Extraction of stylet-driven pacing lead for left bundle branch area pacing.

We present a case where a stylet-driven pacing lead was successfully extracted from the left bundle branch area pacing, 10 months after implantation. The procedure was performed without any complications, using a standard stylet and employing gentle counterclockwise rotations of the lead body.

[Echocardiography in telemedicine: a possible solution for containing waiting lists in cardiology]. / L'ecocardiografia in telemedicina: una possibile soluzione per il contenimento delle liste d'attesa in cardiologia.

BACKGROUND: The length of waiting lists in Italy for outpatient cardiology investigations provided by the National Health System is a serious dysfunction. The shortage of physicians in hospitals makes it difficult to solve this problem by drawing on internal resources. The waiting list at Valduce Hospital in Como for outpatient echocardiographic examinations was 12 months at the beginning of 2018. Therefore, we experimented a new way to deal with this inefficiency. METHODS: Starting in February 2018, we have undertaken in Valduce Hospital a partnership between the Department of Cardiology and an external startup (Ecocardioservice LLC) which guarantees for outpatients on-site performance by sonographers of echocardiographic examinations that are subsequently reported remotely via telemedicine by experienced cardiologists. RESULTS: From February 12, 2018 to July 7, 2022, 20 782 examinations were carried out by this mode. The waiting list was reduced from 12 months to 15-20 days. A new diagnosis or a significant change in pre-existing pathology were detected in 3466 patients well in advance of previous timelines. In 5640 patients we found a known stable pathology. Of the 8926 patients with pathologic examination, 3706 patients were taken over by the Cardiology Department for subsequent investigations, possible hospitalization and, when necessary, interventional or cardiac surgical procedures on an elective basis in 2636 cases (71%) and on an urgent basis in 1070 cases (29%). CONCLUSIONS: In our experience, a system in which echocardiograms are performed on-site by sonographers and then reported in telecardiology by cardiologists outside the facility makes it possible to meet the demands of the local area and free up internal resources. This organization allowed to bring outpatients waiting lists for echocardiography back within acceptable limits and to intercept early a significant proportion of patients with need for further investigations or procedures.

Transcranial direct current stimulation for bipolar depression: systematic reviews of clinical evidence and biological underpinnings.

Despite multiple available treatments for bipolar depression (BD), many patients face sub-optimal responses. Transcranial direct current stimulation (tDCS) has been advocated in the management of different conditions, including BD, especially in treatment-resistant cases. The optimal dose and timing of tDCS, the mutual influence with other concurrently administered interventions, long-term efficacy, overall safety, and biological underpinnings nonetheless deserve additional assessment. The present study appraised the existing clinical evidence about tDCS for bipolar depression, delving into the putative biological underpinnings with a special emphasis on cellular and molecular levels, with the ultimate goal of providing a translational perspective on the matter. Two separate systematic reviews across the PubMed database since inception up to August 8th 2022 were performed, with fourteen clinical and nineteen neurobiological eligible studies. The included clinical studies encompass 207 bipolar depression patients overall and consistently document the efficacy of tDCS, with a reduction in depression scores after treatment ranging from 18% to 92%. The RCT with the largest sample clearly showed a significant superiority of active stimulation over sham. Mild-to-moderate and transient adverse effects are attributed to tDCS across these studies. The review of neurobiological literature indicates that several molecular mechanisms may account for the antidepressant effect of tDCS in BD patients, including the action on calcium homeostasis in glial cells, the enhancement of LTP, the regulation of neurotrophic factors and inflammatory mediators, and the modulation of the expression of plasticity-related genes. To the best of our knowledge, this is the first study on the matter to concurrently provide a synthesis of the clinical evidence and an in-depth appraisal of the putative biological underpinnings, providing consistent support for the efficacy, safety, and tolerability of tDCS.

Functional connectivity changes and symptoms improvement after personalized, double-daily dosing, repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: A pilot study.

BACKGROUND: intrusive thoughts and compulsive behaviors that characterize obsessive compulsive disorder (OCD) are associated to aberrant resting state functional connectivity (rsFC) patterns within the cortico-striatal-thalamo-cortical (CSTC) circuits. A high percentage of OCD patients do not respond to conventional pharmacological treatments or psychotherapy. In these patients, inhibitory repetitive transcranial magnetic stimulation (rTMS) of the Supplementary Motor Area (SMA) resulted in a significant clinical benefit. METHODS: In the current study, we applied a novel protocol of 1-week MRI-guided individualized double-daily sessions of rTMS treatment (1-Hz; 110% of resting Motor Threshold/7200 pulses/day), to bilateral SMA in 9 OCD patients. We tested its (i) feasibility-safety, (ii) clinical efficacy and (iii) rsFC related changes. RESULTS: Patients reported no side effects during and after rTMS. Personalized rTMS treatment led to a significant improvement of OCD symptoms (average 25%; p = .005) and persistence of benefit up to 3-month follow-up. rsFC analysis revealed a significant reduction of connectivity patterns between bilateral SMA and subcortical regions, specifically in the basal ganglia and thalamus. Additional analysis showed that OCD symptoms severity correlates with a higher connectivity pattern between bilateral SMA and subcortical regions. CONCLUSIONS: rTMS double-daily sessions are safe, feasible and effective in OCD. The clinical outcomes, that are consistent with those found in our previous RCT, are linked to a decreased connectivity between SMA and subcortical brain areas implicated in control over obsessions and maladaptive compulsive behavior.

Transcranial Direct Current Stimulation in Obsessive-Compulsive Disorder, Posttraumatic Stress Disorder, and Anxiety Disorders.

Obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and anxiety disorders share the basic clinical feature of anxiety, which probably explains their common response to similar pharmacological and psychological interventions. Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has proved effective in reducing the symptoms of a number of neuropsychiatric disorders. It was also used in healthy subjects to modulate neuropsychological processes that are involved in the pathophysiology of anxiety. We review the published studies in which tDCS was administered to patients with OCD, PTSD, or anxiety disorders. Our systematic search in the major electronic databases resulted in 14 articles for OCD, 1 for an OCD-related disorder (ie, hoarding disorder), 2 for PTSD, and 2 for anxiety disorders. In the studies involving OCD patients, tDCS was targeted to either the dorsolateral prefrontal cortex or the orbitofrontal cortex or the pre-supplementary motor area and induced a clear reduction of obsessive-compulsive symptoms. However, the lack of sham control groups and the great diversity in sample selection and tDCS protocols among studies prevent us from generalizing these results. In the studies involving PTSD and anxiety disorders patients, tDCS was applied over the dorsolateral prefrontal cortex and reduced symptoms, but the number of treated patients is too little to draw any conclusion on efficacy. However, these reports highlighted the importance of combining tDCS with different procedures, including computerized tasks and behavioral paradigms. In conclusion, even in its infancy, the use of tDCS for the treatment of OCD, PTSD, and anxiety disorders does show promise and deserves extensive research effort.

The Psychiatric Neuromodulation Unit: Implementation and Management.

The proven effectiveness of neuromodulation and stimulation techniques for the management of psychiatric disorders has brought strongly needed innovation in psychiatry, given the high prevalence and high costs of treatment resistance. Although evidence-based guidelines in neuromodulation have been implemented to improve the clinical efficacy, safety, and research procedures, practical suggestions on how to design a psychiatric neuromodulation unit (PNU) are not available in the scientific literature. In this contribution, we have combined the results of a literature search with the suggestions of clinical psychiatrists, managers, and bioethicists who have had firsthand experience in building a PNU. Eleven key issues concerning the implementation and management of a PNU were identified: general context, team composition, environment, basic technical equipment, clinical versus research activities, target clinical population, education and training, interdisciplinarity, ethical aspects, regulatory and reimbursement issues, fund-raising, and partnership development. Moreover, a business plan comprising pragmatic solutions and recommendations for designing an efficient PNU was laid out.

Rigor and reproducibility in research with transcranial electrical stimulation: An NIMH-sponsored workshop.

BACKGROUND: Neuropsychiatric disorders are a leading source of disability and require novel treatments that target mechanisms of disease. As such disorders are thought to result from aberrant neuronal circuit activity, neuromodulation approaches are of increasing interest given their potential for manipulating circuits directly. Low intensity transcranial electrical stimulation (tES) with direct currents (transcranial direct current stimulation, tDCS) or alternating currents (transcranial alternating current stimulation, tACS) represent novel, safe, well-tolerated, and relatively inexpensive putative treatment modalities. OBJECTIVE: This report seeks to promote the science, technology and effective clinical applications of these modalities, identify research challenges, and suggest approaches for addressing these needs in order to achieve rigorous, reproducible findings that can advance clinical treatment. METHODS: The National Institute of Mental Health (NIMH) convened a workshop in September 2016 that brought together experts in basic and human neuroscience, electrical stimulation biophysics and devices, and clinical trial methods to examine the physiological mechanisms underlying tDCS/tACS, technologies and technical strategies for optimizing stimulation protocols, and the state of the science with respect to therapeutic applications and trial designs. RESULTS: Advances in understanding mechanisms, methodological and technological improvements (e.g., electronics, computational models to facilitate proper dosing), and improved clinical trial designs are poised to advance rigorous, reproducible therapeutic applications of these techniques. A number of challenges were identified and meeting participants made recommendations made to address them. CONCLUSIONS: These recommendations align with requirements in NIMH funding opportunity announcements to, among other needs, define dosimetry, demonstrate dose/response relationships, implement rigorous blinded trial designs, employ computational modeling, and demonstrate target engagement when testing stimulation-based interventions for the treatment of mental disorders.

Preventing relapse to smoking with transcranial magnetic stimulation: Feasibility and potential efficacy.

Many smokers attempt to quit every year, but 90% relapse within 12 months. Converging evidence suggests relapse is associated with insufficient activation of the prefrontal cortex. Delay discounting rate reflects relative activity in brain regions associated with relapse. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (LDLPFC) increases cortical excitability and reduces delay discounting rates, but little is known about feasibility, tolerability, and potential efficacy for smoking cessation. We hypothesized that 8 sessions of 20Hz rTMS of the LDLPFC combined with an evidence-based self-help intervention will demonstrate feasibility, tolerability, and potential efficacy in a limited double-blind randomized control trial. Smokers (n=29), abstinent for 24h, motivated to quit, and not using cessation medications, were randomized to active 20Hz rTMS at 110% of Motor Threshold or sham stimulation that replicated the look and sound of active stimulation. Stimulation site was located using the 6cm rule and neuro-navigation. Multiple clinical, feasibility, tolerability, and efficacy measures were examined. Active rTMS decreased delay discounting of $100 (F (1, 25.3694)=4.14, p=.05) and $1000 (F (1, 25.169)=8.42, p<.01), reduced the relative risk of relapse 3-fold (RR 0.29, CI 0.10-0.76, Likelihood ratio χ2 with 1 df=6.40, p=.01), increased abstinence rates (active 50% vs. sham 15.4%, Χ2 (df=1)=3.80, p=.05), and increased uptake of the self-help intervention. Clinical, feasibility, and tolerability assessments were favorable. Combining 20Hz rTMS of the LDLPFC with an evidence-based self-help intervention is feasible, well-tolerated, and demonstrates potential efficacy.

Transcranial direct current stimulation for obsessive-compulsive disorder: A randomized, controlled, partial crossover trial.

BACKGROUND: Presupplementary motor area (pre-SMA) hyperactivity has been detected in obsessive-compulsive disorder (OCD) patients. However, it is not understood whether this is a putative primary cause or a compensatory mechanism in OCD pathophysiology. Considering the polarity-dependent effects on cortical excitability of transcranial direct current stimulation (tDCS), we applied cathodal and/or anodal tDCS to the pre-SMA of OCD patients to test which current polarity might better improve symptoms. METHODS: Twelve OCD patients received initially 10 anodal (n = 6) or cathodal (n = 6) daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed bilaterally on the pre-SMA. In case of improvement or no change in symptoms severity, the subjects were maintained on the same current polarity for 10 more sessions. In case of symptoms worsening after the first 10 sessions they were switched to the other polarity for 10 more sessions to test the hypothesis of a polarity-dependent effect. Therefore, each subject received 20 tDCS sessions. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Sheehan Disability Scale (SDS) were administered biweekly to assess changes in symptoms severity. RESULTS: After 10 sessions, 50% of patients who initially received anodal stimulation were switched to cathodal, while 100% of patients initially assigned to cathodal stimulation continued on the same polarity. At the end of the study, a statistically significant decrease was observed in the mean Y-BOCS scores of those patients who underwent cathodal tDCS. No pre-post difference was found in the scores of patients following anodal tDCS. CONCLUSIONS: Cathodal but not anodal tDCS over the pre-SMA significantly improved OCD symptoms.

Polarity-dependent effects of transcranial direct current stimulation in obsessive-compulsive disorder.

About one third of patients with obsessive-compulsive disorder (OCD) fail to experience significant clinical benefit from currently available treatments. Hyperactivity of the presupplementary motor area (pre-SMA) has been detected in OCD patients, but it is not clear whether it is the primary cause or a secondary compensatory mechanism in OCD pathophysiology. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique with polarity-dependent effects on motor cortical excitability. A 33-year-old woman with treatment-resistant OCD received 20 daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed on the pre-SMA, according to the 10-20 EEG system, and the reference electrode on the right deltoid. The first 10 sessions were anodal, while the last 10 were cathodal. Symptoms severity was assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) severity score. In the end of anodal stimulation, OCD symptoms had worsened. Subsequent cathodal stimulation induced a dramatic clinical improvement, which led to an overall 30% reduction in baseline symptoms severity score on the Y-BOCS. Our study supports the hypothesis that pre-SMA hyperfunction might be responsible for OCD symptoms and shows that cathodal inhibitory tDCS over this area might be an option when dealing with treatment-resistant OCD.

Long-Term Efficacy of Repeated Daily Prefrontal Transcranial Magnetic Stimulation (TMS) In Treatmnt-Resistant Depression.

(Reprinted with permission from Depression and Anxiety 2012; 29:833-890).

Neural correlates associated with symptom provocation in pediatric obsessive compulsive disorder after a single session of sham-controlled repetitive transcranial magnetic stimulation.

Treatments for pediatric obsessive-compulsive disorder (OCD) could be enhanced if the physiological changes engendered by treatment were known. This study examined neural correlates of a provocation task in youth with OCD, before and after sham-controlled repetitive transcranial magnetic stimulation (rTMS). We hypothesized that rTMS to the right dorsolateral prefrontal cortex would inhibit activity in cortico-striato-thalamic (CST) circuits associated with OCD to a greater extent than sham rTMS. After baseline (Time 1) functional magnetic resonance imaging (fMRI) during a provocation task, subjects received one session of either fMRI-guided sham (SG; n=8) or active (AG; n=10) 1-Hz rTMS over the rDLPFC for 30min. During rTMS, subjects were presented with personalized images that evoked OCD-related anxiety. Following stimulation, fMRI and the provocation task were repeated (Time 2). Contrary to our prediction for the provocation task, the AG was associated with no changes in BOLD response from Times 1 to 2. In contrast, the SG had a significant increase at Time 2 in BOLD response in the right inferior frontal gyrus and right putamen, which persisted after adjusting for age, gender, and time to scanner as covariates. This study provides an initial framework for TMS interrogation of the CST circuit in pediatric OCD.

Transcranial direct current stimulation in obsessive-compulsive disorder: emerging clinical evidence and considerations for optimal montage of electrodes.

BACKGROUND: Neuromodulation techniques for obsessive-compulsive disorder (OCD) treatment have expanded with greater understanding of the brain circuits involved. Transcranial direct current stimulation (tDCS) might be a potential new treatment for OCD, although the optimal montage is unclear. OBJECTIVE: To perform a systematic review on meta-analyses of repetitive transcranianal magnetic stimulation (rTMS) and deep brain stimulation (DBS) trials for OCD, aiming to identify brain stimulation targets for future tDCS trials and to support the empirical evidence with computer head modeling analysis. METHODS: Systematic reviews of rTMS and DBS trials on OCD in Pubmed/MEDLINE were searched. For the tDCS computational analysis, we employed head models with the goal of optimally targeting current delivery to structures of interest. RESULTS: Only three references matched our eligibility criteria. We simulated four different electrodes montages and analyzed current direction and intensity. CONCLUSION: Although DBS, rTMS and tDCS are not directly comparable and our theoretical model, based on DBS and rTMS targets, needs empirical validation, we found that the tDCS montage with the cathode over the pre-supplementary motor area and extra-cephalic anode seems to activate most of the areas related to OCD.

Randomized Sham Controlled Double-blind Trial of Repetitive Transcranial Magnetic Stimulation for Adults With Severe Tourette Syndrome.

BACKGROUND: A small proportion of individuals with Tourette syndrome (TS) have a lifelong course of illness that fails to respond to conventional treatments. Open label studies have suggested that low frequency (1-Hz) repetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may be effective in reducing tic severity. OBJECTIVE/HYPOTHESIS: To examine the efficacy of rTMS over the SMA for TS in a randomized double-blind sham-controlled trial (RCT). METHODS: We conducted a two-site RCT-rTMS with 20 adults with severe TS for 3 weeks. Treatment consisted of 15 sessions (1-Hz; 30 min; 1800 pulses per day) of active or sham rTMS at 110% of the motor threshold over the SMA. A subsequent 3 week course of active rTMS treatment was offered. RESULTS: Of the 20 patients (16 males; mean age of 33.7 ± 12.2 years), 9 received active and 11 received sham rTMS. After 3 weeks, patients receiving active rTMS showed on average a 17.3% reduction in the YGTSS total tic score compared to a 13.2% reduction in those receiving sham rTMS, resulting in no statistically significant reduction in tic severity (P = 0.27). An additional 3 week open label active treatment for those patients (n = 7) initially randomized to active rTMS resulted in a significant overall 29.7% reduction in tic severity compared to baseline (P = 0.04). CONCLUSION: This RCT did not demonstrate efficacy of 3-week SMA-targeted low frequency rTMS in the treatment of severe adult TS. Further studies using longer or alternative stimulation protocols are warranted.

Transcranial direct current stimulation in psychiatric disorders.

The interest in non-invasive brain stimulation techniques is increasing in recent years. Among these techniques, transcranial direct current stimulation (tDCS) has been the subject of great interest among researchers because of its easiness to use, low cost, benign profile of side effects and encouraging results of research in the field. This interest has generated several studies and randomized clinical trials, particularly in psychiatry. In this review, we provide a summary of the development of the technique and its mechanism of action as well as a review of the methodological aspects of randomized clinical trials in psychiatry, including studies in affective disorders, schizophrenia, obsessive compulsive disorder, child psychiatry and substance use disorder. Finally, we provide an overview of tDCS use in cognitive enhancement as well as a discussion regarding its clinical use and regulatory and ethical issues. Although many promising results regarding tDCS efficacy were described, the total number of studies is still low, highlighting the need of further studies aiming to replicate these findings in larger samples as to provide a definite picture regarding tDCS efficacy in psychiatry.

Comparison of clinical and angiographic prognostic risk scores in elderly patients presenting with acute coronary syndrome and referred for percutaneous coronary intervention.

BACKGROUND: Multiple risk prediction models have been validated in all-age patients presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI); however, they have not been validated specifically in the elderly. METHODS: We calculated the GRACE (Global Registry of Acute Coronary Events) score, the logistic EuroSCORE, the AMIS (Acute Myocardial Infarction Swiss registry) score, and the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score in a consecutive series of 114 patients ≥75 years presenting with ACS and treated with PCI within 24 hours of hospital admission. Patients were stratified according to score tertiles and analysed retrospectively by comparing the lower/mid tertiles as an aggregate group with the higher tertile group. The primary endpoint was 30-day mortality. Secondary endpoints were the composite of death and major adverse cardiovascular events (MACE) at 30 days, and 1-year MACE-free survival. Model discrimination ability was assessed using the area under receiver operating characteristic curve (AUC). RESULTS: Thirty-day mortality was higher in the upper tertile compared with the aggregate lower/mid tertiles according to the logistic EuroSCORE (42% vs 5%; odds ratio [OR] = 14, 95% confidence interval [CI] = 4-48; p <0.001; AUC = 0.79), the GRACE score (40% vs 4%; OR = 17, 95% CI = 4-64; p <0.001; AUC = 0.80), the AMIS score (40% vs 4%; OR = 16, 95% CI = 4-63; p <0.001; AUC = 0.80), and the SYNTAX score (37% vs 5%; OR = 11, 95% CI = 3-37; p <0.001; AUC = 0.77). CONCLUSIONS: In elderly patients presenting with ACS and referred to PCI within 24 hours of admission, the GRACE score, the EuroSCORE, the AMIS score, and the SYNTAX score predicted 30 day mortality. The predictive value of clinical scores was improved by using them in combination.

Modulation of motor cortex excitability in obsessive-compulsive disorder: an exploratory study on the relations of neurophysiology measures with clinical outcome.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) to supplementary motor area (SMA) showed clinical benefit in obsessive-compulsive disorder (OCD). Here we tested whether clinical improvement was associated with enhanced cortical inhibition as measured by single and paired-pulse TMS variables. In 18 OCD patients receiving 4 weeks of either active or sham rTMS in a double-blind randomized trial, we assessed bilateral resting and active motor thresholds (RMT and AMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). We tested correlations between changes in Yale-Brown Obsessive Compulsive Scale-Self-report (Y-BOCS-SR), Clinical Global Impression-Severity subscale (CGI-S) and cortical excitability measures. Active rTMS increased right hemisphere RMT whose change correlated with Y-BOCS-SR improvement. Baseline RMT hemispheric asymmetry, defined as the difference between left and right hemispheres RMT, and its normalization after active rTMS correlated with Y-BOCS-SR and CGI-S improvements. Active rTMS also increased right hemisphere SICI whose change correlated with Y-BOCS-SR and CGI-S at week 4, and with normalization of baseline RMT hemispheric asymmetry. Treatment-induced changes in cortical excitability measures are consistent with an inhibitory action of SMA rTMS on dysfunctional motor circuits in OCD. Correlations of neurophysiology measures with therapeutic outcome are supportive of the role of SMA in the modulation of OCD symptoms.

Randomized sham controlled trial of repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex for the treatment of panic disorder with comorbid major depression.

BACKGROUND: In an open-label trial low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right dorsolateral prefrontal cortex (DLPFC) significantly improved symptoms of panic disorder and major depression. Here we present data of a randomized double-blind study. METHODS: Twenty-five patients were assigned 4 weeks of active or sham rTMS to the right DLPFC. rTMS parameters consisted of 1800 stimuli/day, 1-Hz, at 110% of resting motor threshold. Response was defined as a ≥40% decrease on the panic disorder severity scale and a ≥50% decrease on the Hamilton depression rating scale. At the end of the randomized phase, patients were offered the option of receiving open-label rTMS for an additional 4 weeks. RESULTS: Repeated-measures ANOVA revealed significantly better improvement in panic symptoms with active compared with sham rTMS, but no significant difference in depression. At 4 weeks, response rate for panic disorder was 50% with active rTMS and 8% with sham. After 8 weeks of active rTMS, response rate was 67% for panic and 50% for depressive symptoms. Repeated-measure ANOVA showed significant improvements in panic disorder, major depression, clinical global impression, and social adjustment. Clinical improvement was sustained at 6-month follow-up. LIMITATIONS: Limitation of this study is the relatively small sample size. CONCLUSIONS: Although 4 weeks of rTMS was sufficient to produce a significant effect in panic symptoms, a longer course of treatment resulted in better outcomes for both panic disorder and major depression. These data suggest that inhibitory rTMS to the right DLPFC affects symptoms expression in comorbid anxiety and depression. ClinicalTrials.gov Identifier: NCT00521352.