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OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.
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Benchmarking , Epilepsia del Lóbulo Temporal , Humanos , Epilepsia del Lóbulo Temporal/cirugía , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Niño , Preescolar , Lactante , Complicaciones Posoperatorias/epidemiología , Procedimientos Neuroquirúrgicos/normas , Procedimientos Neuroquirúrgicos/métodos , Epilepsia Refractaria/cirugía , Lobectomía Temporal Anterior/métodosRESUMEN
Neurocysticercosis is almost exclusively caused by Taenia solium tapeworms. We describe a case of neurocysticercosis in Switzerland caused by infection with Taenia martis, the marten tapeworm, and review all 5 published cases of human infection with the marten tapeworm. In epidemiologically nonplausible cases of neurocysticercosis, zoonotic spillover infections should be suspected.
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Mustelidae , Neurocisticercosis , Taenia solium , Taenia , Animales , Humanos , Neurocisticercosis/diagnóstico por imagen , SuizaRESUMEN
PURPOSE: Thoracic disc herniations are uncommon and carry a high risk for neurological deterioration. Traditional surgical approaches include thoracotomy, costotransversectomy or posterior approaches with considerable morbidity. In this technical note with case series, we describe a minimally invasive tubular retractor-assisted retropleural approach for simple and less invasive microsurgical exploration of thoracic disc herniations from a lateral angle. METHODS: Surgical technique consisted of partial rib resection and retropleural dissection followed by the placement of a tubular retractor (METRx Tubes, Medtronic) for an anterior-lateral exposure of the disc and neuroforamen. Epidemiological, clinical and surgical patient data were acquired. RESULTS: Between 2017 and 2020, six patients were surgically treated using the minimally invasive tubular retractor-assisted retropleural approach. Microsurgical exposure of the disc and neural structures was achieved from a lateral direction without requiring thoracotomy or lung deflation. Control imaging confirmed resection in all cases without relevant residuum. As postoperative complications, one dural injury and one postoperative pneumothorax occured. No neurologic deterioration or recurrence occurred during a median follow-up of 3 months. CONCLUSION: The described tubular retractor-assisted retropleural exposure serves as a feasible minimally invasive microsurgical approach to the anterior-lateral thoracic spine.
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Desplazamiento del Disco Intervertebral , Procedimientos Ortopédicos , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Resultado del Tratamiento , Vértebras Torácicas/cirugía , Procedimientos Ortopédicos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodosRESUMEN
BACKGROUND: Aneurismal subarachnoid hemorrhage (SAH) is a type of hemorrhagic stroke that, despite improvement through therapeutic interventions, remains a devastating cerebrovascular disorder that has a high mortality rate and causes long-term disability. Cerebral inflammation after SAH is promoted through microglial accumulation and phagocytosis. Furthermore, proinflammatory cytokine release and neuronal cell death play key roles in the development of brain injury. The termination of these inflammation processes and restoration of tissue homeostasis are of utmost importance regarding the possible chronicity of cerebral inflammation and the improvement of the clinical outcome for affected patients post SAH. Thus, we evaluated the inflammatory resolution phase post SAH and considered indications for potential tertiary brain damage in cases of incomplete resolution. METHODS: Subarachnoid hemorrhage was induced through endovascular filament perforation in mice. Animals were killed 1, 7 and 14 days and 1, 2 and 3 months after SAH. Brain cryosections were immunolabeled for ionized calcium-binding adaptor molecule-1 to detect microglia/macrophages. Neuronal nuclei and terminal deoxyuridine triphosphate-nick end labeling staining was used to visualize secondary cell death of neurons. The gene expression of various proinflammatory mediators in brain samples was analyzed by quantitative polymerase chain reaction. RESULTS: We observed restored tissue homeostasis due to decreased microglial/macrophage accumulation and neuronal cell death 1 month after insult. However, the messenger RNA expression levels of interleukin 6 and tumor necrosis factor α were still elevated at 1 and 2 months post SAH, respectively. The gene expression of interleukin 1ß reached its maximum on day 1, whereas at later time points, no significant differences between the groups were detected. CONCLUSIONS: By the herein presented molecular and histological data we provide an important indication for an incomplete resolution of inflammation within the brain parenchyma after SAH. Inflammatory resolution and the return to tissue homeostasis represent an important contribution to the disease's pathology influencing the impact on brain damage and outcome after SAH. Therefore, we consider a novel complementary or even superior therapeutic approach that should be carefully rethought in the management of cerebral inflammation after SAH. An acceleration of the resolution phase at the cellular and molecular levels could be a potential aim in this context.
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Lesiones Encefálicas , Hemorragia Subaracnoidea , Ratones , Animales , Hemorragia Subaracnoidea/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo , Citocinas/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Even for an experienced neurophysiologist, it is challenging to look at a single graph of an unlabeled motor evoked potential (MEP) and identify the corresponding muscle. We demonstrate that supervised machine learning (ML) can successfully perform this task. METHODS: Intraoperative MEP data from supratentorial surgery on 36 patients was included for the classification task with 4 muscles: Extensor digitorum (EXT), abductor pollicis brevis (APB), tibialis anterior (TA) and abductor hallucis (AH). Three different supervised ML classifiers (random forest (RF), k-nearest neighbors (kNN) and logistic regression (LogReg)) were trained and tested on either raw or compressed data. Patient data was classified considering either all 4 muscles simultaneously, 2 muscles within the same extremity (EXT versus APB), or 2 muscles from different extremities (EXT versus TA). RESULTS: In all cases, RF classifiers performed best and kNN second best. The highest performances were achieved on raw data (4 muscles 83%, EXT versus APB 89%, EXT versus TA 97% accuracy). CONCLUSIONS: Standard ML methods show surprisingly high performance on a classification task with intraoperative MEP signals. This study illustrates the power and challenges of standard ML algorithms when handling intraoperative signals and may lead to intraoperative safety improvements.
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Potenciales Evocados Motores , Músculo Esquelético , Humanos , Potenciales Evocados Motores/fisiología , Músculo Esquelético/fisiologíaRESUMEN
Myeloid cells are an inherent part of the microenvironment of glioblastoma multiforme (GBM). There is growing evidence for their participation in mechanisms of tumor escape, especially in the development of resistance following initially promising anti-VEGF/VEGFR treatment. Thus, we sought to define the capability of myeloid cells to contribute to the expression of proangiogenic molecules in human GBM. We investigated GBM specimens in comparison with anaplastic astrocytoma (WHO grade III) and epilepsy patient samples freshly obtained from surgery. Flow cytometric analyses revealed two distinct CD11b+ CD45+ cell populations in GBM tissues, which were identified as microglia/macrophages and granulocytes. Due to varied granulocyte influx, GBM samples were subdivided into groups with low (GBM-lPMNL) and high (GBM-hPMNL) numbers of granulocytes (polymorphonuclear leukocytes; PMNL), which were related to activation of the microglia/macrophage population. Microglia/macrophages of the GBM-lPMNL group were similar to those of astrocytoma specimens, but those of GBM-hPMNL tissues revealed an altered phenotype by expressing high levels of CD163, TIE2, HIF1α, VEGF, CXCL2 and CD13. Although microglia/macrophages represented the main source of alternative proangiogenic factors, additionally granulocytes participated by production of IL8 and CD13. Moreover, microglia/macrophages of the GBM-hPMNL specimens were highly associated with tumor blood vessels, accompanied by remodeling of the vascular structure. Our data emphasize that tumor-infiltrating myeloid cells might play a crucial role for limited efficacy of anti-angiogenic therapy bypassing VEGF-mediated pathways through expression of alternative proangiogenic factors. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/patología , Glioblastoma/patología , Adulto , Anciano , Animales , Encéfalo/patología , Femenino , Granulocitos/patología , Humanos , Estimación de Kaplan-Meier , Macrófagos/patología , Masculino , Ratones , Microglía/patología , Persona de Mediana Edad , Células Mieloides/patología , Fenotipo , Microambiente TumoralRESUMEN
BACKGROUND: Neuroprotective treatment strategies aiming at interfering with either inflammation or cell death indicate the importance of these mechanisms in the development of brain injury after subarachnoid hemorrhage (SAH). This study was undertaken to evaluate the influence of minocycline on microglia/macrophage cell activity and its neuroprotective and anti-inflammatory impact 14 days after aneurismal SAH in mice. METHODS: Endovascular filament perforation was used to induce SAH in mice. SAH + vehicle-operated mice were used as controls for SAH vehicle-treated mice and SAH + minocycline-treated mice. The drug administration started 4 h after SAH induction and was daily repeated until day 7 post SAH and continued until day 14 every second day. Brain cryosections were immunolabeled for Iba1 to detect microglia/macrophages and NeuN to visualize neurons. Phagocytosis assay was performed to determine the microglia/macrophage activity status. Apoptotic cells were stained using terminal deoxyuridine triphosphate nick end labeling. Real-time quantitative polymerase chain reaction was used to estimate cytokine gene expression. RESULTS: We observed a significantly reduced phagocytic activity of microglia/macrophages accompanied by a lowered spatial interaction with neurons and reduced neuronal apoptosis achieved by minocycline administration after SAH. Moreover, the SAH-induced overexpression of pro-inflammatory cytokines and neuronal cell death was markedly attenuated by the compound. CONCLUSIONS: Minocycline treatment may be implicated as a therapeutic approach with long-term benefits in the management of secondary brain injury after SAH in a clinically relevant time window.
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Lesiones Encefálicas , Fármacos Neuroprotectores , Hemorragia Subaracnoidea , Animales , Antiinflamatorios/farmacología , Apoptosis , Lesiones Encefálicas/complicaciones , Muerte Celular , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Macrófagos , Ratones , Microglía/metabolismo , Minociclina/farmacología , Minociclina/uso terapéutico , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/complicacionesRESUMEN
Subarachnoid hemorrhage is associated with severe neurological deficits for survivors. Among survivors of the initial bleeding, secondary brain injury leads to additional brain damage. Apart from cerebral vasospasm, secondary brain injury mainly results from cerebral inflammation taking place in the brain parenchyma after bleeding. The brain's innate immune system is activated, which leads to disturbances in brain homeostasis, cleavage of inflammatory cytokines and, subsequently, neuronal cell death. The toll-like receptor (TLR)4 signaling pathway has been found to play an essential role in the pathophysiology of acute brain injuries such as subarachnoid hemorrhage (SAH). TLR4 is expressed on the cell surface of microglia, which are key players in the cellular immune responses of the brain. The participants in the signaling pathway, such as TLR4-pathway-like ligands, the receptor itself, and inflammatory cytokines, can act as biomarkers, serving as clues regarding the inflammatory status after SAH. Moreover, protein complexes such as the NLRP3 inflammasome or receptors such as TREM1 frame the TLR4 pathway and are indicative of inflammation. In this review, we focus on the activity of the TLR4 pathway and its contributors, which can act as biomarkers of neuroinflammation or even offer potential new treatment targets for secondary neuronal cell death after SAH.
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Lesiones Encefálicas , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Receptor Toll-Like 4/metabolismo , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptor Activador Expresado en Células Mieloides 1 , Lesiones Encefálicas/metabolismo , Antiinflamatorios/uso terapéutico , Inflamación/metabolismo , Citocinas/metabolismo , BiomarcadoresRESUMEN
BACKGROUND: Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation. METHODS: 7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naïve, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS. RESULTS: Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization. CONCLUSIONS: Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity.
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Antiinflamatorios/administración & dosificación , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/prevención & control , Microglía/metabolismo , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/metabolismo , Aminopiridinas/administración & dosificación , Animales , Lesiones Encefálicas/diagnóstico por imagen , Precondicionamiento Isquémico/métodos , Ratones , Ratones Endogámicos C57BL , Microglía/efectos de los fármacos , Microglía/patología , Pirroles/administración & dosificación , Hemorragia Subaracnoidea/diagnóstico por imagenRESUMEN
OBJECTIVES: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. METHODS: Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. RESULTS: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). CONCLUSIONS: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.
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Toma de Decisiones , Epilepsia Refractaria/psicología , Epilepsia Refractaria/cirugía , Participación del Paciente/psicología , Rol del Médico/psicología , Adolescente , Adulto , Anciano , Niño , Preescolar , Epilepsia Refractaria/diagnóstico por imagen , Electroencefalografía/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Relaciones Médico-Paciente , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
Surgery is the most effective therapeutic approach for medically refractory epilepsies and a safe and cost-efficient treatment in terms of long-term expenses of direct, indirect, and intangible costs. Georgia is a Caucasian low- to middle-income country with a remarkable effort to deal with epileptic diseases, but without an appropriate epilepsy surgery program. To address the needs for such a service in this country, two joint German-Georgian projects were initiated in 2017 and 2019. In the framework of these projects, a productive exchange program involving German and Georgian experts was undertaken in the past two years. This program included training and mentoring for Georgian clinical colleagues, as well as joint case conferences and workshops with the aim of optimizing presurgical diagnostics and preparing for an epilepsy surgery program in Georgia. Finally, a postsurgical medium- and long-term follow-up scheme was organized as the third component of this comprehensive approach. As a result of our efforts, the first patients underwent anterior temporal lobectomy and all of them remain seizure-free up to the present day. Hence, epilepsy surgery is not only feasible, but also already available in Georgia. In this report, we aim to share our experiences in the initiation and implementation of surgical epilepsy intervention in Georgia and illustrate our recent endeavor and achievements.
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Atención a la Salud/métodos , Epilepsia Refractaria/epidemiología , Epilepsia Refractaria/cirugía , Neurocirugia/educación , Neurocirugia/métodos , Adulto , Lobectomía Temporal Anterior/educación , Lobectomía Temporal Anterior/métodos , Lobectomía Temporal Anterior/tendencias , Atención a la Salud/tendencias , Educación/métodos , Educación/tendencias , Femenino , Georgia (República)/epidemiología , Alemania/epidemiología , Humanos , Masculino , Neurocirugia/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.
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Encefalopatías/cirugía , Infecciones por Coronavirus/epidemiología , Urgencias Médicas , Procedimientos Neuroquirúrgicos , Neumonía Viral/epidemiología , Enfermedades de la Médula Espinal/cirugía , Traumatismos Vertebrales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , Estudios de Cohortes , Femenino , Hematoma Subdural Crónico/cirugía , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Hemorragia Subaracnoidea/cirugía , Adulto JovenRESUMEN
BACKGROUND: Traditionally, for subdural grid electrode placement, large craniotomies have been applied for optimal electrode placement. Nowadays, microneurosurgeons prefer patient-tailored minimally invasive approaches. Absolute figures on craniotomy size have never been reported. To elucidate the craniotomy size necessary for successful diagnostics, we reviewed our single-center experience. METHODS: Within 3 years, 58 patients with focal epilepsies underwent subdural grid implantation using patient-tailored navigation-based craniotomies. Craniotomy sizes were measured retrospectively. The number of electrodes and the feasibility of the resection were evaluated. Sixteen historical patients served as controls. RESULTS: In all 58 patients, subdural electrodes were implanted as planned through tailored craniotomies. The mean craniotomy size was 28 ± 15 cm2 via which 55 ± 16 electrodes were implanted. In temporal lobe diagnostics, even smaller craniotomies were applied (21 ± 11 cm2). Craniotomies were significantly smaller than in historical controls (65 ± 23 cm2, p < 0.05), while the mean number of electrodes was comparable. The mean operation time was shorter and complications were reduced in tailored craniotomies. CONCLUSION: Craniotomy size for subdural electrode implantation is controversial. Some surgeons favor large craniotomies, while others strive for minimally invasive approaches. For the first time, we measured the actual craniotomy size for subdural grid electrode implantation. All procedures were straightforward. We therefore advocate for patient-tailored minimally invasive approaches - standard in modern microneurosurgery - in epilepsy surgery as well.
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Craneotomía/métodos , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Electrodos Implantados , Espacio Subdural/diagnóstico por imagen , Espacio Subdural/cirugía , Adolescente , Adulto , Epilepsia Refractaria/fisiopatología , Electroencefalografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Adulto JovenRESUMEN
Human mesial temporal lobe epilepsy (MTLE) features subregion-specific hippocampal neurodegeneration and reactive astrogliosis, including up-regulation of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine synthetase (GS). However, the regional astrocytic expression pattern of GFAP and GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP and GS expression in strict correlation with the local neuronal number in cortical and hippocampal surgical specimens from 16 MTLE patients using immunohistochemistry, stereology and high-resolution image analysis for digital pathology and whole-slide imaging. In the cortex, GS-positive (GS+) astrocytes are dominant in all neuronal layers, with a neuron to GS+ cell ratio of 2:1. GFAP-positive (GFAP+) cells are widely spaced, with a GS+ to GFAP+ cell ratio of 3:1-5:1. White matter astrocytes, on the contrary, express mainly GFAP and, to a lesser extent, GS. In the hippocampus, the neuron to GS+ cell ratio is approximately 1:1. Hippocampal degeneration is associated with a reduction of GS+ astrocytes, which is proportional to the degree of neuronal loss and primarily present in the hilus. Up-regulation of GFAP as a classical hallmark of reactive astrogliosis does not follow the GS-pattern and is prominent in the CA1. Reactive alterations were proportional to the neuronal loss in the neuronal somatic layers (stratum pyramidale and hilus), while observed to a lesser extent in the axonal/dendritic layers (stratum radiatum, molecular layer). We conclude that astrocytic GS is expressed in the neuronal somatic layers and, upon neurodegeneration, is down-regulated proportionally to the degree of neuronal loss.
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Astrocitos/enzimología , Corteza Cerebral/enzimología , Epilepsia del Lóbulo Temporal/enzimología , Glutamato-Amoníaco Ligasa/metabolismo , Neuronas/enzimología , Adulto , Astrocitos/patología , Muerte Celular/fisiología , Corteza Cerebral/patología , Epilepsia Refractaria/enzimología , Epilepsia Refractaria/patología , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/patología , Epilepsia del Lóbulo Temporal/cirugía , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Gliosis/enzimología , Gliosis/patología , Humanos , Inmunohistoquímica , Masculino , Enfermedades Neurodegenerativas/enzimología , Enfermedades Neurodegenerativas/patología , Neuronas/patología , Sustancia Blanca/enzimología , Sustancia Blanca/patologíaRESUMEN
OBJECTIVE: The need for alternative pharmacologic strategies in treatment of epilepsies is pressing for about 30% of patients with epilepsy who do not experience satisfactory seizure control with present treatments. In temporal lobe epilepsy (TLE) even up to 80% of patients are pharmacoresistant, and surgical resection of the ictogenic tissue is only possible for a minority of TLE patients. In this study we investigate purinergic modulation of drug-resistant seizure-like events (SLEs) in human temporal cortex slices. METHODS: Layer V/VI field potentials from a total of 77 neocortical slices from 17 pharmacoresistant patients were recorded to monitor SLEs induced by application of 8 mM [K(+) ] and 50 µm bicuculline. RESULTS: Activating A1 receptors with a specific agonist completely suppressed SLEs in 73% of human temporal cortex slices. In the remaining slices, incidence of SLEs was markedly reduced. Because a subportion of slices can be pharmacosensitive, we tested effects of an A1 agonist, in slices insensitive to a high dose of carbamazepine (50 µm). Also in these cases the A1 agonist was equally efficient. Moreover, ATP and adenosine blocked or modulated SLEs, an effect mediated not by P2 receptors but rather by adenosine A1 receptors. SIGNIFICANCE: Selective activation of A1 receptors mediates a strong anticonvulsant action in human neocortical slices from pharmacoresistant patients. We propose that our human slice model of seizure-like activity is a feasible option for future studies investigating new antiepileptic drug (AED) candidates.
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Epilepsia Refractaria/patología , Neocórtex/efectos de los fármacos , Neocórtex/metabolismo , Receptores Purinérgicos P1/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacología , Adenosina Trifosfato/farmacología , Adulto , Bicuculina/análogos & derivados , Bicuculina/farmacología , Carbamazepina/efectos adversos , Carbamazepina/farmacología , Epilepsia Refractaria/tratamiento farmacológico , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Femenino , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Potasio/farmacología , Purinérgicos/farmacología , Factores de Tiempo , Adulto JovenRESUMEN
Inflammatory changes have been postulated to contribute to secondary brain injury after aneurysmal subarachnoid hemorrhage (SAH). In human specimens after SAH as well as in experimental SAH using mice, we show an intracerebral accumulation of inflammatory cells between days 4 and 28 after the bleeding. Using bone marrow chimeric mice allowing tracing of all peripherally derived immune cells, we confirm a truly CNS-intrinsic, microglial origin of these immune cells, exhibiting an inflammatory state, and rule out invasion of myeloid cells from the periphery into the brain. Furthermore, we detect secondary neuro-axonal injury throughout the time course of SAH. Since neuronal cell death and microglia accumulation follow a similar time course, we addressed whether the occurrence of activated microglia and neuro-axonal injury upon SAH are causally linked by depleting microglia in vivo. Given that the amount of neuronal cell death was significantly reduced after microglia depletion, we conclude that microglia accumulation inflicts secondary brain injury after SAH.
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Lesiones Encefálicas/fisiopatología , Encéfalo/fisiopatología , Microglía/fisiología , Hemorragia Subaracnoidea/fisiopatología , Animales , Encéfalo/patología , Lesiones Encefálicas/patología , Proteínas de Unión al Calcio/metabolismo , Muerte Celular/fisiología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Microglía/patología , Persona de Mediana Edad , Neuroinmunomodulación/fisiología , Neuronas/patología , Neuronas/fisiología , Hemorragia Subaracnoidea/patología , Factores de Tiempo , Quimera por TrasplanteRESUMEN
INTRODUCTION: The most widely used neuro-stimulation treatment for drug-resistant epilepsy is Vagus Nerve Stimulation (VNS) Therapy®. Ictal tachycardia can be an indicator of a seizure and, if monitored, can be used to trigger an additional on-demand stimulation, which may positively influence seizure severity or duration. A new VNS Therapy generator model, AspireSR®, was introduced and approved for CE Mark in February 2014. In enhancement of former models, the AspireSR has incorporated a cardiac-based seizure-detection (CBSD) algorithm that can detect ictal tachycardia and automatically trigger a defined auto-stimulation. To evaluate differences in preoperative, intraoperative and postoperative handling, we compared the AspireSR to a conventional generator model (Demipulse®). METHOD: Between February and September 2014, seven patients with drug-resistant epilepsy and ictal tachycardia were implanted with an AspireSR. Between November 2013 and September 2014, seven patients were implanted with a Demipulse and served as control group. Operation time, skin incision length and position, and complications were recorded. Handling of the new device was critically evaluated. RESULTS: The intraoperative handling was comparable and did not lead to a significant increase in operation time. In our 14 operations, we had no significant short-term complications. Due to its larger size, patients with the AspireSR had significantly larger skin incisions. For optimal heart rate detection, the AspireSR had to be placed significantly more medial in the décolleté area than the Demipulse. The preoperative testing is a unique addition to the implantation procedure of the AspireSR, which may provide minor difficulties, and for which we provide several recommendations and tips. The price of the device is higher than for all other models. CONCLUSIONS: The new AspireSR generator offers a unique technical improvement over the previous Demipulse. Whether the highly interesting CBSD feature will provide an additional benefit for the patients, and will rectify the additional costs, respectively, cannot be answered in the short-term. The preoperative handling is straightforward, provided that certain recommendations are taken into consideration. The intraoperative handling is equivalent to former models-except for the placement of the generator, which might cause cosmetic issues and has to be discussed with the patient carefully. We recommend the consideration of the AspireSR in patients with documented ictal tachycardia to provide a substantial number of patients for later seizure outcome analysis.
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Epilepsia/terapia , Neuroestimuladores Implantables/normas , Procedimientos Quirúrgicos Operativos/normas , Estimulación del Nervio Vago/instrumentación , Adulto , Epilepsia/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Estimulación del Nervio Vago/métodosRESUMEN
BACKGROUND: Brain atrophy after subarachnoid hemorrhage (SAH) has been detected in humans and might serve as a functional read-out parameter for neuropsychological deficits. To determine whether serial magnetic resonance imaging (MRI) can provide information on brain atrophy in animals as well, mice that had undergone experimental SAH were scanned repeatedly after the bleeding. METHODS: Using a 7-T rodent MRI, six mice were evaluated for total hemispheric, cerebrospinal fluid (CSF) and hippocampal volumes on days 1, 2, 4, 21, 28, 42 and 60 after experimental SAH or sham operation, respectively. RESULTS: Repeated MRI scanning demonstrated a very high reproducibility with minimum standard deviation. Nevertheless, no significant differences were found between the two groups concerning hemispherical volumes or hippocampal volumes. A transient but significant increase in CSF volume was detected on days 2 and 60 after SAH. Compared with the existing method, no MRI data on brain atrophy in mice after experimental SAH have been published. CONCLUSION: Repeated brain MRI in mice after experimental SAH did not provide additional information on brain atrophy. Our data suggest that this is not due to a lack of sensitivity of the method. Despite all promising details about MRI, our results should initiate careful consideration (additional sequences/other questions) before its further use in this certain area, especially since it is expensive and associated with demanding logistics.
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Hipocampo/patología , Hemorragia Subaracnoidea/patología , Animales , Atrofia/patología , Imagen por Resonancia Magnética , Ratones , Enfermedades Neurodegenerativas/patología , Tamaño de los Órganos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: Endovascular middle meningeal artery (MMA) occlusion may help reduce the risk of recurrence after burr hole evacuation of chronic subdural hematoma (cSDH) but carries an additional periprocedural risk and remains hampered by logistical and financial requirements. In this study, the authors aimed to describe a simple and fast technique for preoperative MMA localization to permit burr hole cSDH evacuation and MMA occlusion through the same burr hole. METHODS: The authors performed a preclinical anatomical and prospective clinical study, followed by a retrospective feasibility analysis. An anatomical cadaver study with 33 adult human skulls (66 hemispheres) was used to localize a suitable frontal target point above the pterion, where the MMA can be accessed via burr hole trephination. Based on anatomical landmark measurements, the authors designed a template for projected localization of this target point onto the skin. Next, the validity of the template was tested using image guidance in 10 consecutive patients undergoing elective pterional craniotomy, and the feasibility of the target point localization for cSDH accessibility was determined based on hematoma localization in 237 patients who were treated for a space-occupying cSDH in the authors' department between 2014 and 2018. RESULTS: In the anatomical study, the mean perpendicular distance from the zygomatic process to the target point in the frontoparietal bone was 4.1 cm (95% CI 4-4.2 cm). The mean length along the upper margin of the zygomatic process from the middle of the external auditory canal to the point of the perpendicular distance was 2.3 cm (95% CI 2.2-2.4 cm). The template designed according to these measurements yielded high agreement between the template-based target point and the proximal MMA groove inside the frontoparietal bone (right 90.9%; left 93.6%). In the clinical validation, we noted a mean distance of 4 mm (95% CI 2.1-5.9 mm) from the template-based target point to the actual MMA localization. The feasibility analysis yielded that 95% of all cSDHs in this cohort would have been accessible by the new frontal burr hole localization. CONCLUSIONS: A template-based target point approach for MMA localization may serve as a simple, fast, reliable, and cost-effective technique for surgical evacuation of space-occupying cSDHs with MMA obliteration through the same burr hole in a single setting.
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Hematoma Subdural Crónico , Arterias Meníngeas , Humanos , Hematoma Subdural Crónico/cirugía , Hematoma Subdural Crónico/diagnóstico por imagen , Masculino , Arterias Meníngeas/cirugía , Arterias Meníngeas/diagnóstico por imagen , Femenino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Craneotomía/métodos , Estudios de Factibilidad , Anciano de 80 o más Años , Estudios Retrospectivos , Trepanación/métodos , Cadáver , Adulto , Procedimientos Endovasculares/métodosRESUMEN
The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems-nervous, vascular, and immune-is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.