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1.
J Neurosurg ; : 1-9, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35535844

RESUMO

OBJECTIVE: Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients. METHODS: A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors' institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures. RESULTS: Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered. The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS. CONCLUSIONS: The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

2.
J Clin Neurophysiol ; 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35344517

RESUMO

INTRODUCTION: To define the patient characteristics, tumor characteristics, and clinical course of patients with primary brain tumors with high-frequency oscillations (HFOs) recorded on electrocorticography. Furthermore, we evaluated whether the presence of HFOs portends a greater risk of postoperative tumor-related epilepsy and whether the resection of HFO-generating tissue reduces likelihood of postoperative tumor-related epilepsy. METHODS: This was a retrospective study of 35 patients undergoing awake craniotomy for tumor resection, all of whom underwent intraoperative electrocorticography. Electrocorticography data were reviewed to assess the presence of HFOs and determine their contact locations. The data were analyzed to determine whether HFO-generating tissue was included in the resection and relationship to postoperative seizure outcome. RESULTS: Seventeen patients (48.5%) were found to have HFOs. Very few patients (4 of 35, 11.4%) had sharp waves. Patients with and without HFOs did not significantly differ in demographics, presentation, tumor characteristics, or tumor molecular genetics. A history of seizures prior to resection was not associated with the presence of HFOs (P = 0.62), although when patients had seizures during the same hospitalization as the resection, HFOs were more likely to be present (P = 0.045). Extent of HFO resection was not associated with the likelihood of postoperative seizure freedom. CONCLUSIONS: Approximately half (48.5%) of patients undergoing resection for a primary brain tumor had HFOs. Although HFO resection was not shown to lead to improved seizure freedom, this study was limited by a small sample size, and further investigation into HFO resection and patient outcomes in this population is warranted.

4.
World Neurosurg ; 162: 17, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34245878

RESUMO

Arteriovenous malformations (AVMs) are a highly complex array of abnormal arteries and veins that directly fistulize without intervening capillary beds.1 As AVMs can differ in size, location, and morphology, specific clinical management is determined for each individual patient, in conjunction with their specific goals and needs.2 This Video demonstrates the resection of an AVM located in the language area of eloquent cortex of a 38-year-old opera singer. The patient presented to the emergency department with a new-onset seizure. Magnetic resonance imaging including task-based functional imaging demonstrated a left post temporal AVM with associated hemosiderin-stained white matter and language activation just posterior to the lesion. Awake microsurgical resection was recommended given her career as an opera singer and the high-risk location of the AVM in proximity to eloquent language cortex, with additional goals of preventing further risk of hemorrhage and reduction in the risk of epilepsy. The patient underwent a left temporoparietal craniotomy with direct electrical stimulation-based language mapping and monitoring along with microsurgical resection of the AVM with image guidance, confirmed with intraoperative indocyanine green angiography. Postoperative angiography demonstrated no residual AVM with preservation of normal arterial and venous anatomy. At follow-up, the patient was clinically intact, seizure free, and off all antiepileptic medications. At 3 months, she resumed her career as an opera singer. Awake resection with intraoperative functional mapping can be used for select small AVMs to avoid injury to functional tissue and allow more aggressive resection of potentially epileptogenic tissue.

5.
Lancet Oncol ; 22(8): 1103-1114, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214495

RESUMO

BACKGROUND: Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma. METHODS: This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 1010 viral particles administered by 5·00 × 107 NSCs, the second cohort a dose of 1·25 × 1011 viral particles administered by 1·00 × 108 NSCs, and the third cohort a dose of 1·875 × 1011 viral particles administered by 1·50 × 108 NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134. FINDINGS: Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 108 NSCs loading 1·875 × 1011 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 108 NSCs loading 1·875 × 1011 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached). INTERPRETATION: NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial. FUNDING: US National Institutes of Health.


Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Células-Tronco Neurais/transplante , Terapia Viral Oncolítica/métodos , Adenoviridae , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vírus Oncolíticos
6.
World Neurosurg ; 153: e147-e152, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34166830

RESUMO

BACKGROUND: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and intracranial hemorrhage (ICH) may complicate the post-operative course of patients undergoing craniotomy. While prophylaxis with unfractionated heparin (UFH) has been shown to reduce VTE rates, twice-daily (BID) and three-times-daily (TID) UFH dosing regimens have not been compared in neurosurgical procedures. The objective of this study was to explore the association between UFH dosing regimen and rates of VTE and ICH in craniotomy patients. METHODS: A retrospective chart review was conducted for 159 patients at Northwestern University receiving 5000 units/0.5 mL UFH injections either BID (n = 132) or TID (n = 27). General linear regression models were run to predict rates of DVT, PE, and reoperation due to bleeding from UFH dosing regimen while controlling for age at surgery, sex, VTE history, craniotomy for tumor resection, surgery duration, length of stay, reoperation, infections, and IDH/MGMT mutations. RESULTS: Receiving UFH TID was significantly associated with a lower rate of PE when compared with receiving UFH BID (ß = -0.121, P = 0.044; TID rate = 0%, BID rate = 10.6%). UFH TID also showed a trend toward lower rates of DVT (ß = -0.0893, P = 0.295; TID rate = 18.5%, BID rate = 21.2%) when compared with UFH BID. UFH TID showed no significant difference in rate of reoperation for bleeding when compared to UFH BID (ß = -0.00623, P = 0.725; TID rate = 0%, BID rate = 0.8%). CONCLUSIONS: UFH TID dosing is associated with lower rates of PE when compared with BID dosing in patients undergoing craniotomy.


Assuntos
Anticoagulantes/administração & dosagem , Craniotomia , Heparina/administração & dosagem , Hemorragias Intracranianas/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Hemorragia Pós-Operatória/epidemiologia , Embolia Pulmonar/prevenção & controle , Trombose Venosa/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/cirurgia , Esquema de Medicação , Feminino , Glioblastoma/cirurgia , Hematoma/cirurgia , Humanos , Hemorragias Intracranianas/induzido quimicamente , Modelos Lineares , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Hemorragia Pós-Operatória/induzido quimicamente , Embolia Pulmonar/epidemiologia , Reoperação , Estudos Retrospectivos , Trombose Venosa/epidemiologia , Adulto Jovem
7.
J Clin Neurosci ; 86: 1-5, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33775310

RESUMO

The standard of care for idiopathic normal pressure hydrocephalus (iNPH) is placement of a ventriculoperitoneal (VP) shunt. However, VP shunts require intracranial intervention and are associated with notable postoperative complications, with some groups reporting complication rates for VP shunts ranging from 17 to 33%, along with failure rates up to 17.7%. Lumboperitoneal (LP) shunts are an alternative for cerebrospinal fluid diversion that do not require intracranial surgery, thus providing utility in patients where intracranial surgery is not possible or preferred. Here we retrospectively reviewed our 25 patients with LP horizontal-vertical (LP-HV) shunts placement for initial treatment for iNPH from 2014 to 2019. All patients had preoperative gait dysfunction, 16 (64%) had urinary incontinence, and 21 (84%) exhibited cognitive insufficiency. Two weeks post-shunt placement, 23/25 (92%) patients demonstrated improvement in gait, 11/16 (68%) had improvement in incontinence, and 14/21 (66%) had improvement cognitive insufficiency. At six months or greater follow up 13/20 (65%) had improvement in gait, 7/15 (47%) showed improvement in incontinence, and 11/15 (73%) demonstrated improvement in cognitive function. Six patients (24%) required at least one revision of the LP shunt. Shunt malfunctions resulted from CSF leak in one patient, shunt catheter migration in two patients, peritoneal catheter pain in one patient, and clinical symptoms for overdrainage in two patients. Thus, we demonstrate that LP-HV shunt placement is safe and efficacious alternative to VP shunting for iNPH, resulting in notable symptomatic improvement and low risk of overdrainage, and may be considered for patients where cranial approaches should be avoided.


Assuntos
Derivações do Líquido Cefalorraquidiano/métodos , Hidrocefalia de Pressão Normal/cirurgia , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos
8.
Pediatr Radiol ; 51(8): 1531-1534, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33433673

RESUMO

Revascularization of the superior vena cava (SVC) in the context of symptomatic luminal obstruction is a therapeutic intervention performed for SVC syndrome of benign or malignant etiology. Venous occlusion can preclude future access and cause symptoms ranging from mild chest discomfort to the more serious effects of SVC syndrome. This case report demonstrates the treatment of a novel case of SVC syndrome arising from a previously placed SVC stent. An intravascular, extraluminal orphaned ventriculoatrial shunt was used to go through the SVC but around the existing lumen-limiting stent to place a new larger stent for revascularization. This case highlights the need for an innovative approach for complex foreign body retrieval and treatment of chronic SVC occlusion.


Assuntos
Síndrome da Veia Cava Superior , Veia Cava Superior , Causalidade , Humanos , Stents , Síndrome da Veia Cava Superior/diagnóstico por imagem , Síndrome da Veia Cava Superior/cirurgia , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares , Veia Cava Superior/diagnóstico por imagem , Veia Cava Superior/cirurgia
9.
Neural Plast ; 2020: 8893708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029127

RESUMO

Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas classically thought to have critical, static function. The best evidence to date has demonstrated neuroplasticity only in slower growing tumors or through indirect measures such as functional MRI or transcranial magnetic stimulation. In this novel study, we utilize a unique experimental paradigm to show direct evidence of plasticity via serial direct electrocortical stimulation (DES) within primary motor (M1) and somatosensory (S1) cortices in GBM patients. Six patients with glioblastoma multiforme in or near the primary motor or somatosensory cortex were included in this retrospective observational study. These patients had two awake craniotomies with DES to map cortical motor and sensory sites in M1 and S1. Five of six patients exhibited at least one site of neuroplasticity within M1 or S1. Out of the 51 total sites stimulated, 32 (62.7%) demonstrated plasticity. Of these sites, 14 (43.7%) were in M1 and 18 (56.3%) were in S1. These data suggest that even in patients with GBM in or near primary brain regions, significant functional reorganization is possible. This is a new finding which may lead to a better understanding of the fundamental factors promoting or inhibiting plasticity. Further exploration may aid in treatment of patients with brain tumors and other neurologic disorders.


Assuntos
Glioblastoma/fisiopatologia , Córtex Motor/fisiopatologia , Plasticidade Neuronal , Córtex Somatossensorial/fisiopatologia , Adulto , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
eNeuro ; 7(4)2020.
Artigo em Inglês | MEDLINE | ID: mdl-32769159

RESUMO

The ability to grasp and manipulate objects requires controlling both finger movement kinematics and isometric force in rapid succession. Previous work suggests that these behavioral modes are controlled separately, but it is unknown whether the cerebral cortex represents them differently. Here, we asked the question of how movement and force were represented cortically, when executed sequentially with the same finger. We recorded high-density electrocorticography (ECoG) from the motor and premotor cortices of seven human subjects performing a movement-force motor task. We decoded finger movement [0.7 ± 0.3 fractional variance accounted for (FVAF)] and force (0.7 ± 0.2 FVAF) with high accuracy, yet found different spatial representations. In addition, we used a state-of-the-art deep learning method to uncover smooth, repeatable trajectories through ECoG state space during the movement-force task. We also summarized ECoG across trials and participants by developing a new metric, the neural vector angle (NVA). Thus, state-space techniques can help to investigate broad cortical networks. Finally, we were able to classify the behavioral mode from neural signals with high accuracy (90 ± 6%). Thus, finger movement and force appear to have distinct representations in motor/premotor cortices. These results inform our understanding of the neural control of movement, as well as the design of grasp brain-machine interfaces (BMIs).


Assuntos
Interfaces Cérebro-Computador , Córtex Motor , Eletrocorticografia , Força da Mão , Humanos , Movimento
11.
Neural Plast ; 2020: 3648517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714384

RESUMO

There are two neuron-level mechanisms proposed to underlie neural plasticity: recruiting neurons nearby to support the lost function (ipsilesional plasticity) and uncovering latent pathways that can assume the function that was lost (contralesional plasticity). While both patterns have been demonstrated in patient groups following injury, the specific mechanisms underlying each mode of plasticity are poorly understood. In a retrospective case series of 13 patients, we utilize a novel paradigm that analyzes serial fMRI scans in patients harboring intrinsic brain tumors that vary in location and growth kinetics to better understand the mechanisms underlying these two modes of plasticity in the human primary motor cortex. Twelve patients in our series had some degree of primary motor cortex plasticity, an area previously thought to have limited plasticity. Patients harboring smaller lesions with slower growth kinetics and increasing distance from the primary motor region demonstrated recruitment of ipsilateral motor regions. Conversely, larger, faster-growing lesions in close proximity to the primary motor region were associated with activation of the contralesional primary motor cortex, along with increased activation of the supplementary motor area. These data increase our understanding of the adaptive abilities of the brain and may lead to improved treatment strategies for those suffering from motor loss secondary to brain injuries.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Neurônios/patologia , Recuperação de Função Fisiológica/fisiologia , Estudos Retrospectivos
12.
Front Oncol ; 10: 706, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32477945

RESUMO

Background: Perioperative infarcts are a known complication that can occur during the resection of glioblastoma (GBM). Recent studies suggest that gross total and even "supra-total" resections may be associated with an increased survival but the rate of complications, including perioperative ischemia, may increase with these more aggressive resection strategies. However, little is known about the impact that perioperative infarcts have on survival, functional outcomes, and tumor recurrence patterns. Our study attempted to quantify and characterize the functional consequences of a perioperative infarct, as well as risk factors associated with occurrence. Methods: Seventy-three patients with a diagnosis of GBM and perioperative ischemia by MRI were identified from the electronic medical record system. We obtained demographic, prognostic, and stroke risk factor data. Infarct volumes were calculated from diffusion-weighted MRI scans, and subjects were segregated into an infarct cohort or a control cohort based on whether the identified lesion appeared to be an infarct in an arterial distribution or instead appeared to be expected postoperative changes. A multivariate statistical analysis was performed on the dataset. Results: Median age was 58.6 years, median post-op KPS (Karnofsky Performance Status) was 90, and median extent of resection (based on MRI) was 97.8%. Overall, perioperative arterial infarcts were uncommon (2.0%), did not have a statistically significant impact on survival (17.9 vs. 18.9 months), did not worsen neurologic function, and did not alter the pattern of recurrence. Conclusion: Perioperative arterial infarcts were uncommon in our patients despite aggressive resection and when present had no impact on survival or neurologic function. Given the clear benefit of maximal tumor resection, the risk of perioperative infarct should not deter maximal safe resection.

13.
J Neurosurg ; 134(5): 1610-1617, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32442979

RESUMO

OBJECTIVE: Intraoperative stimulation has emerged as a crucial adjunct in neurosurgical oncology, aiding maximal tumor resection while preserving sensorimotor and language function. Despite increasing use in clinical practice of this stimulation, there are limited data on both intraoperative seizure (IS) frequency and the presence of afterdischarges (ADs) in patients undergoing such procedures. The objective of this study was to determine risk factors for IS or ADs, and to determine the clinical consequences of these intraoperative events. METHODS: A retrospective chart review was performed for patients undergoing awake craniotomy (both first time and repeat) at a single institution from 2013 to 2018. Hypothesized risk factors for ADs/ISs in patients were evaluated for their effect on ADs and ISs, including tumor location, tumor grade (I-IV), genetic markers (isocitrate dehydrogenase 1/2, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, chromosome 1p/19q codeletion), tumor volume, preoperative seizure status (yes/no), and dosage of preoperative antiepileptic drugs for each patient. Clinical outcomes assessed in patients with IS or ADs were duration of surgery, length of stay, presence of perioperative deficits, and postoperative seizures. Chi-square analysis was performed for binary categorical variables, and a Student t-test was used to assess continuous variables. RESULTS: A total of 229 consecutive patients were included in the analysis. Thirty-five patients (15%) experienced ISs. Thirteen (37%) of these 35 patients had experienced seizures that were appreciated clinically and noted on electrocorticography simultaneously, while 8 patients (23%) experienced ISs that were electrographic alone (no obvious clinical change). MGMT promoter methylation was associated with an increased prevalence of ISs (OR 3.3, 95% CI 1.2-7.8, p = 0.02). Forty patients (18%) experienced ADs. Twenty-three percent of patients (9/40) with ISs had ADs prior to their seizure, although ISs and ADs were not statistically associated (p = 0.16). The presence of ADs appeared to be correlated with a shorter length of stay (5.1 ± 2.6 vs 6.1 ± 3.7 days, p = 0.037). Of the clinical features assessed, none were found to be predictive of ADs. Neither IS nor AD, or the presence of either IS or AD (65/229 patients), was a predictor for increased length of stay, presence of perioperative deficits, or postoperative seizures. CONCLUSIONS: ISs and ADs, while commonly observed during intraoperative stimulation for brain mapping, do not negatively affect patient outcomes.


Assuntos
Mapeamento Encefálico/efeitos adversos , Craniotomia , Eletrocorticografia/efeitos adversos , Complicações Intraoperatórias/etiologia , Monitorização Intraoperatória/efeitos adversos , Convulsões/etiologia , Adulto , Biomarcadores Tumorais , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/cirurgia , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Humanos , Complicações Intraoperatórias/fisiopatologia , Isocitrato Desidrogenase/genética , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Regiões Promotoras Genéticas , Estudos Retrospectivos , Fatores de Risco , Convulsões/fisiopatologia , Carga Tumoral , Proteínas Supressoras de Tumor/genética , Vigília
14.
Front Neurosci ; 13: 1267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824257

RESUMO

Neural interfaces that directly produce intelligible speech from brain activity would allow people with severe impairment from neurological disorders to communicate more naturally. Here, we record neural population activity in motor, premotor and inferior frontal cortices during speech production using electrocorticography (ECoG) and show that ECoG signals alone can be used to generate intelligible speech output that can preserve conversational cues. To produce speech directly from neural data, we adapted a method from the field of speech synthesis called unit selection, in which units of speech are concatenated to form audible output. In our approach, which we call Brain-To-Speech, we chose subsequent units of speech based on the measured ECoG activity to generate audio waveforms directly from the neural recordings. Brain-To-Speech employed the user's own voice to generate speech that sounded very natural and included features such as prosody and accentuation. By investigating the brain areas involved in speech production separately, we found that speech motor cortex provided more information for the reconstruction process than the other cortical areas.

15.
J Clin Neurosci ; 64: 18-21, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30948314

RESUMO

Survival outcomes for patients with glioblastoma (GBM) are universally poor with only a small percentage of patients surviving five years beyond initial diagnosis. Activation of the immune system against tumor cells is the basis of immunotherapy and aims to facilitate long-term immune surveillance and tumor suppression. Cytomegalovirus (CMV) has emerged as an immunologic target in GBM given that tumor cells have been shown to express the CMV-associated proteins IE1 and pp65. Moreover, vaccine therapy targeting CMV antigens has promoted improved survival outcomes with long-term survivors. In this report, we present the case of a 69 year-old woman with GBM who survived seven years post-diagnosis. Following tumor resection, the patient underwent concomitant radiation and temozolomide therapy that was complicated by CMV colitis and abdominal abscesses. Despite not receiving adjuvant temozolomide, the patient demonstrated a five year progression-free survival before requiring re-resection for radiation necrosis. Following re-resection, the patient survived for two additional years. As the patient's tumor stained positive for CMV antigens IE1 and pp65, it is hypothesized that she developed an immune response against CMV during recovery that contributed to anti-tumor surveillance and prolonged survival. Overall, this case supports further investigation into the role of CMV and immunotherapy in GBM.


Assuntos
Neoplasias Encefálicas/imunologia , Colite/virologia , Infecções por Citomegalovirus/imunologia , Glioblastoma/imunologia , Hospedeiro Imunocomprometido , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/virologia , Quimiorradioterapia/métodos , Colite/complicações , Feminino , Glioblastoma/patologia , Glioblastoma/virologia , Humanos , Proteínas Imediatamente Precoces/imunologia , Fosfoproteínas/imunologia , Temozolomida/uso terapêutico , Proteínas da Matriz Viral/imunologia , Ativação Viral/imunologia
16.
J Neural Eng ; 16(3): 036019, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30831567

RESUMO

OBJECTIVE: Direct synthesis of speech from neural signals could provide a fast and natural way of communication to people with neurological diseases. Invasively-measured brain activity (electrocorticography; ECoG) supplies the necessary temporal and spatial resolution to decode fast and complex processes such as speech production. A number of impressive advances in speech decoding using neural signals have been achieved in recent years, but the complex dynamics are still not fully understood. However, it is unlikely that simple linear models can capture the relation between neural activity and continuous spoken speech. APPROACH: Here we show that deep neural networks can be used to map ECoG from speech production areas onto an intermediate representation of speech (logMel spectrogram). The proposed method uses a densely connected convolutional neural network topology which is well-suited to work with the small amount of data available from each participant. MAIN RESULTS: In a study with six participants, we achieved correlations up to r = 0.69 between the reconstructed and original logMel spectrograms. We transfered our prediction back into an audible waveform by applying a Wavenet vocoder. The vocoder was conditioned on logMel features that harnessed a much larger, pre-existing data corpus to provide the most natural acoustic output. SIGNIFICANCE: To the best of our knowledge, this is the first time that high-quality speech has been reconstructed from neural recordings during speech production using deep neural networks.


Assuntos
Córtex Cerebral/fisiologia , Auxiliares de Comunicação para Pessoas com Deficiência , Eletrocorticografia/métodos , Redes Neurais de Computação , Fala/fisiologia , Humanos , Estimulação Luminosa/métodos
17.
J Neurosci ; 38(46): 9803-9813, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30257858

RESUMO

Speech is a critical form of human communication and is central to our daily lives. Yet, despite decades of study, an understanding of the fundamental neural control of speech production remains incomplete. Current theories model speech production as a hierarchy from sentences and phrases down to words, syllables, speech sounds (phonemes), and the actions of vocal tract articulators used to produce speech sounds (articulatory gestures). Here, we investigate the cortical representation of articulatory gestures and phonemes in ventral precentral and inferior frontal gyri in men and women. Our results indicate that ventral precentral cortex represents gestures to a greater extent than phonemes, while inferior frontal cortex represents both gestures and phonemes. These findings suggest that speech production shares a common cortical representation with that of other types of movement, such as arm and hand movements. This has important implications both for our understanding of speech production and for the design of brain-machine interfaces to restore communication to people who cannot speak.SIGNIFICANCE STATEMENT Despite being studied for decades, the production of speech by the brain is not fully understood. In particular, the most elemental parts of speech, speech sounds (phonemes) and the movements of vocal tract articulators used to produce these sounds (articulatory gestures), have both been hypothesized to be encoded in motor cortex. Using direct cortical recordings, we found evidence that primary motor and premotor cortices represent gestures to a greater extent than phonemes. Inferior frontal cortex (part of Broca's area) appears to represent both gestures and phonemes. These findings suggest that speech production shares a similar cortical organizational structure with the movement of other body parts.


Assuntos
Mapeamento Encefálico/métodos , Eletrocorticografia/métodos , Lobo Frontal/fisiologia , Gestos , Córtex Pré-Frontal/fisiologia , Fala/fisiologia , Adulto , Mapeamento Encefálico/instrumentação , Feminino , Humanos , Masculino , Movimento/fisiologia , Estimulação Luminosa/métodos
18.
J Neurooncol ; 140(2): 395-401, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30084023

RESUMO

PURPOSE: Postoperative stereotactic radiosurgery (SRS) is increasingly utilized following resection of brain metastases (BM); however, there are no volumetric data guiding dose selection. We performed a volumetric analysis to guide cavity SRS dosing for resected BM. METHODS: 83 consecutive patients with gross total resection who underwent postoperative SRS to 90 cavities were identified. The 12 Gy isodose lines (V12total) along with the volume of brain parenchyma receiving 12 Gy excluding cavity fluid, ventricular fluid, and calvarium (V12parenchyma) were contoured. Local recurrence (LR) and radionecrosis (RN) were calculated using cumulative incidence rates. Multivariate analysis (MVA) and cutpoint analysis were conducted. RESULTS: Median follow-up was 12.3 months; median dose was 16 Gy. 1- and 2-year cumulative incidence rates of LR were 7.9% and 11.0%. Radiation dose [hazard ratio (HR) 2.04, p = 0.002] was significantly associated with time to LR on MVA. 1- and 2-year cumulative incidence rates of RN were 2.6% and 5.5% respectively. MVA demonstrated increased risk of RN with a larger V12parenchyma (HR 1.46, p = 0.0496). Cavities ≤ 10 cc showed a low 2-year RN risk (4.3%), but had a modest LR risk (13.9%). A radiation dose ≥ 18 Gy significantly improved LC (HR 4.79, p = 0.01). CONCLUSIONS: V12parenchyma should be examined in postoperative SRS to assess RN risk. Cavities > 10 cc treated with 16 Gy achieved excellent LC and minimal RN at 2 years. Cavities ≤ 10 cc may be better treated with a dose ≥ 18 Gy to significantly improve LC given the low RN rate observed with 16 Gy.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Cuidados Pós-Operatórios , Radiocirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos da radiação , Encéfalo/cirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Dosagem Radioterapêutica
19.
Front Comput Neurosci ; 12: 51, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034331

RESUMO

Everyday human behavior relies upon extraordinary feats of coordination within the brain. In this perspective paper, we argue that the rich temporal structure of music provides an informative context in which to investigate how the brain coordinates its complex activities in time, and how that coordination can be disrupted. We bring insights from the neuroscience of musical rhythm to considerations of timing deficits in Attention Deficit/Hyperactivity Disorder (ADHD), highlighting the significant overlap between neural systems involved in processing musical rhythm and those implicated in ADHD. We suggest that timing deficits warrant closer investigation since they could lead to the identification of potentially informative phenotypes, tied to neurobiological and genetic factors. Our novel interdisciplinary approach builds upon recent trends in both fields of research: in the neuroscience of rhythm, an increasingly nuanced understanding of the specific contributions of neural systems to rhythm processing, and in ADHD, an increasing focus on differentiating phenotypes and identifying distinct etiological pathways associated with the disorder. Finally, we consider the impact of musical experience on rhythm processing and the potential value of musical rhythm in therapeutic interventions.

20.
Cancer ; 124(4): 734-742, 2018 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-29131312

RESUMO

BACKGROUND: Atypical and malignant meningiomas are far less common than benign meningiomas. As aggressive lesions, they are prone to local recurrence and may lead to decreased survival. Although malignant meningiomas typically are treated with maximal surgical resection and adjuvant radiotherapy (RT), to the authors' knowledge the optimal treatment for atypical lesions remains to be defined. There are limited prospective data in this setting. METHODS: The National Cancer Data Base was queried to investigate cases of histologically confirmed meningiomas diagnosed from 2004 to 2014. This included 7811 patients with atypical meningiomas (World Health Organization grade 2) and 1936 patients with malignant meningiomas (World Health Organization grade 3); during the same period, a total of 60,345 patients were diagnosed with benign meningiomas (World Health Organization grade 1). Data collected included patient and tumor characteristics, extent of surgical resection, and use of RT. Survival analysis was performed using Kaplan-Meier estimates with the log-rank test of significance and Cox univariate and multivariate regression. Logistic regression was used to determine factors associated with use of RT. RESULTS: The 5-year overall survival rate was 85.5% in patients with benign meningiomas, 75.9% in patients with atypical meningiomas, and 55.4% in patients with malignant meningiomas (P<.0001). In patients with atypical meningiomas, gross (macroscopic) total resection (GTR) and adjuvant RT were found to be associated with significantly improved survival, independently and especially in unison (GTR plus RT: hazard ratio, 0.47; P = .002). On multivariate analysis, the combination of GTR plus RT was found to be the most important factor for improved survival. However, GTR was associated with significantly lower rates of RT use. CONCLUSIONS: GTR and adjuvant RT appear to be highly associated with improved survival, independent of other factors, in patients with atypical meningiomas. Cancer 2018;124:734-42. © 2017 American Cancer Society.


Assuntos
Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Meningioma/radioterapia , Meningioma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Pessoa de Meia-Idade , Análise Multivariada , Procedimentos Neurocirúrgicos/métodos , Radioterapia Adjuvante/métodos
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