Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study.

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of "relaxed situations" and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient's unique needs.

Image-based analysis and long-term clinical outcomes of deep brain stimulation for Tourette syndrome: a multisite study.

BACKGROUND: Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS: We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS: Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION: The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

Food Bioactive Compounds and Their Interference in Drug Pharmacokinetic/Pharmacodynamic Profiles.

Preclinical and clinical studies suggest that many food molecules could interact with drug transporters and metabolizing enzymes through different mechanisms, which are predictive of what would be observed clinically. Given the recent incorporation of dietary modifications or supplements in traditional medicine, an increase in potential food-drug interactions has also appeared. The objective of this article is to review data regarding the influence of food on drug efficacy. Data from Google Scholar, PubMed, and Scopus databases was reviewed for publications on pharmaceutical, pharmacokinetic, and pharmacodynamic mechanisms. The following online resources were used to integrate functional and bioinformatic results: FooDB, Phenol-Explorer, Dr. Duke's Phytochemical and Ethnobotanical Databases, DrugBank, UniProt, and IUPHAR/BPS Guide to Pharmacology. A wide range of food compounds were shown to interact with proteins involved in drug pharmacokinetic/pharmacodynamic profiles, starting from drug oral bioavailability to enteric/hepatic transport and metabolism, blood transport, and systemic transport/metabolism. Knowledge of any food components that may interfere with drug efficacy is essential, and would provide a link for obtaining a holistic view for cancer, cardiovascular, musculoskeletal, or neurological therapies. However, preclinical interaction may be irrelevant to clinical interaction, and health professionals should be aware of the limitations if they intend to optimize the therapeutic effects of drugs.

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

Importance: Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. Objective: To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. Design, Setting, and Participants: The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. Exposures: Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). Main Outcomes and Measures: Scores on the Yale Global Tic Severity Scale and adverse events. Results: The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]). Conclusions and Relevance: Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

Sixteen years of deep brain stimulation in Tourette's Syndrome: a critical review.

INTRODUCTION: The aim of this paper was to perform a critical and systematic review of the published papers on deep brain stimulation (DBS) for Tourette's Syndrome (TS). EVIDENCE ACQUISITION: A PubMed search on DBS in TS was conducted selecting papers that reported on the clinical outcome of DBS. EVIDENCE SYNTHESIS: The majority of papers were case reports or small series. The thalamus and the globus pallidus internus appear to be the most promising targets. However, in light of the great methodological diversity a balanced comparison of clinical outcome and understanding of the role of DBS in TS remains difficult. CONCLUSIONS: Despite 16 years of experience with DBS in TS a consensus on many issues, foremost on target selection and the age of inclusion continue to be missing. Class I evidence and international collaborations, to increase the number of included patients, are urgently needed, in order to evaluate further the role of DBS in TS.

Is the Charcot and Bernard case (1883) of loss of visual imagery really based on neurological impairment?

INTRODUCTION. The Charcot and Bernard case of visual imagery, Monsieur X, is a classic case in the history of neuropsychology. Published in 1883, it has been considered the first case of visual imagery loss due to brain injury. Also in recent times a neurological valence has been given to it. However, the presence of analogous cases of loss of visual imagery in the psychiatric field have led us to hypothesise functional origins rather than organic. METHODS. In order to assess the validity of such an inference, we have compared the symptomatology of Monsieur X with that found in cases of loss of visual mental images, both psychiatric and neurological, presented in literature. RESULTS. The clinical findings show strong assonances of the Monsieur X case with the symptoms manifested over time by the patients with functionally based loss of visual imagery. CONCLUSION. Although Monsieur X's damage was initially interpreted as neurological, reports of similar symptoms in the psychiatric field lead us to postulate a functional cause for his impairment as well.

Thalamic single-unit and local field potential activity in Tourette syndrome.

Deep brain stimulation (DBS) of the ventralis oralis (VO) complex of the thalamus improves tics in patients with Tourette syndrome (TS). To neurophysiologically describe the VO complex we recorded, in seven patients with TS undergoing DBS electrode implantation, single-unit activity during surgery and local field potentials (LFPs) a few days after surgery. Single unit recordings showed that the VO complex is characterized by a localized pattern of bursting neuronal activity. LFP spectra demonstrated that VO of TS patients has a prominent oscillatory activity at low frequencies (2-7 Hz) and in the alpha-band (8-13 Hz), and a virtually absent beta activity. In each patient, the main LFP frequency significantly correlated with single-unit interburst frequency. In conclusion, we observed an oscillatory bursting activity in the VO as target region in patients with severe TS undergoing DBS surgery.

De novo and rescue DBS leads for refractory Tourette syndrome patients with severe comorbid OCD: a multiple case report.

Invasive treatment for Gilles de la Tourette syndrome has shown interesting results in a number of published reports; it seems to be evolving into a promising therapeutic procedure for those patients demonstrating disabling clinical pictures who are refractory to conservative treatments. There are important issues concerning the stimulated brain target, with different nuclei currently under investigation. Our group asked in this pilot study whether Tourette syndrome could be treated by tailoring specific brain targets for specific symptoms. Deep brain stimulation for Tourette syndrome may thus in the future be tailored and patient specific, utilizing specific target regions for individual clinical manifestations. In our early experience we did not adequately address non-motor clinical symptoms as we only used a thalamic target. More recently in an obsessive compulsive disease cohort we have had success in using the anterior limb of the internal capsule and nucleus accumbens region as targets for stimulation. We therefore explored the option of a "rescue" procedure for our Tourette patients with persistent obsessive-compulsive disorder following ventralis oralis/centromedianus-parafascicularis (Vo/CM-Pf) deep brain stimulation. Following two cases where rescue anterior limb of internal capsule/nucleus accumbens leads were employed, we performed two additional procedures (anterior limb of the internal capsule plus ventralis oralis/centromedianus-parafascicularis and anterior limb of the internal capsule alone) with some mild improvement of comorbid obsessive-compulsive disorder, although the number of observations in this case series was low. Overall, the effects observed with using the anterior limb of the internal capsule either alone or as a rescue were less than expected. In this report we detail our experience with this approach.

Higher level gait disorders in subcortical chronic vascular encephalopathy: a single photon emission computed tomography study.

BACKGROUND: the so-called higher level gait disorders include several types of gait disorders in which there are no major modifications in strength, tone, sensitivity, coordination and balance. Brain activation sites related to walking have been investigated using SPECT in humans. The aim of the study was to investigate brain activation during walking in subjects with high-level gait disorders due to chronic subcortical vascular encephalopathy. SUBJECTS: twelve patients with a chronic vascular encephalopathy were enrolled in the study. Seven subjects had apraxic gait while in the other five the gait was normal. All patients had undergone a recent cerebral magnetic resonance that revealed diffused chronic ischemic lesions within the white matter. METHODS: all 12 patients underwent a regional cerebral blood flow (rCBF) brain SPECT study with (99m)Tc-Bicisate on two separate days and under two different conditions: at rest (baseline) and while walking (functional). RESULTS: the rCBF increase induced by the treadmill test (functional-baseline), bilaterally in the medial frontal gyrus and in the anterior lobes of the cerebellum, resulted significantly (P < 0.001) lower in patients with gait apraxia versus those without it. CONCLUSIONS: this study of the brain with SPECT records the areas of perfusion deficit that appear in apraxic subjects when they walk, compared with the recordings obtained with the same investigation performed at rest.

Botulinum toxin (BoNT) and back pain.

Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.