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Deep brain stimulation (DBS) is an established procedure for the symptomatic treatment of Parkinson's disease. Several deep brain nuclei have been stimulated, producing a wide range of effects on the motor and non-motor symptoms of Parkinson's disease. Long-term, high-quality evidence is available for stimulation of the subthalamic nucleus and globus pallidus internus, both of which uniformly improve motor features, and for stimulation of the thalamic ventralis intermedius, which improves tremor. Short-term data are available for stimulation of other deep brain targets, such as the pedunculopontine nucleus and the centremedian/parafascicular thalamic complex. Some non-motor symptoms improve after DBS, partly because of motor benefit or reduction of drug treatment, and partly as a direct effect of stimulation. More evidence on the effects of DBS on non-motor symptoms is needed and specifically designed studies are warranted.

Our understanding of dysfunction of the gastrointestinal system in patients with Parkinson's disease has increased substantially in the past decade. The entire gastrointestinal tract is affected in these patients, causing complications that range from oral issues, including drooling and swallowing problems, to delays in gastric emptying and constipation. Additionally, small intestinal bacterial overgrowth and Helicobacter pylori infection affect motor fluctuations by interfering with the absorption of antiparkinsonian drugs. The multifaceted role of the gastrointestinal system in Parkinson's disease necessitates a specific and detailed assessment and treatment plan. The presence of pervasive α-synuclein deposition in the gastrointestinal tract strongly implicates this system in the pathogenesis of Parkinson's disease. Future studies elucidating the role of the gastrointestinal tract in the pathological progression of Parkinson's disease might hold potential for early disease detection and development of neuroprotective approaches.

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%–90%), RS (range, 48%–63%) and FUS thalamotomy (range, 35%–75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%–78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET.

Commonly used for Parkinson’s disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming. Deep brain stimulation programming for Parkinson’s disease entails the assessment of a large number of possible simulation settings, requiring numerous clinic visits after surgery. Here, the authors show that patterns of functional MRI can predict the optimal stimulation settings.

In patients with Parkinson’s disease, focused ultrasound ablation of the globus pallidus internus reduced motor impairment and dyskinesias at 3 months. Adverse events included dysarthria, gait disturbance, and loss of taste.

Transcranial ultrasound stimulation (TUS) offers precise, non-invasive neuromodulation, though its impact on human deep brain structures remains underexplored. Here we examined TUS-induced changes in the basal ganglia of 10 individuals with movement disorders (Parkinson’s disease and dystonia) and 15 healthy participants. Local field potentials were recorded using deep brain stimulation (DBS) leads in the globus pallidus internus (GPi). Compared to sham, theta burst TUS (tbTUS) increased theta power during stimulation, while 10 Hz TUS enhanced beta power, with effects lasting up to 40 min. In healthy participants, a stop-signal task assessed tbTUS effects on the GPi, with pulvinar stimulation serving as an active sham. GPi TUS prolonged stop-signal reaction times, indicating impaired response inhibition, whereas pulvinar TUS had no effect. These findings provide direct electrophysiological evidence of TUS target engagement and specificity in deep brain structures, suggesting its potential as a noninvasive DBS strategy for neurological and psychiatric disorders. Transcranial ultrasound stimulation (TUS) is a non-invasive method to modulate deep brain activity. Using direct recordings from implanted electrodes, we showed that TUS engages the human globus pallidus internus, with effects on neural oscillations and behavior.

While there is no breakthrough progress in the medical treatment of essential tremor (ET), in the past decades several remarkable achievements happened in the surgical field, such as radiofrequency thalamotomy, thalamic deep brain stimulation, and gamma knife thalamotomy. The most recent advance in this area is magnetic resonance-guided focused ultrasound (MRgFUS). The purpose of this review is to discuss the new developments and trials of MRgFUS in the treatment of ET and other tremor disorders. MRgFUS is an incisionless surgery performed without anesthesia and ionizing radiation (no risk of cumulative dose and delayed side effects). Studies have shown the safety and effectiveness of unilateral MRgFUS-thalamotomy in the treatment of ET. It has been successfully used in a few patients with Parkinson's disease-related tremor, and in fewer patients with fragile X-associated tremor/ataxia syndrome. The safety and long-term effects of the procedure are still unclear, as temporary and permanent adverse events have been reported as well as recurrence of tremor. MRgFUS is a promising new surgical approach with a number of unknowns and unsolved issues. It represents a valuable option particularly for patients who refused or could not be candidates for other procedures, deep brain stimulation in particular.

Parkinson's disease (PD) patients have impairment of facial expressivity (hypomimia) and difficulties in interpreting the emotional facial expressions produced by others, especially for aversive emotions. We aimed to evaluate the ability to produce facial emotional expressions and to recognize facial emotional expressions produced by others in a group of PD patients and a group of healthy participants in order to explore the relationship between these two abilities and any differences between the two groups of participants. Twenty non-demented, non-depressed PD patients and twenty healthy participants (HC) matched for demographic characteristics were studied. The ability of recognizing emotional facial expressions was assessed with the Ekman 60-faces test (Emotion recognition task). Participants were video-recorded while posing facial expressions of 6 primary emotions (happiness, sadness, surprise, disgust, fear and anger). The most expressive pictures for each emotion were derived from the videos. Ten healthy raters were asked to look at the pictures displayed on a computer-screen in pseudo-random fashion and to identify the emotional label in a six-forced-choice response format (Emotion expressivity task). Reaction time (RT) and accuracy of responses were recorded. At the end of each trial the participant was asked to rate his/her confidence in his/her perceived accuracy of response. For emotion recognition, PD reported lower score than HC for Ekman total score (p<0.001), and for single emotions sub-scores happiness, fear, anger, sadness (p<0.01) and surprise (p = 0.02). In the facial emotion expressivity task, PD and HC significantly differed in the total score (p = 0.05) and in the sub-scores for happiness, sadness, anger (all p<0.001). RT and the level of confidence showed significant differences between PD and HC for the same emotions. There was a significant positive correlation between the emotion facial recognition and expressivity in both groups; the correlation was even stronger when ranking emotions from the best recognized to the worst (R = 0.75, p = 0.004). PD patients showed difficulties in recognizing emotional facial expressions produced by others and in posing facial emotional expressions compared to healthy subjects. The linear correlation between recognition and expression in both experimental groups suggests that the two mechanisms share a common system, which could be deteriorated in patients with PD. These results open new clinical and rehabilitation perspectives.

Neurological disorders of gait, balance and posture are both debilitating and common. Adequate recognition of these so-called disorders of axial mobility is important as they can offer useful clues to the underlying pathology in patients with an uncertain clinical diagnosis, such as those early in the course of neurological disorders. Medical teaching programmes typically take classic clinical presentations as the starting point and present students with a representative constellation of features that jointly characterize a particular axial motor syndrome. However, patients rarely present in this way to a physician in clinical practice. Particularly in the early stages of a disease, patients might display just one (or at best only a few) abnormal signs of gait, balance or posture. Importantly, these individual signs are never pathognomonic for any specific disorder but rather come with an associated differential diagnosis. In this Perspective, we offer a new diagnostic approach in which the presenting signs are taken as the starting point for a focused differential diagnosis and a tailored search into the underlying neurological syndrome.

Over the past 30 years, botulinum toxin (BoNT) has seen an ever-expanding use in disorders afflicting the nervous system [...].Over the past 30 years, botulinum toxin (BoNT) has seen an ever-expanding use in disorders afflicting the nervous system [...].