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1.
World Neurosurg ; 185: e1268-e1279, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38514030

RESUMEN

OBJECTIVES: Using a laboratory-based optical setup, we show that 5-aminolevulinic acid (5ALA) fluorescence is better detected using the endoscope than the microscope. Furthermore, we present our case series of fully endoscopic 5ALA-guided resection of intraparenchymal tumors. METHODS: A Zeiss Pentero microscope was compared with the Karl Storz Hopkins endoscope. The spectra and intensity of each blue light source were measured. Quantitative fluorescence detection thresholds were measured using a spectrometer. Subjective fluorescence detection thresholds were measured by 6 blinded neuro-oncology surgeons. Clinical data were prospectively collected for all consecutive cases of fully endoscopic 5ALA-guided resection of intraparenchymal tumors between 2012 and 2023. RESULTS: The intensity of blue light on the sample was greater for the endoscope than the microscope at working distances less than 20 mm. The quantitative fluorescence detection thresholds were lower for the endoscope than the microscope at both 30-/10-mm working distances. Fluorescence detection threshold was 0.65%-0.80% relative 4-dicyanomethylene-2-methyl-6-p-dimethylaminostyryl-4H-pyranthe concentration (3.20 × 10-7 to 3.94 × 10-7mol/dm-3) for the microscope, 0.40%-0.55% relative concentrations (1.97 × 10-7 to 2.71 × 10-7mol/dm-3) for the endoscope at 30 mm, and 0.15%-0.30% relative concentrations (7.40 × 10-8 to 1.48 × 10-7mol/dm-3) for the endoscope at 10 mm. In total, 49 5ALA endoscope-assisted brain tumor resections were carried out on 45 patients (mean age = 41 years, male = 28). Greater than 95% resection was achieved in 80% of cases and gross total resection in 42%. Gross total resection was achieved in 100% of tumors in noneloquent locations. There was 1 new neurologic deficit. CONCLUSIONS: The endoscope provides enhanced visualization/detection of 5ALA-induced fluorescence compared with the microscope. 5ALA endoscopic-assisted resection of intraparenchymal tumors is safe and feasible.


Asunto(s)
Ácido Aminolevulínico , Neoplasias Encefálicas , Neuroendoscopía , Humanos , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Neuroendoscopía/métodos , Neuroendoscopía/instrumentación , Anciano , Adulto , Fármacos Fotosensibilizantes , Fluorescencia , Cirugía Asistida por Computador/métodos , Microscopía/métodos , Microscopía/instrumentación , Procedimientos Neuroquirúrgicos/métodos
2.
Acta Neurochir (Wien) ; 165(10): 2873-2883, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37491650

RESUMEN

BACKGROUND: Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments. METHODS: We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis. RESULTS: In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries. CONCLUSIONS: Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Adulto , Femenino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/terapia , Neoplasias Meníngeas/epidemiología , Meningioma/diagnóstico , Meningioma/terapia , Meningioma/patología , Estudios Retrospectivos , Resultado del Tratamiento
3.
J Neurooncol ; 161(3): 451-467, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36757526

RESUMEN

INTRODUCTION: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. METHODS: A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with "brain tumors", "brain edema" and "animal models". RESULTS: We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. CONCLUSION: No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.


Asunto(s)
Edema Encefálico , Neoplasias Encefálicas , Animales , Humanos , Imagen por Resonancia Magnética/métodos , Neoplasias Encefálicas/patología , Edema/complicaciones , Edema Encefálico/complicaciones , Encéfalo/patología
4.
Cereb Cortex ; 33(5): 2101-2142, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-35667019

RESUMEN

Diverse neocortical GABAergic neurons specialize in synaptic targeting and their effects are modulated by presynaptic metabotropic glutamate receptors (mGluRs) suppressing neurotransmitter release in rodents, but their effects in human neocortex are unknown. We tested whether activation of group III mGluRs by L-AP4 changes GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in 2 distinct dendritic spine-innervating GABAergic interneurons recorded in vitro in human neocortex. Calbindin-positive double bouquet cells (DBCs) had columnar "horsetail" axons descending through layers II-V innervating dendritic spines (48%) and shafts, but not somata of pyramidal and nonpyramidal neurons. Parvalbumin-expressing dendrite-targeting cell (PV-DTC) axons extended in all directions innervating dendritic spines (22%), shafts (65%), and somata (13%). As measured, 20% of GABAergic neuropil synapses innervate spines, hence DBCs, but not PV-DTCs, preferentially select spine targets. Group III mGluR activation paradoxically increased the frequency of sIPSCs in DBCs (to median 137% of baseline) but suppressed it in PV-DTCs (median 92%), leaving the amplitude unchanged. The facilitation of sIPSCs in DBCs may result from their unique GABAergic input being disinhibited via network effect. We conclude that dendritic spines receive specialized, diverse GABAergic inputs, and group III mGluRs differentially regulate GABAergic synaptic transmission to distinct GABAergic cell types in human cortex.


Asunto(s)
Neocórtex , Receptores de Glutamato Metabotrópico , Humanos , Neocórtex/metabolismo , Parvalbúminas/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Interneuronas/fisiología , Transmisión Sináptica/fisiología , Neuronas GABAérgicas/metabolismo , Dendritas/metabolismo
5.
World Neurosurg ; 167: e217-e221, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35944859

RESUMEN

BACKGROUND: Hemangioblastomas are benign, often cystic tumors occurring most commonly in the cerebellum. We describe resection of cystic cerebellar hemangioblastomas using an endoscope-assisted technique. METHODS: We present a series of 9 cases and discuss the endoscopic technique for resection of cystic hemangioblastoma. Frameless neuronavigation was used in all cases. A small 1- to 1.5-cm corticotomy lined with Surgicel and patties allows access to the peritumoral cyst. Using bimanual microsurgical techniques and the 30-degree rigid endoscope to provide visualization, the mural nodule can be resected and the cyst cavity inspected. RESULTS: Complete resection of the mural nodule was achieved in all cases. One patient had a postsurgery pseudomeningocele requiring ventriculoperitoneal shunt. Hospital length of stay was short for all the patients. CONCLUSIONS: Endoscope-assisted resection is a safe and effective technique for surgical resection of cystic hemangioblastoma.


Asunto(s)
Neoplasias Cerebelosas , Quistes , Hemangioblastoma , Humanos , Hemangioblastoma/diagnóstico por imagen , Hemangioblastoma/cirugía , Hemangioblastoma/patología , Endoscopía/métodos , Neoplasias Cerebelosas/cirugía , Neoplasias Cerebelosas/patología , Endoscopios
6.
J Neurosci ; 41(47): 9702-9719, 2021 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-34667071

RESUMEN

Persistent anion conductances through GABAA receptors (GABAARs) are important modulators of neuronal excitability. However, it is currently unknown how the amplitudes of these currents vary among different cell types in the human neocortex, particularly among diverse GABAergic interneurons. We have recorded 101 interneurons in and near layer 1 from cortical tissue surgically resected from both male and female patients, visualized 84 of them and measured tonic GABAAR currents in 48 cells with an intracellular [Cl-] of 65 mm and in the presence of 5 µm GABA. We compare these tonic currents among five groups of interneurons divided by firing properties and four types of interneuron defined by axonal distributions; rosehip, neurogliaform, stalked-bouton, layer 2-3 innervating and a pool of other cells. Interestingly, the rosehip cell, a type of interneuron only described thus far in human tissue, and layer 2-3 innervating cells exhibit larger tonic currents than other layer 1 interneurons, such as neurogliaform and stalked-bouton cells; the latter two groups showing no difference. The positive allosteric modulators of GABAARs allopregnanolone and DS2 also induced larger current shifts in the rosehip and layer 2-3 innervating cells, consistent with higher expression of the δ subunit of the GABAAR in these neurons. We have also examined how patient parameters, such as age, seizures, type of cancer and anticonvulsant treatment may alter tonic inhibitory currents in human neurons. The cell type-specific differences in tonic inhibitory currents could potentially be used to selectively modulate cortical circuitry.SIGNIFICANCE STATEMENT Tonic currents through GABAA receptors (GABAARs) are a potential therapeutic target for a number of neurologic and psychiatric conditions. Here, we show that these currents in human cerebral cortical GABAergic neurons display cell type-specific differences in their amplitudes which implies differential modulation of their excitability. Additionally, we examine whether the amplitudes of the tonic currents measured in our study show any differences between patient populations, finding some evidence that age, seizures, type of cancer, and anticonvulsant treatment may alter tonic inhibition in human tissue. These results advance our understanding of how pathology affects neuronal excitability and could potentially be used to selectively modulate cortical circuitry.


Asunto(s)
Neuronas GABAérgicas/metabolismo , Interneuronas/metabolismo , Neocórtex/metabolismo , Receptores de GABA-A/metabolismo , Potenciales de Acción/fisiología , Adulto , Anciano , Femenino , Neuronas GABAérgicas/citología , Humanos , Interneuronas/citología , Masculino , Persona de Mediana Edad , Neocórtex/citología
7.
J Neurosurg ; : 1-11, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33007757

RESUMEN

OBJECTIVE: Raman spectroscopy is a biophotonic tool that can be used to differentiate between different tissue types. It is nondestructive and no sample preparation is required. The aim of this study was to evaluate the ability of Raman spectroscopy to differentiate between glioma and normal brain when using fresh biopsy samples and, in the case of glioblastomas, to compare the performance of Raman spectroscopy to predict the presence or absence of tumor with that of 5-aminolevulinic acid (5-ALA)-induced fluorescence. METHODS: A principal component analysis (PCA)-fed linear discriminant analysis (LDA) machine learning predictive model was built using Raman spectra, acquired ex vivo, from fresh tissue samples of 62 patients with glioma and 11 glioma-free brain samples from individuals undergoing temporal lobectomy for epilepsy. This model was then used to classify Raman spectra from fresh biopsies from resection cavities after functional guided, supramaximal glioma resection. In cases of glioblastoma, 5-ALA-induced fluorescence at the resection cavity biopsy site was recorded, and this was compared with the Raman spectral model prediction for the presence of tumor. RESULTS: The PCA-LDA predictive model demonstrated 0.96 sensitivity, 0.99 specificity, and 0.99 accuracy for differentiating tumor from normal brain. Twenty-three resection cavity biopsies were taken from 8 patients after supramaximal resection (6 glioblastomas, 2 oligodendrogliomas). Raman spectroscopy showed 1.00 sensitivity, 1.00 specificity, and 1.00 accuracy for predicting tumor versus normal brain in these samples. In the glioblastoma cases, where 5-ALA-induced fluorescence was used, the performance of Raman spectroscopy was significantly better than the predictive value of 5-ALA-induced fluorescence, which showed 0.07 sensitivity, 1.00 specificity, and 0.24 accuracy (p = 0.0009). CONCLUSIONS: Raman spectroscopy can accurately classify fresh tissue samples into tumor versus normal brain and is superior to 5-ALA-induced fluorescence. Raman spectroscopy could become an important intraoperative tool used in conjunction with 5-ALA-induced fluorescence to guide extent of resection in glioma surgery.

8.
World Neurosurg ; 144: 162-169, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32861903

RESUMEN

BACKGROUND: The interhemispheric fissure provides a natural surgical corridor to access tumors of the deep medial surface of the brain. Conventional microscopic approaches to these tumors are limited by the narrow width of the interhemispheric fissure and need for retraction of brain tissue or traversing overlying cortex. Over the last decade, the endoscope has been used to improve visualization of the operative field in neurosurgery, with benefits in terms of surgical ergonomics and extent of tumor resections. In the context of the interhemispheric fissure, an endoscopic approach may improve visualization of some tumors by providing a brighter, more divergent light source at depth and by enabling the operator to inspect around curved structures (e.g., corpus callosum). CASE DESCRIPTION: In this report, we present a series of 5 cases with tumors at various locations along the anteroposterior extent of the interhemispheric fissure that were resected using an endoscopic ipsilateral interhemispheric approach. CONCLUSIONS: The endoscopic ipsilateral interhemispheric approach is an effective and versatile approach to resection of selected deep medial brain tumors extending anteriorly from the genu of the corpus callosum to the splenium. It has notable advantages over the microscope and can be considered a useful adjunct in the surgeon's armamentarium.


Asunto(s)
Neoplasias Encefálicas/cirugía , Neuroendoscopía/métodos , Procedimientos Neuroquirúrgicos/métodos , Adulto , Anciano , Astrocitoma/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Carcinoma/cirugía , Cuerpo Calloso/cirugía , Femenino , Ganglioglioma/cirugía , Germinoma/cirugía , Glioblastoma/cirugía , Giro del Cíngulo/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Meningioma/cirugía , Persona de Mediana Edad , Estudios Retrospectivos
9.
Neurooncol Pract ; 7(3): 344-355, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32537183

RESUMEN

BACKGROUND: In recent years an increasing number of patients with cerebral metastasis (CM) have been referred to the neuro-oncology multidisciplinary team (NMDT). Our aim was to obtain a national picture of CM referrals to assess referral volume and quality and factors affecting NMDT decision making. METHODS: A prospective multicenter cohort study including all adult patients referred to NMDT with 1 or more CM was conducted. Data were collected in neurosurgical units from November 2017 to February 2018. Demographics, primary disease, KPS, imaging, and treatment recommendation were entered into an online database. RESULTS: A total of 1048 patients were analyzed from 24 neurosurgical units. Median age was 65 years (range, 21-93 years) with a median number of 3 referrals (range, 1-17 referrals) per NMDT. The most common primary malignancies were lung (36.5%, n = 383), breast (18.4%, n = 193), and melanoma (12.0%, n = 126). A total of 51.6% (n = 541) of the referrals were for a solitary metastasis and resulted in specialist intervention being offered in 67.5% (n = 365) of cases. A total of 38.2% (n = 186) of patients being referred with multiple CMs were offered specialist treatment. NMDT decision making was associated with number of CMs, age, KPS, primary disease status, and extent of extracranial disease (univariate logistic regression, P < .001) as well as sentinel location and tumor histology (P < .05). A delay in reaching an NMDT decision was identified in 18.6% (n = 195) of cases. CONCLUSIONS: This study demonstrates a changing landscape of metastasis management in the United Kingdom and Ireland, including a trend away from adjuvant whole-brain radiotherapy and specialist intervention being offered to a significant proportion of patients with multiple CMs. Poor quality or incomplete referrals cause delay in NMDT decision making.

10.
Neurooncol Adv ; 1(1): vdz008, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31608327

RESUMEN

BACKGROUND: The molecular genetic classification of gliomas, particularly the identification of isocitrate dehydrogenase (IDH) mutations, is critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample to accurately characterize its molecular composition. No sample processing is required allowing for rapid analysis of tissue. The aim of this study was to evaluate the ability of Raman spectroscopy to rapidly identify the common molecular genetic subtypes of diffuse glioma in the neurosurgical setting using fresh biopsy tissue. In addition, classification models were built using cryosections, formalin-fixed paraffin-embedded (FFPE) sections and LN-18 (IDH-mutated and wild-type parental cell) glioma cell lines. METHODS: Fresh tissue, straight from neurosurgical theatres, underwent Raman analysis and classification into astrocytoma, IDH-wild-type; astrocytoma, IDH-mutant; or oligodendroglioma. The genetic subtype was confirmed on a parallel section using immunohistochemistry and targeted genetic sequencing. RESULTS: Fresh tissue samples from 62 patients were collected (36 astrocytoma, IDH-wild-type; 21 astrocytoma, IDH-mutated; 5 oligodendroglioma). A principal component analysis fed linear discriminant analysis classification model demonstrated 79%-94% sensitivity and 90%-100% specificity for predicting the 3 glioma genetic subtypes. For the prediction of IDH mutation alone, the model gave 91% sensitivity and 95% specificity. Seventy-nine cryosections, 120 FFPE samples, and LN18 cells were also successfully classified. Meantime for Raman data collection was 9.5 min in the fresh tissue samples, with the process from intraoperative biopsy to genetic classification taking under 15 min. CONCLUSION: These data demonstrate that Raman spectroscopy can be used for the rapid, intraoperative, classification of gliomas into common genetic subtypes.

12.
BMJ Surg Interv Health Technol ; 1(1): e000012, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-35047776

RESUMEN

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurological condition; surgical evacuation is the mainstay of treatment for symptomatic patients. No clear evidence exists regarding the impact of timing of surgery on outcomes. We investigated factors influencing time to surgery and its impact on outcomes of interest. METHODS: Patients with CSDH who underwent burr-hole craniostomy were included. This is a subset of data from a prospective observational study conducted in the UK. Logistic mixed modelling was performed to examine the factors influencing time to surgery. The impact of time to surgery on discharge modified Rankin Scale (mRS), complications, recurrence, length of stay and survival was investigated with multivariable logistic regression analysis. RESULTS: 656 patients were included. Time to surgery ranged from 0 to 44 days (median 1, IQR 1-3). Older age, more favorable mRS on admission, high preoperative Glasgow Coma Scale score, use of antiplatelet medications, comorbidities and bilateral hematomas were associated with increased time to surgery. Time to surgery showed a significant positive association with length of stay; it was not associated with outcome, complication rate, reoperation rate, or survival on multivariable analysis. There was a trend for patients with time to surgery of ≥7 days to have lower odds of favorable outcome at discharge (p=0.061). CONCLUSIONS: This study provides evidence that time to surgery does not substantially impact on outcomes following CSDH. However, increasing time to surgery is associated with increasing length of stay. These results should not encourage delaying operations for patients when they are clinically indicated.

13.
World Neurosurg ; 117: e238-e251, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29902607

RESUMEN

BACKGROUND: Surgical access to the temporal lobe is complex with many eloquent white fiber tracts, requiring careful preoperative surgical planning. Many microsurgical approaches to the temporal lobes are described, each with their own disadvantages. The adoption of the endoscope in neurosurgery has increased the options available when treating these difficult access tumors. We present our experience of a novel, minimally invasive, endoscopic approach to resect temporal lobe tumors. METHODS: All patients undergoing endoscopic temporal lobe tumor resection between December 1, 2011 and December 1, 2017, with a single surgeon, were included. Tumors were resected through a minicraniotomy using a high-definition rigid endoscope with a 0- and 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. RESULTS: There were 45 patients (22 men and 23 women) with a mean age of 53 years. There were 23 (51%) glioblastoma multiforme, 11 (24%) metastases, 7 (16%) astrocytoma, 3 (7%) anaplastic astrocytoma, and 1 (2%) World Health Organization grade I glioneuronal tumor. In 82.2% of cases (37/45), >95% resection was achieved and 42.2% (19/45) of patients achieving gross total resection. CONCLUSIONS: The endoscope has a role in temporal lobe intraparenchymal tumor surgery, especially in 3 illustrative scenarios: 1) medial temporal, parahippocampal-gyrus low-grade nonenhancing gliomas, 2) subcortical high-grade glioma and metastases medial to the sagittal stratum, and 3) recurrent gliomas with cystic resection cavity. The endoscope offers a safe and useful adjunct to the surgeons' armamentarium in brain tumor surgery. A minimally invasive approach also reduces surgical morbidity and length of stay.


Asunto(s)
Neoplasias Encefálicas/cirugía , Glioma/cirugía , Neuroendoscopía/métodos , Lóbulo Temporal/cirugía , Adulto , Anciano , Astrocitoma/cirugía , Neoplasias Encefálicas/secundario , Craneotomía/métodos , Femenino , Glioblastoma/cirugía , Humanos , Masculino , Microcirugia/métodos , Persona de Mediana Edad , Resultado del Tratamiento
14.
BMJ Open ; 8(5): e017593, 2018 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-29794088

RESUMEN

OBJECTIVES: To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway. DESIGN: A model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion. SETTING: Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA. PARTICIPANTS: Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum. MAIN OUTCOME MEASURES: The primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis. RESULTS: Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000-£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40). CONCLUSION: Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway.


Asunto(s)
Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/diagnóstico , Análisis Costo-Beneficio/estadística & datos numéricos , Pruebas Hematológicas/economía , Modelos Económicos , Continuidad de la Atención al Paciente/economía , Vías Clínicas , Humanos , Atención Primaria de Salud/economía , Años de Vida Ajustados por Calidad de Vida , Sensibilidad y Especificidad , Evaluación de la Tecnología Biomédica/organización & administración , Triaje , Reino Unido
15.
Front Cell Neurosci ; 12: 508, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30670948

RESUMEN

Group II metabotropic glutamate receptor (mGluR) ligands are potential novel drugs for neurological and psychiatric disorders, but little is known about the effects of these compounds at synapses of the human cerebral cortex. Investigating the effects of neuropsychiatric drugs in human brain tissue with preserved synaptic circuits might accelerate the development of more potent and selective pharmacological treatments. We have studied the effects of group II mGluR activation on excitatory synaptic transmission recorded from pyramidal neurons of cortical layers 2-3 in acute slices derived from surgically removed cortical tissue of people with epilepsy or tumors. The application of a selective group II mGluR agonist, LY354740 (0.1-1 µM) inhibited the amplitude and frequency of action potential-dependent spontaneous excitatory postsynaptic currents (sEPSCs). This effect was prevented by the application of a group II/III mGluR antagonist, CPPG (0.1 mM). Furthermore, LY354740 inhibited the frequency, but not the amplitude, of action potential-independent miniature EPSCs (mEPSCs) recorded in pyramidal neurons. Finally, LY354740 did slightly reduce cells' input resistance without altering the holding current of the neurons recorded in voltage clamp at -90 mV. Our results suggest that group II mGluRs are mainly auto-receptors that inhibit the release of glutamate onto pyramidal neurons in layers 2-3 in the human cerebral cortex, thereby regulating network excitability. We have demonstrated the effect of a group II mGluR ligand at human cortical synapses, revealing mechanisms by which these drugs could exert pro-cognitive effects and treat human neuropsychiatric disorders.

16.
BMJ Case Rep ; 20172017 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-29025781

RESUMEN

Communicating hydrocephalus may complicate infantile bacterial meningitis, typically presenting with systemic features of infection. We report a rare case of 'subclinical meningoventriculitis' causing obstructive hydrocephalus and its challenging management. A healthy 10-week-old immunocompetent male patient presented with failure to thrive and vomiting, secondary to presumed gastro-oesophageal reflux. The child was neurologically alert, afebrile with normal inflammatory markers. Progressive macrocephaly prompted an MRI confirming triventricular hydrocephalus secondary to aqueductal stenosis. An endoscopic third ventriculostomy was performed however abandoned intraoperatively due to the unexpected finding of intraventricular purulent cerebrospinal fluid. A 6-week course of intravenous ceftriaxone was commenced for Escherichia coli meningoventriculitis. However, the child was readmitted 18 days postoperatively with acute hydrocephalus requiring a ventricular washout and staged ventriculoperitoneal shunt insertion at 4 weeks. Serial head circumference measurements are paramount in the assessment of a paediatric patient. In an immunocompetent child, a subclinical fibropurulent meningoventriculitis can result in several management challenges.


Asunto(s)
Antibacterianos/uso terapéutico , Ceftriaxona/uso terapéutico , Ventriculitis Cerebral/microbiología , Hidrocefalia/microbiología , Meningoencefalitis/microbiología , Politetrafluoroetileno/uso terapéutico , Infecciones Urinarias/terapia , Amoxicilina/uso terapéutico , Ventriculitis Cerebral/complicaciones , Ventriculitis Cerebral/terapia , Derivaciones del Líquido Cefalorraquídeo , Humanos , Hidrocefalia/etiología , Hidrocefalia/terapia , Recién Nacido , Inyecciones , Masculino , Meningoencefalitis/complicaciones , Meningoencefalitis/terapia , Resultado del Tratamiento , Uréter , Ventriculostomía
17.
World Neurosurg ; 93: 246-52, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27312395

RESUMEN

BACKGROUND: There is an increasing drive to deliver a more efficient, cost-effective service leading to shorter stays in hospital. The advent of endoscopic and awake tumor surgery has reduced the morbidity associated with brain tumor resection, allowing patients to mobilize and be discharged earlier. Here, we present the outcomes from a single neurosurgical center in the United Kingdom on a fast track recovery program. METHODS: All consecutive patients undergoing elective endoscopic (n = 65) or awake (n = 10) tumor resection over a 3-year period between 1 December 2011 and 31 January 2015, under a single surgeon, were recruited. Data regarding their length of stay and outcomes were prospectively collated and analyzed. RESULTS: 66.7% of patients could be discharged safely within 1 postoperative day. Of the patients who stayed longer, 76% had a prolonged stay because of either social reasons or failing occupational therapy assessments. Only 6 cases (24%) of prolonged hospital admission were for medical reasons. Patients discharged within 1 day were no more likely to develop postoperative complications compared with those staying for longer (18% vs. 28%; odds ratio, 0.56; 95% confidence interval, 0.18-1.75; P = 0.21). The readmission rates were identical in both groups (16%). The only factor significantly affecting length of stay was World Health Organization performance score, both pre- and postoperative. CONCLUSIONS: An early discharge after endoscopic and awake craniotomy tumor resection is both safe and feasible for most patients and is not associated with increased postoperative morbidity. We recommend that all patients who have good baseline function be offered short stay surgery.


Asunto(s)
Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/cirugía , Sedación Consciente/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Neuroendoscopía/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Craneotomía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Prevalencia , Factores de Riesgo , Resultado del Tratamiento , Reino Unido , Adulto Joven
18.
World Neurosurg ; 82(6): 1198-208, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25084167

RESUMEN

OBJECTIVE: To report a minimally invasive, nontubular endoscopic technique to resect intraparenchymal brain tumors and assess the feasibility, safety, and surgical resection margins achievable by this novel technique. METHODS: Over a 21-month period, 48 patients underwent 50 consecutive endoscopic intraparenchymal tumor resections. Data on surgical morbidity and mortality and length of stay were collected prospectively. The percentage of surgical resection and residual tumor volumes were calculated using preoperative and postoperative volume computed tomography or magnetic resonance imaging. All tumors were resected through a 2-cm minicraniotomy using a high-definition rigid endoscope with a 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. RESULTS: Mean patient age was 53 years. There were 42 supratentorial (19 frontal, 17 temporal, 3 occipital, 1 parietal, and 2 parafalcine) tumors and 8 infratentorial tumors. Mean tumor volume was 41 cm(3). There were 12 metastases, 24 glioblastomas, 4 World Health Organization grade III gliomas, 5 World Health Organization grade I-II gliomas, 3 meningiomas, and 2 hemangioblastomas. On volumetric analysis, the overall mean percent resection was 96%. In 70% of cases, >95% resection was achieved; total resection was achieved in 48% of cases. At 30 days postoperatively, there was 1 new postoperative neurologic deficit; there were no deaths during this period. CONCLUSIONS: Our experience demonstrates that resection of intraparenchymal tumors using a minimally invasive endoscopic technique is technically feasible and safe, achieves good tumor resection margins, and has some potential advantages over a traditional microscopic technique.


Asunto(s)
Neoplasias Encefálicas/cirugía , Endoscopía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Neuroquirúrgicos/métodos , Adulto , Anciano , Pérdida de Sangre Quirúrgica , Endoscopía/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Metástasis de la Neoplasia , Neuroendoscopios , Neuronavegación/métodos , Procedimientos Neuroquirúrgicos/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
19.
Br J Neurosurg ; 28(5): 637-44, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24568533

RESUMEN

OBJECTIVES: Image-guided brain biopsy is an established method to obtain histopathological diagnosis and guide management for cerebral lesions. The study aimed to establish negative biopsy and symptomatic haemorrhage rates at a single centre, and to assess the influence of factors such as lesion location, final pathology and the use of intra-operative smears. METHODS: A retrospective analysis of all frame-based and frameless stereotactic biopsies carried out over 57 months from July 2006 to March 2011. RESULTS: A total of 351 biopsies were undertaken, 256 frame-based (73%) and 95 frameless (27%). Mean age was 57 years (range 18-87). Negative biopsy rate was 5.1%. There was a significantly greater negative biopsy rate in deep brain biopsies (p = 0.011) and in the cerebellum (p < 0.001). Intra-operative smear significantly reduced negative biopsy rates from 11.1% to 3.7% (p = 0.011). If repeat smear was requested, yet not provided, then the negative biopsy rate was 57.1% (p = 0.0085). The overall symptomatic haemorrhage rate was 3.7%. There was a significant increase in haemorrhage rate in deep versus superficial biopsies (p = 0.023) and a significantly greater haemorrhage rate in lymphoma biopsies (p = 0.015). There was no significant increase in haemorrhage rate in high-grade compared with low-grade tumour biopsies. Mortality rates at 7 and 30 days post-operatively were 0.6% and 1.7%, respectively, with mortality after 7 days unrelated to biopsy. CONCLUSION: We advocate intra-operative histopathological analysis to decrease negative biopsy rates and advise increased caution when undertaking biopsies of deep lesions or suspected lymphoma cases due to the potentially increased risk of haemorrhage.


Asunto(s)
Neoplasias Encefálicas/patología , Neuronavegación , Técnicas Estereotáxicas , Cirugía Asistida por Computador , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronavegación/métodos , Estudios Retrospectivos , Técnicas Estereotáxicas/instrumentación , Cirugía Asistida por Computador/métodos , Adulto Joven
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