Purpose
Repetitive Transcranial Magnetic Stimulation (rTMS) has been demonstrated to be effective in body weight control in individuals with obesity. Most clinical trials on rTMS provided a ...reassuring safety profile. In the present work, we present an extensive analysis on both severe and mild Adverse Events (AEs) in obese individuals treated with rTMS.
Methods
We examined the intensity, duration, correlation with the treatment, up to 1 year after the end of rTMS treatment.
Results
Descriptive analysis included a total of 63 subjects undergoing a 5-week deep rTMS experimental treatment for obesity (age 48.3 ± 10.4 years; BMI 36.3 ± 4.4 kg/m
2
): 31 patients were treated with high-frequency rTMS (HF), 13 with low-frequency rTMS (LF), and 19 were sham treated (Sham). Thirty-two subjects (50.8%) reported a total of 52 AEs, including mainly moderate (51.9%) events. The most frequently reported side effects were headaches of moderate intensity (40.4%) and local pain/discomfort (19.2%) and resulted significantly more frequent in HF group compared to other groups (
p
< 0.05). No significant differences among groups were found for the other reported AEs: drowsiness, insomnia, paresthesia, vasovagal reactions, hypertensive crisis. No AEs potentially related to the rTMS arised up to 1 year from the end of the treatment.
Conclusions
This is the first comprehensive safety analysis in obese patients treated with rTMS. The analysis did not reveal any unexpected safety concerns. Only headaches and local pain/discomfort have been significantly more frequent in the HF group, confirming the good tolerability of rTMS even in the obese population potentially more susceptible to side effects of brain stimulation.
Highlights
A safety analysis in obese individuals treated with TMS did not reveal any unexpected safety concern up to 1 year after the end of the treatment.
Only headache and local pain/discomfort have been significantly more frequent in the high-frequency TMS-treated group compared with low-frequency and sham-treated groups.
TMS exhibits a good safety profile in the obese population potentially more susceptible to side effects of brain stimulation.
Aim
To test the hypothesis that deep transcranial magnetic stimulation (dTMS) reduces food craving and causes weight loss via neuromodulation.
Materials and methods
This pilot study was designed as a ...randomized, double‐blind, sham‐controlled study. A total of 33 obese people (nine men, 24 women, mean age 48.1 ± 10.6 years, body mass index BMI 36.9 ± 4.7 kg/m2) were randomized and completed the study: 13 participants underwent a 5‐week treatment with high‐frequency (HF) dTMS (18 Hz; HF group), 10 were treated with low‐frequency (LF) dTMS (1 Hz; LF group), and 10 were sham‐treated (sham group). Food craving, and metabolic and neuro‐endocrine variables were evaluated at baseline, after the 5‐week treatment, and at follow‐up visits (1 month, 6 months, 1 year after the end of treatment).
Results
The mixed‐model analysis for repeated measures showed a significant interaction of time and groups for body weight (P = 0.001) and BMI (P = 0.001), with a significant body weight (−7.83 ± 2.28 kg; P = 0.0009) and BMI (−2.83 ± 0.83, P = 0.0009) decrease in the HF versus the sham group. A decreasing trend in food craving in the HF versus the LF and sham groups (P = 0.073) was observed. A significant improvement of metabolic and physical activity variables was found (P < 0.05) in the HF group.
Conclusions
We demonstrated the safety and efficacy of dTMS, in addition to physical exercise and a hypocaloric diet, in reducing body weight for up to 1 year in obese people. We hypothesize that a possible mechanism of HF dTMS treatment is modulation of the dopaminergic pathway and stimulation of physical activity.
Purpose
Aims of the present study were to investigate a wide array of psychological symptoms through validated psychometric tests, before and after 5 weeks of deep Transcranial Magnetic Stimulation ...(dTMS) in individuals with obesity, and to identify possible relationships with neuroendocrine parameters.
Methods
Forty-five patients with obesity (33 F, 12 M; age 48.8 ± 9.9 years; body wt 97.6 ± 14.2 Kg; BMI 36.2 ± 4.2) were randomized into two groups: 26 received high frequency (HF) dTMS and 19 Sham stimulation for 5 weeks. At baseline and after the 5-week treatment, all patients underwent the following psychometric evaluations: Food Cravings Questionnaire-Trait (FCQ-T) and its subscales, Barratt Impulsiveness Scale-11 (BIS-11), State and Trait Anxiety Inventory (STAI-y1 and STAI-y2), and Beck Depression Inventory (BDI). Hormonal and neuroendocrine markers were assessed at the first and last dTMS session.
Results
By adjusting for baseline variables and treatment arms, a significant decrease in body wt and BMI was found in HF group, both with univariate (
p
= 0.019) and multivariate analyses (
p
= 0.012). Impulsivity significantly decreased in HF group, both with univariate (
p
= 0.031) and multivariate analyses (
p
= 0.011). A positive association between the impulsivity score change and the leptin level variation (
p
= 0.031) was found.
Conclusion
The decrease of impulsivity together with the BMI reduction in individuals with obesity, treated with real stimulation, suggests that impulsivity may be a risk factor for obesity. Treatment with dTMS revealed to be effective in reducing both BMI and impulsivity by enhancing inhibitory capacity of Pre-Frontal Cortex (PFC), and modulating neuroendocrine system, especially leptin.
Aims
Obesity is known to be associated with an altered thermoregulation as well as a dysregulation of sympathetic nervous system (SNS). Considering the ability of deep transcranial magnetic ...stimulation (dTMS) to modulate the SNS, we hypothesized a potential role of dTMS in affecting thermoregulation in obesity. Aims of the study were to monitor the effect of a single session of dTMS on body temperature in subjects with obesity, and to correlate the dTMS-induced changes in body temperature with activation of the SNS (epinephrine and norepinephrine release).
Methods
Twenty-nine subjects with obesity 5 M, 24 F; age 50 (IQR: 58, 38) yrs; BMI 36.1 (IQR: 33.9, 38.7) kg/m
2
were randomized into 2 groups receiving a single session of high frequency stimulation (HF) or sham stimulation. Under neutral thermal conditions, infrared thermography was utilized to assess bilateral fingernail-beds and abdominal temperature.
Results
During a single session HF, the average temperature of both fingernail-beds decreased. Right-hand temperature difference was statistically greater in HF
vs
Sham: median = – 1.45 (IQR: – 2.0, – 1.0) °C for HF,
p =
0.009. While temperature variation in the fingernail-bed of left hand was not statistically significant in HF compared to Sham: median = – 1.26 (IQR: – 1.6, –0.5) °C,
p =
0.064. Concurrently, when estimating the effect of norepinephrine variation on temperature change of fingernail-bed of left hand, a borderline significant positive association was estimated (beta = 1.09,
p =
0.067) in HF.
Conclusions
Deep TMS revealed to be effective in modulating temperature in subjects with obesity, partially reversing obesity-induced alterations in heat production and dissipation with a potential SNS-mediated mechanism.
Purpose
In obesity, metabolic and voluntary factors regulate appetite, and a dysregulation of the reward pathway was demonstrated in all addiction disorders. Deep transcranial magnetic stimulation ...(dTMS) is already used to modulate cerebral dopamine activation in neuro-psychiatric diseases. We presently assess the acute effect of high frequency (HF) and low frequency (LF) dTMS on the modulation of the main neuropeptides and neurotransmitters involved in the reward pathway in obese subjects.
Methods
This study was designed as a double-blind, sham-controlled, randomized clinical trial. Thirty-three obese patients (9 males, 24 females, age 48.1 ± 10.6, BMI 36.4 ± 4.7) were enrolled in the study. All patients were studied during a single dTMS session and blood aliquots were drawn before and after a single dTMS session. Metabolic and neuro-endocrine parameters were evaluated before and after: (1) 18 Hz dTMS (HF, 13 patients); (2) 1 Hz dTMS (LF, 10 patients); (3) Sham treatment (Sham, 10 patients).
Results
No statistically significant variations in metabolic parameters, systolic and diastolic blood pressure, and heart rate were shown acutely. HF showed a significant increase of β-endorphin compared to other groups (
p
= 0.048); a significant increase of ghrelin in LF (
p
= 0.041) was also demonstrated.
Conclusions
A single session of HF dTMS treatment determines in obese subjects an acute increase of β-endorphin level, indicating an activation of the reward pathway. The present findings constitute proof of principle for a potential application of this methodology in obesity treatment.
Aims
Primary outcome of this observational study was to compare weight changes in two groups of overweight and obese individuals: subjects who had a diet prescribed on the base of resting energy ...expenditure (REE) measured by indirect calorimetry and subjects whose REE was estimated by a predictive equation. In addition, we analyzed differences in weight and metabolic parameter variation in subjects with and without an adequate to predicted REE.
Methods
We retrospectively analyzed data of 355 overweight and obese patients: 215 on a diet based on REE measured by indirect calorimetry and 140 following a diet based on REE estimated by the Harris–Benedict equation. Anthropometric and metabolic parameters were evaluated for 18 months from baseline. Propensity score adjustment was used to adjust for known differences between the groups being compared.
Results
A significant greater decrease in body weight was observed in the group that underwent indirect calorimetry compared to the group that did not undergo it (
p
< 0.001). No significant differences were observed between patients with not adequate to predicted REE compared to patients with adequate to predicted REE.
Conclusions
A weight reduction program based on REE measurement appears more effective than a dietary program based on predictive formulas. This study suggests the routine use of indirect calorimetry in all weight reduction procedures.
Cocoa helps maintain endothelium-dependent vasodilation; consumption of hazelnuts has been associated with reduced cardiovascular disease risk. This study assesses the effects of hazelnuts and cocoa ...on vascular reactivity and metabolic profile. Sixty-one healthy volunteers, examined in a randomised, controlled, two-week intervention, received one of six breakfast integrations containing either hazelnuts, cocoa, both or none. Consumption of unpeeled hazelnuts improved HDL-cholesterol (+7.3%, p = .01 vs. baseline, p = .02 vs. control). Brachial artery peak systolic velocities (PSV) at rest increased with hazelnut integrations by 43.4% (p = .04 vs. control) and hazelnut-cocoa integrations by 26.4% (p = .01 vs. control). PSV after 3-min cuff occlusion increased by 60.7% (p = .002 vs. control) with a peeled hazelnut snack and by 64.7% with a hazelnut-cocoa integration (p = .04 vs. control). The combination hazelnut-cocoa may act in a synergic and protective way on cardiovascular system.
We investigated the effects of glucose and diverse breakfasts on glucose increment and ghrelin suppression and cognitive processing of sensory information assessed by frontal P300 evoked potentials. ...In a randomized crossover design, 12 healthy individuals (6M/6F; BMI 22.2 ± 0.4 kg/m2; 27 ± 1.3 years, mean ± SEM) underwent 50 g OGTT (A) and 3 breakfasts (B1: milk and cereals; B2: milk, apple, and chocolate cream-filled sponge cake; B3: milk, apple, bread, and hazelnut chocolate cream) to assess plasma glucose-, insulin-, and ghrelin excursions. An electroencephalography was performed before and 100 min after consumption of each load to measure the latency of frontal P300 evoked potentials as index of cognitive performance. Breakfasts B1 and B2 exhibited significantly lower glycemic and insulinemic responses as compared to A. Breakfast B3 exhibited significantly lower glycemic, but not insulinemic response, as compared to A. Final plasma ghrelin inhibition was more pronounced, albeit not significantly, in all breakfasts with respect to A. P300 latency tended to decrease following each of the three breakfasts, but B3 was the only breakfast capable to elicit a statistically significant reduction in P300 latency with respect to A (p<0.01), suggesting ameliorated cognitive performance. Such amelioration was correlated with the 2-hour final inhibition of plasma ghrelin concentration (r=0.61, p=0.01).
Prader-Willi Syndrome (PWS) is the most common syndromic type of human obesity. Multiple endocrine abnormalities due to hypothalamic dysfunction as well as cognitive and behavioral disorders occur in ...PWS. Hypothalamic dysfunction, dysregulated mesocorticolimbic reward system, and impaired prefrontal cortex (PFC) function are implicated in the pathophysiology of hyperphagia and obesity in PWS. All available therapeutic tools have not fully targeted at counteract the mechanisms underlying obesity in PWS. Previously, we demonstrated the safety and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) in inducing weight loss in obesity by modulating the brain dopaminergic system and enhancing the inhibitory activity of the PFC on eating behaviour (Ferrulli et al, DOM 2019) . In this case-report, for the first time, we tested the efficacy and safety of rTMS in a 23-year-old patient with PWS, in whom repeated interventions aimed at inducing weight loss have failed. A 5-week high frequency (18 Hz) rTMS treatment, associated with diet, resulted in a 3.5% weight loss (127.4 vs. 123 Kg, BMI: 50.4 vs. 48.6 Kg/m2, WHR: 1.14 vs. 1.12) . Concerning the metabolic parameters, an improvement in lipid profile has been shown (CHO/HDL/LDL/TG: 212/40/142/152 vs. 190/40/124/131 mg/dL) . While no significant changes emerged in the psychometric assessment of food craving, impulsiveness, quality of life, self-esteem, interestingly, a robust improvement in the Mini-Mental State Examination score (corrected for age and schooling) has been found from 22 (severe impairment) to 27 (moderate impairment) . The improvement in the cognitive status assessed through the Montreal Cognitive Assessment was weaker (17/30 to 19/30) . In view of the urgent need of novel effective interventions for obesity in PWS, these findings support a potential role of rTMS in reducing food drive and behaviors impacting hyperphagia and obesity in PWS, with a possible impact also on cognitive functions.
Disclosure
A.Ferrulli: None. D.Cannavaro: None. C.Macrì: None. S.Massarini: None. L.Luzi: Advisory Panel; Eli Lilly and Company, Speaker’s Bureau; Eli Lilly and Company, Novo Nordisk.
Funding
IRCCS Multimedica - Ricerca Corrente
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