Kyle A. Smith, Michael Salacz and Paul J. Camarata
Eric C. Leuthardt, Zac Freudenberg, David Bundy and Jarod Roland
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.
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.
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).
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.
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.
Matthew R. MacEwan, Michael R. Talcott, Daniel W. Moran and Eric C. Leuthardt
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.
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.
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.
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.
Jarod L. Roland, Richard L. Price, Ashwin A. Kamath, S. Hassan Akbari, Eric C. Leuthardt, Brandon A. Miller and Matthew D. Smyth
The authors describe 2 cases of triventricular hydrocephalus initially presenting as aqueductal stenosis that subsequently developed tumors of the pineal and tectal region. The first case resembled late-onset idiopathic aqueductal stenosis on serial imaging. Subsequent imaging revealed a new tumor in the pineal region causing mass effect on the midbrain. The second case presented in a more typical pattern of aqueductal stenosis during infancy. On delayed follow-up imaging, an enlarging tectal mass was discovered. In both cases hydrocephalus was successfully treated by cerebrospinal fluid diversion prior to tumor presentation. The differential diagnoses, diagnostic testing, and treatment course for these unusual cases are discussed. The importance of follow-up MRI in cases of idiopathic aqueductal stenosis is emphasized by these exemplar cases.
David Y. A. Dadey, Ashwin A. Kamath, Matthew D. Smyth, Michael R. Chicoine, Eric C. Leuthardt and Albert H. Kim
The precision of laser probe insertion for interstitial thermal therapy of deep-seated lesions is limited by the method of stereotactic guidance. The objective of this study was to evaluate the feasibility of customized STarFix 3D-printed stereotactic platforms to guide laser probe insertion into mesiotemporal and posterior fossa targets.
The authors conducted a retrospective review of 5 patients (12–55 years of age) treated with laser interstitial thermal therapy (LITT) in which STarFix platforms were used for probe insertion. Bone fiducials were implanted in each patient's skull, and subsequent CT scans were used to guide the design of each platform and incorporate desired treatment trajectories. Once generated, the platforms were mounted on the patients' craniums and used to position the laser probe during surgery. Placement of the laser probe and the LITT procedure were monitored with intraoperative MRI. Perioperative and follow-up MRI were performed to identify and monitor changes in target lesions.
Accurate placement of the laser probe was observed in all cases. For all patients, thermal ablation was accomplished without intraoperative complications. Of the 4 patients with symptomatic lesions, 2 experienced complete resolution of symptoms, and 1 reported improved symptoms compared with baseline.
Customized stereotactic platforms were seamlessly incorporated into the authors' previously established LITT workflow and allowed for accurate treatment delivery.
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.
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.
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.
Jarod L. Roland, Natalie Griffin, Carl D. Hacker, Ananth K. Vellimana, S. Hassan Akbari, Joshua S. Shimony, Matthew D. Smyth, Eric C. Leuthardt and David D. Limbrick Jr.
Cerebral mapping for surgical planning and operative guidance is a challenging task in neurosurgery. Pediatric patients are often poor candidates for many modern mapping techniques because of inability to cooperate due to their immature age, cognitive deficits, or other factors. Resting-state functional MRI (rs-fMRI) is uniquely suited to benefit pediatric patients because it is inherently noninvasive and does not require task performance or significant cooperation. Recent advances in the field have made mapping cerebral networks possible on an individual basis for use in clinical decision making. The authors present their initial experience translating rs-fMRI into clinical practice for surgical planning in pediatric patients.
The authors retrospectively reviewed cases in which the rs-fMRI analysis technique was used prior to craniotomy in pediatric patients undergoing surgery in their institution. Resting-state analysis was performed using a previously trained machine-learning algorithm for identification of resting-state networks on an individual basis. Network maps were uploaded to the clinical imaging and surgical navigation systems. Patient demographic and clinical characteristics, including need for sedation during imaging and use of task-based fMRI, were also recorded.
Twenty patients underwent rs-fMRI prior to craniotomy between December 2013 and June 2016. Their ages ranged from 1.9 to 18.4 years, and 12 were male. Five of the 20 patients also underwent task-based fMRI and one underwent awake craniotomy. Six patients required sedation to tolerate MRI acquisition, including resting-state sequences. Exemplar cases are presented including anatomical and resting-state functional imaging.
Resting-state fMRI is a rapidly advancing field of study allowing for whole brain analysis by a noninvasive modality. It is applicable to a wide range of patients and effective even under general anesthesia. The nature of resting-state analysis precludes any need for task cooperation. These features make rs-fMRI an ideal technology for cerebral mapping in pediatric neurosurgical patients. This review of the use of rs-fMRI mapping in an initial pediatric case series demonstrates the feasibility of utilizing this technique in pediatric neurosurgical patients. The preliminary experience presented here is a first step in translating this technique to a broader clinical practice.