Tourette syndrome is a chronic neurodevelopmental disorder characterised by motor and phonic tics that can substantially diminish the quality of life of affected individuals. Evaluating and treating ...Tourette syndrome is complex, in part due to the heterogeneity of symptoms and comorbidities between individuals. The underlying pathophysiology of Tourette syndrome is not fully understood, but recent research in the past 5 years has brought new insights into the genetic variations and the alterations in neurophysiology and brain networks contributing to its pathogenesis. Treatment options for Tourette syndrome are expanding with novel pharmacological therapies and increased use of deep brain stimulation for patients with symptoms that are refractory to pharmacological or behavioural treatments. Potential predictors of patient responses to therapies for Tourette syndrome, such as specific networks modulated during deep brain stimulation, can guide clinical decisions. Multicentre data sharing initiatives have enabled several advances in our understanding of the genetics and pathophysiology of Tourette syndrome and will be crucial for future large-scale research and in refining effective treatments.
Background
Adult horses with proprioceptive ataxia and behavior changes that have histologic lesions consistent with neurodegenerative disease have been increasingly recognized.
Hypothesis/Objectives
...Describe the history, clinical findings and histopathologic features of horses presented to a referral institution with neuroaxonal degeneration.
Animals
One hundred horses with a necropsy diagnosis of neuroaxonal degeneration compatible with neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM).
Methods
Retrospective study of horses presented to the University of Pennsylvania, New Bolton Center, between 2017 and 2021 with a necropsy diagnosis of eNAD/EDM.
Results
Affected horses had a median age of 8 years (range, 1‐22), and the majority were Warmbloods (72). Sixty‐eight horses had behavioral changes, and all 100 had proprioceptive ataxia (median grade, 2/5). Fifty‐seven horses had abnormal findings on cervical vertebral radiographs, and 14 had myelographic findings consistent with compressive myelopathy. No antemortem diagnostic test results were consistently associated with necropsy diagnosis of neurodegenerative disease. All 100 horses had degenerative lesions characteristic of eNAD in the brainstem gray matter, and 24 had concurrent degenerative features of EDM in the spinal cord white matter.
Conclusions and Clinical Importance
Clinical and histopathologic findings in this large group of horses with neurodegenerative disease were most consistent with eNAD/EDM, but with a different signalment and clinical presentation from earlier descriptions. The increasing occurrence of neurodegenerative disease in horses and the safety risk posed emphasize the importance of focused research in affected horses.
BackgroundDeep 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.MethodsWe 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.ResultsTics 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.ConclusionThe 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.
Deep brain stimulation (DBS) has advanced treatment options for a variety of neurologic and neuropsychiatric conditions. As the technology for DBS continues to progress, treatment efficacy will ...continue to improve and disease indications will expand. Hardware advances such as longer-lasting batteries will reduce the frequency of battery replacement and segmented leads will facilitate improvements in the effectiveness of stimulation and have the potential to minimize stimulation side effects. Targeting advances such as specialized imaging sequences and "connectomics" will facilitate improved accuracy for lead positioning and trajectory planning. Software advances such as closed-loop stimulation and remote programming will enable DBS to be a more personalized and accessible technology. The future of DBS continues to be promising and holds the potential to further improve quality of life. In this review we will address the past, present and future of DBS.
Background Late gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation ...( AF ) ablation success at 1 year, but the association between left atrial fibrosis and long-term ablation success has not been studied. Methods and Results Late gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0-10%; II , 10-20%; III , 20-30%; and IV , >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow-up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57-4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12-12.69). Conclusions The degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow-up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.
Circadian rhythms have been shown in the subthalamic nucleus (STN) in Parkinson's disease (PD), but only a few studies have focused on the globus pallidus internus (GPi). This retrospective study ...investigates GPi circadian rhythms in a large cohort of subjects with PD (130 recordings from 93 subjects) with GPi activity chronically recorded in their home environment. We found a significant change in GPi activity between daytime and nighttime in most subjects (82.4%), with a reduction in GPi activity at nighttime in 56.2% of recordings and an increase in activity in 26.2%. GPi activity in higher frequency bands ( > 20 Hz) was more likely to decrease at night and in patients taking extended-release levodopa medication. Our results suggest that circadian fluctuations in the GPi vary across individuals and that increased power at night might be due to the reemergence of pathological neural activity. These findings should be considered to ensure successful implementation of adaptive neurostimulation paradigms in the real-world.
Deep brain stimulation (DBS) has emerged as a promising treatment for select patients with refractory major depressive disorder (MDD). The clinical effectiveness of DBS for MDD has been demonstrated ...in meta-analyses, open-label studies, and a few controlled studies. However, randomized controlled trials have yielded mixed outcomes, highlighting challenges that must be addressed prior to widespread adoption of DBS for MDD. These challenges include tracking MDD symptoms objectively to evaluate the clinical effectiveness of DBS with sensitivity and specificity, identifying the patient population that is most likely to benefit from DBS, selecting the optimal patient-specific surgical target and stimulation parameters, and understanding the mechanisms underpinning the therapeutic benefits of DBS in the context of MDD pathophysiology. In this review, we provide an overview of the latest clinical evidence of MDD DBS effectiveness and the recent technological advancements that could transform our understanding of MDD pathophysiology, improve the clinical outcomes for MDD DBS, and establish a path forward to develop more effective neuromodulation therapies to alleviate depressive symptoms.
Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to ...predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.
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