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Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) and the subthalamic nucleus (STN) has become an established treatment for Parkinson’s disease (PD), a recent meta-analysis of outcomes is lacking. To address this gap, we performed a meta-analysis of bilateral STN- and GPi-DBS studies published from 1990-08/2019. Studies with ≥10 subjects reporting Unified Parkinson’s Disease Rating Scale (UPDRS) III motor scores at baseline and 6–12 months follow-up were included. Several outcome variables were analyzed and adverse events (AE) were summarized. 39 STN studies (2035 subjects) and 5 GPi studies (292 subjects) were eligible. UPDRS-II score after surgery in the stimulation-ON/medication-OFF state compared to preoperative medication-OFF state improved by 47% with STN-DBS and 18.5% with GPi-DBS. UPDRS-III score improved by 50.5% with STN-DBS and 29.8% with GPi-DBS. STN-DBS improved dyskinesia by 64%, daily OFF time by 69.1%, and quality of life measured by PDQ-39 by 22.2%, while Levodopa Equivalent Daily Dose (LEDD) was reduced by 50.0%. For GPi-DBS information regarding dyskinesia, OFF time, PDQ-39 and LEDD was insufficient for further analysis. Correlation analysis showed that preoperative L-dopa responsiveness was highly predictive of the STN-DBS motor outcome across all studies. Most common surgery-related AE were infection (5.1%) and intracranial hemorrhage (3.1%). Despite a series of technological advances, outcomes of modern surgery are still comparable with those of the early days of DBS. Recent changes in target selection with a preference of GPi in elderly patients with cognitive deficits and more psychiatric comorbidities require more published data for validation.

Background Stereotactic biopsies for brainstem lesions are frequently performed to yield an accurate diagnosis and help guide subsequent management. In this study, we summarize our experience with different stereotactic approaches to brainstem lesions of different locations and discuss possible implications for safety and diagnostic yield. Methods We retrospectively analyzed 23 adult patients who underwent a stereotactic biopsy for brainstem lesions between October 2011 and December 2019. Depending on the location supra- or infratentorial, trajectories were planned. We assessed the postoperative complications during the hospital stay as well as the diagnostic yield. Results A supratentorial transfrontal approach was used in 16 (70%) cases, predominantly for lesions in the midbrain, upper pons, and medulla oblongata. An infratentorial, transcerebellar-transpeduncular approach was used in 7 (30%) cases mainly for lesions within the lower pons. All biopsies were confirmed to represent pathological tissue and a definitive diagnosis was achieved in 21 cases (91%). Three patients (13%) had transient weakness in the contralateral part of the body in the immediate postoperative period, which improved spontaneously. There was no permanent morbidity or mortality in this series of patients. Conclusion Lesions of various locations within the brainstem can be successfully targeted via either a supratentorial transfrontal or an infratentorial transcerebellar transpeduncular approach. Our high diagnostic yield of over 90% and the low rate of complications underlines the diagnostic importance of this procedure in order to guide the medical management of these patients.

Epilepsy is defined by the abrupt emergence of harmful seizures, but the nature of these regime shifts remains enigmatic. From the perspective of dynamical systems theory, such critical transitions occur upon inconspicuous perturbations in highly interconnected systems and can be modeled as mathematical bifurcations between alternative regimes. The predictability of critical transitions represents a major challenge, but the theory predicts the appearance of subtle dynamical signatures on the verge of instability. Whether such dynamical signatures can be measured before impending seizures remains uncertain. Here, we verified that predictions on bifurcations applied to the onset of hippocampal seizures, providing concordant results from in silico modeling, optogenetics experiments in male mice and intracranial EEG recordings in human patients with epilepsy. Leveraging pharmacological control over neural excitability, we showed that the boundary between physiological excitability and seizures can be inferred from dynamical signatures passively recorded or actively probed in hippocampal circuits. Of importance for the design of future neurotechnologies, active probing surpassed passive recording to decode underlying levels of neural excitability, notably when assessed from a network of propagating neural responses. Our findings provide a promising approach for predicting and preventing seizures, based on a sound understanding of their dynamics. Understanding the sudden regime shifts leading to epileptic seizures is crucial for developing preventive measures. This research reveals that subtle dynamical changes can indicate impending seizures, and highlights the effectiveness of active probing over passive recording in assessing neural excitability in hippocampal circuits.

How can one trace the brain’s orderly directed signals amid a tangle of nerve fibers? Because direct access to actual brain signaling is rare in humans, the precise wiring diagrams for cortico-limbic communication during sleep and wake remain essentially unmapped, hampering progress in neuroscience. Now, a unique neurosurgical window on the human brain allows for electrically mapping cortical connections at the hospital, but studies so far have relied on average signals, masking the dynamic nature of signal flow across brain regions and vigilance states. To causally estimate signal flow, we repeatedly probed cortico-limbic networks with short-lived electrical pulses over days and assessed the variable fate of each transmitted signal on a single-trial basis. In the resulting openly available dataset, we characterized signaling probabilities and directionality across thousands of local and long-range cortico-limbic connections over days. Challenging established views, we found that limbic structures send twice as many signals as they receive, in both wakefulness and sleep. Our findings provide a fundamental framework for causally interpreting signal flow in the brain and formulating therapeutic strategies for brain network disorders. Here, the authors mapped signal flow over days from intracranial brain recordings in humans. Across vigilance stages, limbic structures sent twice as many signals as they received from the neocortex, challenging the long-standing hypothesis of flow reversal in sleep.

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson’s disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort of 24 Parkinson’s disease patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS’ leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest i) the best lead level, ii) the best contact, and iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56 percent. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41 percent. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact’s effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects.

Background Open and stereotactic transfrontal or transcerebellar approaches have been used to biopsy brainstem lesions. Method In this report, a stereotactic posterior and midline approach to the distal medulla oblongata under microscopic view is described. The potential advantages and limitations are discussed, especially bilateral damage of the X nerve nuclei. Conclusion This approach should be considered for biopsy of distal and posterior lesions. We strongly recommend the use of direct microscopic view to identify the medullary vessels, confirm the midline entry point, and avoid potential shift of the medulla. Further experience is needed to confirm safety and success rate of this approach.

Sleep-wake disturbances (SWD) are frequent in Parkinson's disease (PD). The effect of deep brain stimulation (DBS) on SWD is poorly known. In this study we examined the subjective and objective sleep-wake profile and the quality of life (QoL) of PD patients in the context of subthalamic DBS. We retrospectively analyzed data from PD patients and candidates for DBS in the nucleus suthalamicus (STN). Pre-DBS, sleep-wake assessments included subjective and objective (polysomnography, vigilance tests and actigraphy) measures. Post-DBS, subjective measures were collected. QoL was assessed using the Parkinson's Disease Questionnaire (PDQ-39) and the RAND SF-36-item Health Survey (RAND SF-36). Data from 74 PD patients (62% male, mean age 62.2 years, SD = 8.9) with a mean UPDRS-III (OFF) of 34.2 (SD = 14.8) and 11.8 (SD = 4.5) years under PD treatment were analyzed. Pre-DBS, daytime sleepiness, apathy, fatigue and depressive symptoms were present in 49%, 34%, 38% and 25% of patients respectively but not always as co-occurring symptoms. Sleep-wake disturbances were significantly correlated with QoL scores. One year after STN DBS, motor signs, QoL and sleepiness improved but apathy worsened. Changes in QoL were associated with changes in sleepiness and apathy but baseline sleep-wake functions were not predictive of STN DBS outcome. In PD patients presenting for STN DBS, subjective and objective sleep-wake disturbances are common and have a negative impact on QoL before and after neurosurgery. Given the current preliminary evidence, prospective observational studies assessing subjective and objective sleep-wake variables prior to and after DBS are needed.

Segmented deep brain stimulation leads in the subthalamic nucleus have shown to increase therapeutic window using directional stimulation. However, it is not fully understood how these segmented leads with reduced electrode size modify the volume of tissue activated (VTA) and how this in turn relates with clinically observed therapeutic and side effect currents. Here, we investigated the differences between directional and omnidirectional stimulation and associated VTAs with patient-specific therapeutic and side effect currents for the two stimulation modes. Nine patients with Parkinson's disease underwent DBS implantation in the subthalamic nucleus. Therapeutic and side effect currents were identified intraoperatively with a segmented lead using directional and omnidirectional stimulation (these current thresholds were assessed in a blinded fashion). The electric field around the lead was simulated with a finite-element model for a range of stimulation currents for both stimulation modes. VTAs were estimated from the electric field by numerical differentiation and thresholding. Then for each patient, the VTAs for given therapeutic and side effect currents were projected onto the patient-specific subthalamic nucleus and lead position. Stimulation with segmented leads with reduced electrode size was associated with a significant reduction of VTA and a significant increase of radial distance in the best direction of stimulation. While beneficial effects were associated with activation volumes confined within the anatomical boundaries of the subthalamic nucleus at therapeutic currents, side effects were associated with activation volumes spreading beyond the nucleus' boundaries. The clinical benefits of segmented leads are likely to be obtained by a VTA confined within the subthalamic nucleus and a larger radial distance in the best stimulation direction, while steering the VTA away from unwanted fiber tracts outside the nucleus. Applying the same concepts at a larger scale and in chronically implanted patients may help to predict the best stimulation area.

Epilepsy surgery is a potentially curative treatment option for pharmacoresistent patients. If non-invasive methods alone do not allow to delineate the epileptogenic brain areas the surgical candidates undergo long-term monitoring with intracranial EEG. Visual EEG analysis is then used to identify the seizure onset zone for targeted resection as a standard procedure. Despite of its great potential to assess the epileptogenicty of brain tissue, quantitative EEG analysis has not yet found its way into routine clinical practice. To demonstrate that quantitative EEG may yield clinically highly relevant information we retrospectively investigated how post-operative seizure control is associated with four selected EEG measures evaluated in the resected brain tissue and the seizure onset zone. Importantly, the exact spatial location of the intracranial electrodes was determined by coregistration of pre-operative MRI and post-implantation CT and coregistration with post-resection MRI was used to delineate the extent of tissue resection. Using data-driven thresholding, quantitative EEG results were separated into normally contributing and salient channels. In patients with favorable post-surgical seizure control a significantly larger fraction of salient channels in three of the four quantitative EEG measures was resected than in patients with unfavorable outcome in terms of seizure control (median over the whole peri-ictal recordings). The same statistics revealed no association with post-operative seizure control when EEG channels contributing to the seizure onset zone were studied. We conclude that quantitative EEG measures provide clinically relevant and objective markers of target tissue, which may be used to optimize epilepsy surgery. The finding that differentiation between favorable and unfavorable outcome was better for the fraction of salient values in the resected brain tissue than in the seizure onset zone is consistent with growing evidence that spatially extended networks might be more relevant for seizure generation, evolution and termination than a single highly localized brain region (i.e. a \"focus\") where seizures start.