Prospective evaluation of transoral outlet reduction (TORe) after Roux-en-Y gastric bypass (RYGB) failure.

BACKGROUND AND AIMS: Weight regain after RYGB is multifactorial including dilatation of the gastro-jejunal anastomosis. Transoral outlet reduction (TORe) procedure is a minimally invasive alternative to surgical anastomotic revision. METHODS: We conducted a prospective, multicenter, simple blind, randomized study in patients with weight regain following RYGB, comparing the efficacy of conventional nutritional and behavioral management associated with a TORe procedure (TORe group) with conventional management alone and a Sham procedure (Sham group). The main objective of this study was to evaluate the percentage of excess weight loss (%EWL) at 12 months after endoscopy. RESULTS: From January 2015 to January 2019, 73 subjects were randomized in four French Bariatric centers. The final analysis involved 50 subjects, 25 in each group, 44 women, 6 men, with an average BMI of 40.6 kg/m2. At 12 months, the average %EWL was significantly higher in the TORe group than in the Sham group (13.5 ± 14.1 vs. - 0.77 ± 17.1; p = 0.002). Cohen's d was 0.91, indicating a large effect size of the procedure on the %EWL. There was no significant difference between groups concerning the improvement of obesity-related comorbidities (diabetes and dyslipidemia) and quality of life at 12 months. We report frequent adverse events in the TORe group (20% had adverse events related to the procedure). Three adverse events were serious, including two perforations of the gastro-jejunal anastomosis after TORe group that led to the premature termination of the study. CONCLUSIONS: After RYGBP failure linked to the dilatation of the gastro-jejunal anastomosis, TORe procedure with nutritional management results in significantly higher %EWL at 12 months compared to patients with nutritional management alone. As surgery, this minimally invasive endoscopic procedure can be associated with severe adverse events.

Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.

Narcolepsy with cataplexy is a sleep disorder caused by deficiency in the hypothalamic neuropeptide hypocretin/orexin (HCRT), unanimously believed to result from autoimmune destruction of hypocretin-producing neurons. HCRT deficiency can also occur in secondary forms of narcolepsy and be only temporary, suggesting it can occur without irreversible neuronal loss. The recent discovery that narcolepsy patients also show loss of hypothalamic (corticotropin-releasing hormone) CRH-producing neurons suggests that other mechanisms than cell-specific autoimmune attack, are involved. Here, we identify the HCRT cell-colocalized neuropeptide QRFP as the best marker of HCRT neurons. We show that if HCRT neurons are ablated in mice, in addition to Hcrt, Qrfp transcript is also lost in the lateral hypothalamus, while in mice where only the Hcrt gene is inactivated Qrfp is unchanged. Similarly, postmortem hypothalamic tissues of narcolepsy patients show preserved QRFP expression, suggesting the neurons are present but fail to actively produce HCRT. We show that the promoter of the HCRT gene of patients exhibits hypermethylation at a methylation-sensitive and evolutionary-conserved PAX5:ETS1 transcription factor-binding site, suggesting the gene is subject to transcriptional silencing. We show also that in addition to HCRT, CRH and Dynorphin (PDYN) gene promoters, exhibit hypermethylation in the hypothalamus of patients. Altogether, we propose that HCRT, PDYN, and CRH are epigenetically silenced by a hypothalamic assault (inflammation) in narcolepsy patients, without concurrent cell death. Since methylation is reversible, our findings open the prospect of reversing or curing narcolepsy.

Music therapy for health workers to reduce stress, mental workload and anxiety: a systematic review.

BACKGROUND: The physical and mental exhaustion of health care workers urgently needs to be addressed as a public health priority. Benefits of music on stress parameters have been extensively reported. METHODS: We carried out a systematic review to examine the efficacy of music interventions on stress parameters by selecting studies conducted in genuine care stress conditions. To approach the potential benefit of music therapy (MT) versus music medicine (MM), we followed international music-based intervention guidelines. RESULTS: Five outcomes were considered in our studies: stress, anxiety, mental workload, burnout risk and psychosomatic symptoms. Corresponding measures, including psychological, physiological questionnaires or stress biological parameters, showed significant results for the majority of them in music groups. Implications of music types, designs and limitations are discussed. Only one study compared MM and MT with an advantage for customized playlists over time. CONCLUSIONS: In spite of heterogeneity, music interventions seem to significantly decrease stress parameters. The individual, customized supports with MT may be a crucial condition for this specific professional category. The impact of MT versus MM, the number of music sessions and the effect over time need to be explored.

Nutritional Status of Patients with Facioscapulohumeral Muscular Dystrophy.

In patients with facioscapulohumeral muscular dystrophy (FSHD), a rare genetic neuromuscular disease, reduced physical performance is associated with lower blood levels of vitamin C, zinc, selenium, and increased oxidative stress markers. Supplementation of vitamin C, vitamin E, zinc, and selenium improves the quadriceps' physical performance. Here, we compared the nutritional status of 74 women and 85 men with FSHD. Calorie intake was lower in women with FSHD than in men. Moreover, we assessed vitamin C, vitamin E, zinc, copper, and selenium intakes in diet and their concentrations in the plasma. Vitamin E, copper, and zinc intake were lower in women with FSHD than in men, whereas plasma vitamin C, copper levels, and copper/zinc ratio were higher in women with FSHD than in men. The dietary intake and plasma concentrations of the studied vitamins and minerals were not correlated in both sexes. A well-balanced and varied diet might not be enough in patients with FSHD to correct the observed vitamin/mineral deficiencies. A low energy intake is a risk factor for suboptimal intake of proteins, vitamins, and minerals that are important for protein synthesis and other metabolic pathways and that might contribute to progressive muscle mass loss. Antioxidant supplementation and higher protein intake seem necessary to confer protection against oxidative stress and skeletal muscle mass loss.

Interactions between the regulatory peptide 26RFa (QRFP) and insulin in the regulation of glucose homeostasis in two complementary models: The high fat 26RFa-deficient mice and the streptozotocin insulin-deficient mice.

The regulatory peptide 26RFa (QRFP) is involved in the control of glucose homeostasis at the periphery by acting as an incretin, and in the brain by mediating the central antihyperglycemic effect of insulin, indicating the occurrence of a close relationship between 26RFa and insulin in the regulation of glucose metabolism. Here, we investigated the physiological interactions between 26RFa and insulin in two complementary models i.e. a model of obese/hyperglycemic mice deficient for 26RFa and a model of diabetic mice deficient for insulin. For this, transgenic 26RFa-deficient mice were made obese and chronically hyperglycemic by a 3-month high fat diet (HFD) and second group of mice was made diabetic by destruction of the ß cells of the pancreatic islets using a single injection of streptozotocin. Our data reveal that 26RFa deficiency does not impact significantly the "glycemic" phenotype of the HFD mice. The pancreatic islets, liver, white adipose tissue masses are not altered by the lack of 26RFa production but the brown adipose tissue (BAT) weight is significantly increased in these animals. In diabetic insulin-deficient mice, the injection of 26RFa does not exhibit any beneficial effect on the impaired glucose homeostasis characterizing this model. Finally, we show that streptozotocin diabetic mice display lowered plasma 26RFa levels as compared to untreated mice, whereas the expression of the peptide in the duodenum is not affected. Taken together, the present results indicate that dysregulation of glucose homeostasis in obese/hyperglycemic mice is not aggravated by the absence of 26RFa that may be compensated by the increase of BAT mass. In diabetic insulin-deficient mice, the antihypergycemic effect of 26RFa is totally blunted probably as a result of the impaired insulin production characterizing this model, avoiding therefore the action of the peptide.

A Regional Network Organization for Thrombectomy for Acute Ischemic Stroke in the Anterior Circulation; Timing, Safety, and Effectiveness.

BACKGROUND: Mechanical thrombectomy (MT) in association with intravenous thrombolysis is recommended for treatment of acute ischemic stroke (AIS), with large vessel occlusion (LVO) in the anterior circulation. Because MT is only available in comprehensive stroke centers (CSC), the challenge of stroke organization is to ensure equitable access to the fastest endovascular suite. Our aim was to evaluate the feasibility, efficacy, and safety of MT in patients initially managed in 1 CSC (mothership), compared with patients first managed in primary stroke center (PSC), and then transferred to the CSC for MT (drip-and-ship). METHODS: We retrospectively analyzed 179 consecutive patients (93 in the mothership group and 86 in the drip-and-ship group), with AIS secondary to LVO in the anterior cerebral circulation and a clinical-radiological mismatch (NIHSS ≥ 8 and DWI-ASPECT score ≥5), up to 6 hours after symptoms onset. We evaluated 3-month functional modified Rankin scale (mRS), periprocedural time management, mortality, and symptomatic intracranial haemorrhage (sICH). RESULTS: Despite significant longer process time in the drip-and-ship group, mRS ≤ 2 at 3 months (39.8% versus 44.1%, P = .562), Thrombolysis in cerebral infarction 2b-3 (85% versus 78%, P = .256), and sICH (7.0% versus 9.7%, P = .515) were similar in both group regardless of baseline clinical or radiological characteristics. After multivariate logistic regression, the predictive factors for favorable outcome were age (odds ratio [OR] -5years= 1.32, P < .001), initial NIHSS (OR -5points = 1.59, P = .010), absence of diabetes (OR = 3.35, P = .075), and the delay magnetic resonance imagining-puncture (OR -30min = 1.16, P = .048). CONCLUSIONS: Our study showed encouraging results from a regional protocol of MT comparing patients transferred from PSC or brought directly in CSC.

Chemical, biological and molecular modelling analyses to probe into the pharmacological potential of Antidesma madagascariense Lam.: A multifunctional agent for developing novel therapeutic formulations.

Antidesma madagascariense Lam. (AM), an indigenous medicinal plant to the Mascarene Islands, is used for the treatment of several diseases. We endeavoured to validate its use via evaluating the kinetics of inhibition of crude aqueous extract (CAE) and crude methanol extract (CME) of AM against key metabolic enzymes (pancreatic lipase, cholesterol esterase [CEase], acetylcholinesterase [AChE], and urease). In vitro antiglycation, antioxidant, cytotoxicity using iCELLigence real time cell analysis system and WST-1 methods, were used. LC-ESI-MS/MS was employed to determine the phenolic composition of the extracts and interaction of selected compounds to the studied enzymes was determined using in silico docking. AChE was inhibited by the CME of AM and CEase by the CAE. Both extracts were active inhibitors of urease and pancreatic lipase. Hyperoside (271.97 µg/g extract), present in large amount in the CME, docked to the enzymatic pocket of urease and CEase. The extracts showed competitive and mixed inhibition of urease and pancreatic lipase, respectively. The antioxidant capacity of the CME (6.61 µg GAE/mg crude extract) was higher compared to CAE (2.20 µg GAE/mg crude extract). AM extracts were significantly (p < 0.05) less potent than aminoguanidine in preventing advanced glycation end products formation. Toxicological screening revealed that both extracts were non-toxic on HEK-293 cells. AM crude extracts at concentrations ranging from 78 to 312 µg/ml did not cause a visible change in cell morphology compared to control. This study supports the safe use of AM as a biomedicine for the management and/or treatment of common non-communicable diseases.

Prevalence of Antipsychotic-Treated Patients in a Cohort of Adult Addicted Patients.

PURPOSE: The objective of this cross-sectional study was to describe and estimate the prevalence of antipsychotics (AP) in a cohort of addicted patients, and to compare the profiles of addictive patients receiving AP or not. METHODS: We included all adult patients seen at the addiction care center of Montpellier University Hospital, between January 1, 2015, and March 31, 2015. Demographic, clinical, and therapeutic data were collected from the patients' medical records. RESULTS: During the study period, 415 patients were included, with a mean age of 38 ± 10 years. They were mostly men (73.3%), French (54.9%), and unemployed (61.8%). Among the study population, 93 patients (patients treated with AP [trAP], 22.4%) were treated by 111 different AP, mainly cyamemazine (29.0% of treated patients), aripiprazole (20.4%), olanzapine (17.2%), and quetiapine (16.1%), mostly in monotherapy (80.6%) and by oral route (93.2% of AP). Psychiatric history was more frequent in trAP than in those without AP (untrAP) (55.9% vs 35.4% respectively; P < 0.001). Professional activity tended to be less frequent in patients with AP (25.3% vs 38.9%, P = 0.08).When compared with untrAP, trAP consumed more amphetamine (10.8% vs 4.4%; P = 0.02) and tended to consume less opiates (7.5% vs 14.9%; P = 0.06); the consumptions of cannabis (43.0% vs 35.7%; P = 0.20) and cocaine (22.6% vs 16.8%; P = 0.20) were not statistically different.Opiate maintenance therapy was reported in 63.7% of trAP and 68.4% of untrAP (P = 0.41): it consisted of methadone (trAP, 60.3% vs untrAP, 56.5%) and buprenorphine (trAP, 39.7% vs untrAP, 43.5%). CONCLUSIONS: The concomitant management of psychiatric and substance use disorders in the same center may explain the high prevalence of trAP in this study. Cannabis and psychostimulants may have been used in these patients as self-medication for mental disease-related symptoms or adverse effects of APs.

Effect of food deprivation on the hypothalamic gene expression of the secretogranin II-derived peptide EM66 in rat.

EM66 is a peptide derived from the chromogranin, secretogranin II (SG-II). Recent findings in mice indicate that EM66 is a novel anorexigenic neuropeptide that regulates hypothalamic feeding behavior, at least in part, by activating the POMC neurons of the arcuate nucleus. The present study aimed to investigate the mechanism of action of EM66 in the control of feeding behavior and, more specifically, its potential interactions with the NPY and POMC systems in rat. We analyzed by Q-PCR the gene expression of the EM66 precursor, SG-II, in hypothalamic extracts following 2, 3, or 4 days of food deprivation and compared it with the expression levels of the two major neuropeptidergic systems, that is, POMC and NPY, modulating feeding behavior. Our results show that fasting for 2 and 3 days has no effect on SG-II mRNA levels. However, 4 days of food deprivation induced a significant alteration in the expression levels of the three genes studied, with a significant increase in SG-II and NPY mRNAs, and conversely, a significant decrease in POMC mRNA. These data indicate that the EM66 gene expression is modulated by a negative energy status and suggest interactions between EM66 and NPY to regulate food intake through the POMC system.

Multiple pharmacological targets, cytotoxicity, and phytochemical profile of Aphloia theiformis (Vahl.) Benn.

Aphloia theiformis (Vahl.) Benn. (AT) is traditionally used in Sub-Saharan African countries including Mauritius as a biomedicine for the management of several diseases. However, there is a dearth of experimental studies to validate these claims. We endeavoured to evaluate the inhibitory effects of crude aqueous extract as traditionally used together with the crude methanol extracts of AT leaves on urease, angiotensin (I) converting enzyme (ACE), acetylcholinesterase (AChE), cholesterol esterase (CEase), glycogen phosphorylase a (GPa), and glycation in vitro. The crude extract showing potent activity against the studied enzymes was further partitioned using different solvents of increasing polarity. The enzyme inhibitory and antiglycation activities of each fraction was assessed. Kinetic of inhibition of the active crude extract/fractions on the aforementioned enzymes was consequently determined using Lineweaver-Burk plots. An ultra-high performance liquid chromatography (UHPLC-UV/MS) system was used to establish the phytochemical profile of AT. The real time cell analysis system (iCELLigence™) was used to monitor any cellular cytotoxicity of AT. Crude methanolextract (CME) was a potent inhibitor of the studied enzymes, with IC50 ranging from 696.22 to 19.73µg/mL. CME (82.5%) significantly (p<0.05) inhibited glycation and was comparable to aminoguanidine (81.5%). Ethyl acetate and n-butanol fractions of CME showed non-competitive, competitive, and uncompetitive mode of inhibition against ACE, CEase, and AChE respectively. Mangiferin, a xanthone glucoside was present in CME, ethyl acetate, and n-butanol fractions. Active extract/fractions were found to be non-cytotoxic (IC50>20µg/mL) according to the U.S National Cancer Institute plant screening program. This study has established baseline data that tend to justify the traditional use of AT and open new avenues for future biomedicine development.

Effects of Aphloia theiformis on key enzymes related to diabetes mellitus.

CONTEXT: Aphloia theiformis (Vahl.) Benn. (Flacourtiaceae) (AT) is traditionally used for the management of diabetes mellitus (DM), but there is no scientific data regarding activity against enzymes linked to this condition. OBJECTIVE: To evaluate the kinetics of AT on key enzymes inhibition related to DM, and establish the antioxidant profile of AT. MATERIALS AND METHODS: Dried powdered AT leaves were used to prepare crude methanol extract (70% v/v) (CME). Kinetics of CME (5000 to 156.25 µg/mL) on α-amylase, α-glucosidase, and lipase inhibition were studied. CME was partitioned using solvents of increasing polarity and kinetics of enzyme inhibition of each fraction (1000-31.25 µg/mL) was evaluated. Potent fractions were combined to assess any synergistic effect. Total phenol, flavonoid, tannin, anthocyanin contents, and antioxidant capacity of AT was evaluated using standard spectrophotometric methods. RESULTS: CME, ethyl acetate, and n-butanol fractions showed potent inhibitory activities against the enzymes with IC50 ranging from 22.94-939.97 µg/mL. Significant (p < 0.05) reduction in IC50 (15.72 and 157.03 µg/mL against α-amylase and lipase, respectively) was observed when ethyl acetate and n-butanol fractions were combined; showing synergism. The extracts showed noncompetitive inhibition against α-amylase and α-glucosidase. Ethyl acetate, n-butanol fractions, and CME showed highest antioxidant capacities (0.44-1.41 µg GAE/mg sample), and phenol content (211.74-675.53 µg GAE/mg sample). CONCLUSION: This study supports the use of AT in the management of DM and provides the rationale for bioactivity guided isolation and characterization of compounds from the ethyl acetate and n-butanol fractions.

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.

26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic ß-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis.

Effects of vitamin C, vitamin E, zinc gluconate, and selenomethionine supplementation on muscle function and oxidative stress biomarkers in patients with facioscapulohumeral dystrophy: a double-blind randomized controlled clinical trial.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disease characterized by progressive weakness and atrophy of specific skeletal muscles. As growing evidence suggests that oxidative stress may contribute to FSHD pathology, antioxidants that might modulate or delay oxidative insults could help in maintaining FSHD muscle function. Our primary objective was to test whether oral administration of vitamin C, vitamin E, zinc gluconate, and selenomethionine could improve the physical performance of patients with FSHD. Adult patients with FSHD (n=53) were enrolled at Montpellier University Hospital (France) in a randomized, double-blind, placebo-controlled pilot clinical trial. Patients were randomly assigned to receive 500 mg vitamin C, 400mg vitamin E, 25mg zinc gluconate and 200 µg selenomethionine (n=26), or matching placebo (n=27) once a day for 17 weeks. Primary outcomes were changes in the two-minute walking test (2-MWT), maximal voluntary contraction, and endurance limit time of the dominant and nondominant quadriceps (MVCQD, MVCQND, TlimQD, and TlimQND, respectively) after 17 weeks of treatment. Secondary outcomes were changes in the antioxidant status and oxidative stress markers. Although 2-MWT, MVCQ, and TlimQ were all significantly improved in the supplemented group at the end of the treatment compared to baseline, only MVCQ and TlimQ variations were significantly different between groups (MVCQD: P=0.011; MVCQND: P=0.004; TlimQD: P=0.028; TlimQND: P=0.011). Similarly, the vitamin C (P<0.001), vitamin E as α-tocopherol (P<0.001), vitamin C/vitamin E ratio (P=0.017), vitamin E γ/α ratio (P=0.022) and lipid peroxides (P<0.001) variations were significantly different between groups. In conclusion, vitamin E, vitamin C, zinc, and selenium supplementation has no significant effect on the 2-MWT, but improves MVCQ and TlimQ of both quadriceps by enhancing the antioxidant defenses and reducing oxidative stress. This trial was registered at clinicaltrials.gov (number: NCT01596803).

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

The effects of music intervention in the management of chronic pain: a single-blind, randomized, controlled trial.

OBJECTIVE: A music intervention method in the management of pain was recently developed while taking account of recommendations in the scientific literature. The objective of this study was to assess the usefulness of this music intervention to the management of patients with chronic pain. METHODS: A controlled, single-blind, randomized trial was used. Eighty-seven patients presenting with lumbar pain, fibromyalgia, inflammatory disease, or neurological disease were included in the study. During their hospitalization, the intervention arm (n=44) received at least 2 daily sessions of music listening between D0 and D10, associated with their standard treatment, and then pursued the music intervention at home until D60 using a multimedia player in which the music listening software program had been installed. The control arm received standard treatment only (n=43). The end points measured at D0, D10, D60, and D90 were: pain (VAS), anxiety-depression (HAD) and the consumption of medication. RESULTS: At D60 in the music intervention arm, this technique enabled a more significant reduction (P<0.001) in pain (6.3 ± 1.7 at D0 vs. 3 ± 1.7 at D60) when compared with the arm without music intervention (6.2 ± 1.5 at D0 vs. 4.6 ± 1.7 at D60). In addition, music intervention contributed to significantly reducing both anxiety/depression and the consumption of anxiolytic agents. DISCUSSION: These results confirm the value of music intervention to the management of chronic pain and anxiety/depression. This music intervention method appears to be useful in managing chronic pain as it enables a significant reduction in the consumption of medication.

Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia: long-term results.

OBJECT: Primary generalized dystonia (PGD) is a medically refractory disease of the brain causing twisting or spasmodic movements and abnormal postures. In more than 30% of cases it is associated with the autosomal DYT1 mutation. Continuous electrical stimulation of the globus pallidus internus (GPi) has been used successfully in the treatment of PGD. The aim of this study was to examine the long-term efficacy and safety of deep brain stimulation (DBS) in the treatment of PGD in children and adults with and without the DYT1 mutation. METHODS: Thirty-one patients with PGD were selected for surgery. Electrodes were bilaterally implanted under stereotactic guidance and connected to neurostimulators that were inserted subcutaneously. Efficacy was evaluated by comparing scores on the clinical and functional Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) before and after implantation. The efficacy of stimulation improved with time. After 2 years, compared with preoperative values, the mean (+/- standard deviation) clinical and functional BFMDRS scores had improved by 79 +/- 19% and 65 +/- 33%, respectively. At the 2-year follow-up examination the improvement was comparable in patients with and without the DYT1 mutation in both the functional (p = 0.12) and clinical (p = 0.33) scores. Children displayed greater improvements in the clinical score than adult patients (p = 0.04) at 2 years of follow up. In contrast, there was no significant difference in functional scores between children and adults (p = 0.95). CONCLUSIONS: Electrical stimulation of the GPi is an effective, reversible, and adaptable treatment for PGD and should be considered for conditions refractory to pharmaceutical therapies.

Comparison of atlas- and magnetic resonance imaging-based stereotactic targeting of the globus pallidus internus in the performance of deep brain stimulation for treatment of dystonia.

OBJECT: To assess the validity of relying on atlases during stereotactic neurosurgery, the authors compared target coordinates in the globus pallidus internus (GPi) obtained using magnetic resonance (MR) imaging with those determined using an atlas. The targets were used in deep brain stimulation (DBS) for the treatment of generalized dystonia. METHODS: Thirty-five patients, who were treated using bilateral DBS of the GPi, were included in this study. The target was selected on three-dimensional MR images by direct visual recognition of the GPi. The coordinates were automatically recorded using dedicated software. They were translated into the anterior commissure-posterior commissure (AC-PC) coordinate system by using a matrix transformation process. The same GPi target was defined, based on the locations of brain structures shown in the atlases of Schaltenbrand and Talairach. Magnetic resonance imaging-based GPi target coordinates were statistically compared with the corresponding atlas-based coordinates by applying the Student t-test. A significant difference (p < 0.001) was demonstrated in x, y, and z directions between MR imaging-based and Schaltenbrand atlas-derived target coordinates. The comparison with normalized Talairach atlas coordinates demonstrated a significant difference (p < 0.01) in the y and z directions, although not in the x direction (p = 0.12). No significant correlation existed between MR imaging-based target coordinates and patient age (p > 0.1). No significant correlation was observed between MR imaging-based target coordinates and patient sex in the y and z directions (p > 0.9), although it was significant in the x direction (p < 0.05). A significant variation in coordinates and the length of the AC-PC line was revealed only in the y direction (p < 0.005). CONCLUSIONS: A significant difference was found between target coordinates obtained by direct visual targeting on MR images (validated by postoperative clinical results) and those obtained by indirect targeting based on atlases.