The current state of electrocorticography-based brain-computer interfaces.

Brain-computer interfaces (BCIs) provide a way for the brain to interface directly with a computer. Many different brain signals can be used to control a device, varying in ease of recording, reliability, stability, temporal and spatial resolution, and noise. Electrocorticography (ECoG) electrodes provide a highly reliable signal from the human brain surface, and these signals have been used to decode movements, vision, and speech. ECoG-based BCIs are being developed to provide increased options for treatment and assistive devices for patients who have functional limitations. Decoding ECoG signals in real time provides direct feedback to the patient and can be used to control a cursor on a computer or an exoskeleton. In this review, the authors describe the current state of ECoG-based BCIs that are approaching clinical viability for restoring lost communication and motor function in patients with amyotrophic lateral sclerosis or tetraplegia. These studies provide a proof of principle and the possibility that ECoG-based BCI technology may also be useful in the future for assisting in the cortical rehabilitation of patients who have suffered a stroke.

Utility and lower limits of frequency detection in surface electrode stimulation for somatosensory brain-computer interface in humans.

OBJECTIVE: Stimulation of the primary somatosensory cortex (S1) has been successful in evoking artificial somatosensation in both humans and animals, but much is unknown about the optimal stimulation parameters needed to generate robust percepts of somatosensation. In this study, the authors investigated frequency as an adjustable stimulation parameter for artificial somatosensation in a closed-loop brain-computer interface (BCI) system. METHODS: Three epilepsy patients with subdural mini-electrocorticography grids over the hand area of S1 were asked to compare the percepts elicited with different stimulation frequencies. Amplitude, pulse width, and duration were held constant across all trials. In each trial, subjects experienced 2 stimuli and reported which they thought was given at a higher stimulation frequency. Two paradigms were used: first, 50 versus 100 Hz to establish the utility of comparing frequencies, and then 2, 5, 10, 20, 50, or 100 Hz were pseudorandomly compared. RESULTS: As the magnitude of the stimulation frequency was increased, subjects described percepts that were "more intense" or "faster." Cumulatively, the participants achieved 98.0% accuracy when comparing stimulation at 50 and 100 Hz. In the second paradigm, the corresponding overall accuracy was 73.3%. If both tested frequencies were less than or equal to 10 Hz, accuracy was 41.7% and increased to 79.4% when one frequency was greater than 10 Hz (p = 0.01). When both stimulation frequencies were 20 Hz or less, accuracy was 40.7% compared with 91.7% when one frequency was greater than 20 Hz (p < 0.001). Accuracy was 85% in trials in which 50 Hz was the higher stimulation frequency. Therefore, the lower limit of detection occurred at 20 Hz, and accuracy decreased significantly when lower frequencies were tested. In trials testing 10 Hz versus 20 Hz, accuracy was 16.7% compared with 85.7% in trials testing 20 Hz versus 50 Hz (p < 0.05). Accuracy was greater than chance at frequency differences greater than or equal to 30 Hz. CONCLUSIONS: Frequencies greater than 20 Hz may be used as an adjustable parameter to elicit distinguishable percepts. These findings may be useful in informing the settings and the degrees of freedom achievable in future BCI systems.

Arteriovenous malformation presenting with epilepsy: a multimodal approach to diagnosis and treatment.

Arteriovenous malformation (AVM) presenting with epilepsy significantly impacts patient quality of life, and it should be considered very much a seizure disorder. Although hemorrhage prevention is the primary treatment aim of AVM surgery, seizure control should also be at the forefront of therapeutic management. Several hemodynamic and morphological characteristics of AVM have been identified to be associated with seizure presentation. This includes increased AVM flow, presence of long pial draining vein, venous outflow obstruction, and frontotemporal location, among other aspects. With the advent of high-throughput image processing and quantification methods, new radiographic attributes of AVM-related epilepsy have been identified. With respect to therapy, several treatment approaches are available, including conservative management or interventional modalities; this includes microsurgery, radiosurgery, and embolization or a combination thereof. Many studies, especially in the domain of microsurgery and radiosurgery, evaluate both techniques with respect to seizure outcomes. The advantage of microsurgery lies in superior AVM obliteration rates and swift seizure response. In addition, by incorporating electrophysiological monitoring during AVM resection, adjacent or even remote epileptogenic foci can be identified, leading to extended lesionectomy and improved seizure control. Radiosurgery, despite resulting in reduced AVM obliteration and prolonged time to seizure freedom, avoids the risks of surgery altogether and may provide seizure control through various antiepileptic mechanisms. Embolization continues to be used as an adjuvant for both microsurgery and radiosurgery. In this study, the authors review the latest imaging techniques in characterizing AVM-related epilepsy, in addition to reviewing each treatment modality.

Jean Talairach: a cerebral cartographer.

Although French psychiatrist-turned-neurosurgeon Jean Talairach (1911-2007) is perhaps best known for the stereotaxic atlas he produced with Pierre Tournoux and Gábor Szikla, he has left his mark on most aspects of modern stereotactic and functional neurosurgery. In the field of psychosurgery, he expressed critique of the practice of prefrontal lobotomy and subsequently was the first to describe the more selective approach using stereotactic bilateral anterior capsulotomy. Turning his attention to stereotaxy, Talairach spearheaded the team at Hôpital Sainte-Anne in the construction of novel stereotaxic apparatus. Cadaveric investigation using these tools and methods resulted in the first human stereotaxic atlas where the use of the anterior and posterior commissures as intracranial reference points was established. This work revolutionized the approach to cerebral localization as well as leading to the development of numerous novel stereotactic interventions by the Sainte-Anne team, including tumor biopsy, interstitial irradiation, thermal ablation, and endonasal procedures. Together with epileptologist Jean Bancaud, Talairach invented the field of stereo-electroencephalography and developed a robust scientific methodology for the assessment and treatment of epilepsy. In this article the authors review Talairach's career trajectory in its historical context and in view of its impact on modern stereotactic and functional neurosurgery.

Neuromodulation with transcranial focused ultrasound.

The understanding of brain function and the capacity to treat neurological and psychiatric disorders rest on the ability to intervene in neuronal activity in specific brain circuits. Current methods of neuromodulation incur a tradeoff between spatial focus and the level of invasiveness. Transcranial focused ultrasound (FUS) is emerging as a neuromodulation approach that combines noninvasiveness with focus that can be relatively sharp even in regions deep in the brain. This may enable studies of the causal role of specific brain regions in specific behaviors and behavioral disorders. In addition to causal brain mapping, the spatial focus of FUS opens new avenues for treatments of neurological and psychiatric conditions. This review introduces existing and emerging FUS applications in neuromodulation, discusses the mechanisms of FUS effects on cellular excitability, considers the effects of specific stimulation parameters, and lays out the directions for future work.

Ultrasonographic features of focal cortical dysplasia and their relevance for epilepsy surgery.

OBJECTIVE Surgery has proven to be the best therapeutic option for drug-refractory cases of focal cortical dysplasia (FCD)-associated epilepsy. Seizure outcome primarily depends on the completeness of resection, rendering the intraoperative FCD identification and delineation particularly important. This study aims to assess the diagnostic yield of intraoperative ultrasound (IOUS) in surgery for FCD-associated drug-refractory epilepsy. METHODS The authors prospectively enrolled 15 consecutive patients with drug-refractory epilepsy who underwent an IOUS-assisted microsurgical resection of a radiologically suspected FCD between January 2013 and July 2016. The findings of IOUS were compared with those of presurgical MRI postprocessing and the sonographic characteristics were analyzed in relation to the histopathological findings. The authors investigated the added value of IOUS in achieving completeness of resection and improving postsurgical seizure outcome. RESULTS The neurosurgeon was able to identify the dysplastic tissue by IOUS in all cases. The visualization of FCD type I was more challenging compared to FCD II and the demarcation of its borders was less clear. Postsurgical MRI showed residual dysplasia in 2 of the 3 patients with FCD type I. In all FCD type II cases, IOUS allowed for a clear intraoperative visualization and demarcation, strongly correlating with presurgical MRI postprocessing. Postsurgical MRI confirmed complete resection in all FCD type II cases. Sonographic features correlated with the histopathological classification of dysplasia (sonographic abnormalities increase continuously in the following order: FCD IA/IB, FCD IC, FCD IIA, FCD IIB). In 1 patient with IOUS features atypical for FCD, histopathological investigation showed nonspecific gliosis. CONCLUSIONS Morphological features of FCD, as identified by IOUS, correlate well with advanced presurgical imaging. The resolution of IOUS was superior to MRI in all FCD types. The appreciation of distinct sonographic features on IOUS allows the intraoperative differentiation between FCD and non-FCD lesions as well as the discrimination of different histological subtypes of FCD. Sonographic demarcation depends on the underlying degree of dysplasia. IOUS allows for more tailored resections by facilitating the delineation of the dysplastic tissue.

Surgical treatment of epilepsy in Vietnam: program development and international collaboration.

OBJECTIVE: The purpose of this report was to describe an international collaboration model to facilitate the surgical treatment of children with epilepsy in Vietnam. METHODS: This model uses three complementary methods to achieve a meaningful expansion in epilepsy surgery capacity: US-based providers visiting Hanoi, Vietnam; Vietnamese providers visiting the US; and ongoing telecollaboration, including case review and real-time mentorship using internet-based communication platforms. RESULTS: Introductions took place during a US neurosurgeon's visit to Vietnam in 2014. Given the Vietnamese surgeon's expertise in intraventricular tumor surgery, the focus of the initial visit was corpus callosotomy. After two operations performed jointly, the Vietnamese surgeon went on to perform 10 more callosotomy procedures in the ensuing 6 months with excellent results. The collaborative work grew and matured in 2016-2017, with 40 pediatric epilepsy surgeries performed from 2015 through 2017. Because pediatric epilepsy care requires far more than neurosurgery, teams traveling to Vietnam included a pediatric neurologist and an electroencephalography (EEG) technologist. Also, in 2016-2017, a neurosurgeon, two neurologists, and an EEG nurse from Vietnam completed 2- to 3-month fellowships at Children's of Alabama (COA) in the US. These experiences improved EEG capabilities and facilitated the development of intraoperative electrocorticography (ECoG), making nonlesional epilepsy treatment more feasible. The final component has been ongoing, i.e., regular communication. The Vietnamese team regularly sends case summaries for discussion to the COA epilepsy conference. Three patients in Vietnam have undergone resection guided by ECoG without the US team present, although there was communication via internet-based telecollaboration tools between Vietnamese and US EEG technologists. To date, two of these three patients remain seizure free. The Vietnamese team has presented the results of their epilepsy experience at two international functional and epilepsy surgery scientific meetings. CONCLUSIONS: Ongoing international collaboration has improved the surgical care of epilepsy in Vietnam. Experience suggests that the combination of in-country and US-based training, augmented by long-distance telecollaboration, is an effective paradigm for increasing the capacity for highly subspecialized, multidisciplinary neurosurgical care.

Toward adaptive deep brain stimulation for dystonia.

The presence of abnormal neural oscillations within the cortico-basal ganglia-thalamo-cortical (CBGTC) network has emerged as one of the current principal theories to explain the pathophysiology of movement disorders. In theory, these oscillations can be used as biomarkers and thereby serve as a feedback signal to control the delivery of deep brain stimulation (DBS). This new form of DBS, dependent on different characteristics of pathological oscillations, is called adaptive DBS (aDBS), and it has already been applied in patients with Parkinson's disease. In this review, the authors summarize the scientific research to date on pathological oscillations in dystonia and address potential biomarkers that might be used as a feedback signal for controlling aDBS in patients with dystonia.

Approaches to closed-loop deep brain stimulation for movement disorders.

OBJECTIVE Deep brain stimulation (DBS) is a safe and effective therapy for movement disorders, such as Parkinson's disease (PD), essential tremor (ET), and dystonia. There is considerable interest in developing "closed-loop" DBS devices capable of modulating stimulation in response to sensor feedback. In this paper, the authors review related literature and present selected approaches to signal sources and approaches to feedback being considered for deployment in closed-loop systems. METHODS A literature search using the keywords "closed-loop DBS" and "adaptive DBS" was performed in the PubMed database. The search was conducted for all articles published up until March 2018. An in-depth review was not performed for publications not written in the English language, nonhuman studies, or topics other than Parkinson's disease or essential tremor, specifically epilepsy and psychiatric conditions. RESULTS The search returned 256 articles. A total of 71 articles were primary studies in humans, of which 50 focused on treatment of movement disorders. These articles were reviewed with the aim of providing an overview of the features of closed-loop systems, with particular attention paid to signal sources and biomarkers, general approaches to feedback control, and clinical data when available. CONCLUSIONS Closed-loop DBS seeks to employ biomarkers, derived from sensors such as electromyography, electrocorticography, and local field potentials, to provide real-time, patient-responsive therapy for movement disorders. Most studies appear to focus on the treatment of Parkinson's disease. Several approaches hold promise, but additional studies are required to determine which approaches are feasible, efficacious, and efficient.

Early outcomes of stereoelectroencephalography followed by MR-guided laser interstitial thermal therapy: a paradigm for minimally invasive epilepsy surgery.

OBJECTIVE Stereoelectroencephalography (sEEG) and MR-guided laser interstitial thermal therapy (MRgLITT) have both emerged as minimally invasive alternatives to open surgery for the localization and treatment of medically refractory lesional epilepsy. Although some data are available about the use of these procedures individually, reports are almost nonexistent on their use in conjunction. The authors' aim was to report early outcomes regarding efficacy and safety of sEEG followed by MRgLITT for localization and ablation of seizure foci in the pediatric population with medically refractory lesional epilepsy. METHODS A single-center retrospective review of pediatric patients who underwent sEEG followed by MRgLITT procedures was performed. Demographic, intraoperative, and outcome data were compiled and analyzed. RESULTS Four pediatric patients with 9 total lesions underwent sEEG followed by MRgLITT procedures between January and September 2017. The mean age at surgery was 10.75 (range 2-21) years. Two patients had tuberous sclerosis and 2 had focal cortical dysplasia. Methods of stereotaxy consisted of BrainLab VarioGuide and ROSA robotic guidance, with successful localization of seizure foci in all cases. The sEEG procedure length averaged 153 (range 67-235) minutes, with a mean of 6 (range 4-8) electrodes and 56 (range 18-84) contacts per patient. The MRgLITT procedure length averaged 223 (range 179-252) minutes. The mean duration of monitoring was 6 (range 4-8) days, and the mean total hospital stay was 8 (range 5-11) days. Over a mean follow-up duration of 9.3 (range 5.1-16) months, 3 patients were seizure free (Engel class I, 75%), and 1 patient saw significant improvement in seizure frequency (Engel class II, 25%). There were no complications. CONCLUSIONS These early data demonstrate that sEEG followed by MRgLITT can be used safely and effectively to localize and ablate epileptogenic foci in a minimally invasive paradigm for treatment of medically refractory lesional epilepsy in pediatric populations. Continued collection of data with extended follow-up is needed.

Preoperative evaluation and surgical management of infants and toddlers with drug-resistant epilepsy.

OBJECTIVE Despite perioperative risks, epilepsy surgery represents a legitimate curative or palliative treatment approach for children with drug-resistant epilepsy (DRE). Several factors characterizing infants and toddlers with DRE create unique challenges regarding optimal evaluation and management. Epilepsy surgery within children < 3 years of age has received moderate attention in the literature, including mainly case series and retrospective studies. This article presents a systematic literature review and explores multidisciplinary considerations for the preoperative evaluation and surgical management of infants and toddlers with DRE. METHODS The study team conducted a systematic literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, targeting studies that investigated children < 3 years of age undergoing surgical treatment of DRE. Using the PubMed database, investigators selected peer-reviewed articles that reported seizure outcomes with or without developmental outcomes and/or perioperative complications. Studies were eliminated based on the following exclusion criteria: sample size < 5 patients; and inclusion of patients > 3 years of age, when demographic and outcomes data could not be separated from the cohort of patients < 3 years of age. RESULTS The study team identified 20 studies published between January 1990 and May 2017 that satisfied eligibility criteria. All selected studies represented retrospective reviews, observational studies, and uncontrolled case series. The compiled group of studies incorporated 465 patients who underwent resective or disconnective surgery (18 studies, 444 patients) or vagus nerve stimulator insertion (2 studies, 21 patients). Patient age at surgery ranged between 28 days and 36 months, with a mean of 16.8 months (1.4 years). DISCUSSION The study team provided a detailed summary of the literature review, focusing on the etiologies, preoperative evaluation, surgical treatments, seizure and developmental outcomes, and potential for functional recovery of infants and toddlers with DRE. Additionally, the authors discussed special considerations in this vulnerable age group from the perspective of multiple disciplines. CONCLUSIONS While presenting notable challenges, pediatric epilepsy surgery within infants and toddlers (children < 3 years of age) offers significant opportunities for improved seizure frequency, neuro-cognitive development, and quality of life. Successful evaluation and treatment of young children with DRE requires special consideration of multiple aspects related to neurological and physiological immaturity and surgical morbidity.

Neuroplasticity and the brain connectome: what can Jean Talairach's reflections bring to modern psychosurgery?

Contrary to common psychosurgical practice in the 1950s, Dr. Jean Talairach had the intuition, based on clinical experience, that the brain connectome and neuroplasticity had a role to play in psychosurgery. Due to the remarkable progress of pharmacology at that time and to the technical limits of neurosurgery, these concepts were not put into practice. Currently, these concepts are being confirmed by modern techniques such as neuroimaging and computational neurosciences, and could pave the way for therapeutic innovation in psychiatry. Psychosurgery commonly uses a localizationist approach, based on the idea that a lesion to a specific area is responsible for a deficit opposite to its function. To psychosurgeons such as Walter Freeman, who performed extensive lesions causing apparently inevitable deficit, Talairach answered with clinical data: complex psychic functions cannot be described that simply, because the same lesion does not provoke the same deficit in different patients. Moreover, cognitive impairment did not always follow efficacious psychosurgery. Talairach suggested that selectively destructing part of a network could open the door to a new organization, and that early psychotherapy could encourage this psychoplasticity. Talairach did not have the opportunity to put these concepts into practice in psychiatric diseases because of the sudden availability of neuroleptics, but connectomics and neuroplasticity gave rise to major advances in intraparenchymal neurosurgery, from epilepsy to low-grade glioma. In psychiatry, alongside long-standing theories implicating focal lesions and diffuse pathological processes, neuroimaging techniques are currently being developed. In mentally healthy individuals, combining diffusion tensor imaging with functional MRI, magnetoencephalography, and electroencephalography allows the determination of a comprehensive map of neural connections in the brain on many spatial scales, the so-called connectome. Ultimately, global neurocomputational models could predict physiological activity, behavior, and subjective feeling, and describe neuropsychiatric disorders. Connectomic studies comparing psychiatric patients with controls have already confirmed the early intuitions of Talairach. As a striking example, massive dysconnectivity has been found in schizophrenia, leading some authors to propose a "dysconnection hypothesis." Alterations of the connectome have also been demonstrated in obsessive-compulsive disorder and depression. Furthermore, normalization of the functional dysconnectivity has been observed following clinical improvement in several therapeutic interventions, from psychotherapy to pharmacological treatments. Provided that mental disorders result from abnormal structural or functional wiring, targeted psychosurgery would require that one be able: 1) to identify the pathological network involved in a given patient; 2) to use neurostimulation to safely create a reversible and durable alteration, mimicking a lesion, in a network compatible with neuroplasticity; and 3) to predict which functional lesion would result in adapted neuronal plasticity and/or to guide neuronal plasticity to promote recovery. All these conditions, already suggested by Talairach, could now be achievable considering modern biomarkers and surgical progress.

Resective surgery for medically refractory epilepsy using intraoperative MRI and functional neuronavigation: the Erlangen experience of 415 patients.

OBJECTIVE: Intraoperative overestimation of resection volume in epilepsy surgery is a well-known problem that can lead to an unfavorable seizure outcome. Intraoperative MRI (iMRI) combined with neuronavigation may help surgeons avoid this pitfall and facilitate visualization and targeting of sometimes ill-defined heterogeneous lesions or epileptogenic zones and may increase the number of complete resections and improve seizure outcome. METHODS: To investigate this hypothesis, the authors conducted a retrospective clinical study of consecutive surgical procedures performed during a 10-year period for epilepsy in which they used neuronavigation combined with iMRI and functional imaging (functional MRI for speech and motor areas; diffusion tensor imaging for pyramidal, speech, and visual tracts; and magnetoencephalography and electrocorticography for spike detection). Altogether, there were 415 patients (192 female and 223 male, mean age 37.2 years; 41% left-sided lesions and 84.9% temporal epileptogenic zones). The mean preoperative duration of epilepsy was 17.5 years. The most common epilepsy-associated pathologies included hippocampal sclerosis (n = 146 [35.2%]), long-term epilepsy-associated tumor (LEAT) (n = 67 [16.1%]), cavernoma (n = 45 [10.8%]), focal cortical dysplasia (n = 31 [7.5%]), and epilepsy caused by scar tissue (n = 23 [5.5%]). RESULTS: In 11.8% (n = 49) of the surgeries, an intraoperative second-look surgery (SLS) after incomplete resection verified by iMRI had to be performed. Of those incomplete resections, LEATs were involved most often (40.8% of intraoperative SLSs, 29.9% of patients with LEAT). In addition, 37.5% (6 of 16) of patients in the diffuse glioma group and 12.9% of the patients with focal cortical dysplasia underwent an SLS. Moreover, iMRI provided additional advantages during implantation of grid, strip, and depth electrodes and enabled intraoperative correction of electrode position in 13.0% (3 of 23) of the cases. Altogether, an excellent seizure outcome (Engel Class I) was found in 72.7% of the patients during a mean follow-up of 36 months (range 3 months to 10.8 years). The greatest likelihood of an Engel Class I outcome was found in patients with cavernoma (83.7%), hippocampal sclerosis (78.8%), and LEAT (75.8%). Operative revisions that resulted from infection occurred in 0.3% of the patients, from hematomas in 1.6%, and from hydrocephalus in 0.8%. Severe visual field defects were found in 5.2% of the patients, aphasia in 5.7%, and hemiparesis in 2.7%, and the total mortality rate was 0%. CONCLUSIONS: Neuronavigation combined with iMRI was beneficial during surgical procedures for epilepsy and led to favorable seizure outcome with few specific complications. A significantly higher resection volume associated with a higher chance of favorable seizure outcome was found, especially in lesional epilepsy involving LEAT or diffuse glioma.

The role of intraoperative MRI in resective epilepsy surgery for peri-eloquent cortex cortical dysplasias and heterotopias in pediatric patients.

OBJECTIVE: Previous studies have demonstrated that an important factor in seizure freedom following surgery for lesional epilepsy in the peri-eloquent cortex is completeness of resection. However, aggressive resection of epileptic tissue localized to this region must be balanced with the competing objective of retaining postoperative neurological functioning. The objective of this study was to investigate the role of intraoperative MRI (iMRI) as a complement to existing epilepsy protocol techniques and to compare rates of seizure freedom and neurological deficit in pediatric patients undergoing resection of perieloquent lesions. METHODS: The authors retrospectively reviewed the medical records of pediatric patients who underwent resection of focal cortical dysplasia (FCD) or heterotopia localized to eloquent cortex regions at the Children's National Health System between March 2005 and August 2015. Patients were grouped into two categories depending on whether they underwent conventional resection (n = 18) or iMRI-assisted resection (n = 11). Patient records were reviewed for factors including demographics, length of hospitalization, postoperative seizure freedom, postoperative neurological deficit, and need for reoperation. Postsurgical seizure outcome was assessed at the last postoperative follow-up evaluation using the Engel Epilepsy Surgery Outcome Scale. RESULTS: At the time of the last postoperative follow-up examination, 9 (82%) of the 11 patients in the iMRI resection group were seizure free (Engel Class I), compared with 7 (39%) of the 18 patients in the control resection group (p = 0.05). Ten (91%) of the 11 patients in the iMRI cohort achieved gross-total resection (GTR), compared with 8 (44%) of 18 patients in the conventional resection cohort (p = 0.02). One patient in the iMRI-assisted resection group underwent successful reoperation at a later date for residual dysplasia, compared with 7 patients in the conventional resection cohort (with 2/7 achieving complete resection). Four (36%) of the patients in the iMRI cohort developed postoperative neurological deficits, compared with 15 patients (83%) in the conventional resection cohort (p = 0.02). CONCLUSIONS: These results suggest that in comparison with a conventional surgical protocol and technique for resection of epileptic lesions in peri-eloquent cortex, the incorporation of iMRI led to elevated rates of GTR and postoperative seizure freedom. Furthermore, this study suggests that iMRI-assisted surgeries are associated with a reduction in neurological deficits due to intraoperative damage of eloquent cortex.

Resection of cerebral gangliogliomas causing drug-resistant epilepsy: short- and long-term outcomes using intraoperative MRI and neuronavigation.

OBJECT Cerebral gangliogliomas (GGs) are highly associated with intractable epilepsy. Incomplete resection due to proximity to eloquent brain regions or misinterpretation of the resection amount is a strong negative predictor for local tumor recurrence and persisting seizures. A potential method for dealing with this obstacle could be the application of intraoperative high-field MRI (iopMRI) combined with neuronavigation. METHODS Sixty-nine patients (31 female, 38 male; median age 28.5 ± 15.4 years) suffering from cerebral GGs were included in this retrospective study. Five patients received surgery twice in the observation period. In 48 of the 69 patients, 1.5-T iopMRI combined with neuronavigational guidance was used. Lesions close to eloquent brain areas were resected with the implementation of preoperative diffusion tensor imaging tractography and blood oxygenation level-dependent functional MRI (15 patients). RESULTS Overall, complete resection was accomplished in 60 of 69 surgical procedures (87%). Two patients underwent biopsy only, and in 7 patients, subtotal resection was accomplished because of proximity to critical brain areas. Excluding the 2 biopsies, complete resection using neuronavigation/iopMRI was documented in 33 of 46 cases (72%) by intraoperative imaging. Remnant tumor mass was identified intraoperatively in 13 of 46 patients (28%). After intraoperative second-look surgery, the authors improved the total resection rate by 9 patients (up to 91% [42 of 46]). Of 21 patients undergoing conventional surgery, 14 (67%) had complete resection without the use of iopMRI. Regarding epilepsy outcome, 42 of 60 patients with seizures (70%) became completely seizure free (Engel Class IA) after a median follow-up time of 55.5 ± 36.2 months. Neurological deficits were found temporarily in 1 (1.4%) patient and permanently in 4 (5.8%) patients. CONCLUSIONS Using iopMRI combined with neuronavigation in cerebral GG surgery, the authors raised the rate of complete resection in this series by 19%. Given the fact that total resection is a strong predictor of long-term seizure control, this technique may contribute to improved seizure outcome and reduced neurological morbidity.

Deep brain stimulation for severe autism: from pathophysiology to procedure.

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

Epileptogenic zone localization using intraoperative gamma oscillation regularity analysis in epilepsy surgery for cavernomas: patient series.

BACKGROUND: In epilepsy surgery for cavernoma with intractable focal epilepsy, removal of the cavernoma with its surrounding hemosiderin deposition and other extended epileptogenic zone has been shown to improve postsurgical seizures. However, there has been no significant association between such an epileptogenic zone and intraoperative electrocorticography (ECoG) findings. The authors recently demonstrated that high regular gamma oscillation (30-70 Hz) regularity (GOR) significantly correlates with epileptogenicity. OBSERVATIONS: The authors evaluated the utility of intraoperative GOR analysis in epilepsy surgery for cavernomas. The authors also analyzed intraoperative ECoG data from 6 patients with cavernomas. The GOR was calculated using a sample entropy algorithm. In 4 patients, the GOR was significantly high in the area with the pathological hemosiderin deposition. In 2 patients with temporal cavernoma, the GOR was significantly high in both the hippocampus and the area with the pathological hemosiderin deposition. ECoG showed no obvious epileptic waveforms in 3 patients, whereas extensive spikes were observed in 3 patients. All patients underwent cavernoma removal plus resection of the area with significantly high GOR. The 2 patients with temporal cavernomas underwent additional hippocampal transection. All patients were seizure free after surgery. LESSONS: The high GOR may be a novel intraoperative marker of the epileptogenic zone in epilepsy surgery for cavernomas.

Repair of a large primary subtemporal encephalocele in a 3-year-old child: case report.

Primary encephaloceles (PEs) present only rarely in the temporal region; in the rare instance that they project through the floor of the middle fossa they are secondary. In this case report the authors report on the management of a giant PE extending through the floor of the middle fossa.An 8-month-old boy presented to the authors' service with a large PE projecting into his neck through a missing left middle fossa floor; the lesion was causing significant meta-, dys-, and hypoplasia of the structures of the anterolateral neck on that side. Surgical goals for this patient included the following: 1) removal of potentially epileptogenic and dysfunctional tissue; 2) preservation of cranial nerves; 3) prevention of cognitive decline or iatrogenic deficit; 4) prevention of CSF leak; 5) reconstruction of skull base; 6) prevention of airway and swallowing compromise; and 7) cosmesis. After a multidisciplinary evaluation with ENT, plastic surgery, and neurology, an operation was performed using a preauricular infratemporal approach when the patient was 3 years old. Gliotic tissue was resected and amygdala, hippocampus, and middle cerebral artery were preserved.The immediate results of the operation showed good immediate outcome. Seizure freedom and neurodevelopment outcomes remain to be seen at follow-up.

Dual responsive neurostimulation implants for epilepsy.

Closed-loop brain-responsive neurostimulation via the RNS System is a treatment option for adults with medically refractory focal epilepsy. Using a novel technique, 2 RNS Systems (2 neurostimulators and 4 leads) were successfully implanted in a single patient with bilateral parietal epileptogenic zones. In patients with multiple epileptogenic zones, this technique allows for additional treatment options. Implantation can be done successfully, without telemetry interference, using proper surgical planning and neurostimulator positioning.Trajectories for the depth leads were planned using neuronavigation with CT and MR imaging. Stereotactic frames were used for coordinate targeting. Each neurostimulator was positioned with maximal spacing to avoid telemetry interference while minimizing patient discomfort. A separate J-shaped incision was used for each neurostimulator to allow for compartmentalization in case of infection. In order to minimize surgical time and risk of infection, the neurostimulators were implanted in 2 separate surgeries, approximately 3 weeks apart.The neurostimulators and leads were successfully implanted without adverse surgical outcomes. The patient recovered uneventfully, and the early therapy settings over several months resulted in preliminary decreases in aura and seizure frequency. Stimulation by one of the neurostimulators did not result in stimulation artifacts detected by the contralateral neurostimulator.

Novel diffusion tractography methodology using Kalman filter prediction to improve preoperative benefit-risk analysis in pediatric epilepsy surgery.

OBJECTIVE: In this study the authors investigated the clinical reliability of diffusion weighted imaging maximum a posteriori probability (DWI-MAP) analysis with Kalman filter prediction in pediatric epilepsy surgery. This approach can yield a suggested resection margin as a dynamic variable based on preoperative DWI-MAP pathways. The authors sought to determine how well the suggested margin would have maximized occurrence of postoperative seizure freedom (benefit) and minimized occurrence of postoperative neurological deficits (risk). METHODS: The study included 77 pediatric patients with drug-resistant focal epilepsy (age 10.0 ± 4.9 years) who underwent resection of their presumed epileptogenic zone. In preoperative DWI tractography from the resected hemisphere, 9 axonal pathways, Ci=1-9, were identified using DWI-MAP as follows: C1-3 supporting face, hand, and leg motor areas; C4 connecting Broca's and Wernicke's areas; C5-8 connecting Broca's, Wernicke's, parietal, and premotor areas; and C9 connecting the occipital lobe and lateral geniculate nucleus. For each Ci, the resection margin, di, was measured by the minimal Euclidean distance between the voxels of Ci and the resection boundary determined by spatially coregistered postoperative MRI. If Ci was resected, di was assumed to be negative (calculated as -1 × average Euclidean distance between every voxel inside the resected Ci volume, ri). Kalman filter prediction was then used to estimate an optimal resection margin, d*i, to balance benefit and risk by approximating the relationship between di and ri. Finally, the authors defined the preservation zone of Ci that can balance the probability of benefit and risk by expanding the cortical area of Ci up to d*i on the 3D cortical surface. RESULTS: In the whole group (n = 77), nonresection of the preoperative preservation zone (i.e., actual resection margin d*i greater than the Kalman filter-defined d*i) accurately predicted the absence of postoperative motor (d*1-3: 0.93 at seizure-free probability of 0.80), language (d*4-8: 0.91 at seizure-free probability of 0.81), and visual deficits (d*9: 0.90 at seizure-free probability of 0.75), suggesting that the preservation of preoperative Ci within d*i supports a balance between postoperative functional deficit and seizure freedom. The subsequent subgroup analyses found that preservation of preoperative Ci =1-4,9 within d*i =1-4,9 may provide accurate deficit predictions independent of age and seizure frequency, suggesting that the DWI-based surgical margin can be effective for surgical planning even in young children and across a range of epilepsy severity. CONCLUSIONS: Integrating DWI-MAP analysis with Kalman filter prediction may help guide epilepsy surgery by visualizing the margins of the eloquent white matter pathways to be preserved.