Citations

Background: Spinal cord (SC) atrophy is a key imaging biomarker of progressive multiple sclerosis (MS). Progressive MS is more common in men and postmenopausal women. Objective: Investigate the impact of sex and menopause on SC measurements in persons with MS (pwMS). Methods: In pwMS and age- and sex-matched controls, upper cervical SC area from brain MRI (UCC brain ) was obtained. Impact of sex and menopause on UCC brain (adjusted for total intracranial volume) and its association with progression and disability, including MS functional composite (MSFC), were investigated. Results: UCC brain was smaller in pwMS ( n = 118, 51.4 ± 5.3 mm 2 ) than controls ( n = 118, 54.2 ± 4.4 mm 2 , p < 0.001) and inversely correlated with older age in pwMS ( r = −0.24, p = 0.010) but not in controls ( r = −0.025, p = 0.786). In 173 pwMS (413 brain MRIs), UCC brain was smaller in men (49.5 ± 5.9 mm 2 ) than women (51.6 ± 5.5 mm 2 , p = 0.001), postmenopausal women (49.4 ± 5.6 mm 2 ) than premenopausal women (52.9 ± 4.1 mm 2 , p < 0.001), and progressive (47.5 ± 5.6 mm 2 ) than relapsing MS (52.1 ± 5.2 mm 2 , p < 0.001). UCC brain also correlated with disease duration ( r = −0.39, p < 0.001), 9-hole peg test ( r = −0.26, p = 0.005), and severe ambulatory disability (Expanded Disability Status Scale ⩾6) ( r = −0.27, p < 0.001). Conclusion: UCC brain , a biomarker of progressive MS, is inversely associated with age, disease duration, male sex, and menopause, highlighting the potential impact of sex and hormones on neurodegeneration in MS.

Abstract This study aimed to evaluate the effect of intrathecal (IT) recombinant human arylsulfatase A (rhASA) on magnetic resonance imaging (MRI)‐assessed brain tissue changes in children with metachromatic leukodystrophy (MLD). In total, 510 MRI scans were collected from 12 intravenous (IV) rhASA‐treated children with MLD, 24 IT rhASA‐treated children with MLD, 32 children with untreated MLD, and 156 normally developing children. Linear mixed models were fitted to analyze the time courses of gray matter (GM) volume and fractional anisotropy (FA) in the posterior limb of the internal capsule. Time courses for demyelination load and FA in the centrum semiovale were visualized using locally estimated scatterplot smoothing regression curves. All assessed imaging parameters demonstrated structural evidence of neurological deterioration in children with MLD. GM volume was significantly lower at follow‐up (median duration, 104 weeks) in IV rhASA‐treated versus IT rhASA‐treated children. GM volume decline over time was steeper in children receiving low‐dose (10 or 30 mg) versus high‐dose (100 mg) IT rhASA. Similar effects were observed for demyelination. FA in the posterior limb of the internal capsule showed a higher trend over time in IT rhASA‐treated versus children with untreated MLD, but FA parameters were not different between children receiving the low doses versus those receiving the high dose. GM volume in IT rhASA‐treated children showed a strong positive correlation with 88‐item Gross Motor Function Measure score over time. In some children with MLD, IT administration of high‐dose rhASA may delay neurological deterioration (assessed using MRI), offering potential therapeutic benefit.

AbstractBackgroundFood intake is regulated by homeostatic and hedonic systems that interact in a complex neuro‐hormonal network. Dysregulation in energy intake can lead to obesity (OB) or anorexia nervosa (AN). However, little is known about the neurohormonal response patterns to food intake in normal weight (NW), OB, and AN.Material & MethodsDuring an ad libitum nutrient drink (Ensure®) test (NDT), participants underwent three pseudo‐continuous arterial spin labeling (pCASL) MRI scans. The first scan was performed before starting the NDT after a > 12 h overnight fast (Hunger), the second after reaching maximal fullness (Satiation), and the third 30‐min after satiation (postprandial fullness). We measured blood levels of ghrelin, cholecystokinin (CCK), glucagon‐like peptide (GLP‐1), and peptide YY (PYY) with every pCASL‐MRI scan. Semiquantitative cerebral blood flow (CBF) maps in mL/100 gr brain/min were calculated and normalized (nCBF) with the CBF in the frontoparietal white matter. The hypothalamus (HT), nucleus accumbens [NAc] and dorsal striatum [DS] were selected as regions of interest (ROIs).ResultsA total of 53 participants, 7 with AN, 17 with NW (body‐mass index [BMI] 18.5–24.9 kg/m2), and 29 with OB (BMI ≥30 kg/m2) completed the study. The NW group had a progressive decrease in all five ROIs during the three stages of food intake (hunger, satiation, and post‐prandial fullness). In contrast, participants with OB showed a minimal change from hunger to postprandial fullness in all five ROIs. The AN group had a sustained nCBF in the HT and DS, from hunger to satiation, with a subsequent decrease in nCBF from satiation to postprandial fullness. All three groups had similar hormonal response patterns with a decrease in ghrelin, an increase in GLP‐1 and PYY, and no change in CCK.ConclusionConditions of regulated (NW) and dysregulated (OB and AN) energy intake are associated with distinctive neurohormonal activity patterns in response to hunger, satiation, and postprandial fullness.

High-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) shows promise as a treatment for treatment-resistant depression in adolescents. Conventional rTMS coil placement strategies include the 5 cm, the Beam F3, and the magnetic resonance imaging (MRI) neuronavigation methods. The purpose of this study was to use electric field (E-field) models to compare the three targeting approaches to a computational E-field optimization coil placement method in depressed adolescents. Ten depressed adolescents (4 females, age: 15.9±1.1) participated in an open-label rTMS treatment study and were offered MRI-guided rTMS five times per week over 6–8 weeks. Head models were generated based on individual MRI images, and E-fields were simulated for the four targeting approaches. Results showed a significant difference in the induced E-fields at the L-DLPFC between the four targeting methods (χ2=24.7, p<0.001). Post hoc pairwise comparisons showed that there was a significant difference between any two of the targeting methods (Holm adjusted p<0.05), with the 5 cm rule producing the weakest E-field (46.0±17.4V/m), followed by the F3 method (87.4±35.4V/m), followed by MRI-guided (112.1±14.6V/m), and followed by the computational approach (130.1±18.1V/m). Variance analysis showed that there was a significant difference in sample variance between the groups (K2=8.0, p<0.05), with F3 having the largest variance. Participants who completed the full course of treatment had median E-fields correlated with depression symptom improvement (r=−0.77, p<0.05). E-field models revealed limitations of scalp-based methods compared to MRI guidance, suggesting computational optimization could enhance dose delivery to the target.