex matched controls underwent high-resolution 7 Tesla MRI. Hypothalamic nuclei were segmented using a validated atlas, and normalized volumes and T1 values were compared between the two groups using univariate analyses and linear mixed models (LMM). Results: LMM revealed group-specific, nucleus-dependent age trajectories for both volume (p ≤ 0.001) and T1 values (p = 0.015). Post-hoc analyses revealed divergent age-related volume trajectories between groups in the lateral hypothalamus (LH) and the paraventricular nucleus (PaVN), all pFDR < 0.05. LH volume was increased in younger patients compared to younger controls and decreased in older patients compared to older controls. Younger patients exhibited higher volumes in the LH and ventromedial nucleus (VM) than controls. The covariance between LH and VM volumes was significantly stronger in patients than in controls. For T1, age-related trajectories diverged between groups in the suprachiasmatic (SC) and dorsomedial (DM) nuclei. Conclusions: Hypothalamic involvement in NT1 is nucleus-specific, affecting several nodes of the orexin network (LH, VM, PaVN, SC, DM) in an age-dependent, non-monotonic manner across volume and microstructure. These findings are consistent with a biphasic hypothesis of early tissue swelling, particularly in the LH, followed by a subsequent decrease in volume.
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BibTeX
@misc{ricci2026dependence,
title = {{Age dependence of macro-and microstructural modulation of hypothalamic nuclei in Narcolepsy Type 1 - an in vivo 7T MRI study}},
author = {Veronica Ricci and Benoit Testud and Coleen Roger and Hugo Dary and Kahina Hammam and Yves Dauvilliers and Fabrice Bartolomei and Maxime Guye and Jean-Philippe Ranjeva and Isabelle Lambert},
howpublished = {HAL},
year = {2026},
month = sep,
url = {https://hal.science/hal-05749797v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Age dependence of macro-and microstructural modulation of hypothalamic nuclei in Narcolepsy Type 1 - an in vivo 7T MRI study
AU - Veronica Ricci
AU - Benoit Testud
AU - Coleen Roger
AU - Hugo Dary
AU - Kahina Hammam
AU - Yves Dauvilliers
AU - Fabrice Bartolomei
AU - Maxime Guye
AU - Jean-Philippe Ranjeva
AU - Isabelle Lambert
PY - 2026
DA - 2026/09/11
PB - HAL
UR - https://hal.science/hal-05749797v1
AB - Study objectives: Previous imaging studies have produced conflicting results regarding structural changes to the hypothalamus in patients with narcolepsy type 1 (NT1). Our aim was to investigate volumetric and microstructural alterations across hypothalamic nuclei using ultrahigh-field magnetic resonance imaging (MRI). Methods: Fifteen NT1 patients (cerebrospinal fluid orexin ≥ 110 pg/mL) and 30 age-and sex matched controls underwent high-resolution 7 Tesla MRI. Hypothalamic nuclei were segmented using a validated atlas, and normalized volumes and T1 values were compared between the two groups using univariate analyses and linear mixed models (LMM). Results: LMM revealed group-specific, nucleus-dependent age trajectories for both volume (p ≤ 0.001) and T1 values (p = 0.015). Post-hoc analyses revealed divergent age-related volume trajectories between groups in the lateral hypothalamus (LH) and the paraventricular nucleus (PaVN), all pFDR < 0.05. LH volume was increased in younger patients compared to younger controls and decreased in older patients compared to older controls. Younger patients exhibited higher volumes in the LH and ventromedial nucleus (VM) than controls. The covariance between LH and VM volumes was significantly stronger in patients than in controls. For T1, age-related trajectories diverged between groups in the suprachiasmatic (SC) and dorsomedial (DM) nuclei. Conclusions: Hypothalamic involvement in NT1 is nucleus-specific, affecting several nodes of the orexin network (LH, VM, PaVN, SC, DM) in an age-dependent, non-monotonic manner across volume and microstructure. These findings are consistent with a biphasic hypothesis of early tissue swelling, particularly in the LH, followed by a subsequent decrease in volume.
ER -