Intraoperative application and early experience with novel high-resolution, high-channel-count thin-film electrodes for human microelectrocorticography.

OBJECTIVE: The study objective was to evaluate intraoperative experience with newly developed high-spatial-resolution microelectrode grids composed of poly(3,4-ethylenedioxythiophene) with polystyrene sulfonate (PEDOT:PSS), and those composed of platinum nanorods (PtNRs). METHODS: A cohort of patients who underwent craniotomy for pathological tissue resection and who had high-spatial-resolution microelectrode grids placed intraoperatively were evaluated. Patient demographic and baseline clinical variables as well as relevant microelectrode grid characteristic data were collected. The primary and secondary outcome measures of interest were successful microelectrode grid utilization with usable resting-state or task-related data, and grid-related adverse intraoperative events and/or grid dysfunction. RESULTS: Included in the analysis were 89 cases of patients who underwent a craniotomy for resection of neoplasms (n = 58) or epileptogenic tissue (n = 31). These cases accounted for 94 grids: 58 PEDOT:PSS and 36 PtNR grids. Of these 94 grids, 86 were functional and used successfully to obtain cortical recordings from 82 patients. The mean cortical grid recording duration was 15.3 ± 1.15 minutes. Most recordings in patients were obtained during experimental tasks (n = 52, 58.4%), involving language and sensorimotor testing paradigms, or were obtained passively during resting state (n = 32, 36.0%). There were no intraoperative adverse events related to grid placement. However, there were instances of PtNR grid dysfunction (n = 8) related to damage incurred by suboptimal preoperative sterilization (n = 7) and improper handling (n = 1); intraoperative recordings were not performed. Vaporized peroxide sterilization was the most optimal sterilization method for PtNR grids, providing a significantly greater number of usable channels poststerilization than did steam-based sterilization techniques (median 905.0 [IQR 650.8-935.5] vs 356.0 [IQR 18.0-597.8], p = 0.0031). CONCLUSIONS: High-spatial-resolution microelectrode grids can be readily incorporated into appropriately selected craniotomy cases for clinical and research purposes. Grids are reliable when preoperative handling and sterilization considerations are accounted for. Future investigations should compare the diagnostic utility of these high-resolution grids to commercially available counterparts and assess whether diagnostic discrepancies relate to clinical outcomes.

A Method of Intraoperative Registration Verification to Prevent Accuracy Errors in Robot-Assisted Stereotactic Electroencephalography Electrode Placement.

BACKGROUND: Robotic-assisted stereotactic electroencephalography (sEEG) electrode placement is increasingly common at specialized epilepsy centers. High accuracy and low complication rates are essential to realizing the benefits of sEEG surgery. The aim of this study was to describe for the first time in the literature a method for a stereotactic registration checkpoint to verify intraoperative accuracy during robotic-assisted sEEG and to report our institutional experience with this technique. METHODS: All cases performed with this technique since the adoption of robotic-assisted sEEG at our institution were retrospectively reviewed. RESULTS: In 4 of 111 consecutive sEEG operations, use of the checkpoint detected an intraoperative registration error, which was addressed before completion of sEEG electrode placement. CONCLUSIONS: The use of a registration checkpoint in robotic-assisted sEEG surgery is a simple technique that can prevent electrode misplacement and improve the safety profile of this procedure.

Expansile duraplasty and obex exploration compared with bone-only decompression for Chiari malformation type I in children: retrospective review of outcomes and complications.

OBJECTIVE: While a select population of pediatric patients with Chiari malformation type I (CM-I) remain asymptomatic, some patients present with tussive headaches, neurological deficits, progressive scoliosis, and other debilitating symptoms that necessitate surgical intervention. Surgery entails a variety of strategies to restore normal CSF flow, including increasing the posterior fossa volume via bone decompression only, or bone decompression with duraplasty, with or without obex exploration. The indications for duraplasty and obex exploration following bone decompression remain controversial. The objective of this study was to describe an institutional series of pediatric patients undergoing surgery for CM-I, performed by a single neurosurgeon. For patients presenting with a syrinx, the authors compared outcomes following bone-only decompression with duraplasty only and with duraplasty including obex exploration. Clinical outcomes evaluated included resolution of syrinx, scoliosis, presenting symptoms, and surgical complications. METHODS: A retrospective review was conducted of the medical records of 276 consecutive pediatric patients with CM-I operated on at a single institution between 2001 and 2015 by the senior author. Imaging findings of tonsillar descent, associated syrinx (syringomyelia or syringobulbia), basilar invagination, and clinical assessment of CM-I-attributable symptoms and scoliosis were recorded. In patients presenting with a syrinx, clinical outcomes, including syrinx resolution, symptom resolution, and impact on scoliosis progression, were compared for three surgical groups: bone-only/posterior fossa decompression (PFD), PFD with duraplasty (PFDwD), and PFD with duraplasty and obex exploration (PFDwDO). RESULTS: PFD was performed in 25% of patients (69/276), PFDwD in 18% of patients (50/276), and PFDwDO in 57% of patients (157/276). The mean follow-up was 35 ± 35 months. Nearly half of the patients (132/276, 48%) had a syrinx. In patients presenting with a syrinx, PFDwDO was associated with a significantly higher likelihood of syrinx resolution relative to PFD only (HR 2.65, p = 0.028) and a significant difference in time to symptom resolution (HR 2.68, p = 0.033). Scoliosis outcomes did not differ among treatment groups (p = 0.275). Complications were not significantly higher when any duraplasty (PFDwD or PFDwDO) was performed following bone decompression (p > 0.99). CONCLUSIONS: In this series of pediatric patients with CM-I, patients presenting with a syrinx who underwent expansile duraplasty with obex exploration had a significantly greater likelihood of syrinx and symptom resolution, without increased risk of CSF-related complications, compared to those who underwent bone-only decompression.

Pediatric Low-Grade Gliomas.

Brain tumors constitute the largest source of oncologic mortality in children and low-grade gliomas are among most common pediatric central nervous system tumors. Pediatric low-grade gliomas differ from their counterparts in the adult population in their histopathology, genetics, and standard of care. Over the past decade, an increasingly detailed understanding of the molecular and genetic characteristics of pediatric brain tumors led to tailored therapy directed by integrated phenotypic and genotypic parameters and the availability of an increasing array of molecular-directed therapies. Advances in neuroimaging, conformal radiation therapy, and conventional chemotherapy further improved treatment outcomes. This article reviews the current classification of pediatric low-grade gliomas, their histopathologic and radiographic features, state-of-the-art surgical and adjuvant therapies, and emerging therapies currently under study in clinical trials.

Diffusion tensor imaging reveals microstructural differences between subtypes of trigeminal neuralgia.

OBJECTIVE: Trigeminal neuralgia (TN) is an uncommon idiopathic facial pain syndrome. To assist in diagnosis, treatment, and research, TN is often classified as type 1 (TN1) when pain is primarily paroxysmal and episodic or type 2 (TN2) when pain is primarily constant in character. Recently, diffusion tensor imaging (DTI) has revealed microstructural changes in the symptomatic trigeminal root and root entry zone of patients with unilateral TN. In this study, the authors explored the differences in DTI parameters between subcategories of TN, specifically TN1 and TN2, in the pontine segment of the trigeminal tract. METHODS: The authors enrolled 8 patients with unilateral TN1, 7 patients with unilateral TN2, and 23 asymptomatic controls. Patients underwent DTI with parameter measurements in a region of interest within the pontine segment of the trigeminal tract. DTI parameters were compared between groups. RESULTS: In the pontine segment, the radial diffusivity (p = 0.0049) and apparent diffusion coefficient (p = 0.023) values in TN1 patients were increased compared to the values in TN2 patients and controls. The DTI measures in TN2 were not statistically significant from those in controls. When comparing the symptomatic to asymptomatic sides in TN1 patients, radial diffusivity was increased (p = 0.025) and fractional anisotropy was decreased (p = 0.044) in the symptomatic sides. The apparent diffusion coefficient was increased, with a trend toward statistical significance (p = 0.066). CONCLUSIONS: Noninvasive DTI analysis of patients with TN may lead to improved diagnosis of TN subtypes (e.g., TN1 and TN2) and improve patient selection for surgical intervention. DTI measurements may also provide insights into prognosis after intervention, as TN1 patients are known to have better surgical outcomes than TN2 patients.

Preserved evoked conscious perception of phosphenes with direct stimulation of deafferented primary visual cortex.

The premise of neuro-rehabilitation after injury is to access the residual capacity of the nervous system to improve function. We describe a patient who developed a quadrantopsia and drug-resistant focal epilepsy after an arteriovenous malformation hemorrhage. Thirty years later, he underwent placement of subdural electrodes for seizure mapping. Phosphenes were elicited in the blind right visual field with stimulation of occipital cortex. This case demonstrates that visual cortex may retain functional organization after a partial subcortical visual pathway injury. This persistent conscious mapping suggests that disconnected visual cortex could serve as a region for interfacing with neural prosthetic devices for acquired blindness.

Direct Electrophysiological Correlates of Body Ownership in Human Cerebral Cortex.

Over the past decade, numerous neuroimaging studies based on hemodynamic markers of brain activity have examined the feeling of body ownership using perceptual body-illusions in humans. However, the direct electrophysiological correlates of body ownership at the cortical level remain unexplored. To address this, we studied the rubber hand illusion in 5 patients (3 males and 2 females) implanted with intracranial electrodes measuring cortical surface potentials. Increased high-γ (70-200 Hz) activity, an index of neuronal firing rate, in premotor and intraparietal cortices reflected the feeling of ownership. In both areas, high-γ increases were intimately coupled with the subjective illusion onset and sustained both during and in-between touches. However, intraparietal activity was modulated by tactile stimulation to a higher degree than the premotor cortex through effective connectivity with the hand-somatosensory cortex, which suggests different functional roles. These findings constitute the first intracranial electrophysiological characterization of the rubber hand illusion and extend our understanding of the dynamic mechanisms of body ownership.

Ownership of an artificial limb induced by electrical brain stimulation.

Replacing the function of a missing or paralyzed limb with a prosthetic device that acts and feels like one's own limb is a major goal in applied neuroscience. Recent studies in nonhuman primates have shown that motor control and sensory feedback can be achieved by connecting sensors in a robotic arm to electrodes implanted in the brain. However, it remains unknown whether electrical brain stimulation can be used to create a sense of ownership of an artificial limb. In this study on two human subjects, we show that ownership of an artificial hand can be induced via the electrical stimulation of the hand section of the somatosensory (SI) cortex in synchrony with touches applied to a rubber hand. Importantly, the illusion was not elicited when the electrical stimulation was delivered asynchronously or to a portion of the SI cortex representing a body part other than the hand, suggesting that multisensory integration according to basic spatial and temporal congruence rules is the underlying mechanism of the illusion. These findings show that the brain is capable of integrating "natural" visual input and direct cortical-somatosensory stimulation to create the multisensory perception that an artificial limb belongs to one's own body. Thus, they serve as a proof of concept that electrical brain stimulation can be used to "bypass" the peripheral nervous system to induce multisensory illusions and ownership of artificial body parts, which has important implications for patients who lack peripheral sensory input due to spinal cord or nerve lesions.

Task-Specific Somatosensory Feedback via Cortical Stimulation in Humans.

Cortical stimulation through electrocorticographic (ECoG) electrodes is a potential method for providing sensory feedback in future prosthetic and rehabilitative applications. Here, we evaluate human subjects' ability to continuously modulate their motor behavior based on feedback from direct surface stimulation of the somatosensory cortex. Subjects wore a dataglove that measured their hand aperture position and received one of three stimuli over the hand sensory cortex based on their current hand position as compared to a target aperture position. Using cortical stimulation feedback, subjects adjusted their hand aperture to move towards the target aperture region. One subject was able to achieve accuracies and R2 values well above chance (best performance: R2 = 0.93; accuracy = 0.76/1). Performance dropped during the catch trial (same stimulus independent of the position) to below chance levels, suggesting that the subject had been using the varied sensory feedback to modulate their motor behavior. To our knowledge, this study represents one of the first demonstrations of using direct cortical surface stimulation of the human sensory cortex to perform a motor task, and is a first step towards developing closed-loop human sensorimotor brain-computer interfaces.

Flat-panel fluoroscopy O-arm-guided percutaneous radiofrequency cordotomy: a new technique for the treatment of unilateral cancer pain.

BACKGROUND: Percutaneous radiofrequency cordotomy (PRFC) involves controlled ablation of the anterolateral quadrant of the spinal cord, thereby relieving pain. Evolving from a morbid open surgery, the procedure has been modernized through the application of physiological target confirmation, well-regulated thermal ablation, and improved intraoperative imaging. OBJECTIVE: To evaluate the utility in PRFC of a new high-resolution, portable flat-panel fluoroscopic imaging technology, the O-arm Imaging System. The O-arm allows traditional 2-dimensional fluoroscopy in addition to axial and 3-dimensional reconstructed computed tomography imaging. METHODS: PRFC was performed using the O-arm Imaging System in 6 patients with unilateral cancer pain. RESULTS: Patients experienced 90% to 100% initial pain relief, with 50% to 100% sustained pain relief at the time of death at 2 to 12 months. There were no complications. CONCLUSION: Portable flat-panel fluoroscopy allows high-resolution, readily updated computed tomography and fluoroscopic image guidance during PRFC. Use of this new technology may assist neurosurgeons in providing an important analgesic intervention at centers possessing the imaging technology.

Four-decade maintenance of analgesia with percutaneous cordotomy.

The management of severe, medically intractable pain is a significant challenge for neurosurgeons and pain management physicians. An existing technique that can effectively alleviate contralateral chronic pain is cordotomy, interruption of the lateral spinothalamic tract of the spinal cord. Since 1912, cordotomy has evolved from a relatively morbid open surgical procedure to a percutaneous radiofrequency procedure with low morbidity. However, since cordotomy is utilized primarily in cancer pain patients, long-term patient follow-up is rare, and the potential duration of analgesia following cordotomy is not known. Here we describe a case with a 41-year follow-up of percutaneous cordotomy for noncancer pain that resulted in over 35 years of complete analgesia, the longest recorded in the literature to date. This case demonstrates that percutaneous cordotomy can provide long-lasting, complete analgesia in some patients and merits continuation as a part of the neurosurgical arsenal of pain therapies.

Deep brain stimulation for movement disorders.

Deep brain stimulation (DBS) is a widely employed therapeutic modality for the treatment of movement disorders. Full FDA approval or humanitarian device exemption has been made for Parkinson's disease, tremor, and dystonia. In this review, we describe the indications and selection criteria, target selection, and outcomes for each of these conditions. In addition, we describe the operative techniques utilized in DBS surgery and look forward to new developments in DBS on the horizon.

Using PC12 cells to evaluate poly(caprolactone) and collagenous microcarriers for applications in nerve guide fabrication.

Tissue-engineered nerve guides can provide mechanical support as well as chemical stimulation for nerve regeneration. PC12 cells were used to test the novel combination of poly(caprolactone) (PCL) and macroporous collagen-based microcarriers (CultiSphers) as an initial phase in the fabrication of multichanneled nerve guides. Laminin-coated PCL was an effective matrix for the attachment, proliferation, and viability of PC12 cells, relative to uncoated PCL. PC12 cells attached to laminin-coated PCL and extended neurites when cultured in the presence of nerve growth factor (NGF). PC12 cells attached and proliferated on CultiSphers and extended neurites in response to NGF. A novel PCL/CultiSpher composite material also supported PC12 attachment and proliferation and provides a potentially useful material for the fabrication of synthetic nerve guides.

Lymphocytic-plasmacytic enteritis in 24 dogs.

Lymphocytic-plasmacytic enteritis (LPE) was diagnosed by intestinal biopsy in 24 dogs with chronic small intestinal diarrhea. Vomiting, weight loss, and reduced appetite were frequent. Breed predispositions were not documented, although four patients were German Shepherd dogs. Hypoproteinemia, hypoalbuminemia, and hypoglobulinemia were common and most likely a result of protein-losing enteropathy. Other biochemical abnormalities were uncommon. Intestinal malabsorption was common. Neutrophilia (sometimes with increased band neutrophils), monocytosis, lymphopenia, and eosinopenia were the most consistent hematologic abnormalities. The severity of the lymphocytic-plasmacytic infiltration was not significantly different (P greater than 0.05) between regions of small intestine. However, the severity of cellular infiltration often varied among different regions of small intestine in the same dog. Changes in villous architecture and lacteal dilation were common. Intestinal nematode infestation was diagnosed in five dogs, and pancreatic exocrine insufficiency was diagnosed in one dog. In the remaining 18 dogs, besides LPE, no other associated or concurrent intestinal disease was diagnosed.