Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

BACKGROUND/OBJECTIVES: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB). SUBJECTS/METHODS: Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models. RESULTS: Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes. CONCLUSION: T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen-level dependent response to glucose ingestion.

OBJECTIVE: In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS: Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS: Children with obesity (N = 11) had longer T2 relaxation times, consistent with gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION: Imaging signs of hypothalamic gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

Sleep onset uncovers thalamic abnormalities in patients with idiopathic generalised epilepsy.

The thalamus is crucial for sleep regulation and the pathophysiology of idiopathic generalised epilepsy (IGE), and may serve as the underlying basis for the links between the two. We investigated this using EEG-fMRI and a specific emphasis on the role and functional connectivity (FC) of the thalamus. We defined three types of thalamic FC: thalamocortical, inter-hemispheric thalamic, and intra-hemispheric thalamic. Patients and controls differed in all three measures, and during wakefulness and sleep, indicating disorder-dependent and state-dependent modification of thalamic FC. Inter-hemispheric thalamic FC differed between patients and controls in somatosensory regions during wakefulness, and occipital regions during sleep. Intra-hemispheric thalamic FC was significantly higher in patients than controls following sleep onset, and disorder-dependent alterations to FC were seen in several thalamic regions always involving somatomotor and occipital regions. As interactions between thalamic sub-regions are indirect and mediated by the inhibitory thalamic reticular nucleus (TRN), the results suggest abnormal TRN function in patients with IGE, with a regional distribution which could suggest a link with the thalamocortical networks involved in the generation of alpha rhythms. Intra-thalamic FC could be a more widely applicable marker beyond patients with IGE.