Search

“Asleep” deep brain stimulation using general anesthesia and intraoperative MR imaging guidance is considered “off-label” use by current FDA guidelines but is widely used in neurosurgical practice, and excellent safety has been demonstrated using first-generation, omnidirectional electrodes. Safety data for second-generation, directional electrodes in the interventional MR imaging environment have not yet been published. Herein, we report 34 cases of asleep deep brain stimulation using second-generation, directional electrodes in an interventional MR imaging suite at a single institution. Procedural complications and imaging data are described. All patients underwent postoperative MR imaging with fully implanted (“internalized”) electrodes after scalp closure; 4 patients also underwent MR imaging with “externalized” electrodes before scalp closure. No MR imaging–related complications were observed, and procedural complication rates were comparable to prior series. This suggests that the use of second-generation, directional electrodes in the interventional MR imaging environment appears to be safe when following manufacturer-published imaging guidelines.

Background Peripheral neurostimulation (PNS) for medically refractory trigeminal pain is an emerging alternative to traditional surgical approaches, with safety and efficacy demonstrated in several retrospective series and a prospective trial currently in progress. Many existing studies suffer from relatively small numbers and short or inconsistent follow-up, making balanced treatment assessment difficult. Materials and methods Consecutive cases of trial and permanent placement of trigeminal branch stimulation electrodes by a single surgeon from May 2014 through January 2019 were retrospectively reviewed from a prospectively collected database, following the PROCESS guidelines for surgical case series. Outcomes were assessed at six months and at last follow-up. Results Ninteen patients underwent trial electrode placement, with 15 patients undergoing permanent system placement. The most common diagnoses were idiopathic trigeminal neuralgia Type 2 (N = 8) and trigeminal neuropathic pain (N = 7). Median follow-up was 14 months (range 6-58 months). At last follow-up, 12 of 15 implanted patients (80%) were still receiving stimulation, with mean (median) pain reduction of 52.3% (47.5%). Infection and revision rates were high, although erosion and migration, which have typically plagued trigeminal PNS surgery, did not occur. Implanted systems were well-tolerated, with excellent cosmetic outcomes and high patient satisfaction that proved durable over long follow-up. Conclusions We present a single-institution series of PNS for complex craniofacial pain involving the trigeminal nerve. The procedure is safe, effective and durable over at least one year in the large majority of a well-selected patient population.

Background Hemophilia is generally considered a contraindication to deep brain stimulation (DBS) and other elective intracranial surgery because of the elevated risk of perioperative hemorrhage. Two prior case reports have suggested, however, that DBS may be safe in patients with hemophilia who undergo appropriate factor replacement. Here, we describe a third case of DBS surgery for medically refractory essential tremor (ET) in a patient with hemophilia A. Case Description A 68-year-old right-handed man with mild hemophilia A presented for a 10-year history of bilateral (right greater than left), medically refractory ET. The patient was considered an appropriate candidate for DBS by a multidisciplinary movement disorders conference, and hematology consultation was obtained. Baseline preoperative laboratory results showed a quantitative factor VIII (FVIII) level of 38%. Perioperative management consisted of daily intravenous bolus doses of recombinant FVIII from the morning of surgery to postoperative day 10. The patient underwent uncomplicated unilateral DBS placement in the left ventralis intermedius thalamus. Intra- and postoperative imaging showed no hemorrhage. His postoperative course was uncomplicated except for a single self-limited episode of hematuria requiring no intervention. Conclusions DBS placement for ET may be safe in patients with coexisting hemophilia A if appropriate FVIII replacement is given, which may be delivered as bolus infusions rather than continuous infusion.

Direct targeting methods for stereotactic neurosurgery in the treatment of essential tremor have been the subject of active research over the past decade but have not yet been systematically reviewed. We present a clinically oriented topic review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses Group guidelines. Our focus is studies using advanced magnetic resonance imaging (MRI) techniques (ultrahigh-field structural MRI, diffusion-weighted imaging, diffusion-tensor tractography, and functional MRI) for patient specific, in vivo identification of the ventral intermediate nucleus and the dentato-rubro-thalamic tract.

Background Malignant melanotic schwannian tumors (MMSTs) are rare peripheral nerve sheath tumors that typically exhibit benign clinical presentation and histopathology but malignant long-term behavior. Case Description We report a case of a 22-year-old male with a T9-11 MMST who presented with acute paraplegia and complete loss of sacral function. Despite emergent decompression, he did not recover motor, sensory or bladder function, although bowel function did normalize. Conclusions The anatomic location and rapid presentation of permanent deficits are suggestive of infarction of the spinal cord supplied by the artery of Adamkiewicz, a rare presentation of this disorder and of spinal schwannomas in general.

The thalamus and its nuclei are largely indistinguishable on standard T1 or T2 weighted MRI. While diffusion tensor imaging based methods have been proposed to segment the thalamic nuclei based on the angular orientation of the principal diffusion tensor, these are based on echo planar imaging which is inherently limited in spatial resolution and suffers from distortion. We present a multi-atlas segmentation technique based on white-matter-nulled MP-RAGE imaging that segments the thalamus into 12 nuclei with computation times on the order of 10 min on a desktop PC; we call this method THOMAS (THalamus Optimized Multi Atlas Segmentation). THOMAS was rigorously evaluated on 7T MRI data acquired from healthy volunteers and patients with multiple sclerosis by comparing against manual segmentations delineated by a neuroradiologist, guided by the Morel atlas. Segmentation accuracy was very high, with uniformly high Dice indices: at least 0.85 for large nuclei like the pulvinar and mediodorsal nuclei and at least 0.7 even for small structures such as the habenular, centromedian, and lateral and medial geniculate nuclei. Volume similarity indices ranged from 0.82 for the smaller nuclei to 0.97 for the larger nuclei. Volumetry revealed that the volumes of the right anteroventral, right ventral posterior lateral, and both right and left pulvinar nuclei were significantly lower in MS patients compared to controls, after adjusting for age, sex and intracranial volume. Lastly, we evaluated the potential of this method for targeting the Vim nucleus for deep brain surgery and focused ultrasound thalamotomy by overlaying the Vim nucleus segmented from pre-operative data on post-operative data. The locations of the ablated region and active DBS contact corresponded well with the segmented Vim nucleus. Our fast, direct structural MRI based segmentation method opens the door for MRI guided intra-operative procedures like thalamotomy and asleep DBS electrode placement as well as for accurate quantification of thalamic nuclear volumes to follow progression of neurological disorders.

Background: Peripheral neurostimulation (PNS) for medically refractory trigeminal and craniofacial pain is an emerging alternative to traditional surgical approaches. Technical problems with craniofacial PNS have included electrode migration and erosion, limiting the utility and cost-effectiveness of this procedure. Objective: To review our institutional surgical technique for trigeminal PNS implantation, focusing on a novel technique for electrode anchoring. Methods: Consecutive cases of permanent craniofacial PNS placement by a single surgeon over 36 months were reviewed for surgical technique and technical outcomes. Electrodes were placed percutaneously with open anchoring to the pericranium at a separate parietal incision. Results: Sixteen systems (53 electrodes) were implanted in 14 patients. Median follow-up was 13 months (range, 5–29 months). Electrode placement was successful in all cases with no intraoperative complications. There was 1 lead migration (6.3% per patient; 1.8% per lead) and no cases of erosion. Two patients (14.3%) required explant for infection, 1 of whom was successfully reimplanted. Three patients (21.4%) underwent surgical revision other than for infection. Conclusions: We present an improved method for craniofacial PNS surgery which introduces a separate incision for electrode anchoring at the parietal boss. This technique simplifies the procedure and greatly reduces rates of erosion and migration, improving patient comfort and satisfaction.

We describe a new application of acoustoelectric imaging for non-invasive mapping of the location, magnitude and polarity of current generated by a clinical deep brain stimulation (DBS) device. Ultrasound at 1MHz was focused near the DBS device as short current pulses were injected across different DBS leads. A recording electrode detected the high-frequency acoustoelectric interaction signal. Linear scans of the US beam produced time-varying images of the magnitude and polarity of the induced current, enabling precise localization of the DBS leads within 0.70mm, a detection threshold of 1.75mA at 1 MPa and a sensitivity of 0.52 ± 0.07 μV/(mA*MPa). Monopole and dipole configurations in saline were repeated through a human skullcap. Despite 13.8-dB ultrasound attenuation through bone, acoustoelectric imaging was still >10dB above background with a sensitivity of 0.56 ± 0.10 μV/(mA*MPa). This proof-of-concept study indicates that selective mapping of lead currents through a DBS device may be possible using non-invasive acoustoelectric imaging.

There is an acknowledged need for higher-quality evidence to quantify the benefit of surgical procedures, yet not enough has been done to improve the evidence base. This lack of evidence can prevent fully informed decision-making, lead to unnecessary or even harmful treatment, and contribute to wasteful expenditures of scare health care resources. Barriers to evidence generation include not only the long-recognized technical difficulties and ethical challenges of conducting randomized surgical trials, but also legal challenges that limit incentives to conduct surgical research as well as market-based challenges that make it difficult for those funding surgical research to recoup investment costs. These legal and market dynamics differ substantially from those surrounding new drug or device development. Nevertheless, obstacles could be overcome and overall expenditures could be reduced if a share of federal health care agency budgets were reallocated to generating randomized trial data, standardizing outcome measures, and conducting observational studies analogous to those that have been facilitated for drugs via the Food and Drug Administration’s Sentinel Initiative. Until better quality evidence is available, ethical principles require adequate disclosure of the limited evidence base supporting current surgical procedures.

Objective: New innovations in deep brain stimulation (DBS) enable directional current steering – allowing more precise electrical stimulation of the targeted brain structures for Parkinson's disease, essential tremor and other neurological disorders. While intra-operative navigation through MRI or CT approaches millimeter accuracy for placing the DBS leads, no existing modality provides feedback of the currents as they spread from the contacts through the brain tissue. In this study, we investigate transcranial acoustoelectric imaging (tAEI) as a new modality to non-invasively image and characterize current produced from a directional DBS lead. tAEI uses ultrasound (US) to modulate tissue resistivity to generate detectable voltage signals proportional to the local currents. Approach: An 8-channel directional DBS lead (Infinity 6172ANS, Abbott Inc) was inserted inside three adult human skulls submerged in 0.9% NaCl. A 2.5MHz linear array delivered US pulses through the transtemporal window and focused near the contacts on the lead, while a custom amplifier and acquisition system recorded the acoustoelectric (AE) interaction used to generate images. Main Results: tAEI detected monopolar current with stimulation pulses as short as 100 µs with an SNR ranging from 10 – 27 dB when using safe US pressure (mechanical indices

The efficacy of deep brain stimulation (DBS) for relieving motor symptoms from Parkinson’s disease or essential tremor is highly dependent on accurate placement of the electrode. New current-steering electrodes can reduce the burden of placement by directing the stimulating currents toward the target locations. However, no imaging modality exists in the clinic or operating room to provide feedback of the currents as they are delivered/steered from the contacts. In this study we investigate the prospects of high resolution, transcranial acoustoelectric imaging (AEI) as a method for non-invasively imaging DBS currents. A DBS electrode was inserted into a brain gel phantom inside a human skull and monopoles were generated at individual contacts. A linear array ultrasound (US) transducer was coupled to the temporal window and focused toward the DBS electrode to induce AE signals proportional to the time-varying current densities. The AE signals using an injected current of 11 mA and focal pressures of 2.04 MPa were detected with SNRs between 716 dB, mean accuracy along the length of the electrode of 0.35 mm, radial separation of segmented contacts in a ring-triplet of 1.21 mm, mean monopole FWHMs of 3.54 mm, and a sensitivity of 0.283 pVfmA/MPa. Our results advocate AEI as a promising tool for providing non-invasive, high resolution feedback of the spread of current from a directional DBS electrode with potential roles in enhancing placement of the electrode and chronically monitoring the integrity of the stimulation.

Among patients with intractable epilepsy, the most commonly performed surgical procedure is craniotomy for amygdalohippocampectomy (AH). Stereotactic laser amygdalohippocampotomy (SLAH) has also been recently employed as a minimally invasive treatment for intractable temporal lobe epilepsy (TLE). Among patients treated with AH and SLAH approximately 65% and 54% of patients become seizure-free, respectively. Therefore, selection criteria for surgical candidates with improved prognostic value for post-operative seizure-free outcome are greatly needed. In this study, we perform RNA sequencing (RNA-Seq) on whole blood leukocyte samples taken from 16 patients with intractable TLE prior to SLAH to test the hypothesis that pre-operative leukocyte RNA expression profiles are prognostic for post-operative seizure outcome. Multidimensional scaling analysis of the RNA expression data indicated separate clustering of patients with seizure free (SF) and non-seizure-free (NSF) outcomes. Differential expression (DE) analysis performed on SF versus NSF groups revealed 24 significantly differentially expressed genes (≥2.0-fold change, p-value

Objective. This study employs a human head model with real skull to demonstrate the feasibility of transcranial acoustoelectric brain imaging (tABI) as a new modality for electrical mapping of deep dipole sources during treatment of epilepsy with much better resolution and accuracy than conventional mapping methods. Approach. This technique exploits an interaction between a focused ultrasound (US) beam and tissue resistivity to localize current source densities as deep as 63 mm at high spatial resolution (1 to 4 mm) and resolve fast time-varying currents with sub-ms precision. Main results. Detection thresholds through a thick segment of the human skull at biologically safe US intensities was below 0.5 mA and within range of strong currents generated by the human brain. Significance. This work suggests that 4D tABI may emerge as a revolutionary modality for real-time high-resolution mapping of neuronal currents for the purpose of monitoring, staging, and guiding treatment of epilepsy and other brain disorders characterized by abnormal rhythms.

Objective Facial pain refractory to medical treatments may benefit from neurosurgical interventions. Only a few studies have reported on the efficacy of peripheral trigeminal stimulation and more specifically supraorbital nerve (SON) and infraorbital nerve (ION) stimulation for the treatment of facial pain. Patients and methods In the present study, we identified all patients at our institution who underwent SON and/or ION stimulation for treatment of facial pain due to post-herpetic, traumatic or idiopathic etiology. Relevant pre and post-operative outcomes were analyzed. Results We identified 15 patients who underwent SON and/or ION stimulation. Among them, 12 (80 %) endorsed >50 % pain relief during the trial stimulation period. After a median follow-up of 5.8 months with permanent implantation, 1 patient (8.3 %) was diagnosed with lead erosion and IPG migration, two patients had lead infections (16.7 %) and one (8.3 %) had wound dehiscence. No lead migrations were identified during the long-term follow-up. The VAS score showed a statistically significant reduction from a median pre-operative score of 7 to a post-operative score of 1.8 (p = 0.011), which corresponded to a 74.3 % average pain reduction. Conclusion SON and/or ION stimulation can be an effective treatment for intractable facial pain due to post-herpetic, traumatic or idiopathic etiology; however the complication rate is relatively high. Future prospective studies with longer follow-up periods are warranted.

Deep brain stimulation (DBS) is an effective treatment for a variety of brain disorders, including Parkinson's disease, depression and chronic pain. However, there is no reliable method to non-invasively image electric current flow generated by a DBS. In this study, we demonstrate 4D current source density imaging based on the acoustoelectric (AE) effect, which integrates an ultrasound beam with electrical recording, to map current flow produced by a clinical DBS device. AE imaging was able to accurately determine the polarity, magnitude and location of the current densities near the DBS device placed in physiologic saline with a signal-to-noise ratio of 17.1 dB using stimulation parameters similar to what are used on patients. Pulse echo (PE) ultrasound was acquired simultaneously to provide additional information regarding the spatial coordinates and structure of the DBS without need of additional techniques. These results suggest that AE imaging combined with PE ultrasound may provide valuable feedback during and after implantation of a DBS device.

Deep brain stimulation (DBS) has proven remarkably safe and effective in the treatment of movement disorders. As a result, it is being increasingly applied to a range of neurologic and psychiatric disorders, including medically refractory epilepsy. This review will examine the use of DBS in epilepsy, including known targets, mechanisms of neuromodulation and seizure control, published clinical evidence, and novel technologies. Cortical and deep neuromodulation for epilepsy has a long experimental history, but only recently have better understanding of epileptogenic networks, precise stereotactic techniques, and rigorous trial design combined to improve the quality of available evidence and make DBS a viable treatment option. Nonetheless, underlying mechanisms, anatomical targets, and stimulation parameters remain areas of active investigation.

Interictal brain energy metabolism and glutamate-glutamine cycling are impaired in epilepsy and may contribute to seizure generation. We used the zero-flow microdialysis method to measure the extracellular levels of glutamate, glutamine, and the major energy substrates glucose and lactate in the epileptogenic and the nonepileptogenic cortex and hippocampus of 38 awake epileptic patients during the interictal period. Depth electrodes attached to microdialysis probes were used to identify the epileptogenic and the nonepileptogenic sites. The epileptogenic hippocampus had surprisingly high basal glutamate levels, low glutamine/glutamate ratio, high lactate levels, and indication for poor glucose utilization. The epileptogenic cortex had only marginally increased glutamate levels. We propose that interictal energetic deficiency in the epileptogenic hippocampus could contribute to impaired glutamate reuptake and glutamate-glutamine cycling, resulting in persistently increased extracellular glutamate, glial and neuronal toxicity, increased lactate production together with poor lactate and glucose utilization, and ultimately worsening energy metabolism. Our data suggest that a different neurometabolic process underlies the neocortical epilepsies.

To assess the format, content, method, and placement of medical ethics education in medical schools; the faculty and curricular resources and institutional structure and support of medical ethics; and the perceptions of ethics education among deans of medical education and medical ethics course directors at U.S. and Canadian medical schools.Two questionnaires were mailed to 125 U.S. medical schools and 16 Canadian schools: one to be completed by the deans of medical education and one to be completed by the medical ethics course director. Descriptive statistics were used to compare responses.In all, 123 (87%) deans and 91 (64%) course directors responded, providing information about 91 schools (six Canadian). All responding institutions offered some formal instruction in medical ethics, and among these, 71 (78%) incorporated ethics into required preclinical courses. The primary pedagogic course structure was small-group discussion and the primary pedagogic method was case discussions. One-fifth of schools provided no funding for ethics teaching, and 47 (52%) did not fund curricular development in ethics. Institutions with a dedicated ethics faculty member were twice as likely to have a mandatory introductory ethics course (64% versus 32%, p.05). The primary obstacles to ethics education were thought to be a lack of time in the curriculum, a lack of qualified teachers, and a lack of time in faculty schedules.Within a few decades the number of U.S. and Canadian medical schools requiring medical ethics has increased. Nevertheless, significant variation in the content, method, and timing of ethics education suggests consensus about curricular content and pedagogic methods remains lacking. Further progress in ethics education may depend on institutions' willingness to devote more curricular time and funding to medical ethics.