Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography (ECoG) and subthalamic local field potential (LFP) recordings were performed OFF therapy (N = 22), ON dopaminergic medication (N = 18) and ON subthalamic deep brain stimulation (N = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography (EMG). In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Personalizing Deep Brain Stimulation Using Advanced Imaging Sequences.

OBJECTIVE: With a growing appreciation for interindividual anatomical variability and patient-specific brain connectivity, advanced imaging sequences offer the opportunity to directly visualize anatomical targets for deep brain stimulation (DBS). The lack of quantitative evidence demonstrating their clinical utility, however, has hindered their broad implementation in clinical practice. METHODS: Using fast gray matter acquisition T1 inversion recovery (FGATIR) sequences, the present study identified a thalamic hypointensity that holds promise as a visual marker in DBS. To validate the clinical utility of the identified hypointensity, we retrospectively analyzed 65 patients (26 female, mean age = 69.1 ± 12.7 years) who underwent DBS in the treatment of essential tremor. We characterized its neuroanatomical substrates and evaluated the hypointensity's ability to predict clinical outcome using stimulation volume modeling and voxelwise mapping. Finally, we determined whether the hypointensity marker could predict symptom improvement on a patient-specific level. RESULTS: Anatomical characterization suggested that the identified hypointensity constituted the terminal part of the dentatorubrothalamic tract. Overlap between DBS stimulation volumes and the hypointensity in standard space significantly correlated with tremor improvement (R2  = 0.16, p = 0.017) and distance to hotspots previously reported in the literature (R2  = 0.49, p = 7.9e-4). In contrast, the amount of variance explained by other anatomical atlas structures was reduced. When accounting for interindividual neuroanatomical variability, the predictive power of the hypointensity increased further (R2  = 0.37, p = 0.002). INTERPRETATION: Our findings introduce and validate a novel imaging-based marker attainable from FGATIR sequences that has the potential to personalize and inform targeting and programming in DBS for essential tremor. ANN NEUROL 2022;91:613-628.

Local Field Potentials Predict Motor Performance in Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) is an effective treatment option for patients with Parkinson's disease (PD). However, clinical programming remains challenging with segmented electrodes. OBJECTIVE: Using novel sensing-enabled neurostimulators, we investigated local field potentials (LFPs) and their modulation by DBS to assess whether electrophysiological biomarkers may facilitate clinical programming in chronically implanted patients. METHODS: Sixteen patients (31 hemispheres) with PD implanted with segmented electrodes in the subthalamic nucleus and a sensing-enabled neurostimulator were included in this study. Recordings were conducted 3 months after DBS surgery following overnight withdrawal of dopaminergic medication. LFPs were acquired while stimulation was turned OFF and during a monopolar review of both directional and ring contacts. Directional beta power and stimulation-induced beta power suppression were computed. Motor performance, as assessed by a pronation-supination task, clinical programming and electrode placement were correlated to directional beta power and stimulation-induced beta power suppression. RESULTS: Better motor performance was associated with stronger beta power suppression at higher stimulation amplitudes. Across directional contacts, differences in directional beta power and the extent of stimulation-induced beta power suppression predicted motor performance. However, within individual hemispheres, beta power suppression was superior to directional beta power in selecting the contact with the best motor performance. Contacts clinically activated for chronic stimulation were associated with stronger beta power suppression than non-activated contacts. CONCLUSIONS: Our results suggest that stimulation-induced ß power suppression is superior to directional ß power in selecting the clinically most effective contact. In sum, electrophysiological biomarkers may guide programming of directional DBS systems in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Christmas-Related Reduction in Beta Activity in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus (STN) beta (13 - 35 Hz) activity is a biomarker reflecting motor state in Parkinson's disease (PD). Adaptive deep brain stimulation (DBS) aims to use beta activity for therapeutic adjustments, but many aspects of beta activity in real-life situations are unknown. OBJECTIVE: The aim was to investigate Christmas-related influences on beta activity in PD. METHODS: Differences in Christmas Day to nonfestive daily averages in chronic biomarker recordings in 4 PD patients with a sensing-enabled STN DBS implant were retrospectively analyzed. Sweet-spot and whole-brain network connectomic analyses were performed. RESULTS: Beta activity was significantly reduced on Christmas Eve in all patients (4.00-9.00 p.m.: -12.30 ± 10.78%, P = 0.015). A sweet spot in the dorsolateral STN connected recording sites to motor, premotor, and supplementary motor cortices. CONCLUSIONS: We demonstrate that festive events can reduce beta biomarker activity. We conclude that circadian and holiday-related changes should be considered when tailoring adaptive DBS algorithms to patient demands. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Surgical Site Infections Associated With Implanted Pulse Generators for Deep Brain Stimulation: Meta-Analysis and Systematic Review.

OBJECTIVES: The aim of this study was to identify and systematically analyze relevant literature on surgical site infections (SSIs) associated with implantable pulse generator (IPG) procedures for deep brain stimulation (DBS). MATERIALS AND METHODS: In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic review and meta-analyses of 58 studies that reported SSI rates of 11,289 patients and 15,956 IPG procedures. A meta-analysis of proportions was performed to estimate the pooled proportion of SSIs across DBS procedures in general and to estimate the proportion of SSIs that occur at the IPG pocket. Moreover, a meta-analysis of odds ratio (OR) was conducted on those studies that reported their results of applying topical vancomycin powder during closure of the IPG wound. Results are presented as rates and OR with 95% CIs. RESULTS: The pooled proportion of SSIs was 4.9% (95% CI, 4.1%-6.1%) among all DBS procedures. The dominant SSI localization was the IPG pocket in 61.2% (95% CI, 53.4%-68.5%). A trend toward a beneficial effect of vancomycin powder over standard wound closure was found with an OR of 0.46 (95% CI, 0.21-1.02). Most studies (79.1%) that reported their treatment strategy in case of SSI had a strict protocol of removal of the IPG, followed by antimicrobial treatment and reimplantation of the IPG once the SSI had been eradicated. CONCLUSIONS: The IPG pocket was identified as the main site of SSI after DBS procedures. Most studies recommend complete IPG removal, antimicrobial treatment, and reimplantation of an IPG once the SSI has been eradicated. Future studies are needed to clarify the role of alternative approaches (eg, topical vancomycin powder) in the prevention of SSI associated with IPG.

High Frequency of Low-Virulent Microorganisms Detected by Sonication of Implanted Pulse Generators: So What?

INTRODUCTION: Deep brain stimulation (DBS) has become a well-established treatment modality for a variety of conditions over the last decades. Multiple surgeries are an essential part in the postoperative course of DBS patients if nonrechargeable implanted pulse generators (IPGs) are applied. So far, the rate of subclinical infections in this field is unknown. In this prospective cohort study, we used sonication to evaluate possible microbial colonization of IPGs from replacement surgery. METHODS: All consecutive patients undergoing IPG replacement between May 1, 2019 and November 15, 2020 were evaluated. The removed hardware was investigated using sonication to detect biofilm-associated bacteria. Demographic and clinical data were analyzed. RESULTS: A total of 71 patients with a mean (±SD) of 64.5 ± 15.3 years were evaluated. In 23 of these (i.e., 32.4%) patients, a positive sonication culture was found. In total, 25 microorganisms were detected. The most common isolated microorganisms were Cutibacterium acnes (formerly known as Propionibacterium acnes) (68%) and coagulase-negative Staphylococci (28%). Within the follow-up period (5.2 ± 4.3 months), none of the patients developed a clinical manifest infection. DISCUSSIONS/CONCLUSIONS: Bacterial colonization of IPGs without clinical signs of infection is common but does not lead to manifest infection. Further larger studies are warranted to clarify the impact of low-virulent pathogens in clinically asymptomatic patients.

Deep brain stimulation for Parkinson's disease-related postural abnormalities: a systematic review and meta-analysis.

Deep brain stimulation (DBS) has become a well-established treatment modality for Parkinson's disease (PD), especially regarding motor fluctuations, dyskinesias, and tremor. Although postural abnormalities (i.e., Camptocormia [CC] and Pisa syndrome [Pisa]) are known to be a major symptom of PD as well, the influence of DBS on postural abnormalities is unclear. The objective of this study is to analyze the existing literature regarding DBS for PD-associated postural abnormalities in a systematic review and meta-analysis. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review and meta-analysis of 18 studies that reported the effect of DBS regarding postural abnormalities. After screening of 53 studies, a total of 98 patients (44 female, 53 males, 1 not reported; mean age: 62.3, range 30-83 years) with postural abnormalities (CC n = 98; Pisa n = 11) were analyzed from 18 included studies. Of those patients, 94.9% underwent STN-DBS and 5.1% had GPi as DBS target area. A positive outcome was reported for 67.8% with CC and 72.2% with Pisa. In the meta-analysis, younger age and lower pre-operative UPDRS-III (ON/OFF) were found as positive predictive factors for a positive effect of DBS. DBS might be a potentially effective treatment option for PD-associated postural abnormalities. However, the level of evidence is rather low, and definition of postoperative outcome is heterogenous between studies. Therefore larger, prospective trials are necessary to give a clear recommendation.

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery.

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.

A noninvasive method to quantify the impairment of spinal motion ability in Parkinson's disease.

PURPOSE: There is a high demand on spinal surgery in patients with Parkinson's disease (PD) but the results are sobering. Although detailed clinical and radiological diagnostics were carried out with great effort and expense, the biodynamic properties of the spine of PD patients have never been considered. We propose a noninvasive method to quantify the impairment of motion abilities in patients with PD. METHODS: We present an analytical cross-sectional study of 21 patients with severe PD. All patients underwent a biodynamic assessment during a standardized movement-choreography. Thus, individual spinal motion profiles of each patient were objectively assessed and compared with a large comparative cohort of individuals without PD. Moreover, clinical scores to quantify motor function and lumbar back pain were collected and X-ray scans of the spine in standing position were taken and analysed. RESULTS: Biodynamic measurement showed that 36.9% of the assessed motions of all PD patients were severely impaired. Men were generally more functionally impaired than women, in 52% of all motion parameters. The neurological and radiological diagnostics recorded pathological values, of which UPDRS-III ON correlated with findings of the biodynamics assessment (R = 0.52, p = 0.02). CONCLUSIONS: The decision to operate on a PD patient's spine is far-reaching and requires careful consideration. Neurological and radiological scores did not correlate with the biodynamics of the spine. The resulting motion profile could be used as individual predictive factor to estimate whether patients are eligible for spinal surgery or alternative therapies.

Morphological Abnormalities in the Basal Ganglia of Dystonia Patients.

OBJECTIVE: The pathophysiology of dystonia is poorly understood. As opposed to secondary forms of dystonia, primary dystonia has long been believed to lack any neuroanatomical substrate. During trajectory planning for DBS, however, conspicuous T2-hyperinstensive signal alterations (SA) were registered within the target region, even in young patients, where ischemia is rare. METHODS: Fifty MRIs of primary dystonia patients scheduled for DBS were analyzed. Total basal ganglia (BG) volumes, as well as proportionate SA volumes, were measured and compared to 50 age-matched control patients. RESULTS: There was a 10-fold preponderance of percentaged SA within the globus pallidus (GP) in dystonia patients. The greatest disparity was in young patients <25 years. Also, total BG volume differences were observed with larger GP and markedly smaller putamen and caudate in the dystonia group. CONCLUSIONS: BG morphology in primary dystonia differed from a control population. Volume reductions of the putamen and caudate may reflect functional degeneration, while volume increases of the GP may indicate overactivity. T2-hyperintensive SA in the GP of young primary dystonia patients, where microvascular lesions are highly unlikely, are striking. Their pathogenic role remains unclear.

The Effects of Deep Brain Stimulation of the Subthalamic Nucleus on Vascular Endothelial Growth Factor, Brain-Derived Neurotrophic Factor, and Glial Cell Line-Derived Neurotrophic Factor in a Rat Model of Parkinson's Disease.

OBJECTIVE: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has evolved as a powerful therapeutic alternative for the treatment of Parkinson's disease (PD). Despite its clinical efficacy, the mechanisms of action have remained poorly understood. In addition to the immediate symptomatic effects, long-term neuroprotective effects have been suggested. Those may be mediated through neurotrophic factors (NFs) like vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF). Here, the impact of DBS on the expression of NFs was analysed in a rat model of PD. METHODS: Unilateral 6-hydroxydopamine (6-OHDA) lesioned rats received DBS in the STN using an implantable microstimulation system, sham DBS in the STN, or no electrode placement. Continuous unilateral STN-DBS (current intensity 50 µA, frequency 130 Hz, and pulse width 52 µs) was conducted for 14 days. Rats were then sacrificed and brains shock frozen. Striata and motor cortices were dissected with a cryostat. Levels of VEGF, BDNF, and GDNF were analysed, both by quantitative PCR and colorimetric ELISA. RESULTS: PCR revealed a significant upregulation of only BDNF mRNA in the ipsilateral striata of the DBS group, when compared to the sham-stimulated group. There was no significant increase in VEGF mRNA or GDNF mRNA. ELISA analysis showed augmentations of BDNF, VEGF, as well as GDNF protein in the ipsilateral striata after DBS compared to sham stimulation. In the motor cortex, significant increases after DBS were observed for BDNF only, not for the other 2 NFs. CONCLUSIONS: The upregulation of trophic factors induced by STN-DBS may participate in its long-term therapeutic efficacy and potentially neuroprotective effects.

Risk of Infection after Deep Brain Stimulation Surgery with Externalization and Local-Field Potential Recordings: Twelve-Year Experience from a Single Institution.

INTRODUCTION: Deep brain stimulation (DBS) has been an established surgical procedure in the field of functional neurosurgery for many years. The experimental electrophysiological method of local field potential (LFP) recordings in postsurgically externalized patients has made substantial contributions to the better understanding of pathophysiologies underlying movement disorders. As interest in LFP recordings for the development of improved stimulation strategies increases, this study's aim was to provide evidence concerning safety of this research method, in a major DBS center. METHODS: We retrospectively analyzed incidence and infection characteristics in adult patients who underwent two-staged DBS surgery with temporary externalization of leads in our center between January 2008 and November 2019. We focused on whether patients had participated in LFP recordings, and evaluated incidence of infections at 3 months and 1 year after the surgery based on medical records. Infection rates were compared to major DBS studies and reports focusing on the risk of infection due to externalization of DBS leads. Results were visualized using descriptive statistics. RESULTS: Between January 2008 and November 2019, DBS surgery was performed in 528 patients (389/139 patients in the LFP/non-LFP group), mainly for movement disorders such as Parkinson's disease (308), dystonia (93), and essential tremor (86). Of the patients, 72.9% participated in LFP recordings. The incidence of infections in the acute postsurgical phase (3 months) was 2.46% and did not differ significantly between the LFP group (1.8%) and the non-LFP group (4.32%). The overall incidence after 1 year amounted to 3.6% (19 patients) with no difference between LFP/non-LFP groups. Incidence rates reported in the literature show a large variety (2.6-10%), and the incidence reported here is within the lower range of reported incidences. DISCUSSION/CONCLUSION: This study demonstrates that DBS is a surgical procedure with a low risk of infection in a large patient cohort. Importantly, it shows that LFP recordings do not have a significant effect on the incidence of infections in patients with externalization. With a representative cohort of more than 380 patients participating in LFP-recordings, this underlines LFP as a safe method in research and supports further use of this method, for example, for the development of adaptive stimulation protocols.

Clinical Efficacy of Bilateral Deep Brain Stimulation Does Not Change After Implantable Pulse Generator Replacement but the Impedances Do: A Prospective Study.

BACKGROUND: Deep brain stimulation (DBS) is an approved therapy option for movement disorders such as Parkinson's disease (PD), essential Tremor (ET), and dystonia. While current research focuses on rechargeable implantable pulse generators (IPGs), little is known about changes of the motor functions after IPG replacement and the consequences of additionally implanted hardware. OBJECTIVE: To assess changes of the motor functions, the therapy impedances, and the total electric energy delivered (TEED) after elective IPG replacement. METHODS: We prospectively acquired the data of 47 patients with PD, ET, and dystonia treated with bilateral DBS. Motor functions were rated prior to and after surgery using the revised Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS-III), the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTM-TRS), and the Unified Dystonia Rating Scale (UDRS). Furthermore, the therapy impedances and TEED were assessed at the aforementioned times. RESULTS: While preoperative motor scores were 48.32 ± 17.16 in PD, 39.71 ± 12.28 in ET, and 18.48 ± 16.30 in dystonia patients, postoperative scores were 47.84 ± 24.33, 32.86 ± 15.82, and 15.02 ± 15.17, respectively. Only in dystonia patients, motor scores significantly differed. Perioperative therapy impedance changes were 142.66 ± 105.35 Ω (Kinetra® to Activa® PC), -68.75 ± 43.05 Ω (Activa® PC to Activa® PC), and - 51.38 ± 38.75 Ω (Activa® PC to Activa® RC). Perioperative TEED changes were - 37.15 ± 38.87 µJ, 2.03 ± 35.91 µJ, and 12.39 ± 6.31 µJ in that first, second, and third group, respectively. Both the therapy impedances and TEED significantly differed between groups. CONCLUSION: Although there were no statistically significant changes in the motor functions of all patients after elective IPG replacement, the therapy impedances were significantly higher and TEED was significantly lower after IPG replacement with concurrent Pocket Adapter implantation.

Utilization of the Intraoperative Mobile AIRO® CT Scanner in Stereotactic Surgery: Workflow and Effectiveness.

BACKGROUND: In frame-based stereotactic surgery, intraoperative imaging is crucial. It generally follows a workflow including preoperative MRI and intraoperative frame-based CT. The intraoperative transport of the anesthetized and intubated patient to and from the CT unit can be time-consuming and cumbersome. Here, we report the first 50 patients who underwent stereotactic biopsies using the mobile AIRO® intraoperative CT (iCT) scanner. METHODS: A conventional stereotactic frame was mounted to the AIRO® carbon table via carbon adapter. 0°gantry thin-slice iCT was performed. The imaging data were transferred to a conventional stereotaxy working unit. After fusion of the preoperative MRI and AIRO® iCT, the stereotactic system was built based on the iCT, and trajectories were calculated accordingly. RESULTS: The frame-based stereotactic iCT was easy to implement and successfully accomplished in all patients. The MRI/iCT image fusion was feasible in all of the studies. A conclusive histological result was obtained in 46 of the 50 cases included. There was no bleeding complication. Net surgery time was reduced by 38 min, on average. CONCLUSION: We conclude that the AIRO® system is a safe, easy-to-use, and sufficiently accurate iCT for CT frame-based stereotactic biopsy planning that results in a considerable reduction of surgery time. In the future, it remains to be evaluated if the accuracy rates and intraoperative workflow will permit its application in deep brain stimulation and other functional procedures as well.

Longevity of Implantable Pulse Generators in Bilateral Deep Brain Stimulation for Movement Disorders.

BACKGROUND: Deep brain stimulation (DBS) is a well-established therapy for otherwise intractable movement disorders. Thus far, most patients receive nonrechargeable implantable pulse generators (IPG). Eventually, another intervention to replace the IPG is inevitable. OBJECTIVE: We assessed IPG model-specific differences in longevity in patients planned for IPG replacement. Also, we evaluated the influence of the total electric energy delivered (TEED), the amount of previous IPG replacements, and previous IPG model changes on the longevity. METHODS: We collected the demographic data and DBS settings of 47 patients (19 with Parkinson's disease, 7 with essential tremor, and 21 with dystonia) that were treated either with Medtronic's Kinetra® (N = 16) or Activa® PC (N = 31). Statistical analysis was performed using Mann-Whitney U test and Spearman's rank correlation. RESULTS: Battery longevity was shorter in the Activa PC than in the Kinetra (40.16 ± 15.22 vs. 70.35 ± 24.45 months; p < 0.001). Further analysis showed an inverse correlation of the longevity to TEED (r = -0.529; p < 0.001) and the number of previous IPG replacements (r = -0.588; p < 0.001). Furthermore, patients with more frequent replacements had higher TEED (r = 0.501; p < 0.001) and patients, whose Kinetra was replaced with the Activa PC before, had shorter IPG longevity (28.36 ± 9.82 vs. 45.78 ± 14.19 months; p = 0.006). CONCLUSION: Our findings imply that IPG longevity is shorter in the Activa PC compared to the Kinetra. Higher TEED and more frequent IPG replacements might reduce IPG longevity.

Critical illness myopathy and GLUT4: significance of insulin and muscle contraction.

RATIONALE: Critical illness myopathy (CIM) has no known cause and no treatment. Immobilization and impaired glucose metabolism are implicated. OBJECTIVES: We assessed signal transduction in skeletal muscle of patients at risk for CIM. We also investigated the effects of evoked muscle contraction. METHODS: In a prospective observational and interventional pilot study, we screened 874 mechanically ventilated patients with a sepsis-related organ-failure assessment score greater than or equal to 8 for 3 consecutive days in the first 5 days of intensive care unit stay. Thirty patients at risk for CIM underwent euglycemic-hyperinsulinemic clamp, muscle microdialysis studies, and muscle biopsies. Control subjects were healthy. In five additional patients at risk for CIM, we performed corresponding analyses after 12-day, daily, unilateral electrical muscle stimulation with the contralateral leg as control. MEASUREMENTS AND MAIN RESULTS: We performed successive muscle biopsies and assessed systemic insulin sensitivity and signal transduction pathways of glucose utilization at the mRNA and protein level and glucose transporter-4 (GLUT4) localization in skeletal muscle tissue. Skeletal muscle GLUT4 was trapped at perinuclear spaces, most pronounced in patients with CIM, but resided at the sarcolemma in control subjects. Glucose metabolism was not stimulated during euglycemic-hyperinsulinergic clamp. Insulin signal transduction was competent up to p-Akt activation; however, p-adenosine monophosphate-activated protein kinase (p-AMPK) was not detectable in CIM muscle. Electrical muscle stimulation increased p-AMPK, repositioned GLUT4, locally improved glucose metabolism, and prevented type-2 fiber atrophy. CONCLUSIONS: Insufficient GLUT4 translocation results in decreased glucose supply in patients with CIM. Failed AMPK activation is involved. Evoked muscle contraction may prevent muscle-specific AMPK failure, restore GLUT4 disposition, and diminish protein breakdown. Clinical trial registered with http://www.controlled-trials.com (registration number ISRCTN77569430).

Approaches to temporal lobe lesions: a proposal for classification.

BACKGROUND: Tumor surgery in the temporal region is challenging due to anatomical complexity and the versatility of surgical approaches. The aim was to categorize temporal lobe tumors based on anatomical, functional, and vascular considerations and to devise a systematic field manual of surgical approaches. METHODS: Tumors were classified into four main types with assigned approaches: Type I-lateral: transcortical; type II-polar: pterional/transcortical; type III-central: transsylvian/trans-opercular; type IV-mesial: transsylvian/trans-cisternal if more anterior (=Type IV A), and supratentorial/infraoccipital if more posterior (=type IV B). 105 patients have been operated on prospectively using the advocated guidelines. Outcomes were evaluated. CONCLUSION: Systematic application of the proposed classification facilitated a tailored approach, with gross total tumor resection of 88 %. Neurological and surgical morbidity were less than 10 %. The proposed classification may prove a valuable tool for surgical planning.

Pin penetration depths in the neurocranium using a three-pin head fixation device.

In estimated 10-15% of neurosurgical interventions employing a conventional three-pin head fixation device (HFD) the patient's head loses position due to slippage. At present no scientifically based stability criterion exists to potentially prevent the intraoperative loss of head position or skull fractures. Here, data on the skull penetration depth both on the single and two-pin side of a three-pin HFD are presented, providing scientific evidence for a stability criterion for the invasive three-pin head fixation. Eight fresh, chemically untreated human cadaveric heads were sequentially pinned 90 times in total in a noncommercially calibrated clamp screw applying a predefined force of 270 N (approximately 60 lbf) throughout. Three head positions were pinned each in standardized manner for the following approaches: prone, middle fossa, pterional. Titanium-aluminum alloy pins were used, varying the pin-cone angle on the single-pin side from 36° to 55° and on the two-pin side from 25° to 36°. The bone-penetration depths were directly measured by a dial gauge on neurocranium. The penetration depths on the single-pin side ranged from 0.00 mm (i.e., no penetration) to 6.17 mm. The penetration depths on the two-pin side ranged from 0.00 mm (no penetration) to 4.48 mm. We measured a significantly higher penetration depth for the anterior pin in comparison to the posterior pin on the two-pin side in prone position. One pin configuration (50°/25°) resulted in a quasi-homogenous pin depth distribution between the single- and the two-pin side. Emanating from the physical principle that pin depths behave proportionate to pin pressure distribution, a quasi-homogenous pin penetration depth may result in higher resilience against external shear forces or torque, thus reducing potential complications such as slippage and depressed skull fractures. The authors propose that the pin configuration of 50°/25° may be superior to the currently used uniform pin-cone angle distribution in common clinical practice (36°/36°). However, future research may identify additional influencing factors to improve head fixation stability.

Modulation of subthalamic beta oscillations by movement, dopamine, and deep brain stimulation in Parkinson's disease.

Subthalamic beta band activity (13-35 Hz) is known as a real-time correlate of motor symptom severity in Parkinson's disease (PD) and is currently explored as a feedback signal for closed-loop deep brain stimulation (DBS). Here, we investigate the interaction of movement, dopaminergic medication, and deep brain stimulation on subthalamic beta activity in PD patients implanted with sensing-enabled, implantable pulse generators. We recorded subthalamic activity from seven PD patients at rest and during repetitive movements in four conditions: after withdrawal of dopaminergic medication and DBS, with medication only, with DBS only, and with simultaneous medication and DBS. Medication and DBS showed additive effects in improving motor performance. Distinct effects of each therapy were seen in subthalamic recordings, with medication primarily suppressing low beta activity (13-20 Hz) and DBS being associated with a broad decrease in beta band activity (13-35 Hz). Movement suppressed beta band activity compared to rest. This suppression was most prominent when combining medication with DBS and correlated with motor improvement within patients. We conclude that DBS and medication have distinct effects on subthalamic beta activity during both rest and movement, which might explain their additive clinical effects as well as their difference in side-effect profiles. Importantly, subthalamic beta activity significantly correlated with motor symptoms across all conditions, highlighting its validity as a feedback signal for closed-loop DBS.