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1.
Epilepsia ; 65(5): 1314-1321, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456604

RESUMO

OBJECTIVE: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. METHODS: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. RESULTS: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st-3rd quartile) intervals observed were 10.1 (3.8-21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5-28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6-4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001). SIGNIFICANCE: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.


Assuntos
Diagnóstico Tardio , Epilepsia Resistente a Medicamentos , Humanos , Feminino , Masculino , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Retrospectivos , Diagnóstico Tardio/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Adulto Jovem , Encaminhamento e Consulta/estatística & dados numéricos , Procedimentos Neurocirúrgicos
2.
Neuromodulation ; 27(4): 792-799, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38159098

RESUMO

BACKGROUND: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. MATERIALS AND METHODS: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. RESULTS: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). CONCLUSIONS: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.


Assuntos
Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Disparidades em Assistência à Saúde , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Estimulação Encefálica Profunda/estatística & dados numéricos , Estimulação Encefálica Profunda/métodos , Epilepsia Resistente a Medicamentos/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/tendências , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Estados Unidos/epidemiologia
3.
Epilepsia ; 64(7): 1910-1924, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37150937

RESUMO

OBJECTIVE: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (µECoG) arrays, which provide high spatial resolution over large cortical surface areas. METHODS: We used novel liquid crystal polymer thin-film µECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. RESULTS: We found visually delineable subregions of elevated HFO activity within each µECoG recording. Forty-seven percent of HFOs occurred on single 200-µm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our µECoG recordings. SIGNIFICANCE: These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.


Assuntos
Ondas Encefálicas , Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Eletroencefalografia/métodos , Epilepsia/cirurgia , Epilepsia/diagnóstico , Encéfalo , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/cirurgia
4.
Stereotact Funct Neurosurg ; 101(5): 314-318, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37690446

RESUMO

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies. METHODS: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. RESULTS: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. CONCLUSION: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.


Assuntos
Tremor Essencial , Doença de Parkinson , Humanos , Feminino , Idoso , Masculino , Tremor , Estudos Prospectivos , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/cirurgia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/cirurgia , Imageamento por Ressonância Magnética/métodos , Anticoagulantes/efeitos adversos , Espectroscopia de Ressonância Magnética , Resultado do Tratamento
5.
Neuroimage ; 237: 118135, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-33951517

RESUMO

Conventional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology, or the low spatial resolution of conventional magnetic resonance imaging (MRI). Postmortem high-resolution MRI circumvents the challenges associated with both modalities. A single human brainstem specimen extending from the rostral diencephalon through the caudal medulla was prepared for imaging after the brain was removed from a 65-year-old male within 24 h of death. The specimen was formalin-fixed for two weeks, then rehydrated and placed in a custom-made MRI compatible tube and immersed in liquid fluorocarbon. MRI was performed in a 7-Tesla scanner with 120 unique diffusion directions. Acquisition time for anatomic and diffusion images were 14 h and 208 h, respectively. Segmentation was performed manually. Deterministic fiber tractography was done using strategically chosen regions of interest and avoidance, with manual editing using expert knowledge of human neuroanatomy. Anatomic and diffusion images were rendered with isotropic resolutions of 50 µm and 200 µm, respectively. Ninety different structures were segmented and labeled, and 11 different fiber bundles were rendered with tractography. The complete atlas is available online for interactive use at https://www.civmvoxport.vm.duke.edu/voxbase/login.php?return_url=%2Fvoxbase%2F. This atlas presents multiple contrasting datasets and selected tract reconstruction with unprecedented resolution for MR imaging of the human brainstem. There are immediate applications in neuroanatomical education, with the potential to serve future applications for neuroanatomical research and enhanced neurosurgical planning through "safe" zones of entry into the human brainstem.


Assuntos
Atlas como Assunto , Tronco Encefálico , Imagem de Tensor de Difusão , Substância Cinzenta , Substância Branca , Autopsia , Tronco Encefálico/anatomia & histologia , Tronco Encefálico/diagnóstico por imagem , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/diagnóstico por imagem , Humanos , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem
6.
Neuromodulation ; 24(5): 829-842, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33368872

RESUMO

INTRODUCTION: Freezing of gait (FoG) is one of the most disabling yet poorly understood symptoms of Parkinson's disease (PD). FoG is an episodic gait pattern characterized by the inability to step that occurs on initiation or turning while walking, particularly with perception of tight surroundings. This phenomenon impairs balance, increases falls, and reduces the quality of life. MATERIALS AND METHODS: Clinical-anatomical correlations, electrophysiology, and functional imaging have generated several mechanistic hypotheses, ranging from the most distal (abnormal central pattern generators of the spinal cord) to the most proximal (frontal executive dysfunction). Here, we review the neuroanatomy and pathophysiology of gait initiation in the context of FoG, and we discuss targets of central nervous system neuromodulation and their outcomes so far. The PubMed database was searched using these key words: neuromodulation, freezing of gait, Parkinson's disease, and gait disorders. CONCLUSION: Despite these investigations, the pathogenesis of this process remains poorly understood. The evidence presented in this review suggests FoG to be a heterogenous phenomenon without a single unifying pathologic target. Future studies rigorously assessing targets as well as multimodal approaches will be essential to define the next generation of therapeutic treatments.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Marcha , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/terapia , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Qualidade de Vida , Caminhada
7.
Neuroimage ; 196: 200-206, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981859

RESUMO

Human spinal white matter tract anatomy has been mapped using post mortem histological information with the help of molecular tracing studies in animal models. This study used 7 Tesla diffusion MR tractography on a human cadaver that was harvested 24 hours post mortem to evaluate cuneate fasciculus anatomy in cervical spinal cord. Based on this method, for the first time much more nuanced tractographic anatomy was used to investigate possible new routes for cuneate fasciculus in the posterior and lateral funiculus. Additionally, current molecular tracing studies were reviewed, and confirmatory data was presented along with our radiological results. Both studies confirm that upon entry to the spinal cord, upper cervical level tracts (C1-2-3) travel inside lateral funiculus and lower level tracts travel medially inside the posterior funiculus after entry at posterolateral sulcus which is different than traditional knowledge of having cuneate fasciculus tracts concentrated in the lateral part of posterior funiculus.


Assuntos
Medula Cervical/anatomia & histologia , Medula Cervical/diagnóstico por imagem , Imagem de Tensor de Difusão , Processamento de Imagem Assistida por Computador/métodos , Substância Branca/anatomia & histologia , Substância Branca/diagnóstico por imagem , Vias Aferentes/anatomia & histologia , Vias Aferentes/diagnóstico por imagem , Humanos , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/diagnóstico por imagem
8.
Neurosurg Focus ; 47(3): E4, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473677

RESUMO

Lesion-symptom correlations shaped the early understanding of cortical localization. The classic Broca-Wernicke model of cortical speech and language organization underwent a paradigm shift in large part due to advances in brain mapping techniques. This initially started by demonstrating that the cortex was excitable. Later, advancements in neuroanesthesia led to awake surgery for epilepsy focus and tumor resection, providing neurosurgeons with a means of studying cortical and subcortical pathways to understand neural architecture and obtain maximal resection while avoiding so-called critical structures. The aim of this historical review is to highlight the essential role of direct electrical stimulation and cortical-subcortical mapping and the advancements it has made to our understanding of speech and language cortical organization. Specifically, using cortical and subcortical mapping, neurosurgeons shifted from a localist view in which the brain is composed of rigid functional modules to one of dynamic and integrative large-scale networks consisting of interconnected cortical subregions.


Assuntos
Mapeamento Encefálico/história , Córtex Cerebral , Idioma/história , Rede Nervosa , Neurocirurgiões/história , Fala , Vigília , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Estimulação Elétrica , História do Século XIX , Humanos , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia
9.
Neuromodulation ; 21(1): 87-92, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28961362

RESUMO

OBJECTIVES: Unplanned 30-day readmission rates contribute significantly to growing national healthcare expenditures. Drivers of unplanned 30-day readmission after spinal cord stimulator (SCS) implantation are relatively unknown. The aim of this study was to determine drivers of 30-day unplanned readmission following SCS implantation. METHODS: The National Readmission Database was queried to identify all patients who underwent SCS implantation for the 2013 calendar year. Patients were grouped by readmission status, "No Readmission" and "Unplanned 30-day Readmission." Patient demographics and comorbidities were collected for each patient. The primary outcome of interest was the rate of unplanned 30-day readmissions and associated driving factors. A multivariate analysis was used to determine independent predictors of unplanned 30-day readmission after SCS implantation. RESULTS: We identified 1521 patients who underwent SCS implantation, with 113 (7.4%) experiencing an unplanned readmission within 30 days. Baseline patient demographics, comorbidities, and hospital characteristics were similar between both cohorts. The three main drivers for 30-day readmission after SCS implantation include: 1) infection (not related to SCS device), 2) infection due to device (limited to only hardware infection), and 3) mechanical complication of SCS device. Furthermore, obesity was found to be an independent predictor of 30-day readmission (OR: 1.86, p = 0.008). CONCLUSION: Our study suggests that infectious and mechanical complications are the primary drivers of unplanned 30-day readmission after SCS implantation, with obesity as an independent predictor of unplanned readmission. Given the technological advancements in SCS, repeated studies are necessary to identify factors associated with unplanned 30-day readmission rates after SCS implantation to improve patient outcomes and reduce associated costs.


Assuntos
Condução de Veículo/estatística & dados numéricos , Dor Crônica/epidemiologia , Dor Crônica/terapia , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estimulação da Medula Espinal/efeitos adversos , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Comorbidade , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
10.
Epilepsia ; 58(12): 2133-2142, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28994113

RESUMO

OBJECTIVE: Medically refractory epilepsy is a debilitating disorder that is particularly challenging to treat in patients who have already failed a surgical resection. Evidence regarding outcomes of further epilepsy surgery is limited to small case series and reviews. Therefore, our group performed the first quantitative meta-analysis of the literature from the past 30 years to assess for rates and predictors of successful reoperations. METHODS: A PubMed search was conducted for studies reporting outcomes of repeat epilepsy surgery. Studies were excluded if they reported fewer than five eligible patients or had average follow-ups < 1 year, and patients were excluded from analysis if they received a nonresective intervention. Outcomes were stratified by each variable of interest, and quantitative meta-analysis was performed to generate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Seven hundred eighty-two patients who received repeat resective epilepsy surgery from 36 studies were included. Engel I outcome was observed in 47% (n = 369) of patients. Significant predictors of seizure freedom included congruent over noncongruent electrophysiology data (OR = 3.6, 95% CI = 1.6-8.2), lesional over nonlesional epilepsy (OR = 3.2, 95% CI = 1.9-5.3), and surgical limitations over disease-related factors associated with failure of the first surgery (OR = 2.6, 95% CI = 1.3-5.3). Among patients with at least one of these predictors, seizure freedom was achieved in 58%. Conversely, the use of invasive monitoring was associated with worse outcome (OR = 0.4, 95% CI = 0.2-0.9). Temporal lobe over extratemporal/multilobe resection (OR = 1.5, 95% CI = 0.8-3.0) and abnormal over normal preoperative magnetic resonance imaging (OR = 1.9, 95% CI = 0.6-5.4) showed nonsignificant trends toward seizure freedom. SIGNIFICANCE: This analysis supports considering further resection in patients with intractable epilepsy who continue to have debilitating seizures after an initial surgery, especially in the context of factors predictive of a favorable outcome.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Reoperação , Eletroencefalografia , Humanos , Resultado do Tratamento
11.
J Neurooncol ; 130(2): 367-375, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27650193

RESUMO

Vestibular schwannoma (VS) surgery requires appropriate patient selection, meticulous microsurgical technique and optimal post-operative care. Focused radiation is an effective alternative for the treatment of smaller VSs. For VS surgery to remain a reasonable option, surgery must be performed with a limited number of complications. Complication rates for VS surgery have increased over the last decade. This is likely due to (1) decreased surgical volume and as a result decreased microsurgical experience, (2) larger tumors undergoing surgery while smaller tumors are reserved for radiation, and (3) surgery for previously radiated tumors resulting in more difficult anatomic dissection. Appropriate management of complications is paramount. Herein, we discuss complications related to VS microsurgery and methods of avoidance. Specifically, we discuss the most frequently encountered complications, intraoperative monitoring and finally, methods of addressing these complications. With meticulous microsurgical technique, careful intraoperative monitoring and vigilant perioperative care one will ensure optimal patient outcomes.


Assuntos
Complicações Intraoperatórias , Microcirurgia/efeitos adversos , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/prevenção & controle , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/prevenção & controle , Traumatismos dos Nervos Cranianos/etiologia , Traumatismos dos Nervos Cranianos/prevenção & controle , Cefaleia/etiologia , Cefaleia/prevenção & controle , Humanos , Hidrocefalia/etiologia , Hidrocefalia/prevenção & controle , Meningite/etiologia , Meningite/prevenção & controle , Monitorização Intraoperatória , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/prevenção & controle
12.
Proc Natl Acad Sci U S A ; 110(3): 966-71, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23277556

RESUMO

Gaucher disease is caused by mutations of the GBA gene that encodes the lysosomal enzyme glucocerebrosidase (GCase). GBA mutations often result in protein misfolding and premature degradation, but usually exert less effect on catalytic activity. In this study, we identified the molecular mechanism by which histone deacetylase inhibitors increase the quantity and activity of GCase. Specifically, these inhibitors limit the deacetylation of heat shock protein 90, resulting in less recognition of the mutant peptide and GCase degradation. These findings provide insight into a possible therapeutic strategy for Gaucher disease and other genetic disorders by modifying molecular chaperone and protein degradation pathways.


Assuntos
Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/enzimologia , Glucosilceramidase/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Chaperonas Moleculares/metabolismo , Acetilação , Degradação Associada com o Retículo Endoplasmático , Doença de Gaucher/genética , Doença de Gaucher/metabolismo , Glucosilceramidase/genética , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Modelos Biológicos , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Mutagênese Sítio-Dirigida , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutação , Dobramento de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
13.
Blood ; 121(13): 2563-6, 2013 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-23361906

RESUMO

Hypoxia-inducible factors (HIFs) control the cellular response to hypoxia and, when dysregulated, contribute to tumorigenesis. Previously, we identified 2 gain-of-function somatic mutations in patients presenting with multiple paragangliomas or somatostatinomas, and polycythemia. Here, we report 2 additional unique HIF2A mutations, which disrupt the hydroxylation domain recognized by prolyl hydroxylase domain-2 containing protein, leading to stabilization of HIF-2α and increased expression of hypoxia-related genes.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Mutação , Oxigênio/metabolismo , Neoplasias Pancreáticas/genética , Paraganglioma/genética , Policitemia/genética , Somatostatinoma/genética , Neoplasias Abdominais/genética , Neoplasias Abdominais/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Criança , Pré-Escolar , Feminino , Células HeLa , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Mutação/fisiologia , Neoplasias Pancreáticas/metabolismo , Paraganglioma/metabolismo , Filogenia , Policitemia/metabolismo , Somatostatinoma/metabolismo
14.
Cell Mol Life Sci ; 70(22): 4201-11, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23420481

RESUMO

Astrocytic activation is a cellular response to disturbances of the central nervous system (CNS). Recent advances in cellular and molecular biology have demonstrated the remarkable changes in molecular signaling, morphology, and metabolism that occur during astrocyte activation. Based on these studies, it has become clear that the astrocyte activation process is regulated by a variety of signaling pathways, which result in metabolic support, wound healing and scar formation. While normal astrocyte activation pathways drive homeostasis and/or repair in the CNS, dysregulation of these pathways can lead to astrocyte abnormalities, including glioma formation with similar phenotypes as reactive astrocytes. We review the principle pathways responsible for astrocytic activation, as well as their potential contribution to tumor formation in the CNS.


Assuntos
Astrócitos/metabolismo , Carcinogênese , Astrócitos/citologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Sistema Nervoso Central/metabolismo , Citoesqueleto/metabolismo , Matriz Extracelular/metabolismo , Junções Comunicantes/metabolismo , Humanos , Integrinas/metabolismo , Receptores de Superfície Celular/metabolismo , Transdução de Sinais
15.
Artigo em Inglês | MEDLINE | ID: mdl-38635386

RESUMO

External ventricular drain (EVD) is a common, yet challenging neurosurgical procedure of placing a catheter into the brain ventricular system that requires prolonged training for surgeons to improve the catheter placement accuracy. In this paper, we introduce NeuroLens, an Augmented Reality (AR) system that provides neurosurgeons with guidance that aides them in completing an EVD catheter placement. NeuroLens builds on prior work in AR-assisted EVD to present a registered hologram of a patient's ventricles to the surgeons, and uniquely incorporates guidance on the EVD catheter's trajectory, angle of insertion, and distance to the target. The guidance is enabled by tracking the EVD catheter. We evaluate NeuroLens via a study with 33 medical students and 9 neurosurgeons, in which we analyzed participants' EVD catheter insertion accuracy and completion time, eye gaze patterns, and qualitative responses. Our study, in which NeuroLens was used to aid students and surgeons in inserting an EVD catheter into a realistic phantom model of a human head, demonstrated the potential of NeuroLens as a tool that will aid and educate novice neurosurgeons. On average, the use of NeuroLens improved the EVD placement accuracy of the year 1 students by 39.4%, of the year 2 -4 students by 45.7%, and of the neurosurgeons by 16.7%. Furthermore, students who focused more on NeuroLens-provided contextual guidance achieved better results, and novice surgeons improved more than the expert surgeons with NeuroLens's assistance.

16.
AJNR Am J Neuroradiol ; 45(3): 302-304, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38272573

RESUMO

We report on a 75-year-old woman with a history of right MCA aneurysm clipping and medically refractive right-hand tremor. We successfully performed focused ultrasound thalamotomy of the left ventral intermediate nucleus under MR imaging-guidance at 3T. A thorough pretreatment evaluation of MR thermometry was critical to ensure that adequate precision could be achieved at the intended target. The tremor showed a 75% decrease at 24 hours postprocedure and a 50% decrease at a 3-month follow-up. There were no immediate adverse events.


Assuntos
Tremor Essencial , Tremor , Feminino , Humanos , Idoso , Resultado do Tratamento , Tálamo/diagnóstico por imagem , Tálamo/cirurgia , Imageamento por Ressonância Magnética/métodos , Instrumentos Cirúrgicos
17.
bioRxiv ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38645037

RESUMO

Impulsive choices prioritize smaller, more immediate rewards over larger, delayed, or potentially uncertain rewards. Impulsive choices are a critical aspect of substance use disorders and maladaptive decision-making across the lifespan. Here, we sought to understand the neuronal underpinnings of expected reward and risk estimation on a trial-by-trial basis during impulsive choices. To do so, we acquired electrical recordings from the human brain while participants carried out a risky decision-making task designed to measure choice impulsivity. Behaviorally, we found a reward-accuracy tradeoff, whereby more impulsive choosers were more accurate at the task, opting for a more immediate reward while compromising overall task performance. We then examined how neuronal populations across frontal, temporal, and limbic brain regions parametrically encoded reinforcement learning model variables, namely reward and risk expectation and surprise, across trials. We found more widespread representations of reward value expectation and prediction error in more impulsive choosers, whereas less impulsive choosers preferentially represented risk expectation. A regional analysis of reward and risk encoding highlighted the anterior cingulate cortex for value expectation, the anterior insula for risk expectation and surprise, and distinct regional encoding between impulsivity groups. Beyond describing trial-by-trial population neuronal representations of reward and risk variables, these results suggest impaired inhibitory control and model-free learning underpinnings of impulsive choice. These findings shed light on neural processes underlying reinforced learning and decision-making in uncertain environments and how these processes may function in psychiatric disorders.

18.
Oper Neurosurg (Hagerstown) ; 26(1): 22-27, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37747336

RESUMO

BACKGROUND AND OBJECTIVES: Cordotomy, the selective disconnection of the nociceptive fibers in the spinothalamic tract, is used to provide pain palliation to oncological patients suffering from intractable cancer-related pain. Cordotomies are commonly performed using a cervical (C1-2) percutaneous approach under imaging guidance and require patients' cooperation to functionally localize the spinothalamic tract. This can be challenging in patients suffering from extreme pain. It has recently been demonstrated that intraoperative neurophysiology monitoring by electromyography may aid in safe lesion positioning. The aim of this study was to evaluate the role of compound muscle action potential (CMAP) in deeply sedated patients undergoing percutaneous cervical cordotomy (PCC). METHODS: A retrospective analysis was conducted of all patients who underwent percutaneous cordotomy while deeply sedated between January 2019 and November 2022 in 2 academic centers. The operative report, neuromonitoring logs, and clinical medical records were evaluated. RESULTS: Eleven patients underwent PCC under deep sedation. In all patients, the final motor assessment prior to ablation was done using the electrophysiological criterion alone. The median threshold for evoking CMAP activity at the lesion site was 0.9 V ranging between 0.5 and 1.5 V (average 1 V ± 0.34 V SD). An immediate, substantial decrease in pain was observed in 9 patients. The median pain scores (Numeric Rating Scale) decreased from 10 preoperatively (range 8-10) to a median 0 (range 0-10) immediately after surgery. None of our patients developed motor deficits. CONCLUSION: CMAP-guided PCC may be feasible in deeply sedated patients without added risk to postoperative motor function. This technique should be considered in a group of patients who are not able to undergo awake PCC.


Assuntos
Cordotomia , Dor Intratável , Humanos , Cordotomia/métodos , Eletromiografia , Estudos Retrospectivos , Tratos Espinotalâmicos/cirurgia
19.
Clin Neuropsychol ; 38(1): 150-163, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-36974932

RESUMO

Objective: Essential tremor (ET), while defined by progressive motor symptoms, is increasingly associated with cognitive impairments (e.g. attention, memory, and executive functions). This study characterizes the cognitive profile of individuals with ET on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a commonly-used neuropsychological screening measure. Method: Seventy-seven individuals (mean age: 70.6, 34% female) diagnosed with ET and being considered for surgical/procedural intervention were recruited from a Movement Disorders Clinic. All participants completed the RBANS, Grooved Pegboard Test (GPB), and Fahn, Tolosa, Marin Tremor Scale (FTMTS) in the clinical evaluation of their tremor. Results: One-sample t-tests found Immediate Memory, Language, Attention, and Total Scale Index scores to be significantly lower than the expected population mean (p < .05). List Learning, Semantic Fluency, Coding, and List Recall subtests were significantly lower and Picture Naming was significantly higher than the expected population mean (p < .05). GPB scores were correlated with the Attention Index as well as List Learning and Coding subtests. FTMTS Severity was correlated with the Coding subtest and FTMTS Disability was correlated with the Figure Recall subtest. Conclusions: Results support prior literature indicating cognitive weaknesses in those with ET. Individuals with ET had poorer global cognitive abilities, with specific decrements in Immediate Memory, Attention, and Language. Notably, the Attention Index and Coding subtest were most affected by motor functioning. Cognitive screening measures, like the RBANS, can efficiently identify strengths and weaknesses in individuals with ET seeking surgical/procedural interventions.


Assuntos
Transtornos Cognitivos , Tremor Essencial , Humanos , Feminino , Idoso , Masculino , Transtornos Cognitivos/diagnóstico , Tremor Essencial/diagnóstico , Tremor Essencial/complicações , Tremor/complicações , Testes Neuropsicológicos , Cognição
20.
BMJ Neurol Open ; 6(1): e000582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618151

RESUMO

Background: Essential tremor (ET) is a movement disorder that affects 4%-5% of adults >65 years. For patients with medically refractory ET, neurosurgical interventions such as deep brain stimulation (DBS) and unilateral MR-guided focused ultrasound thalamotomy (MRgFUS) are available. In this retrospective cohort study, we examined the demographics of patients with ET who have received MRgFUS and evaluated trends in DBS usage in the USA after the introduction of MRgFUS in 2016. Methods: We used multiple databases to examine the demographics of patients who received DBS and MRgFUS, and trends in DBS. To assess the demographics, we queried the TriNetX database from 2003 to 2022 to identify patients diagnosed with ET and stratify them by DBS or MRgFUS treatment by using Current Procedural Terminology codes. Patient demographics were reported as frequencies and percentages. To examine the trends in DBS for ET, the yearly frequency of DBS procedures done for ET between 2012 and 2019 was extracted from the National Inpatient Sample (NIS) database, and breakpoint analysis was performed. Additionally, the yearly frequency of MRgFUS procedures for ET was obtained from Insightec Exlabate. Results: Most of the patients (88.69%) in the cohort extracted from TriNetX database self-identified as white, followed by black or African American (2.40%) and Asian (0.52%). A higher percentage of black patients received MRgFUS treatment than DBS (4.10% vs 1.88%). According to the NIS database, from 2012 to 2020, 13 525 patients received DBS for ET. Conclusion: This study provides an overview of the characteristics of patients who undergo DBS or MRgFUS. We found notable differences in sex and race among patients who underwent each treatment type. Additionally, until at least the beginning of 2020, the number of DBS procedures for ET was not negatively affected after the introduction of MRgFUS.

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