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Eric C. Leuthardt, Zac Freudenberg, David Bundy and Jarod Roland

Object

There is a growing interest in the use of recording from the surface of the brain, known as electrocorticography (ECoG), as a practical signal platform for brain-computer interface application. The signal has a combination of high signal quality and long-term stability that may be the ideal intermediate modality for future application. The research paradigm for studying ECoG signals uses patients requiring invasive monitoring for seizure localization. The implanted arrays span cortex areas on the order of centimeters. Currently, it is unknown what level of motor information can be discerned from small regions of human cortex with microscale ECoG recording.

Methods

In this study, a patient requiring invasive monitoring for seizure localization underwent concurrent implantation with a 16-microwire array (1-mm electrode spacing) placed over primary motor cortex. Microscale activity was recorded while the patient performed simple contra- and ipsilateral wrist movements that were monitored in parallel with electromyography. Using various statistical methods, linear and nonlinear relationships between these microcortical changes and recorded electromyography activity were defined.

Results

Small regions of primary motor cortex (< 5 mm) carry sufficient information to separate multiple aspects of motor movements (that is, wrist flexion/extension and ipsilateral/contralateral movements).

Conclusions

These findings support the conclusion that small regions of cortex investigated by ECoG recording may provide sufficient information about motor intentions to support brain-computer interface operations in the future. Given the small scale of the cortical region required, the requisite implanted array would be minimally invasive in terms of surgical placement of the electrode array.

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Eric C. Leuthardt, Gerwin Schalk, Jarod Roland, Adam Rouse and Daniel W. Moran

The notion that a computer can decode brain signals to infer the intentions of a human and then enact those intentions directly through a machine is becoming a realistic technical possibility. These types of devices are known as brain-computer interfaces (BCIs). The evolution of these neuroprosthetic technologies could have significant implications for patients with motor disabilities by enhancing their ability to interact and communicate with their environment. The cortical physiology most investigated and used for device control has been brain signals from the primary motor cortex. To date, this classic motor physiology has been an effective substrate for demonstrating the potential efficacy of BCI-based control. However, emerging research now stands to further enhance our understanding of the cortical physiology underpinning human intent and provide further signals for more complex brain-derived control. In this review, the authors report the current status of BCIs and detail the emerging research trends that stand to augment clinical applications in the future.

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Kyle A. Smith, Michael Salacz and Paul J. Camarata

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Donncha F. O'Brien, Tae Sung Park, Joan A. Puglisi, David R. Collins and Eric C. Leuthardt

Object. The authors performed a long-term evaluation of gait status to determine the frequency with which orthopedic operations for cerebral palsy are conducted before and after selective dorsal rhizotomy (SDR) and the relation between pre- and post-SDR orthopedic surgery and age.

Methods. Fifty-two patients with spastic quadriplegia were prospectively followed for 5 to 9 years. All children were evaluated and underwent SDR at St. Louis Children's Hospital. Preoperative scores for gait function and details of previous orthopedic procedures were recorded for two age groups: those 2 to 5 (Group 1) and those 6 to 14 years of age (Group 2). Data were collected from parents who completed a questionnaire a mean of 7.5 years after SDR. Relations between gait status and the number/type of pre- and post-SDR orthopedic procedures, rate of improvement after SDR, benefit of operation according to parents, and return of spasticity were analyzed.

Forty-nine percent of patients in Group 1 and 25% of those in Group 2 had improved gait scores. The interaction between pre- or post-SDR time frame and walking mode was statistically significant (p = 0.004). Among those children who had not undergone orthopedic surgery before SDR, the incidence of surgery post-SDR was higher in the older children (Group 2) than the younger children (Group 1 [70% compared with 34%]). Parents of 75% of the Group 1 patients and 88% of the Group 2 patients felt that their children benefited from SDR.

Conclusions. The results of this study highlight the effect of SDR on gait status in children with spastic quadriplegic cerebral palsy. The percentage of patients needing orthopedic operations was not as high as reported previously. Parents indicated that SDR was beneficial to their children.

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David Y. A. Dadey, Ashwin A. Kamath, Eric C. Leuthardt and Matthew D. Smyth

Subependymal giant cell astrocytoma (SEGA) is a rare tumor occurring almost exclusively in patients with tuberous sclerosis complex. Although open resection remains the standard therapy, complication rates remain high. To minimize morbidity, less invasive approaches, such as endoscope-assisted resection, radiosurgery, and chemotherapy with mTOR pathway inhibitors, are also used to treat these lesions. Laser interstitial thermal therapy (LITT) is a relatively new modality that is increasingly used to treat a variety of intracranial lesions. In this report, the authors describe two pediatric cases of SEGA that were treated with LITT. In both patients the lesion responded well to this treatment modality, with tumor shrinkage observed on follow-up MRI. These cases highlight the potential of LITT to serve as a viable minimally invasive therapeutic approach to the management of SEGAs in the pediatric population.

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Matthew R. MacEwan, Michael R. Talcott, Daniel W. Moran and Eric C. Leuthardt

OBJECTIVE

Instrumented spinal fusion continues to exhibit high failure rates in patients undergoing multilevel lumbar fusion or pseudarthrosis revision; with Grade II or higher spondylolisthesis; or in those possessing risk factors such as obesity, tobacco use, or metabolic disorders. Direct current (DC) electrical stimulation of bone growth represents a unique surgical adjunct in vertebral fusion procedures, yet existing spinal fusion stimulators are not optimized to enhance interbody fusion. To develop an advanced method of applying DC electrical stimulation to promote interbody fusion, a novel osteogenic spinal system capable of routing DC through rigid instrumentation and into the vertebral bodies was fabricated. A pilot study was designed to assess the feasibility of osteogenic instrumentation and compare the ability of osteogenic instrumentation to promote successful interbody fusion in vivo to standard spinal instrumentation with autograft.

METHODS

Instrumented, single-level, posterior lumbar interbody fusion (PLIF) with autologous graft was performed at L4–5 in adult Toggenburg/Alpine goats, using both osteogenic spinal instrumentation (plus electrical stimulation) and standard spinal instrumentation (no electrical stimulation). At terminal time points (3 months, 6 months), animals were killed and lumbar spines were explanted for radiographic analysis using a SOMATOM Dual Source Definition CT Scanner and high-resolution Microcat II CT Scanner. Trabecular continuity, radiodensity within the fusion mass, and regional bone formation were examined to determine successful spinal fusion.

RESULTS

Quantitative analysis of average bone density in pedicle screw beds confirmed that electroactive pedicle screws used in the osteogenic spinal system focally enhanced bone density in instrumented vertebral bodies. Qualitative and quantitative analysis of high-resolution CT scans of explanted lumbar spines further demonstrated that the osteogenic spinal system induced solid bony fusion across the L4–5 disc space as early as 6 weeks postoperatively. In comparison, inactive spinal instrumentation with autograft was unable to promote successful interbody fusion by 6 months postoperatively.

CONCLUSIONS

Results of this study demonstrate that novel osteogenic spinal instrumentation supports interbody fusion through the focal delivery of DC electrical stimulation. With further technical development and scientific/clinical validation, osteogenic spinal instrumentation may offer a unique alternative to biological scaffolds and pharmaceutical adjuncts used in spinal fusion procedures.

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Ammar H. Hawasli, Albert H. Kim, Gavin P. Dunn, David D. Tran and Eric C. Leuthardt

Evolving research has demonstrated that surgical cytoreduction of a high-grade glial neoplasm is an important factor in improving the prognosis of these difficult tumors. Recent advances in intraoperative imaging have spurred the use of stereotactic laser ablation (laser interstitial thermal therapy [LITT]) for intracranial lesions. Among other targets, laser ablation has been used in the focal treatment of high-grade gliomas (HGGs). The revived application of laser ablation for gliomas parallels major advancements in intraoperative adjuvants and groundbreaking molecular advances in neuro-oncology. The authors review the research on stereotactic LITT for the treatment of HGGs and provide a potential management algorithm for HGGs that incorporates LITT in clinical practice.

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Donncha F. O'Brien, Tae-Sung Park, Joan A. Puglisi, David R. Collins, Eric C. Leuthardt and Jeffrey R. Leonard

Object

A retrospective study was performed to determine the following: 1) whether children who walk independently after selective dorsal rhizotomy (SDR) undergo fewer subsequent orthopedic operations than those who walk with assistance; and 2) the effect of age at SDR on the rate of orthopedic operations.

Methods

The cases of 158 children with spastic diplegia who were 2 to 14 years of age when they underwent SDR were followed over a 5- to 9-year period. Patients were grouped by age at the time of SDR as follows: 2 to 3 years (Group 1), 4 to 7 years (Group 2), and 8 to 14 years (Group 3). Follow-up data showed that children in all age groups who walked independently after SDR underwent fewer orthopedic operations than did children who walked with assistance. Overall rates of orthopedic surgery 5 to 9 years after SDR at last follow up were 24% for independent walkers and 51% for assisted walkers. Two-way categorical analysis (age group by ambulation) yielded a highly significant effect of ambulation (p = 0.0003). Children in Group 1 needed the fewest orthopedic operations at follow-up evaluation. In the older age groups (Groups 2 and 3), those who walked independently at the time of SDR underwent fewer orthopedic operations after SDR than did walkers who required assistance (p = 0.01).

Conclusions

These data are of value in advising parents about the likelihood of orthopedic surgery based on the child's gait status both at the time of SDR and at follow-up evaluation. Orthopedic surgery is more likely in patients destined to be nonambulators.

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Diane J. Aum, David H. Kim, Thomas L. Beaumont, Eric C. Leuthardt, Gavin P. Dunn and Albert H. Kim

There has been increasing awareness that glioblastoma, which may seem histopathologically similar across many tumors, actually represents a group of molecularly distinct tumors. Emerging evidence suggests that cells even within the same tumor exhibit wide-ranging molecular diversity. Parallel to the discoveries of molecular heterogeneity among tumors and their individual cells, intense investigation of the cellular biology of glioblastoma has revealed that not all cancer cells within a given tumor behave the same. The identification of a subpopulation of brain tumor cells termed “glioblastoma cancer stem cells” or “tumor-initiating cells” has implications for the management of glioblastoma. This focused review will therefore summarize emerging concepts on the molecular and cellular heterogeneity of glioblastoma and emphasize that we should begin to consider each individual glioblastoma to be an ensemble of molecularly distinct subclones that reflect a spectrum of dynamic cell states.

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Guy M. Genin, Stuart P. Rosenberg, Laura M. Seger, Elizabeth L. Tran, Dennis J. Rivet and Eric C. Leuthardt

Halo orthoses present a paradox. On the one hand, the nominally rigid immobilization they provide to the head aims to remove loads on the cervical spine following injury or surgery, and the devices are retightened routinely to maintain this. On the other hand, bone growth and remodeling are well known to require mechanical stressing. How are these competing needs balanced? To understand this trade-off in an effective, commercial halo orthosis, the authors quantified the response of a commercial halo orthosis to physiological loading levels, applied symmetrically about the sagittal plane. They showed for the first time that after a few cycles of loading analogous to a few steps taken by a patient, the support presented by a standard commercial halo orthosis becomes nonlinear. When analyzed through straightforward structural modeling, these data revealed that the nonlinearity permits mild head motion while severely restricting larger motion. These observations are useful because they open the possibility that halo orthosis installation could be optimized to transfer mild spinal loads that support healing while blocking pathological loads.