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Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified.We enrolled 50 children who were undergoing epilepsy surgery into a translational research study. Resected tissue was divided for clinical neuropathologic evaluation and genomic analysis. We performed exome and RNA sequencing to identify somatic variation and we confirmed our findings using high-depth targeted DNA sequencing.We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). In agreement with previous studies, we identified somatic variation affecting solute carrier family 35 member A2 (SLC35A2) and mechanistic target of rapamycin kinase (MTOR) pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) of patients with Type I focal cortical dysplasia (FCD)s. Somatic variation in mitogen-activated protein kinase (MAPK) pathway genes (i.e., fibroblast growth factor receptor 1 [FGFR1], FGFR2, B-raf proto-oncogene, serine/threonine kinase [BRAF], and KRAS proto-oncogene, GTPase [KRAS]) was associated with low-grade epilepsy-associated developmental tumors. RNA sequencing enabled the detection of somatic structural variation that would have otherwise been missed, and which accounted for more than one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes not yet associated with focal cortical dysplasia.These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

The impact of neurosurgical resident hospital coverage system, performed via a night float (12-hour shifts overnight) or a 24-hour call, on neurological surgery resident training and patient care is unknown.Retrospective review comparing night float and 24-hour call coverage on trainee surgical experience, elective time, annual program surveys, patient outcomes, and length of stay.The Ohio State Wexner Medical Center Neurosurgery residency program, Columbus, Ohio.The neurosurgical residents from 2016 to 2019.Monthly cases performed by junior residents significantly increased after transitioning to a 24-hour call schedule (18 versus 30, p0.001). There were no differences for total cases among program graduates during this time (p = 0.7). Trainee elective time significantly increased after switching to 24-hour call coverage (18 versus 24 months after the transition; p = 0.004). Risk-adjusted mortality and length of stay indices were not different (0.5 versus 0.3, p = 0.1; 0.9 versus 0.9; p = 0.3). Program surveys had minimal change after the transition to 24-hour call.Transitioning from a night float to a 24-hour call coverage system led to improved junior resident case volume and elective time without detrimental effect on patient-related outcomes.

OBJECTIVE Dural sealants are commonly used in posterior fossa decompression with duraplasty (PFDD) for Chiari malformation type I (CMI). Prior evidence suggests that combining certain sealants with some graft material is associated with an increased rate of complications. In 2018, the authors noted an increased rate of symptomatic pseudomeningocele and aseptic meningitis after PFDD in CMI patients. The authors utilized retrospective and prospective analyses to test the hypothesis that complication rates increase with the use or combination of certain sealants and grafts. METHODS The analysis was split into 2 periods. The authors retrospectively reviewed patients who underwent PFDD for CMI at their center between August 12, 2011, and December 31, 2018. The authors then eliminated use of DuraSeal on the basis of the retrospective analysis and prospectively examined complication rates from January 1, 2019, to August 4, 2021. The authors defined a complication as symptomatic pseudomeningocele, bacterial or aseptic meningitis, cerebrospinal fluid leak, subdural hygroma, hydrocephalus, surgical site infection, or wound dehiscence. RESULTS From 2011 to 2018, complications occurred in 24.5% of 110 patients. Sealant choice was correlated with complication rates: no sealant (0%), Tisseel (6%), and DuraSeal (15.3%) (p < 0.001). No difference in complication rate was noted on the basis of choice of graft material (p = 0.844). After eliminating DuraSeal, the authors followed 40 patients who underwent PFDD after 2018. The complication rate decreased to 12.5%. All complications after 2018 were associated with Tisseel. CONCLUSIONS At the authors’ single center, use of sealants in PFDD surgery for CMI, especially DuraSeal, was correlated with a higher complication rate. Eliminating DuraSeal led to a significant decrease in the rate of symptomatic pseudomeningocele and aseptic meningitis.

Leptomeningeal carcinomatosis (LMC) is a form of CNS cancer metastasis with severe morbidity. Intrathecal chemotherapy (ITC) administration through an implanted ventricular catheter reservoir (IVCR) is often utilized. Additionally, a nuclear imaging flow study can be performed prior to ITC administration to assess cerebrospinal fluid (CSF) flow. The clinical impact of a CSF flow study is unclear. A retrospective chart review identified 31 patients with LMC that underwent IVCR placement between 2011 and 2019. Data extracted included patient demographics, nuclear imaging flow study, surgical complications, ITC toxicities and outcomes. Potential drug-induced neurologic toxicities (headache, nausea/vomiting, altered mental status, etc.) were noted in (n = 4/16) 25% of patients who underwent a flow study prior to initiation of ITC, compared to (n = 1/15) 6.6% of patients who did not undergo a flow study. Median overall survival (OS) was 4.0 and 32.8 months for the patients that underwent a flow study versus patients who did not, respectively (p

Carole A. Miller, M.D., was born (May 7, 1939) and raised in Kalamazoo, Michigan. She obtained her undergraduate and medical degrees at the Ohio State University. She went on to complete her neurosurgical training at the Ohio State University Medical Center. After her first faculty role at the University of Michigan (1971), she returned to the Ohio State University Medical Center (1975) where she spent nearly 4 decades. She thrived in the specialty, achieving in every facet of academic practice including scientific contributions, graduate medical education, clinical care, and leadership roles within her academic department, locally, and at the national level of organized neurosurgery. Dr. Miller passed away peacefully, on October 28, 2015, after a courageous battle with cancer. Based on her essential programmatic and specialty-related contributions, she is remembered as the 'founding mother' of neurosurgery at the Ohio State University.

Epilepsy-associated developmental lesions, including malformations of cortical development and low-grade developmental tumors, represent a major cause of drug-resistant seizures requiring surgical intervention in children. Brain-restricted somatic mosaicism has been implicated in the genetic etiology of these lesions; however, many contributory genes remain unidentified. We enrolled 50 children undergoing epilepsy surgery into a translational research study. We performed exome and RNA-sequencing of resected brain tissue samples to identify somatic variation. We uncovered candidate disease-causing somatic variation affecting 28 patients (56%), as well as candidate germline variants affecting 4 patients (8%). We confirmed somatic findings using high-depth targeted DNA sequencing. In agreement with previous studies, we identified somatic variation affecting SLC35A2 and MTOR pathway genes in patients with focal cortical dysplasia. Somatic gains of chromosome 1q were detected in 30% (3 of 10) Type I FCD patients. Somatic variation of MAPK pathway genes (i.e., FGFR1, FGFR2, BRAF, KRAS) was associated with low-grade epilepsy-associated developmental tumors. Somatic structural variation accounted for over one-half of epilepsy-associated tumor diagnoses. Sampling across multiple anatomic regions revealed that somatic variant allele fractions vary widely within epileptogenic tissue. Finally, we identified putative disease-causing variants in genes (EEF2, NAV2, PTPN11) not yet associated with focal cortical dysplasia. These results further elucidate the genetic basis of structural brain abnormalities leading to focal epilepsy in children and point to new candidate disease genes.

Pediatric pituitary adenomas are a rare medical entity that makes up a small portion of intracranial tumors in children and adolescents. Although benign, the majority of these lesions are secreting functional tumors with the potential for physiological sequela that can profoundly affect a child’s development. In this review, we discuss the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to treat these tumors. The management of pituitary tumors requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver comprehensive care.

Pedicle and lateral mass screws are the most common means of rigid fixation in posterior cervical spine fusions. Various other techniques such as translaminar screw placement, paravertebral foramen screw fixation, sublaminar and spinous process wiring, cement augmentation, and others have been developed for primary fixation or as salvage methods. Use of these techniques can be limited by a prior history of osteotomies, poor bone density, destruction of the bone-screw interface, and unfavorable vascular and osseous anatomy.Here, the authors report on the novel application of cervical sublaminar polyester bands as an adjunct salvage method or additional fixation point used with traditional methods in the revision of prior constructs. While sublaminar polyester bands have been used for decades in pediatric scoliosis surgery in the thoracolumbar spine, they have yet to be utilized as a method of fixation in the cervical spine. In both cases described here, sublaminar banding proved crucial for fixation points where traditional fixation techniques would have been less than ideal. Further study is required to determine the full application of sublaminar polyester bands in the cervical spine as well as its outcomes.

Phosphatase and tensin homologue (PTEN) regulates cell growth and survival through inhibition of the mammalian target of rapamycin (MTOR) signalling pathway. Germline genetic variation of PTEN is associated with autism, macrocephaly and PTEN hamartoma tumour syndromes. The effect of developmental PTEN somatic mutations on nervous system phenotypes is not well understood, although brain somatic mosaicism of MTOR pathway genes is an emerging cause of cortical dysplasia and epilepsy in the paediatric population. Here we report two somatic variants of PTEN affecting a single patient presenting with intractable epilepsy and hemimegalencephaly that varied in clinical severity throughout the left cerebral hemisphere. High-throughput sequencing analysis of affected brain tissue identified two somatic variants in PTEN. The first variant was present in multiple cell lineages throughout the entire hemisphere and associated with mild cerebral overgrowth. The second variant was restricted to posterior brain regions and affected the opposite PTEN allele, resulting in a segmental region of more severe malformation, and the only neurons in which it was found by single-nuclei RNA-sequencing had a unique disease-related expression profile. This study reveals brain mosaicism of PTEN as a disease mechanism of hemimegalencephaly and furthermore demonstrates the varying effects of single- or bi-allelic disruption of PTEN on cortical phenotypes.

OBJECTIVE Despite the increasing incidence of spinal epidural abscess (SEA), the baseline parameters potentially predictive of treatment failure remain poorly characterized. In this study, the authors identify the relevant baseline parameters that predict multimodal treatment failure in patients with either intravenous drug use (IVDU)–associated SEA or non-IVDU–associated SEA. METHODS The authors reviewed the electronic medical records of a large institutional series of consecutive patients with diagnosed SEA between January 2011 and December 2017 to characterize epidemiological trends as well as the complement of baseline measures that are predictive of failure after multimodal treatment in patients with and without concomitant IVDU. The independent impact of clinical and imaging factors in detecting treatment failure was assessed by performing stepwise binary logistic regression analysis. RESULTS A total of 324 consecutive patients with diagnosed SEA were identified. Overall, 226 patients (69.8%) had SEA related to other causes and 98 (30.2%) had a history of recent IVDU. While non-IVDU SEA admission rates remained constant, year-over-year admissions of patients with IVDU SEA nearly tripled. At baseline, patients with IVDU SEA were distinct in many respects including younger age, greater unemployment and disability, less frequent diabetes mellitus (DM), and more frequent methicillin-resistant Staphylococcus aureus infection. However, differences in length of stay, loss to follow-up, and treatment failure did not reach statistical significance between the groups. The authors constructed independent multivariate logistic regression models for treatment failure based on identified parameters in the two cohorts. For the non-IVDU cohort, the authors identified four variables as independent factors: DM, hepatitis B/C, osteomyelitis, and compression deformity severity. In contrast, for patients with IVDU, the authors identified three variables: albumin, endocarditis, and endplate destruction. Receiver operating characteristic and area under the curve (AUC) analyses were undertaken for the multivariate models predicting the likelihood of treatment failure in the two cohorts (AUC = 0.88 and 0.89, respectively), demonstrating that the derived models could adequately predict the risk of multimodal treatment failure. Treatment failure risk factor point scales were derived for the identified variables separately for both cohorts. CONCLUSIONS Patients with IVDU SEA represent a unique population with a distinct set of baseline parameters that predict treatment failure. Identification of relevant prognosticating factors will allow for the design of tailored treatment and follow-up regimens.

Over the last few years, while expanding its clinical indications from movement disorders to epilepsy and psychiatry, the field of deep brain stimulation (DBS) has seen significant innovations. Hardware developments have introduced directional leads to stimulate specific brain targets and sensing electrodes to determine optimal settings via feedback from local field potentials. In addition, variable-frequency stimulation and asynchronous high-frequency pulse trains have introduced new programming paradigms to efficiently desynchronize pathological neural circuitry and regulate dysfunctional brain networks not responsive to conventional settings. Overall, these innovations have provided clinicians with more anatomically accurate programming and closed-looped feedback to identify optimal strategies for neuromodulation. Simultaneously, software developments have simplified programming algorithms, introduced platforms for DBS remote management via telemedicine, and tools for estimating the volume of tissue activated within and outside the DBS targets. Finally, the surgical accuracy has improved thanks to intraoperative magnetic resonance or computerized tomography guidance, network-based imaging for DBS planning and targeting, and robotic-assisted surgery for ultra-accurate, millimetric lead placement. These technological and imaging advances have collectively optimized DBS outcomes and allowed “asleep” DBS procedures. Still, the short- and long-term outcomes of different implantable devices, surgical techniques, and asleep vs. awake procedures remain to be clarified. This expert review summarizes and critically discusses these recent innovations and their potential impact on the DBS field.

We received so many biographies of women neurosurgery leaders for this issue that only a selection could be condensed here. In all of them, the essence of a leader shines through. Many are included as “first” of their country or color or other achievement. All of them are included as outstanding—in clinical, academic, and organized neurosurgery. Two defining features are tenacity and service. When faced with shocking discrimination, or numbing indifference, they ignored it or fought valiantly. When choosing their life’s work, they chose service, often of the most neglected—those with pain, trauma, and disability. These women inspire and point the way to a time when the term “women leaders” as an exception is unnecessary.—Katharine J. Drummond, MD, on behalf of this month’s topic editors

Background: The efficacy and safety of radiosurgery led to paradigm shift in the management of cavernous sinus meningiomas. Nevertheless, patients are still significantly affected by cranial nerve deficits related to the mass effect of these tumors. Our management strategy involves the combination of a functional surgical decompression followed by radiation therapy. Methods: We reviewed a single institution's cohort of patients who underwent endoscopic endonasal decompression (EED) for symptomatic meningiomas primarily involving the cavernous sinus (CS) from 2010 to 2016. The preoperative neuro-ophthalmological exam was compared to the 1- and 6-month postoperative exams. The patient's length of hospital stay, complications, and radiological and clinical follow-up were noted. Results: A total of 17 patients underwent EED for CS meningiomas that fit our radiological criteria. The final outcome at the 6-month visit showed five patients (62.5%) with normalization of deficit and three patients (37.5%) with partial improvement of the CNII deficit. Out of the 12 patients who had cavernous sinus cranial nerves (CSCN) deficits, the final outcome at the 6-month visit showed four patients (33.33%) with normalization of deficit, seven patients (58.3%) with partial improvement, and one patient (8.33%) with no improvement. There were no intraoperative complications. Conclusion: The EED for CS meningiomas is a valuable technique when addressing acute/subacute CNII and CSCN deficits. This conservative surgical approach showed good functional outcomes, low morbidity, and low complication rates. However, it does not exempt the need for radiosurgery/radiation therapy for control of tumor growth.

Craniopharyngioma has historically been recognized to be a formidable pathology primarily due to its proximity to critical neurovascular structures and the challenging surgical corridors that surgeons have tried to reach this lesion.In this work, we review the medical and surgical management of these tumors with a focus on clinical presentation, diagnostic identification, surgical approach, and associated adjuvant therapies. We will also discuss our current treatment paradigm using endoscopic, open, and combined approaches to craniopharyngiomas. The management of craniopharyngiomas requires a multidisciplinary team of surgeons, endocrinologists, and neuroanesthesiologists as well as neurocritical care specialists to deliver the most comprehensive and safest surgical resection with minimal postoperative morbidity.

Intracranial hypotension and cerebrospinal fluid (CSF) leaks may occur secondary to numerous pathologies, including trauma, iatrogenic injury, or even in a spontaneous manner. A diagnostic hallmark of intracranial hypotension is the presence of low CSF volume rather than low CSF pressure. As such, intracranial hypotension may occur in the setting of low, normal, or elevated intracranial pressure. The diagnostic evaluation of this pathology, in addition to localization of a potential leak, can be challenging, requiring numerous noninvasive and invasive imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), lumbar puncture, myelography, or cisternography. While medical management can provide symptomatic relief, definitive treatment of the source of the pathology depends on the etiology of the CSF leak. Depending on the source and localization of the CSF leak, less invasive means of CSF diversion may be sufficient, or patients may require definitive repair of the CSF fistula. Ultimately, proper evaluation and correct diagnosis of the pathology driving the CSF leak frame the paradigm for treatment of intracranial hypotension.

The optimal approach for deep vein thrombosis (DVT) prophylaxis in the neurosurgery patient is a challenge of balancing the reduction in incidence of DVT and pulmonary embolus (PE) without risking an increase in catastrophic hemorrhages. In this article, the authors review the current literature on DVT/PE prophylaxis in neurosurgery. Mechanical and pharmacologic DVT prophylaxis strategies are discussed in terms of their efficacy in reducing DVT/PE rates as well as safety in terms of catastrophic hemorrhages. The authors offer recommendations regarding the best approach given the current state of the literature.

Introducing neural sensing and decoding to open-loop neurostimulation technologies has the potential to significantly improve the diagnosis and treatment of a wide variety of diseases treated through bioelectronic medicine. Chronically implanted multi-electrode arrays (MEA) can be used for such neural sensing and are critical for obtaining data of high spatial and temporal resolution to provide accurate decoding. Signals recorded from these arrays include local field potentials (LFP), and multiunit (MU) and single-unit (SU) activity. LFP offer signal stability over time, but at the expense of decreased spatial resolution. SU activity, on the other hand, offers better spatial resolution, but is considered less stable in chronic applications. MU activity, which represents an aggregate spiking activity of a population of neurons on the order of several hundred microns away from the recording tip, is considered a signal that can offer a compromise between the two signals. Here we used a wavelet decomposition method to extract and characterize the LFP, MU and SU signals obtained from a 96-channel MEA implanted in the motor cortex of a nonhuman primate over a 7.5-month period. We observed that not only are the MU signals more stable over time compared with SU activity, but that they are also significantly less correlated among electrodes compared with LFP over the spatial scale of the implanted array. Histological analysis of tissue sections also revealed a 51% reduction in the number of neuronal cell bodies within a radius around the electrode tips of the implanted tissue compared with control tissue. Our results indicate that MU activity offers long-term signal stability with less correlated signals, potentially providing an effective signal for neural sensing in bioelectronic medicine.

Refractory otalgia or deep ear pain is a complex clinical problem that poses significant challenges to the physicians. Here we report a case of a 39 year old female who presented to us with deep right ear pain which started following cholesteatoma excision 11 years ago. Since onset of right ear pain, she had multiple ear surgeries including microvascular decompression and excision of right temporal bone before presentation. Following neuropsychological assessment and excluding underlying depression/anxiety, she underwent peripheral nerve field stimulation (PFNS) trial. She had a successful PFNS trial and underwent permanent implantation of PFNS and pulse generator. She had > 50% reduction in her pain intensity on VAS and pain medications. She required explantation due to superficial infection; however she was satisfied with her therapy and looking forward for reimplantation. We report the first case of successful management of refractory deep ear pain using PFNS with a review of pertinent literature.

Converging evidence suggests that reinstatement of neural activity underlies our ability to successfully retrieve memories. However, the temporal dynamics of reinstatement in the human cortex remain poorly understood. One possibility is that neural activity during memory retrieval, like replay of spiking neurons in the hippocampus, occurs at a faster timescale than during encoding. We tested this hypothesis in 34 participants who performed a verbal episodic memory task while we recorded high gamma (62–100 Hz) activity from subdural electrodes implanted for seizure monitoring. We show that reinstatement of distributed patterns of high gamma activity occurs faster than during encoding. Using a time-warping algorithm, we quantify the timescale of the reinstatement and identify brain regions that show significant timescale differences between encoding and retrieval. Our data suggest that temporally compressed reinstatement of cortical activity is a feature of cued memory retrieval.SIGNIFICANCE STATEMENTWe show that cued memory retrieval reinstates neural activity on a faster timescale than was present during encoding. Our data therefore provide a link between reinstatement of neural activity in the cortex and spontaneous replay of cortical and hippocampal spiking activity, which also exhibits temporal compression, and suggest that temporal compression may be a universal feature of memory retrieval.

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications.

At the turn of the twentieth century, the only computational device used in neurosurgical procedures was the brain of the surgeon. Today, most neurosurgical procedures rely at least in part on the use of a computer to help perform surgeries accurately and safely. The techniques that revolutionized neurosurgery were mostly developed after the 1950s. Just before that era, the transistor was invented in the late 1940s, and the integrated circuit was invented in the late 1950s. During this time, the first automated, programmable computational machines were introduced. The rapid progress in the field of neurosurgery not only occurred hand in hand with the development of modern computers, but one also can state that modern neurosurgery would not exist without computers. The focus of this article is the impact modern computers have had on the practice of neurosurgery. Neuroimaging, neuronavigation, and neuromodulation are examples of tools in the armamentarium of the modern neurosurgeon that owe each step in their evolution to progress made in computer technology. Advances in computer technology central to innovations in these fields are highlighted, with particular attention to neuroimaging. Developments over the last 10 years in areas of sensors and robotics that promise to transform the practice of neurosurgery further are discussed. Potential impacts of advances in computers related to neurosurgery in developing countries and underserved regions are also discussed. As this article illustrates, the computer, with its underlying and related technologies, is central to advances in neurosurgery over the last half century.

BACKGROUND AND PURPOSE: Reperfusion following intra-arterial stroke therapy is associated with improved clinical outcomes. However, the degree of reperfusion needed to achieve successful outcomes is unknown. The purpose of this analysis was to determine whether the degree of reperfusion has an impact on final infarct volumes and clinical outcomes. MATERIALS AND METHODS: A retrospective analysis identified 88 consecutive patients who underwent intra-arterial therapy for acute anterior circulation stroke. Reperfusion was graded by using the TICI scale into none (TICI 0 or 1), partial (TICI 2a), or near-complete (TICI 2b/3). Baseline characteristics were compared. For each of these groups, we compared discharge disposition and final infarct volumes. RESULTS: Near-complete, partial, and no reperfusion occurred in 44.3%, 26.1%, and 29.6% of patients, respectively. Baseline characteristics were similar across all 3 groups. The median NIHSS score was 15. Significant differences in discharge disposition were seen, with 41.0% of the TICI 2b/3 group discharged home versus 17.4% of TICI 2a and 7.7% of TICI 0/1. In-hospital mortality was 12.8% for TICI 2b/3 compared with 39.1% for TICI 2a and 34.6% for TICI 0/1. Patients with near-complete reperfusion were significantly more likely to have infarct volumes ≤70 mL (OR = 12.1; 95% CI, 2.7–54.2), compared with patients with partial reperfusion (OR = 2.2; 95% CI, 0.5–9.6). CONCLUSIONS: Significant differences exist in outcomes and infarct volumes between partial (TICI 2a) and near-complete (TICI 2b/3) reperfusion following intra-arterial stroke therapy. Further trials should separately report these groups to facilitate comparison among treatment paradigms.

Objective: To determine the feasibility and efficacy of occipital nerve stimulation (ONS) in patients with refractory headaches secondary to idiopathic intracranial hypertension (IIH). Background: IIH is a syndrome characterized by elevated intracranial pressures in the absence of a mass lesion. These patients typically present with chronic and intractable headaches. Cerebrospinal fluid (CSF) diversion fails in relieving the headache in a significant proportion of this population. ONS has been shown to be effective in medically refractory headaches and to our knowledge, has not been attempted as a therapeutic modality in this population. Methods: Four patients with occipital predominant chronic daily headaches and IIH who failed medical management underwent bilateral ONSs. Octopolar percutaneous electrodes were implanted in the defined area of pain. Visual Analog Scale (VAS) was used as an outcome measure. Patient demographics and surgical complications were also reviewed in this retrospective study. Following the trial period, all patients had >50% pain reduction resulting in permanent implantation. Results: All 4 patients had an average improvement of their VAS scores by 75%, with 85% spatial coverage and the remainder of the uncovered region being frontal. Sustained benefits were seen up to 3 years of follow-up. One patient had a lead erosion requiring removal followed by delayed re-implantation and another lost treatment efficacy at 2 years resulting in explantation. One patient required CSF diversion due to visual threat during the follow-up period but maintained sustained benefit from her ONS. Conclusions: Bilateral ONS may be a useful treatment option in the management of selected patients with IIH, after standard surgical interventions have been attempted. Bilateral ONS may provide therapeutic option for management of residual headaches in these complicated patients.

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology for people worldwide living with the effects of paralysis.

Intractable epilepsy can be treated with surgery, and multiple studies have shown that surgery can be more effective than prolonged medical therapy for carefully chosen patients with intractable epilepsy. Surgical options fall into three broad categories: resection techniques, disconnection surgeries, and neuromodulation involving electrical stimulation. Patients who have concordant findings on EEG and imaging (e.g., a lesion that coincides with a seizure focus in a noneloquent area) are candidates for surgical resection. Patients without concordant findings can undergo palliative surgeries such as disconnection surgeries, or they could be candidates for neuromodulation.

Primary motor cortex (MI), a key region for voluntary motor control, has been considered a first choice as the source of neural signals to control prosthetic devices for humans with paralysis. Less is known about the potential for other areas of frontal cortex as prosthesis signal sources. The frontal cortex is widely engaged in voluntary behavior. Single neuron recordings in monkey frontal cortex beyond MI have readily identified activity related to planning and initiating movement direction, remembering movement instructions over delays, or mixtures of these features (Kurata & Wise, 1988; Boussaoud & Wise, 1993; Crammond & Kalaska, 1994, 2000). Human functional imaging and lesion studies also support this role (Toni et al., 1999; Simon et al., 2002). Intraoperative mapping during deep brain stimulator placement in humans (Benabid et al., 1989) provides a unique opportunity to evaluate potential prosthesis control signals derived from non-primary areas and to expand our understanding of frontal lobe function and its role in movement disorders. Here we show that recordings from small groups of human prefrontal/premotor cortex neurons can provide information about movement planning, production and decision making sufficient to decode the planned direction of movement. Thus, additional frontal areas, beyond M1, may be valuable signal sources for human neuromotor prostheses.

Recently, we proposed a Kalman filter method to model the probabilistic relationship between neural firing in motor cortex and hand kinematics. In this paper, we demonstrate on-line, closed-loop, neural control of cursor motion using the Kalman filter. In this task a monkey moves a cursor on a computer monitor using either a manipulandum or their neural activity recorded with a chronically implanted micro-electrode array. A number of advantages of the Kalman filter were explored during the on-line tasks and we found that the Kalman filter had superior performance to previously reported linear regression methods. While the results suggest the applicability of the Kalman filter for neural prosthesis applications, we observed the decoded cursor position was noisier under brain control as compared with manual control using the manipulandum. To smooth the cursor motion without decreasing accuracy we propose a method that smoothes the neural firing rates. This smoothing method is described and its validity is quantitatively evaluated with recorded data.