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1.  Advances in myelin imaging with potential clinical application to pediatric imaging 
Neurosurgical focus  2013;34(4):E9.
White matter development and myelination are critical processes in neurodevelopment. Myelinated white matter facilitates the rapid and coordinated brain messaging required for higher-order cognitive and behavioral processing. Whereas several neurological disorders such as multiple sclerosis are associated with gross white matter damage and demyelination, other disorders such as epilepsy may involve altered myelination in the efferent or afferent white matter pathways adjoining epileptic foci. Current MRI techniques including T1 weighting, T2 weighting, FLAIR, diffusion tensor imaging, and MR spectroscopy permit visualization of gross white matter abnormalities and evaluation of underlying white matter fiber architecture and integrity, but they provide only qualitative information regarding myelin content. Quantification of these myelin changes could provide new insight into disease severity and prognosis, reveal information regarding spatial location of foci or lesions and the associated affected neural systems, and create a metric to evaluate treatment efficacy. Multicomponent analysis of T1 and T2 relaxation data, or multicomponent relaxometry (MCR), is a quantitative imaging technique that is sensitive and specific to myelin content alteration. In the past, MCR has been associated with lengthy imaging times, but a new, faster MCR technique (mcDESPOT) has made quantitative analysis of myelin content more accessible for clinical research applications. The authors briefly summarize traditional white matter imaging techniques, describe MCR and mcDESPOT, and discuss current and future clinical applications of MCR, with a particular focus on pediatric epilepsy.
PMCID: PMC3777219  PMID: 23544415
myelin; epilepsy; imaging; multicomponent relaxometry
2.  Imaging pre-ictal hemodynamic changes in neocortical epilepsy 
Neurosurgical focus  2013;34(4):E10.
The ability to predict seizure occurrence is extremely important to trigger abortive therapies and to warn patients and their caregivers. Optical imaging of hemodynamic parameters such as blood flow, blood volume and tissue and hemoglobin oxygenation has already been shown to successfully localize epileptic events with high spatial and temporal resolution. The ability to actually predict seizure occurrence using hemodynamic parameters is less well explored.
In this paper, we will critically review the literature on data from neocortical epilepsy using optical imaging and discus these pre-ictal hemodynamic changes findings and its application in neurosurgery.
Recent optical mapping studies have demonstrated pre-ictal hemodynamic changes in both human and animal neocortex.
Optical measurements of blood flow and oxygenation may become increasingly important for predicting as well as localizing epileptic events. The ability to successfully predict ictal onsets may be useful to trigger closed-loop abortive therapies.
PMCID: PMC3961761  PMID: 23544406
epilepsy; seizure; optical imaging; neurosurgery
3.  Association of functional magnetic resonance imaging indices with postoperative language outcomes in patients with primary brain tumors 
Neurosurgical focus  2013;34(4):E6.
Functional MRI (fMRI) has the potential to be a useful presurgical planning tool to treat patients with primary brain tumor. In this study the authors retrospectively explored relationships between language-related postoperative outcomes in such patients and multiple factors, including measures estimated from task fMRI maps (proximity of lesion to functional activation area, or lesion-to-activation distance [LAD], and activation-based language lateralization, or lateralization index [LI]) used in the clinical setting for presurgical planning, as well as other factors such as patient age, patient sex, tumor grade, and tumor volume.
Patient information was drawn from a database of patients with brain tumors who had undergone preoperative fMRI-based language mapping of the Broca and Wernicke areas. Patients had performed a battery of tasks, including word-generation tasks and a text-versus-symbols reading task, as part of a clinical fMRI protocol. Individually thresholded task fMRI activation maps had been provided for use in the clinical setting. These clinical imaging maps were used to retrospectively estimate LAD and LI for the Broca and Wernicke areas.
There was a relationship between postoperative language deficits and the proximity between tumor and Broca area activation (the LAD estimate), where shorter LADs were related to the presence of postoperative aphasia. Stratification by tumor location further showed that for posterior tumors within the temporal and parietal lobes, more bilaterally oriented Broca area activation (LI estimate close to 0) and a shorter Wernicke area LAD were associated with increased postoperative aphasia. Furthermore, decreasing LAD was related to decreasing LI for both Broca and Wernicke areas. Preoperative deficits were related to increasing patient age and a shorter Wernicke area LAD.
Overall, LAD and LI, as determined using fMRI in the context of these paradigms, may be useful indicators of postsurgical outcomes. Whereas tumor location may influence postoperative deficits, the results indicated that tumor proximity to an activation area might also interact with how the language network is affected as a whole by the lesion. Although the derivation of LI must be further validated in individual patients by using spatially specific statistical methods, the current results indicated that fMRI is a useful tool for predicting postoperative outcomes in patients with a single brain tumor.
PMCID: PMC3954579  PMID: 23544412
functional magnetic resonance imaging; brain tumor; aphasia
4.  In vivo performance of a microelectrode neural probe with integrated drug delivery 
Neurosurgical focus  2009;27(1):E8.
The availability of sophisticated neural probes is a key prerequisite in the development of future brain machine interfaces (BMI). In this study, we developed and validated a neural probe design capable of simultaneous drug delivery and electrophysiology recordings in vivo. Focal drug delivery has promise to dramatically extend the recording lives of neural probes, a limiting factor to clinical adoption of BMI technology.
To form the multifunctional neural probe, we affixed a 16-channel microfabricated silicon electrode array to a fused silica catheter. Three experiments were conducted to characterize the performance of the device. Experiment 1 examines cellular damage from probe insertion and the drug distribution in tissue. Experiment 2 measures the effects of saline infusions delivered through the probe on concurrent electrophysiology. Experiment 3 demonstrates that a physiologically relevant amount of drug can be delivered in a controlled fashion. For these experiments, Hoechst and propidium iodide were used to assess insertion trauma and the tissue distribution of the infusate. Artificial cerebral spinal fluid and tetrodotoxin were injected to determine the efficacy of drug delivery.
The newly developed multifunctional neural probes were successfully inserted into rat cortex and were able to deliver fluids and drugs that resulted in the expected electrophysiological and histological responses. The damage from insertion of the device into brain tissue was substantially less than the volume of drug dispersion in tissue. Electrophysiological activity, including both individual spikes as well as local field potentials, was successfully recorded with this device during real-time drug delivery. No significant changes were seen in response to delivery of artificial cerebral spinal fluid as a control experiment, whereas delivery of tetrodotoxin produced the expected result of suppressing all spiking activity in the vicinity of the catheter outlet.
Multifunctional neural probes such as the ones developed and validated within this study have great potential to help further understand the design space and criteria for the next generation of neural probe technology. By incorporating integrated drug delivery functionality into the probes, new treatment options for neurological disorders and regenerative neural interfaces utilizing localized and feedback controlled delivery of drugs can be realized in the near future.
PMCID: PMC3938951  PMID: 19569896
Drug delivery; neural engineering; microelectrode array
5.  Patient-assessed satisfaction and outcome after microsurgical resection of cavernomas causing epilepsy 
Neurosurgical focus  2010;29(3):E16.
Microsurgical resection of supratentorial cavernomas associated with intractable epilepsy is performed frequently. Despite its common occurrence, little is known about patient perceptions of microsurgical resection for cavernomas. This survey study was performed to investigate patient perceived outcome after surgery for cavernomas associated with intractable epilepsy.
The authors’ surgical database was searched for cavernoma resection performed between 1971 and July of 2006. Of the initial 173 patients identified, 102 met criteria for medically intractable seizures. These 102 patients were then mailed a survey to determine follow-up and patient satisfaction. Thirty-nine surveys were returned as undeliverable, and 30 (48%) of the remaining 63 patients responded.
The average age at surgery for patients responding to this survey was 40 ± 16 years compared with 35 ± 15 years for all 102 patients. At prolonged follow-up, 87% of patients reported being seizure-free. Of those with seizures, 2 (7%) reported being nearly seizure-free (rare disabling seizures), 2 (7%) believed they had a worthwhile improvement in seizure frequency, and no patient (0%) in this series believed they did not have a worthwhile improvement in seizure frequency. Ninety percent of responders stated they definitely, and 10% probably, would have surgery again. No patient responded that they probably or definitely would not have epilepsy surgery. Mean clinical follow-up was 36 ± 8 months and survey follow-up was 97 ± 13 months for these 30 patients. Use of the mail-in survey increased follow-up length 2.7 times longer compared with clinical follow-up.
It is clear from this select group of survey responders that patients undergoing surgery for cavernomas associated with medically intractable epilepsy are happy they underwent surgery (100%) and had excellent surgical outcomes (87% seizure-free) at prolonged follow-up of 97 ± 13 months. These survey results support that microsurgical resection for cavernomas is highly effective and significantly improves these patients’ quality of life.
PMCID: PMC3920597  PMID: 20809757
cavernoma; epilepsy; survey; patient outcome; postal questionnaire
6.  The role of secondary motor and language cortices in morbidity and mortality: A retrospective fMRI study of surgical planning for patients with intracranial tumors 
Neurosurgical focus  2013;34(4):10.3171/2013.2.FOCUS12410.
Functional magnetic resonance imaging (fMRI) is commonly utilized by neurosurgeons to pre-operatively identify brain regions associated with essential behaviors, such as language and motor abilities. This study investigated the relationship between the distance from tumor border area to functional activations in secondary motor and language cortices to patient morbidity and mortality.
Patients with primary or metastatic brain tumors who underwent pre-operative fMRI motor and language mapping were selected from a large database of tumor patients. The lesion-to-activation distance (LAD) was measured in each subject relative to the supplementary motor area for motor tasks and pre-supplementary motor area for language tasks. The association between LAD and the incidence of deficits was investigated using Fisher’s exact tests of significance. The impact of other variables, including age, handedness, gender, and tumor grade were also investigated. In a subset of subjects, logistic regression was performed to identify the likelihood of deficits based on LAD to primary and secondary regions. Finally, Mantel-Cox log-rank tests were performed to determine whether survival time significantly related to LAD to secondary motor and language areas.
A significant association was observed between LAD to the SMA and the incidence of motor deficits, with the percentage of patients with deficits dropping for those in the LAD > 2 cm group. The relationship between LAD to the pSMA and the incidence of language deficits was not significant. Logistic regression demonstrated that the LAD to primary sensorimotor cortex does affect the incidence of motor deficits, but LAD to SMA does not. Finally, we observed no relationship between LAD to secondary regions and patient mortality.
These results demonstrate that LAD to SMA structures does affect morbidity, although not to the extent of LAD to primary structures. In addition, motor deficits are significantly associated with LAD to secondary structures, but language deficits are not. This should be considered by neurosurgeons for patient consultation and pre-operative planning.
PMCID: PMC3817821  PMID: 23544413
Lesion-activation distance; morbidity; fMRI; tumor; SMA; preSMA
7.  Characterizing the relationship between fMRI derived measures and clinical outcomes in vascular lesion patients 
Neurosurgical focus  2013;34(4):10.3171/2013.2.FOCUS12417.
Background and Purpose
Functional magnetic resonance imaging (fMRI) has proven to be an effective component of pretreatment planning in patients harboring a variety of different brain lesions. Our group has recently reported significant relationships concerning distances between brain tumor border and area of functional activation (Lesion-to-Activation-Distance; LAD) with regard to patient morbidity and mortality. This study further examines the relationship between LAD, focusing on a host of vascular lesions, and pre- and posttreatment morbidity.
Materials and Methods
This study included a sample population (n=106) of patients with vascular lesions, primarily arteriovenous malformations (AVM) and cavernomas. These patients underwent pretreatment fMRI-based motor mapping (n=72) or language mapping (n=84). The impact of LAD and other variables derived from the patient medical record were analyzed with respect to functional deficits in terms of morbidity (weakness and/or aphasia).
In patients with no pretreatment deficits, there was trend for a significant relationship between Wernicke's area LAD and posttreatment language deficits. In patients with or without pretreatment deficits, a trend toward significance was observed between sensorimotor LAD and posttreatment motor deficits. Additionally, lesion type (AVMs or cavernomas) impacted posttreatment deficits with more patients with cavernomas showing posttreatment language deficits than patients with AVMs. This difference was however not observed for posttreatment motor deficits.
These findings suggest that the proximity of a vascular lesion to sensorimotor and language areas is a relevant parameter in estimating patient prognosis in the peri-operative period. Additionally, vascular lesion type and existence of pretreatment deficits play a significant role in outcomes.
PMCID: PMC3807681  PMID: 23544414
8.  Volumetric analysis of syringomyelia following hindbrain decompression for Chiari malformation Type I: syringomyelia resolution follows exponential kinetics 
Neurosurgical focus  2011;31(3):E4.
Resolution of syringomyelia is common following hindbrain decompression for Chiari malformation, yet little is known about the kinetics governing this process. The authors sought to establish the volumetric rate of syringomyelia resolution.
A retrospective cohort of patients undergoing hindbrain decompression for a Chiari malformation Type I with preoperative cervical or thoracic syringomyelia was identified. Patients were included in the study if they had at least 3 neuroimaging studies that detailed the entirety of their preoperative syringomyelia over a minimum of 6 months postoperatively. The authors reconstructed the MR images in 3 dimensions and calculated the volume of the syringomyelia. They plotted the syringomyelia volume over time and constructed regression models using the method of least squares. The Akaike information criterion and Bayesian information criterion were used to calculate the relative goodness of fit. The coefficients of determination R2 (unadjusted and adjusted) were calculated to describe the proportion of variability in each individual data set accounted for by the statistical model.
Two patients were identified as meeting inclusion criteria. Plots of the least-squares best fit were identified as 4.01459e−0.0180804x and 13.2556e−0.00615859x. Decay of the syringomyelia followed an exponential model in both patients (R2 = 0.989582 and 0.948864).
Three-dimensional analysis of syringomyelia resolution over time enables the kinetics to be estimated. This technique is yet to be validated in a large cohort. Because syringomyelia is the final common pathway for a number of different pathological processes, it is possible that this exponential only applies to syringomyelia related to treatment of Chiari malformation Type I.
PMCID: PMC3731038  PMID: 21882909
Chiari malformation; syringomyelia; syrinx; MR imaging; volumetrics
9.  Cell therapies for traumatic brain injury 
Neurosurgical focus  2008;24(0):E18.
Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.
PMCID: PMC3721356  PMID: 18341394
cell therapy; clinical trial; stem cells; traumatic brain injury
10.  Emerging clinical imaging techniques for cerebral cavernous malformations: a systematic review 
Neurosurgical focus  2010;29(3):E6.
Cerebral cavernous malformations (CCM) are divided into sporadic and familial forms. For clinical imaging, T2-weighted gradient-echo sequences have been shown to be more sensitive than conventional sequences. Recently more advanced imaging techniques such as high-field and susceptibility-weighted magnetic resonance imaging has been employed for the evaluation of CCMs. Furthermore, diffusion tensor imaging and functional magnetic resonance imaging have been applied to the preoperative and intraoperative management of these lesions. In this paper, the authors attempt to provide a concise review of the emerging imaging methods utilized in the clinical diagnosis and treatment of CCMs.
PMCID: PMC3708641  PMID: 20809764
magnetic resonance imaging; cavernoma; cavernous malformations; susceptibility-weighted imaging; gradient echo; functional magnetic resonance imaging
11.  Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury 
Neurosurgical focus  2008;25(4):E3.
Current standard of care for patients with severe traumatic brain injury (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever, and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra) does not require serum monitoring or have significant pharmacokinetic interactions. In the current study, the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI.
Data were prospectively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy. Patients underwent 1-hour electroencephalographic (EEG) monitoring if they displayed persistent coma, decreased mental status, or clinical signs of seizures. The EEG results were grouped into normal and abnormal findings, with abnormal EEG findings further categorized as seizure activity or seizure tendency.
Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15 cases the results were normal and in 8 abnormal; 1 patient had seizure activity, whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group received EEG monitoring, with all results being normal. Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity (p = 0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG findings (p = 0.003).
Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis.
PMCID: PMC3705765  PMID: 18828701
antiepileptic drug; posttraumatic seizure; seizure prophylaxis; traumatic brain injury
12.  Decoding movement-related cortical potentials from electrocorticography 
Neurosurgical focus  2009;27(1):E11.
Control signals for brain-machine interfaces may be obtained from a variety of sources, each with their own relative merits. Electrocorticography (ECoG) provides better spatial and spectral resolution than scalp electroencephalography and does not include the risks attendant upon penetration of the brain parenchyma associated with single and multiunit recordings. For these reasons, subdural electrode recordings have been proposed as useful primary or adjunctive control signals for brain-machine interfaces. The goal of the present study was to determine if 2D control signals could be decoded from ECoG.
Six patients undergoing invasive monitoring for medically intractable epilepsy using subdural grid electrodes were asked to perform a motor task involving moving a joystick in 1 of 4 cardinal directions (up, down, left, or right) and a fifth condition (“trigger”). Evoked activity was synchronized to joystick movement and analyzed in the theta, alpha, beta, gamma, and high-gamma frequency bands.
Movement-related cortical potentials could be accurately differentiated from rest with very high accuracy (83–96%). Further distinguishing the movement direction (up, down, left, or right) could also be resolved with high accuracy (58–86%) using information only from the high-gamma range, whereas distinguishing the trigger condition from the remaining directions provided better accuracy.
Two-dimensional control signals can be derived from ECoG. Local field potentials as measured by ECoG from subdural grids will be useful as control signals for a brain-machine interface.
PMCID: PMC3686514  PMID: 19569886
brain-machine interface; local field potentials; electrocorticography; motor control; epilepsy
13.  A Stepwise Illustration of the Translabyrinthine Approach to a Large Cystic Vestibular Schwannoma 
Neurosurgical focus  2012;33(3):E11.
Of the presigmoid approaches, the translabyrinthine approach is often used when a large exposure is needed to the cerebello-pontine angle, but hearing preservation is not a concern. At our institution, this approach is performed in collboration with ENT/Otolaryngology for temporal bone drilling and exposure.
In this video and paper, we demonstrate the use of the translabyrinthine approach for resection of a large cystic vestibular schwannoma, delineating the steps of positioning, opening, temporal bone drilling, tumor resection and closure.
Gross total resection was obtained in this patient. His postoperative facial function was House-Brackmann grade II on the side ipsilateral to the tumor, although this improved with time.
The translabyrinthine approach to the cerebello-pontine angle is an excellent approach for masses that extend toward the midline or anterior to the pons. Although hearing is sacrificed, facial nerve function is generally spared.
PMCID: PMC3675780  PMID: 22937845
Translabyrinthine; Vestibular Schwannoma; Surgical Technique; Video
14.  Human cortical prostheses: lost in translation? 
Neurosurgical focus  2009;27(1):E5.
Direct brain control of a prosthetic system is the subject of much popular and scientific news. Neural technology and science have advanced to the point that proof-of-concept systems exist for cortically-controlled prostheses in rats, monkeys, and even humans. However, realizing the dream of making such technology available to everyone is still far off. Fortunately today there is great public and scientific interest in making this happen, but it will only occur when the functional benefits of such systems outweigh the risks. In this article, the authors briefly summarize the state of the art and then highlight many issues that will directly limit clinical translation, including system durability, system performance, and patient risk. Despite the challenges, scientists and clinicians are in the desirable position of having both public and fiscal support to begin addressing these issues directly. The ultimate challenge now is to determine definitively whether these prosthetic systems will become clinical reality or forever unrealized.
PMCID: PMC3614414  PMID: 19569893
brain-machine interface; brain-computer interface; motor; communication; prostheses; performance; risk
15.  Symptomatic intracranial arterial disease: incidence, natural history, diagnosis, and management 
Neurosurgical focus  2011;30(6):E14.
Symptomatic intracranial arterial disease is associated with a high rate of recurrent ischemic events. The management of this condition is controversial, with some advocating medical therapy as a sole means of treatment and others recommending endovascular therapy in addition to best medical management. In rare cases, surgical intervention is considered. A thorough review of the available literature was performed, and treatment recommendations based on these data are provided.
PMCID: PMC3593273  PMID: 21631215
intracranial stenosis; cerebral ischemia; balloon angioplasty; extracranial-intracranial bypass
16.  Quantitative and qualitative 5-aminolevulinic acid–induced protoporphyrin IX fluorescence in skull base meningiomas 
Neurosurgical focus  2011;30(5):E8.
Complete resection of skull base meningiomas provides patients with the best chance for a cure; however, surgery is frequently difficult given the proximity of lesions to vital structures, such as cranial nerves, major vessels, and venous sinuses. Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative assessment of protoporphyrin IX (PpIX) fluorescence following the exogenous administration of 5-aminolevulinic acid (ALA) has demonstrated utility in malignant glioma resection but limited use in meningiomas. Here the authors demonstrate the use of ALA-induced PpIX fluorescence guidance in resecting a skull base meningioma and elaborate on the advantages and disadvantages provided by both quantitative and qualitative fluorescence methodologies in skull base meningioma resection.
A 52-year-old patient with a sphenoid wing WHO Grade I meningioma underwent tumor resection as part of an institutional review board–approved prospective study of fluorescence-guided resection. A surgical microscope modified for fluorescence imaging was used for the qualitative assessment of visible fluorescence, and an intraoperative probe for in situ fluorescence detection was utilized for quantitative measurements of PpIX. The authors assessed the detection capabilities of both the qualitative and quantitative fluorescence approaches.
The patient harboring a sphenoid wing meningioma with intraorbital extension underwent radical resection of the tumor with both visibly and nonvisibly fluorescent regions. The patient underwent a complete resection without any complications. Some areas of the tumor demonstrated visible fluorescence. The quantitative probe detected neoplastic tissue better than the qualitative modified surgical microscope. The intraoperative probe was particularly useful in areas that did not reveal visible fluorescence, and tissue from these areas was confirmed as tumor following histopathological analysis.
Fluorescence-guided resection may be a useful adjunct in the resection of skull base meningiomas. The use of a quantitative intraoperative probe to detect PpIX concentration allows more accurate determination of neoplastic tissue in meningiomas than visible fluorescence and is readily applicable in areas, such as the skull base, where complete resection is critical but difficult because of the vital structures surrounding the pathology.
PMCID: PMC3116440  PMID: 21529179
skull base meningioma; fluorescence-guided resection; protoporphyrin IX; 5-aminolevulinic acid; optical spectroscopy; biophotonics
Neurosurgical focus  2010;28(1):E10.
Subarachnoid hemorrhage (SAH) is a devastating neurological injury associated with significant patient morbidity and mortality. Since the first demonstration of cerebral vasospasm nearly 60 years ago, the preponderance of research focused on strategies to limit arterial narrowing and delayed cerebral ischemia following SAH. However, recent clinical and pre-clinical data indicates a functional dissociation between cerebral vasospasm and neurological outcome, signaling the need for a paradigm shift in the study of brain injury following SAH. Early brain injury (EBI) may contribute to the poor outcome and early mortality following SAH; however, elucidation of the complex cellular mechanisms underlying EBI remains a major challenge. The advent of modern neuroproteomics has rapidly advanced scientific discovery by allowing proteome-wide screening in an objective, non-biased manner, providing novel mechanisms of brain physiology and injury. In the context of neurosurgery, proteomic analysis of patient-derived cerebrospinal fluid will permit the identification of biomarkers and/or novel drug targets, which may not be intuitively linked with any particular disease. In the present report, we discuss the utility of neuroproteomics with a focus on the roles for this technology in understanding SAH. We also provide data from our laboratory, which identifies high-mobility group box protein-1 (HMGB1) as a potential biomarker of neurological outcome following SAH in humans.
PMCID: PMC3151677  PMID: 20043714
Early Brain Injury; Hemorrhagic stroke; Cerebral aneurysm; Inflammation; Cerebrospinal Fluid; Biomarker
18.  Development of intraoperative electrochemical detection: wireless instantaneous neurochemical concentration sensor for deep brain stimulation feedback 
Neurosurgical focus  2010;29(2):E6.
Deep brain stimulation (DBS) is effective when there appears to be a distortion in the complex neurochemical circuitry of the brain. Currently, the mechanism of DBS is incompletely understood; however, it has been hypothesized that DBS evokes release of neurochemicals. Well-established chemical detection systems such as microdialysis and mass spectrometry are impractical if one is assessing changes that are happening on a second-to-second time scale or for chronically used implanted recordings, as would be required for DBS feedback. Electrochemical detection techniques such as fast-scan cyclic voltammetry (FSCV) and amperometry have until recently remained in the realm of basic science; however, it is enticing to apply these powerful recording technologies to clinical and translational applications. The Wireless Instantaneous Neurochemical Concentration Sensor (WINCS) currently is a research device designed for human use capable of in vivo FSCV and amperometry, sampling at subsecond time resolution. In this paper, the authors review recent advances in this electrochemical application to DBS technologies. The WINCS can detect dopamine, adenosine, and serotonin by FSCV. For example, FSCV is capable of detecting dopamine in the caudate evoked by stimulation of the subthalamic nucleus/substantia nigra in pig and rat models of DBS. It is further capable of detecting dopamine by amperometry and, when used with enzyme linked sensors, both glutamate and adenosine. In conclusion, WINCS is a highly versatile instrument that allows near real-time (millisecond) detection of neurochemicals important to DBS research. In the future, the neurochemical changes detected using WINCS may be important as surrogate markers for proper DBS placement as well as the sensor component for a “smart” DBS system with electrochemical feedback that allows automatic modulation of stimulation parameters. Current work is under way to establish WINCS use in humans.
PMCID: PMC2939376  PMID: 20672923
deep brain stimulation; dopamine; adenosine; serotonin; fast-scan cyclic voltammetry; amperometry; electrochemistry
19.  Designing ideal conduits for peripheral nerve repair 
Neurosurgical focus  2009;26(2):E5.
Nerve tubes, guides, or conduits are a promising alternative for autologous nerve graft repair. The first biodegradable empty single lumen or hollow nerve tubes are currently available for clinical use and are being used mostly in the repair of small-diameter nerves with nerve defects of < 3 cm. These nerve tubes are made of different biomaterials using various fabrication techniques. As a result these tubes also differ in physical properties. In addition, several modifications to the common hollow nerve tube (for example, the addition of Schwann cells, growth factors, and internal frameworks) are being investigated that may increase the gap that can be bridged. This combination of chemical, physical, and biological factors has made the design of a nerve conduit into a complex process that demands close collaboration of bioengineers, neuroscientists, and peripheral nerve surgeons. In this article the authors discuss the different steps that are involved in the process of the design of an ideal nerve conduit for peripheral nerve repair.
PMCID: PMC2978041  PMID: 19435445
biomaterial; growth factor; nerve conduit; nerve guide; nerve tube; polymer; Schwann cell
20.  Human neocortical electrical activity recorded on nonpenetrating microwire arrays: applicability for neuroprostheses 
Neurosurgical focus  2009;27(1):E9.
The goal of this study was to determine whether a nonpenetrating, high-density microwire array could provide sufficient information to serve as the interface for decoding motor cortical signals.
Arrays of nonpenetrating microwires were implanted over the human motor cortex in 2 patients. The patients performed directed stereotypical reaching movements in 2 directions. The resulting data were used to determine whether the reach direction could be distinguished through a frequency power analysis.
Correlation analysis revealed decreasing signal correlation with distance. The gamma-band power during motor planning allowed binary classification of gross directionality in the reaching movements. The degree of power change was correlated to the underlying gyral pattern.
The nonpenetrating microwire platform showed good potential for allowing differentiated signals to be recorded with high spatial fidelity without cortical penetration.
PMCID: PMC2941644  PMID: 19569897
human; motor cortex; electrocorticoencephalography; neuroprosthesis
21.  Evolution of brain-computer interfaces: going beyond classic motor physiology 
Neurosurgical focus  2009;27(1):E4.
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.
PMCID: PMC2920041  PMID: 19569892
brain-computer interface; neuroprosthetic; cortical physiology
22.  Quantitative hemodynamic studies in moyamoya disease: A review 
Neurosurgical focus  2009;26(4):E5.
Moyamoya disease is characterized by a chronic stenoocclusive vasculopathy affecting the terminal internal carotid arteries. The clinical presentation and outcome of moyamoya disease remain varied based on angiographic studies alone, and much work has been done to study cerebral hemodynamics in this group of patients. The ability to measure cerebral blood flow (CBF) accurately continues to improve with time, and with it a better understanding of the pathophysiological mechanisms in patients with moyamoya disease. The main imaging techniques used to evaluate cerebral hemodynamics include PET, SPECT, xenon-enhanced CT, dynamic perfusion CT, MR imaging with dynamic susceptibility contrast and with arterial spin labeling, and Doppler ultrasonography. More invasive techniques include intraoperative ultrasonography. The authors review the current knowledge of CBF in this group of patients and the role each main quantitative method has played in evaluating them, both in the disease state and after surgical intervention.
PMCID: PMC2905646  PMID: 19335131
moyamoya disease; cerebral blood flow; hemodynamics; xenon study; positron emission tomography; single-photon emission computed tomography; perfusion imaging
23.  NINDS Support for Brain Machine Interface Technology 
Neurosurgical focus  2009;27(1):E14.
Brain-machine interfaces (BMIs) offer the promise of restoring communication, enabling control of assistive devices, and volitional control of extremities in paralyzed individuals. Working in multidisciplinary teams, neurosurgeons can play an invaluable role in design, development, and demonstration of novel BMI technology. At the NIH, the National Institute of Neurological Disorders and Stroke has a long history in supporting neural engineering and prosthetics efforts including BMI and these research opportunities continue today. The purpose of this editorial is to provide a brief overview of the opportunities and programs available currently available to support BMI projects.
PMCID: PMC2742776  PMID: 19569889
24.  Microscale recording from human motor cortex: implications for minimally invasive electrocorticographic brain-computer interfaces 
Neurosurgical focus  2009;27(1):E10.
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.
PMCID: PMC2875251  PMID: 19569885
electrocorticography; brain-computer interface; motor cortex
25.  Getting signals into the brain: visual prosthetics through thalamic microstimulation 
Neurosurgical focus  2009;27(1):E6.
Common causes of blindness are diseases that affect the ocular structures, such as glaucoma, retinitis pigmentosa, and macular degeneration, rendering the eyes no longer sensitive to light. The visual pathway, however, as a predominantly central structure, is largely spared in these cases. It is thus widely thought that a device-based prosthetic approach to restoration of visual function will be effective and will enjoy similar success as cochlear implants have for restoration of auditory function. In this article the authors review the potential locations for stimulation electrode placement for visual prostheses, assessing the anatomical and functional advantages and disadvantages of each. Of particular interest to the neurosurgical community is placement of deep brain stimulating electrodes in thalamic structures that has shown substantial promise in an animal model. The theory of operation of visual prostheses is discussed, along with a review of the current state of knowledge. Finally, the visual prosthesis is proposed as a model for a general high-fidelity machine-brain interface.
PMCID: PMC2848996  PMID: 19569894
visual prosthesis; deep brain stimulation; visual function

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