The Relationship of Electrophysiologic Subthalamic Nucleus Length as a Predictor of Outcomes in Deep Brain Stimulation for Parkinson Disease.

BACKGROUND: Intraoperative measurement of subthalamic nucleus (STN) width through microelectrode recording (MER) is a common proxy for optimal electrode location during deep brain stimulation (DBS) surgery for Parkinson disease. We assessed whether the MER-determined STN width is a predictor of postoperative Unified Parkinson Disease Rating Scale (UPDRS) improvement. METHODS: Records were reviewed for patients who underwent single-sided STN DBS placement for Parkinson disease between 2005 and 2010 at the UAB Medical Center. Reviews of preoperative and 3-month postoperative UPDRS part III, intraoperative MER records, and postoperative MRI scans were conducted. RESULTS: The final cohort consisted of 73 patients (mean age 59 ± 9.7 years, length of disease 13 ± 9.7 years). STN widths were defined as depths associated with increased background activity and motor-driven, spiking action potentials on MER. The mean contralateral UPDRS improvement was 58% (± 24). The mean STN width was 5.1 mm (± 1.6, min = 0.0, max = 8.7). No significant relationship between STN width and UPDRS improvement was found, with and without AC-PC normalization (R2 < 0.05). CONCLUSION: This analysis raises questions about seeking the maximal electrophysiological width of STN as a proxy for optimal outcome in DBS for PD. We suggest this strategy for DBS placement in Parkinson disease be subject to more robust prospective investigation.

Directional Deep Brain Stimulation-A Step in the Right Direction? A Systematic Review of the Clinical and Therapeutic Efficacy of Directional Deep Brain Stimulation in Parkinson Disease.

BACKGROUND: The use of directional deep brain stimulation (dDBS) electrodes for the treatment of movement disorders such as Parkinson disease (PD) has become relatively widespread. However, the efficacy of dDBS relative to its omnidirectional deep brain stimulation (oDBS) counterpart is not well characterized. This systematic review aims to synthesize the literature comparing clinical and therapeutic outcomes of dDBS relative to oDBS in patients with PD. METHODS: A systematic literature search for studies with comparative clinical outcome data between dDBS and oDBS was performed across the PubMed, Ovid MEDLINE, and Web of Science databases. Data including therapeutic window (TW) and surrogate measures and the Unified Parkinson's Disease Rating Scale score were collected and summarized across multiple time periods. RESULTS: Ten studies met the eligibility criteria. Three of these studies evaluated motor performance in the form of Unified Parkinson's Disease Rating Scale III, with none finding differences between dDBS and oDBS. Two studies assessed quality-of-life measures with neither finding differences between dDBS and oDBS. TW or a surrogate measure was assessed in 6 studies; 5 studies found an increase or strong trend toward increase in dDBS relative to oDBS. CONCLUSIONS: The current evidence, although limited by bias, does suggest that dDBS in the treatment of PD yields improvements in motor symptoms and quality of life that are comparable to oDBS; TW and surrogate measures are consistently improved in patients with PD under a directional configuration relative to omnidirectional.

Equivalency of Protection From Natural Immunity in COVID-19 Recovered Versus Fully Vaccinated Persons: A Systematic Review and Pooled Analysis.

We present a systematic review and pooled analysis of clinical studies to date that (1) specifically compare the protection of natural immunity in the COVID-recovered versus the efficacy of complete vaccination in the COVID-naive, and (2) the added benefit of vaccination in the COVID-recovered, for prevention of subsequent SARS-CoV-2 infection. Using the PRISMA 2020 guidance, we first conducted a systematic review of available literature on PubMed, MedRxIV and FDA briefings to identify clinical studies either comparing COVID vaccination to natural immunity or delineating the benefit of vaccination in recovered individuals. After assessing eligibility, studies were qualitatively appraised and formally graded using the NOS system for observational, case-control and RCTs. Incidence rates were tabulated for the following groups: never infected (NI) and unvaccinated (UV), NI and vaccinated (V), previously infected (PI) and UV, PI and V. Pooling were performed by grouping the RCTs and observational studies separately, and then all studies in total. Risk ratios and differences are reported for individual studies and pooled groups, in 1) NPI/V vs PI/UV and 2) PI/UV vs PI/V analysis. In addition, the number needed to treat (NNT) analysis was performed for vaccination in naïve and previously infected cohorts. Nine clinical studies were identified, including three randomized controlled studies, four retrospective observational cohorts, one prospective observational cohort, and a case-control study. The NOS quality appraisals of these articles ranged from four to nine (out of nine stars). All of the included studies found at least statistical equivalence between the protection of full vaccination and natural immunity; and, three studies found superiority of natural immunity. Four observational studies found a statistically significant incremental benefit to vaccination in the COVID-recovered individuals. In a total pooled analysis, the incidence in NPI/V trended higher than PI/UV groups (RR=1.86 [95%CI 0.77-4.51], P=0.17). Vaccination in COVID-recovered individuals provided modest protection from reinfection (RR=1.82 [95%CI 1.21-2.73], P=0.004), but the absolute risk difference was extremely small (AR= 0.004 person-years [95% CI 0.001-0.007], P=0.02). The NNT to prevent one annual case of infection in COVID-recovered patients was 218, compared to 6.5 in COVID-naïve patients, representing a 33.5-fold difference in benefit between the two populations. COVID-recovered individuals represent a distinctly different benefit-risk calculus. While vaccinations are highly effective at protecting against infection and severe COVID-19 disease, our review demonstrates that natural immunity in COVID-recovered individuals is, at least, equivalent to the protection afforded by complete vaccination of COVID-naïve populations. There is a modest and incremental relative benefit to vaccination in COVID-recovered individuals; however, the net benefit is marginal on an absolute basis. Therefore, vaccination of COVID-recovered individuals should be subject to clinical equipoise and individual preference.

Construction of relational topographies from the quantitative measurements of functional deep brain stimulation using a 'roving window' interpolation algorithm.

The delivery of stimulus by a deep brain stimulation (DBS) contact electrode at a particular location may lead to a quantifiable physiologic effect, both intraoperatively and postoperatively. Consequently, measured data values can be attributed to discrete scattered points in neuroanatomic space, allowing for interpolative techniques to generate a topographic map of spatial patterns. Ultimately, by relating the topographies of various intraoperative measurements to the postoperative counterparts and neuroanatomic atlases, outcome-guided adjustments to electrode position can be pursued intraoperatively. In this study, 52 Parkinson's disease patients were tested with a postoperative trial of stimulation and thresholds were recorded for motor adverse effects. A 'roving window' interpolation algorithm was adapted to generate a topographic map of voltage threshold along selected axial, coronal and sagittal planes. By developing these relational topographies for a variety of intraoperative and postoperative effects, a multivariable approach towards DBS optimization emerges.

A Cupriavidus Pauculus Infection in a Patient with a Deep Brain Stimulation Implant.

While deep brain stimulation (DBS) is now standard therapy for the treatment of Parkinson's disease, essential tremor, and dystonia, infections remain one of the most common perioperative complications. In this report, we describe a 58-year-old female with a history of medically refractory Parkinson's disease, who underwent magnetic resonance (MR)-guided bilateral subthalamic DBS. While the initial surgery and programming were successful, she returned in follow-up with signs of a generator pocket infection. She was taken to surgery for hardware explantation, and cultures revealed multispecies growth which included the rare Cupriavidus pauculus species. This is the first report of C. pauculus infection in conjunction with a neuromodulation device. We provide a literature review and discussion of C. pauculus, and its implications in the context of DBS surgery.

Economic Inequities in the Application of Neuromodulation Devices.

Background  There is a significant upfront cost for the use of neuromodulation devices. The high cost of these devices may lead to disproportionate application in geographical regions with different levels of financial resources. The purpose of this study was to determine if there is geographic based economic inequity in the application of neuromodulation devices in the United States. Methods  Population and average household income data by county from the year 2010 were obtained from publicly available databases on the US Census website. The number of stimulators sold by county in the years 2009 and 2010 were provided by two of the four neuromodulation companies with commercially available products. Pearson correlation and t-test statistics were performed. Results  Of the 3142 U.S. counties analyzed, only 689 placed neuromodulation devices during this period of time. There was a difference in average household income between counties with device implants ($49,663) and counties with no device implants ($41,314), which was statistically significant (p<0.001). Conclusion  Analysis of neuromodulation devices placed in 2009 and 2010 from 50% of neuromodulation companies demonstrated that there was an income disparity between counties in which implantation of devices occurred and counties in which there were no device implantations.

Assessing the Economic Efficiency of Physician On-call Payments.

On-call services provided by physicians are critical to the function of a robust healthcare delivery system, but such services are not generally accounted for by standard physician productivity metrics, such as the work relative value unit (wRVU). There is significant diversity on how physicians are compensated, if at all, for these on-call services. Simultaneously, there exists a considerable shortage, particularly in the surgical subspecialties, for on-call coverage - most commonly in rural and underserved communities. While we agree that "call" services should undergo standardized valuation, we suggest that the wRVU is an ill-posed metric for this purpose as its primary role is to value discrete physician services provided to patients. In contradistinction, "call" is a physician service to a hospital - the disproportionate beneficiary of the service. We maintain that systemic and regulatory factors undervalue physician on-call compensation relative to the hospital's value chain and lead to call shortages that impact patient care and foster inequity. Finally, we urge subspecialty professional organizations to develop guidelines for call valuation.

Presentation and Treatment of a Combined Median Nerve Schwannoma and a C7 Discogenic Radiculopathy.

Cervical radiculopathy and peripheral nerve pathology often compete in the differential diagnosis of extremity pain, weakness, and numbness, and frequently, coexist. In this report, we describe a 73-year-old male with a previously asymptomatic left anteromedial proximal upper arm mass, who presented with progressive radicular arm pain, proximal and distal upper extremity weakness, and hand numbness. Clinical investigation revealed a prominent C6-7 disc herniation and a median nerve sheath tumor, with electromyography (EMG)/nerve conduction velocity (NCV) studies suggestive of acute radiculopathy. He was treated in a staged surgical fashion, with the nerve sheath tumor resection first, followed by a standard C6-7 anterior cervical discectomy and fusion (ACDF) two weeks later. The patient made a full recovery. We provide a literature review and discussion of the "double crush" hypothesis.

A method to project clinical outcome topographies onto preoperative MRI to guide direct DBS targeting.

The use of intraoperative MR and direct DBS targeting, relies on anatomical rather than functional data. Historical clinical outcome databases that have recorded stimulation location and magnitude of effect, can provide a useful adjunct in DBS targeting strategies. We present a method for generating clinical outcome topographies, and merging regions of effect onto a pre-operative MR, for surgical planning. The clinical outcome topographies are consistent with more intuitive strategies used by neurosurgeons. This method provides theoretical guidance during DBS target planning.

Presurgical Rehearsals for Patients Considering "Awake" Deep Brain Stimulation.

Simulated surgical environments are rapidly gaining adoption in training students, residents, and members of specialized surgical teams. However, minimal attention has been given to the use of simulated surgical environments to educate patients on surgical processes, particularly procedures that require the active participation of the patient. "Awake" neurosurgery provides a unique situation in which patients openly participate in their operation. We describe a case report, in which a 62-year-old male was referred for "awake" deep brain stimulation implantation, in relation to medically refractory Parkinson's disease. The patient had significant concerns regarding anxiety and claustrophobia, and toleration of the "awake" procedure. Consequently, we designed a simulated OR environment and process, to recreate the physical experience of the procedure, with minimal cost or risk. This experience was crucial in determining the care plan, as after this experience, the patient opted for an "asleep" alternative. Thus, in certain settings, presurgical rehearsals may have a dramatic impact in the overall course of care.

Ultrasound characterization of interface oscillation as a proxy for ventriculoperitoneal shunt function.

Hydrocephalus, where cerebrospinal fluid (CSF) production rate is greater than reabsorption rate, leads to impaired neurological function if left untreated. Ventriculoperitoneal shunts (VPS) are implanted in the brain ventricles to route CSF. VPS systems have a high failure rate, and failure symptoms resemble symptoms of common maladies. The current gold standard for shunt diagnosis, surgical intervention, poses high risk and requires an expensive procedure for patients. Current non-invasive methods lack proper insight to assist physicians. We propose a noninvasive method of characterizing the oscillation of the shunt's pressure-relief valve to assist physicians in shunt diagnosis. Brightness-mode and motion-mode ultrasound images can be used to determine fluid flow. Blockage in the system could be detected by observing the phase change of the ultrasound signal in different flow cases with or without perturbation. Future testing and implementation can allow for the use of this method in localizing and identifying the modality of failure.

Telemedicine with mobile devices and augmented reality for early postoperative care.

Advanced features are being added to telemedicine paradigms to enhance usability and usefulness. Virtual Interactive Presence (VIP) is a technology that allows a surgeon and patient to interact in a "merged reality" space, to facilitate both verbal, visual, and manual interaction. In this clinical study, a mobile VIP iOS application was introduced into routine post-operative orthopedic and neurosurgical care. Survey responses endorse the usefulness of this tool, as it relates to The virtual interaction provides needed virtual follow-up in instances where in-person follow-up may be limited, and enhances the subjective patient experience.

Spatial topographies of unilateral subthalamic nucleus deep brain stimulation efficacy for ipsilateral, contralateral, midline, and total Parkinson disease motor symptoms.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation is a successful intervention for medically refractory Parkinson disease, although its efficacy depends on optimal electrode placement. Even though the predominant effect is observed contralaterally, modest improvements in ipsilateral and midline symptoms are also observed. OBJECTIVE: To elucidate the role of contact location of unilateral deep brain stimulation on contralateral, ipsilateral, and axial subscores of Parkinson disease motor symptoms. METHODS: Eighty-six patients receiving first deep brain stimulation STN electrode placements were identified, yielding 73 patients with 3-month follow-up. Total preoperative and postoperative Unified Parkinson Disease Rating Scale Part III scores were obtained and divided into contralateral, ipsilateral, and midline subscores. Contact location was determined on immediate postoperative magnetic resonance imaging. A 3-dimensional ordinary "kriging" algorithm generated spatial interpolations for total, ipsilateral, contralateral, and midline symptom categories. Interpolative reconstructions were performed in the axial planes (z = -0.5, -1.0, -1.5, -3.5, -4.5, -6.0) and a sagittal plane (x = 12.0). Interpolation error and significance were quantified by use of a cross-validation technique and quantile-quantile analysis. RESULTS: There was an overall reduction in Unified Parkinson Disease Rating Scale Part III symptoms: total = 37.0 ± 24.11% (P < .05), ipsilateral = 15.9 ± 51.8%, contralateral = 56.2 ± 26.8% (P < .05), and midline = 26.5 ± 34.7%. Kriging interpolation was performed and cross-validated with quantile-quantile analysis with high correlation (R2 > 0.92) and demonstrated regions of efficacy for each symptom category. Contralateral symptoms demonstrated broad regions of efficacy across the peri-STN area. The ipsilateral and midline regions of efficacy were constrained and located along the dorsal STN and caudal zona incerta. CONCLUSION: We provide evidence for a unique functional topographic window in which contralateral, ipsilateral, and midline structures may achieve the best efficacy. Although there are overlapping regions, laterality demonstrates distinct topographies. Surgical optimization should target the intersection of optimal regions for these symptom categories.

A novel MEA/AFM platform for measurement of real-time, nanometric morphological alterations of electrically stimulated neuroblastoma cells.

Studies of electrically induced morphological changes in neurons have either been limited by the resolution of light microscopy or the cell fixation required for electron microscopy. Atomic force microscopy (AFM), however, mechanically maps cell topography, offering exquisite resolution of evolving processes in three dimensions. In this paper, we present a microelectrode array (MEA) based platform for the real-time detection of subtle, electrically induced variations in neuronal morphology, with AFM. This platform required the customized design and production of a silicon-based MEA, integration with a commercial AFM, and the development of biological techniques for culture of neuroblastoma (SH-SY5Y) cells onto the device. Biphasic pulse trains (1 Hz) of electric current were delivered to a microelectrode interfaced with a neuroblastoma cell, and the AFM continuously recorded a cross-sectional height profile. Proof-of-principle experiments demonstrate that electric stimulation may induce fluctuations ranging in the 100-300-nm range, 75-fold greater than the systemic resolution, but smaller than the resolution of light microscopy modalities. In addition, the real-time capabilities of AFM captured a collapse (30%-40%) of a neurite cross section, seconds after electric stimulation. Ultimately, this platform can be used to nanocharacterize cell responses to electric stimulation and other biochemical cues, for use in neuronal patterning and regeneration studies.

Virtual interactive presence for real-time, long-distance surgical collaboration during complex microsurgical procedures.

OBJECT: The shortage of surgeons compels the development of novel technologies that geographically extend the capabilities of individual surgeons and enhance surgical skills. The authors have developed "Virtual Interactive Presence" (VIP), a platform that allows remote participants to simultaneously view each other's visual field, creating a shared field of view for real-time surgical telecollaboration. METHODS: The authors demonstrate the capability of VIP to facilitate long-distance telecollaboration during cadaveric dissection. Virtual Interactive Presence consists of local and remote workstations with integrated video capture devices and video displays. Each workstation mutually connects via commercial teleconferencing devices, allowing worldwide point-to-point communication. Software composites the local and remote video feeds, displaying a hybrid perspective to each participant. For demonstration, local and remote VIP stations were situated in Indianapolis, Indiana, and Birmingham, Alabama, respectively. A suboccipital craniotomy and microsurgical dissection of the pineal region was performed in a cadaveric specimen using VIP. Task and system performance were subjectively evaluated, while additional video analysis was used for objective assessment of delay and resolution. RESULTS: Participants at both stations were able to visually and verbally interact while identifying anatomical structures, guiding surgical maneuvers, and discussing overall surgical strategy. Video analysis of 3 separate video clips yielded a mean compositing delay of 760 ± 606 msec (when compared with the audio signal). Image resolution was adequate to visualize complex intracranial anatomy and provide interactive guidance. CONCLUSIONS: Virtual Interactive Presence is a feasible paradigm for real-time, long-distance surgical telecollaboration. Delay, resolution, scaling, and registration are parameters that require further optimization, but are within the realm of current technology. The paradigm potentially enables remotely located experts to mentor less experienced personnel located at the surgical site with applications in surgical training programs, remote proctoring for proficiency, and expert support for rural settings and across different counties.

Virtual interactive presence and augmented reality (VIPAR) for remote surgical assistance.

BACKGROUND: Surgery is a highly technical field that combines continuous decision-making with the coordination of spatiovisual tasks. OBJECTIVE: We designed a virtual interactive presence and augmented reality (VIPAR) platform that allows a remote surgeon to deliver real-time virtual assistance to a local surgeon, over a standard Internet connection. METHODS: The VIPAR system consisted of a "local" and a "remote" station, each situated over a surgical field and a blue screen, respectively. Each station was equipped with a digital viewpiece, composed of 2 cameras for stereoscopic capture, and a high-definition viewer displaying a virtual field. The virtual field was created by digitally compositing selected elements within the remote field into the local field. The viewpieces were controlled by workstations mutually connected by the Internet, allowing virtual remote interaction in real time. Digital renderings derived from volumetric MRI were added to the virtual field to augment the surgeon's reality. For demonstration, a fixed-formalin cadaver head and neck were obtained, and a carotid endarterectomy (CEA) and pterional craniotomy were performed under the VIPAR system. RESULTS: The VIPAR system allowed for real-time, virtual interaction between a local (resident) and remote (attending) surgeon. In both carotid and pterional dissections, major anatomic structures were visualized and identified. Virtual interaction permitted remote instruction for the local surgeon, and MRI augmentation provided spatial guidance to both surgeons. Camera resolution, color contrast, time lag, and depth perception were identified as technical issues requiring further optimization. CONCLUSION: Virtual interactive presence and augmented reality provide a novel platform for remote surgical assistance, with multiple applications in surgical training and remote expert assistance.

The use of multiplanar trajectory planning in the stereotactic placement of depth electrodes.

OBJECTIVE: To assess the value of multiplanar reconstruction software in trajectory planning for depth electrode insertion in medically refractory epilepsy. METHODS: A series of 29 patients undergoing frame-based hippocampal depth electrode insertion were identified. In 19 patients, preoperative trajectory planning was conducted in axial, coronal, and sagittal planes using standard-axis software. In 10 patients, preoperative trajectory planning was conducted with multiplanar reconstruction software. Postoperative magnetic resonance imaging scans were evaluated to study the quality of insertion. Target accuracy was assessed by measuring the mean shortest distance to strictly defined hippocampal borders in the coronal plane ("coronal deviation"). Additionally, the number of electrode contacts placed within the amygdalohippocampal structure was assessed. RESULTS: With the use of multiplanar reconstruction software, there was a statistically insignificant increase in coronal deviation (standard-axis software group, 0.09 +/- 0.50 mm; multiplanar reconstruction group, 0.37 +/- 1.16 mm). However, the use of multiplanar planning strategies resulted in approximately one additional electrode contact inserted in the amygdalohippocampal structure (standard-axis software group, 3.42 +/- 0.89; multiplanar reconstruction group, 4.36 +/- 0.93; P < 0.01). CONCLUSION: The use of reconstructed planes in preoperative trajectory planning allows for the insertion of additional electrode contacts within the target structure.