Motor evoked potentials versus Macrostimulation in predicting the postoperative motor threshold in STN Deep brain stimulation.

INTRODUCTION: Accuracy is crucial in Deep Brain Stimulation (DBS). Electrophysiological and image-based techniques are used to avoid suboptimal positioning. Macrostimulation is the gold standard to delineate the therapeutic window intraoperatively. Despite this, electrode revision rates due to malpositioning are as high as 17%. The goal was to compare motor evoked potentials (MEPs) with the gold standard of Macrostimulation. We assessed accuracy and precision as well as the correlation in predicting motor side effects at the initial mapping 4 weeks postoperatively. METHODS: In this prospective study intraoperative MEPs from 94 contacts in 16 patients undergoing STN DBS under local anesthesia were correlated to the postoperative threshold for stimulation-induced motor side effects and compared to intraoperative Macrostimulation. Analysis of accuracy, precision and correlation (Pearson) was performed. RESULTS: MEPs of the upper extremity had a mean percentage error of 25% (SD 38.8%) and correlated significantly with the motor threshold at postoperative mapping (R=0.235). Macrostimulation was less accurate and precise with a mean percentage error of - 68% (SD 78.8%) but had a higher correlation (R=0.388). MEPs rarely (3%) overestimated the threshold by maximally 1 mA. In contrast, Macrostimulation overestimated the threshold by over 1 mA in 69% leading to a false sense of security. CONCLUSION: MEPs are feasible in an awake setting during Deep Brain Stimulation in the STN for PD patients. MEPs of the upper extremity are more accurate and precise predicting the motor threshold and avoid a false sense of security in comparison to the gold standard of Macrostimulation.

Validation of 3D fluoroscopy for image-guidance registration in depth electrode implantation for medically refractory epilepsy.

BACKGROUND: Frame registration is a critical step to ensure accurate electrode placement in stereotactic procedures such as stereoelectroencephalography (SEEG) and is routinely done by merging a computed tomography (CT) scan with the preoperative magnetic resonance (MR) examination. Three-dimensional fluoroscopy (XT) has emerged as a method for intraoperative electrode verification following electrode implantation and more recently has been proposed as a registration method with several advantages. METHODS: We compared the accuracy of SEEG electrode placement by frame registration with CT and XT imaging by analyzing the Euclidean distance between planned and post-implantation trajectories of the SEEG electrodes to calculate the error in both the entry (EP) and target (TP) points. Other variables included radiation dose, efficiency, and complications. RESULTS: Twenty-seven patients (13 CT and 14 XT) underwent placement of SEEG electrodes (319 in total). The mean EP and TP errors for the CT group were 2.3 mm and 3.3 mm, respectively, and 1.9 mm and 2.9 mm for the XT group, with no statistical difference (p = 0.75 and p = 0.246). The time to first electrode placement was similar (XT, 82 ± 10 min; CT, 84 ± 22 min; p = 0.858) and the average radiation exposure with XT (234 ± 55 mGy*cm) was significantly lower than CT (1245 ± 123 mGy*cm) (p < 0.0001). Four complications were documented with equal incidence in both groups. CONCLUSIONS: The use of XT as a method for registration resulted in similar implantation accuracy compared with CT. Advantages of XT are the substantial reduction in radiation dose and the elimination of the need to transfer the patient out of the room which may have an impact on patient safety and OR efficiency.

The accuracy of 3D fluoroscopy (XT) vs computed tomography (CT) registration in deep brain stimulation (DBS) surgery.

BACKGROUND: Stereotactic registration is the most critical step ensuring accuracy in deep brain stimulation (DBS) surgery. 3D fluoroscopy (XT) is emerging as an alternative to CT. XT has been shown to be safe and effective for intraoperative confirmation of lead position following implantation. However, there is a lack of studies evaluating the suitability of XT to be used for the more crucial step of registration and its capability of being merged to a preoperative MRI. This is the first study comparing accuracy, efficiency, and radiation exposure of XT- vs CT-based stereotactic registration and XT/MRI merging in deep brain stimulation. METHODS: Mean absolute differences and Euclidean distance between planned (adjusted for intraoperative testing) and actual lead trajectories were calculated for accuracy of implantation. The radiation dose from each scan was recorded as the dose length product (DLP). Efficiency was measured as the time between the patient entering the operating room and the initial skin incision. A one-way ANOVA compared these parameters between patients that had either CT- or XT-based registration. RESULTS: Forty-one patients underwent DBS surgery-25 in the CT group and 16 in the XT group. The mean absolute difference between CT and XT was not statistically significant in the x (p = 0.331), y (p = 0.951), or z (p = 0.807) directions. The Euclidean distance between patient groups did not differ significantly (p = 0.874). The average radiation exposure with XT (220.0 ± 0.1 mGy*cm) was significantly lower than CT (1269.3 ± 112.9 mGy*cm) (p < 0.001). There was no significant difference in registration time between CT (107.8 ± 23.1 min) and XT (106.0 ± 18.2 min) (p = 0.518). CONCLUSION: XT-based frame registration was shown to result in similar implantation accuracy and significantly less radiation exposure compared with CT. Our results surprisingly showed no significant difference in registration time, but this may be due to a learning curve effect.

Case Studies in Neuroscience: Evidence of motor thalamus reorganization following bilateral forearm amputations.

Following injury, functional improvement can result from central nervous system plasticity. Use-dependent plasticity of motor systems is evident, for example, in recovery of function resulting from rehabilitative interventions. Here, we present a single patient who underwent bilateral microelectrode-guided stereotactic implantation of deep brain stimulating leads for the treatment of essential tremor 52 yr following bilateral arm amputations. The tremor affected his upper extremities and had rendered him unable to perform fine motor tasks with his prostheses, significantly reducing his independence. We found a large territory of neurons in the ventral intermediate nucleus of his thalamus that responded to shoulder protraction, the movement that he used to control fine motor movements of his terminal hook prostheses. We propose that reorganization of this motor nucleus may have occurred secondary to a use-dependent gain of function in neurons that were previously involved in hand movement. NEW & NOTEWORTHY We had a unique opportunity to record neurons in the ventrointermediate (Vim) motor nucleus of thalamus in a patient with essential tremor, decades following bilateral forearm amputations. We demonstrate that a large region of Vim is active during shoulder protraction-the movement used to operate the patient's mechanical prostheses. We suggest that this provides evidence of human motor thalamic plasticity.

A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers.

AIM: To evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics of PRN1008, a novel Bruton's tyrosine kinase (BTK) inhibitor, in healthy volunteers, and thus determine the dose range for future clinical studies. METHODS: This was a two-part randomized, placebo controlled study in healthy volunteers using a liquid formulation. Part I was a single ascending dose design with dose levels of 50-1200 mg (n = 6 active, two placebos per cohort); Part II was a multiple ascending dose design, with dose regimens ranging from 300 to 900 mg daily, either four times or twice daily for 10 days. Plasma pharmacokinetics, adverse events, vital signs, electrocardiograms and laboratory parameters were assessed. BTK occupancy in peripheral blood mononuclear cells was evaluated as a marker of target engagement. RESULTS: PRN1008 was rapidly absorbed following oral administration, and was safe and well tolerated in all dose regimens evaluated in both single and multiple doses. PRN1008 demonstrated a large volume of distribution, and a half-life of approximately 3-4 h. BTK occupancy of >90% was observed within 4 h after dosing in both single and multiple dose regimens, and was closely linked to maximum plasma concentration. BTK occupancy decay was slow (-1.6% h-1 ), and occupancy was sustained despite drug concentrations being undetectable. No severe or serious adverse events occurred, and the most common adverse events were gastrointestinal in nature. CONCLUSIONS: PRN1008 was safe and well-tolerated following oral administration, and achieved high, sustained levels of BTK occupancy in peripheral blood mononuclear cells.

Carotid artery visualization during anterior skull base surgery: a novel protocol for neuronavigation.

Detailed knowledge of the vascular anatomy of the anterior skull base is critical to successful surgery in this area. Whereas conventional neuronavigational approaches combine MRI (+/- contrast) for tumor visualization and CT (+/- C) for bony and vascular anatomy, we describe the Canadian and Austrian experiences using a novel protocol integrating MR angiography (MRA) into surgical neuronavigation to provide superior visualization of the carotid arteries. The pre-operative imaging protocol employs a T1-weighted, 3D fast spoiled gradient echo MRI (+/- C) for soft tissue anatomy, a plain CT for bony anatomy, and a 3D time-of-flight MR angiography for carotid anatomy. The series are imported into the Medtronic StealthStation((R)) TREON((R)) Treatment Guidance System; during intra-operative neuronavigation, each series (MRI, CT, MRA) can be viewed individually, or layered and viewed as a composite image. Our protocol has important advantages. First, it provides detailed tissue, tumor, vascular and bony anatomy. Second, a contrast CT is not necessary; this is important, as numerous reports have highlighted the nephrotoxic nature of radiographic contrast material. Third, visualization of the carotid system is superior than can be obtained from CT angiography. We use this unique imaging protocol routinely for our endoscopic transsphenoidal surgeries to provide superior visualization of the carotid arteries during anterior skull base surgery.

Robotic long-distance telementoring in neurosurgery.

OBJECTIVE: To test the feasibility of long-distance telementoring in neurosurgery by providing subspecialized expertise in real time to another neurosurgeon performing a surgical procedure in a remote location. METHODS: A robotic telecollaboration system (Socrates; Computer Motion, Inc., Santa Barbara, CA) capable of controlling the movements of a robotic arm, of handling two-way video, and of audio communication as well as transmission of neuronavigational data from the remote operating room was used for the telementoring procedures. Four integrated services digital network lines with a total speed of transmission of 512 kilobytes per second provided telecommunications between a large academic center (Halifax, Nova Scotia) and a community-based center (Saint John, New Brunswick) located 400 km away. RESULTS: Long-distance telementoring was used in three craniotomies for brain tumors, a craniotomy for an arteriovenous malformation, a carotid endarterectomy, and a lumbar laminectomy. There were no surgical complications during the procedures, and all patients had uneventful outcomes. The neurosurgeons in the remote location believed that the input from the mentors was useful in all of the cases and was crucial in the removal of a mesial temporal lobe glioma and resection of an occipital arteriovenous malformation. CONCLUSION: Our initial experience with long-distance robotic-assisted telementoring in six cases indicates that telementoring is feasible, reliable, and safe. Although still in its infancy, telementoring has the potential to improve surgical care, to enhance neurosurgical training, and to have a major impact on the delivery of neurosurgical services throughout the world.

Stabilization clamp for insertion of deep brain stimulation electrodes: technical note.

BACKGROUND: Deep brain stimulation (DBS) electrodes are being implanted with increasing frequency for the management of movement disorders and chronic pain. Success with this neuro-augmentative technique requires accurate electrode lead placement. In order to enhance accuracy of final lead placement and ease of insertion, we describe a useful and reliable DBS electrode lead stabilization device developed and used at our centre. MATERIALS AND METHODS: The DBS electrode stabilization device consists of a 2-clamp system designed to fit the Leksell stereotactic frame. The clamps work in series to secure the stereotactic lead at the time of its final positioning in the desired subcortical target without the need of fluoroscopic control. RESULTS: The DBS electrode stabilization device has been used in 30 patients for 54 electrode implantations at our institution since 2000. Postoperative magnetic resonance imaging was performed in all cases and confirmed accurate placement of the electrodes. CONCLUSIONS: Accurate electrode lead placement is critical for the clinical efficacy of DBS systems. The simple and reliable stabilization device described here is easy to operate and enhances the final placement accuracy of DBS electrode leads.