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OBJECTIVE: The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy. METHODS: Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4). RESULTS: Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002). INTERPRETATION: This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138-1148.
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Eletroencefalografia , Epilepsia do Lobo Frontal , Convulsões , Humanos , Criança , Masculino , Feminino , Epilepsia do Lobo Frontal/cirurgia , Epilepsia do Lobo Frontal/fisiopatologia , Epilepsia do Lobo Frontal/diagnóstico , Pré-Escolar , Eletroencefalografia/métodos , Estudos Retrospectivos , Adolescente , Convulsões/fisiopatologia , Convulsões/cirurgia , Convulsões/diagnóstico , Lactente , Lobo Frontal/fisiopatologia , Gravação em Vídeo/métodosRESUMO
Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. ßFSIQ = -1.9, SEFSIQ = 0.3, PFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%-43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. rrb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. ßFSIQ = 0.9, SEFSIQ = 0.3, PFSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.
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Epilepsia Resistente a Medicamentos , Testes Neuropsicológicos , Humanos , Feminino , Criança , Masculino , Adolescente , Estudos Retrospectivos , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia/cirurgia , Epilepsia/psicologia , Estudos de Coortes , Testes de Inteligência , Procedimentos NeurocirúrgicosRESUMO
BACKGROUND: Malformations of cortical development (MCDs) in children with focal epilepsy pose significant diagnostic challenges, and a precise radiological diagnosis is crucial for surgical planning. New MRI sequences and the use of artificial intelligence (AI) algorithms are considered very promising in this regard, yet studies evaluating the relative contribution of each diagnostic technique are lacking. METHODS: The study was conducted using a dedicated "EPI-MCD MR protocol" with a 3 Tesla MRI scanner in patients with focal epilepsy and previously negative MRI. MRI sequences evaluated included 3D FLAIR, 3D T1 MPRAGE, T2 Turbo Spin Echo (TSE), 3D T1 MP2RAGE, and Arterial Spin Labelling (ASL). Two paediatric neuroradiologists scored each sequence for localisation and extension of the lesion. The MELD-FCD AI classifier's performance in identifying pathological findings was also assessed. We only included patients where a diagnosis of MCD was subsequently confirmed on histology and/or sEEG. RESULTS: The 3D FLAIR sequence showed the highest yield in detecting epileptogenic lesions, with 3D T1 MPRAGE, T2 TSE, and 3D T1 MP2RAGE sequences showing moderate to low yield. ASL was the least useful. The MELD-FCD classifier achieved a 69.2% true positive rate. In one case, MELD identified a subtle area of cortical dysplasia overlooked by the neuroradiologists, changing the management of the patient. CONCLUSIONS: The 3D FLAIR sequence is the most effective in the MRI-based diagnosis of subtle epileptogenic lesions, outperforming other sequences in localisation and extension. This pilot study emphasizes the importance of careful assessment of the value of additional sequences.
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AIM: To evaluate a lesion detection algorithm designed to detect focal cortical dysplasia (FCD) in children undergoing stereoelectroencephalography (SEEG) as part of their presurgical evaluation for drug-resistant epilepsy. METHOD: This was a prospective, single-arm, interventional study (Idea, Development, Exploration, Assessment, and Long-Term Follow-Up phase 1/2a). After routine SEEG planning, structural magnetic resonance imaging sequences were run through an FCD lesion detection algorithm to identify putative clusters. If the top three clusters were not already sampled, up to three additional SEEG electrodes were added. The primary outcome measure was the proportion of patients who had additional electrode contacts in the SEEG-defined seizure-onset zone (SOZ). RESULTS: Twenty patients (median age 12 years, range 4-18 years) were enrolled, one of whom did not undergo SEEG. Additional electrode contacts were part of the SOZ in 1 out of 19 patients while 3 out of 19 patients had clusters that were part of the SOZ but they were already implanted. A total of 16 additional electrodes were implanted in nine patients and there were no adverse events from the additional electrodes. INTERPRETATION: We demonstrate early-stage prospective clinical validation of a machine learning lesion detection algorithm used to aid the identification of the SOZ in children undergoing SEEG. We share key lessons learnt from this evaluation and emphasize the importance of robust prospective evaluation before routine clinical adoption of such algorithms. WHAT THIS PAPER ADDS: The focal cortical dysplasia detection algorithm collocated with the seizure-onset zone (SOZ) in 4 out of 19 patients. The algorithm changed the resection boundaries in 1 of 19 patients undergoing stereoelectroencephalography for drug-resistant epilepsy. The patient with an altered resection due to the algorithm was seizure-free 1 year after resective surgery. Overall, the algorithm did not increase the proportion of patients in whom SOZ was identified.
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Epilepsia Resistente a Medicamentos , Epilepsia , Displasia Cortical Focal , Criança , Humanos , Pré-Escolar , Adolescente , Eletroencefalografia/métodos , Estudos Retrospectivos , Epilepsia/diagnóstico , Epilepsia/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , ConvulsõesRESUMO
BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).
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Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Hematoma Subdural Crônico/tratamento farmacológico , Administração Oral , Idoso , Terapia Combinada , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Pessoas com Deficiência , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hematoma Subdural Crônico/complicações , Hematoma Subdural Crônico/mortalidade , Hematoma Subdural Crônico/cirurgia , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Reoperação/estatística & dados numéricos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. METHODS: We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. RESULTS: A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. SIGNIFICANCE: Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful.
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Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Feminino , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia/diagnóstico , Epilepsia/genética , Epilepsia/cirurgia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/cirurgia , Testes GenéticosRESUMO
OBJECTIVE: The accurate prediction of seizure freedom after epilepsy surgery remains challenging. We investigated if (1) training more complex models, (2) recruiting larger sample sizes, or (3) using data-driven selection of clinical predictors would improve our ability to predict postoperative seizure outcome using clinical features. We also conducted the first substantial external validation of a machine learning model trained to predict postoperative seizure outcome. METHODS: We performed a retrospective cohort study of 797 children who had undergone resective or disconnective epilepsy surgery at a tertiary center. We extracted patient information from medical records and trained three models-a logistic regression, a multilayer perceptron, and an XGBoost model-to predict 1-year postoperative seizure outcome on our data set. We evaluated the performance of a recently published XGBoost model on the same patients. We further investigated the impact of sample size on model performance, using learning curve analysis to estimate performance at samples up to N = 2000. Finally, we examined the impact of predictor selection on model performance. RESULTS: Our logistic regression achieved an accuracy of 72% (95% confidence interval [CI] = 68%-75%, area under the curve [AUC] = .72), whereas our multilayer perceptron and XGBoost both achieved accuracies of 71% (95% CIMLP = 67%-74%, AUCMLP = .70; 95% CIXGBoost own = 68%-75%, AUCXGBoost own = .70). There was no significant difference in performance between our three models (all p > .4) and they all performed better than the external XGBoost, which achieved an accuracy of 63% (95% CI = 59%-67%, AUC = .62; pLR = .005, pMLP = .01, pXGBoost own = .01) on our data. All models showed improved performance with increasing sample size, but limited improvements beyond our current sample. The best model performance was achieved with data-driven feature selection. SIGNIFICANCE: We show that neither the deployment of complex machine learning models nor the assembly of thousands of patients alone is likely to generate significant improvements in our ability to predict postoperative seizure freedom. We instead propose that improved feature selection alongside collaboration, data standardization, and model sharing is required to advance the field.
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Epilepsia , Criança , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia/diagnóstico , Epilepsia/cirurgia , Convulsões/diagnóstico , Convulsões/cirurgia , Aprendizado de MáquinaRESUMO
Epilepsy surgery is an established safe and effective treatment for selected candidates with drug-resistant epilepsy. In this opinion piece, we outline the clinical and experimental evidence for selectively considering epilepsy surgery prior to drug resistance. Our rationale for expedited surgery is based on the observations that (i) a high proportion of patients with lesional epilepsies (e.g. focal cortical dysplasia, epilepsy-associated tumours) will progress to drug resistance; (ii) surgical treatment of these lesions, especially in non-eloquent areas of brain, is safe; and (iii) earlier surgery may be associated with better seizure outcomes. Potential benefits beyond seizure reduction or elimination include less exposure to antiseizure medications, which may lead to improved developmental trajectories in children and optimize long-term neurocognitive outcomes and quality of life. Further, there exists emerging experimental evidence that brain network dysfunction exists at the onset of epilepsy, where continuing dysfunctional activity could exacerbate network perturbations. This in turn could lead to expanded seizure foci and contribution to the comorbidities associated with epilepsy. Taken together, we rationalize that epilepsy surgery, in carefully selected cases, may be considered prior to drug resistance. Last, we outline the path forward, including the challenges associated with developing the evidence base and implementing this paradigm into clinical care.
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Encefalopatias , Epilepsia Resistente a Medicamentos , Epilepsia , Criança , Humanos , Qualidade de Vida , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Epilepsia/complicações , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/complicações , Convulsões/complicações , Resultado do Tratamento , Encefalopatias/complicações , Resistência a Medicamentos , Estudos RetrospectivosRESUMO
One outstanding challenge for machine learning in diagnostic biomedical imaging is algorithm interpretability. A key application is the identification of subtle epileptogenic focal cortical dysplasias (FCDs) from structural MRI. FCDs are difficult to visualize on structural MRI but are often amenable to surgical resection. We aimed to develop an open-source, interpretable, surface-based machine-learning algorithm to automatically identify FCDs on heterogeneous structural MRI data from epilepsy surgery centres worldwide. The Multi-centre Epilepsy Lesion Detection (MELD) Project collated and harmonized a retrospective MRI cohort of 1015 participants, 618 patients with focal FCD-related epilepsy and 397 controls, from 22 epilepsy centres worldwide. We created a neural network for FCD detection based on 33 surface-based features. The network was trained and cross-validated on 50% of the total cohort and tested on the remaining 50% as well as on 2 independent test sites. Multidimensional feature analysis and integrated gradient saliencies were used to interrogate network performance. Our pipeline outputs individual patient reports, which identify the location of predicted lesions, alongside their imaging features and relative saliency to the classifier. On a restricted 'gold-standard' subcohort of seizure-free patients with FCD type IIB who had T1 and fluid-attenuated inversion recovery MRI data, the MELD FCD surface-based algorithm had a sensitivity of 85%. Across the entire withheld test cohort the sensitivity was 59% and specificity was 54%. After including a border zone around lesions, to account for uncertainty around the borders of manually delineated lesion masks, the sensitivity was 67%. This multicentre, multinational study with open access protocols and code has developed a robust and interpretable machine-learning algorithm for automated detection of focal cortical dysplasias, giving physicians greater confidence in the identification of subtle MRI lesions in individuals with epilepsy.
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Epilepsias Parciais , Epilepsia , Malformações do Desenvolvimento Cortical , Humanos , Estudos Retrospectivos , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Epilepsia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Aprendizado de Máquina , Epilepsias Parciais/diagnóstico por imagemRESUMO
OBJECTIVE: Leptomeningeal metastasis (LM) is associated with altered CSF flow dynamics in 50%-70% of patients. Approximately 1%-5% of patients develop symptomatic LM-associated hydrocephalus (LM-H), which adversely impacts quality of life (QOL), functional status, and overall survival (OS). There is equipoise for CSF diversion procedures in LM-H. This systematic review and meta-analysis aimed to assess the effect of CSF diversion on OS and QOL in this context. METHODS: This systematic review was conducted according to the PRISMA guidelines. PubMed/Medline, Embase, Web of Science, and Scopus were searched for articles that evaluated the role of CSF diversion for LM-H due to systemic cancer in adult patients. A meta-analysis was conducted using random effects models, with mean differences and 95% CIs reported. Bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. RESULTS: Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate HRs for median OS, suggesting no significant effect of shunting on OS (pooled HR 0.42, 95% CI 0.09-1.94, p = 0.27). A difference between preoperative and postoperative Karnofsky Performance Status of mean 17.6 points (95% CI 10.44-24.68, p < 0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67%-100% was observed, with high rates of improvement for headaches and nausea and lower rates for cranial nerve palsies. Complication rates across 9 studies ranged from 0% to 21.1%. CONCLUSIONS: Based on the present findings, shunting does not improve OS but does relieve symptoms, suggesting that individuals who exhibit certain symptoms should be considered for CSF diversion. The present findings prompt the generation of a standardized decision-making tool and a critical analysis of the individual patient risk-benefit ratio. Implementation of these will optimize surgical management of LM-H patients.
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Hidrocefalia , Neoplasias , Humanos , Adulto , Qualidade de Vida , Hidrocefalia/etiologia , Neoplasias/complicações , Procedimentos Neurocirúrgicos/efeitos adversos , Cefaleia/cirurgiaRESUMO
OBJECTIVE: Little is known about the impact of academic training on Neurosurgery in the United Kingdom (UK). The aim was to understand the early career clinical and research training journeys of potential future clinical academics, with a view to informing future policy and strategy to improve career development for academic neurosurgical trainees and consultants in the UK. METHODS: An online survey from the Society of British Neurological Surgeons (SBNS) academic committee was distributed to both the SBNS and British Neurosurgical Trainee Association (BNTA) mailing lists in early 2022. Neurosurgical trainees for any period between 2007 and 2022 or who had done any dedicated academic or clinical academic placement were encouraged to complete the survey. RESULTS: Sixty responses were received. Six (10%) were females and fifty-four (90%) were males. At the time of response, nine (15.0%) were clinical trainees, four (6.7%) were Academic Clinical Fellows (ACF), six (10.0%) were Academic Clinical Lecturers (ACL), four (6.7%) were post-CCT fellows, eight (13.3%) were NHS consultants, eight (13.3%) were academic consultants, eighteen (30.0%) were out of the programme (OOP) pursuing a PhD potentially returning to training, whilst three (5.0%) had left neurosurgery training entirely and no longer performing clinical neurosurgery. The mentorship was sought in most programmes, which tended to be informal. Self-reported success on a scale of 0 to 10 with 10 being the most successful, was greatest in the MD and the "Other research degree/fellowship group" which does not include a PhD. There was a significant positive association between completing a PhD and having an academic consultant appointment (Pearson Chi-Square = 5.33, p = 0.021). CONCLUSIONS: This study provides a snapshot to better understand the opinions of academic training in neurosurgery within the UK. Establishing clear, modifiable, and achievable goals, as well as providing tools for research success, may contribute to the success of this nationwide academic training.
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OBJECTIVE: To extend the IDEAL framework for device innovation, IDEAL-D, to include the preclinical stage of development (stage 0). BACKGROUND: In previous work, the IDEAL collaboration has proposed frameworks for new surgical techniques and complex therapeutic technologies, the central tenet being that development and evaluation can and should proceed together in an ordered and logical manner that balances innovation and safety. METHODS: Following agreement at the IDEAL Collaboration Council, a multidisciplinary working group was formed comprising 12 representatives from healthcare, academia, industry, and a patient advocate. The group conducted a series of discussions following the principles used in the development of the original IDEAL framework. Importantly, IDEAL aims for maximal transparency, optimal validity in the evaluation of primary effects, and minimization of potential risk to patients or others. The proposals were subjected to further review and editing by members of the IDEAL Council before a final consensus version was adopted. RESULTS: In considering which studies are required before a first-in-human study, we have: (1) classified devices according to what they do and the risks they carry, (2) classified studies according to what they show about the device, and (3) made recommendations based on the principle that the more invasive and high risk a device is, the greater proof required of their safety and effectiveness before progression to clinical studies (stage 1). CONCLUSIONS: The proposed recommendations for preclinical evaluation of medical devices represent a proportionate and pragmatic approach that balances the de-risking of first-in-human translational studies against the benefits of rapid translation of new devices into clinical practice.
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Equipamentos e Provisões , Pesquisa Translacional Biomédica , Desenho de Equipamento , Segurança de Equipamentos , Equipamentos e Provisões/classificação , Humanos , Medição de RiscoRESUMO
OBJECTIVE: Drug-resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome. METHODS: The MELD (Multi-centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging-based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom. RESULTS: FCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%. SIGNIFICANCE: FCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data-driven atlases and predictive models are essential for evidence-based, precision medicine and risk counseling in epilepsy.
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Epilepsia Resistente a Medicamentos , Epilepsia , Malformações do Desenvolvimento Cortical , Criança , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/diagnóstico por imagem , Epilepsia/etiologia , Epilepsia/cirurgia , Liberdade , Humanos , Imageamento por Ressonância Magnética , Malformações do Desenvolvimento Cortical/complicações , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/cirurgia , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/etiologia , Convulsões/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Subdural empyema is a neurosurgical emergency requiring prompt diagnosis and treatment. There is a debate between the benefits and risks of starting early antibiotics prior to surgical drainage as this is purported to reduce the rate of microbiological diagnosis. Here, we describe our experience of treating this potentially life-threatening condition, advocating for the early commencement of antibiotics and importance of source control in its treatment. METHODS: Retrospective review of a prospectively collected electronic departmental database included all patients who were admitted to our unit with a diagnosis of subdural empyema over an 11-year period (2008-2018). Basic demographic data were collected. Further data pertaining to mode of presentation, surgical approach, causative organism, post-operative antibiotic regime, anti-seizure medications, length of hospital stay, further surgery, and neurological outcomes were extracted. RESULTS: Thirty-six children underwent 44 operations for subdural empyema at our institution during the study period. Median age was 11.0 (range 0.2-15.8); 47.2% (17/36) were female. Over time, there was decreasing use of burr holes and increasing use of craniectomy as the index surgery. Using a combination of extended culture and polymerase chain reaction, a microbiological diagnosis was achieved in all 36 cases; the commonest causative microorganism was of the Streptococcus anginosus group of bacteria. Seven patients underwent repeat surgery, and 4 patients underwent a concurrent ENT procedure. No risk factors were significant in predicting the likelihood of re-operation (location of subdural empyema, age, index surgery type, inflammatory markers, concurrent ENT procedure, and microorganism) although it was notable that none of the patients undergoing a concurrent ENT procedure underwent repeat surgery (p = 0.29). Median length of stay was 12 days (range 3-74), and there were no inpatient or procedure-related mortalities. Clinical outcomes were good with 94.4% (34/36) categorized as modified Rankin Scale 0-3 at discharge and there were 2 cranioplasty-related complications. CONCLUSIONS: We observed an evolution of practice from limited surgical approaches towards more extensive index surgery over the study period. Given that a microorganism was isolated in all cases using a comprehensive approach, initiation of antibiotic therapy should not be delayed on presentation. Concurrent ENT surgery may be an important factor in providing aggressive source control thereby reducing the need for repeat surgery.
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Empiema Subdural , Antibacterianos/uso terapêutico , Criança , Craniotomia , Empiema Subdural/tratamento farmacológico , Empiema Subdural/cirurgia , Feminino , Humanos , Reoperação , Estudos RetrospectivosRESUMO
OBJECTIVE: Entrance to neurosurgical training is highly competitive. Without proper advice, information and opportunities, talented individuals may be dissuaded from applying. The Neurology and Neurosurgery Interest Group (NANSIG) organises a Careers Day in Neurosurgery every year. Our objective was to assess the overall utility of a neurosurgery careers day and the perceived factors that attract and detract from the specialty, from attendees of the ninth annual neurosurgery careers day. METHODS: Eighteen-item pre-conference and 19-item post-conference questionnaires were disseminated electronically to conference attendees. Questions aimed to capture: (i) baseline demographics; (ii) previous experience and exposure in neurosurgery; (iii) interest in neurosurgery; (iv) understanding training and a career in neurosurgery; (v) perceived factors of attraction and dissuasion of neurosurgery; and (vi) perceived value, quality and educational purpose of the conference. RESULTS: In total, 77 delegates attended the careers day. Most did not have a formal neurosurgical rotation during medical school (24.7%, n = 19), but almost half had gained neurosurgical experience and presented research work. The careers day increased knowledge of the neurosurgical application process (median Likert score 3/5 to 4/5, p < 0.01), duration of training (72.7-88.3%), and desire to pursue a career in neurosurgery (75.3-81.8%). The most commonly reported factors attracting delegates to neurosurgery were interest in neuroanatomy (80.5%, n = 62), practical skills (64.9%, n = 50), and impact on patients (62.3%, n = 48). The most common dissuasive factors were competition to entry (64.9%, n = 50), long working hours (40.3%, n = 31), and other career interests (35.1%, n = 27). Almost all would recommend the event to a colleague (94.9%, n = 73). CONCLUSIONS: Formal undergraduate exposure to neurosurgery is limited. Neurosurgery careers days increase awareness and understanding of the application process and improve interest in a selected cohort. The factors attracting applicants to neurosurgery remain practical links to neuroanatomy, opportunities in neurosurgery for innovation and research, and direct impact on patients.
Assuntos
Neurologia , Neurocirurgia , Estudantes de Medicina , Humanos , Neurocirurgia/educação , Escolha da Profissão , Opinião Pública , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.
Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Malformações do Desenvolvimento Cortical , Idoso , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsia/cirurgia , Estudos de Viabilidade , Humanos , Lactente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Advances in medical care have led to more premature babies surviving the neonatal period. In these babies, germinal matrix haemorrhage (GMH), intraventricular haemorrhage (IVH) and posthaemorrhagic ventricular dilatation (PHVD) are the most important determinants of long-term cognitive and developmental outcomes. In this review, we discuss current neurosurgical management of IVH and PHVD, including the importance of early diagnosis of PHVD, thresholds for intervention, options for early management through the use of temporising measures and subsequent definitive CSF diversion. We also discuss treatment options for the evolving paradigm to manage intraventricular blood and its breakdown products. We review the evidence for techniques such as drainage, irrigation, fibrinolytic therapy (DRIFT) and neuroendoscopic lavage in the context of optimising cognitive, neurodevelopmental and quality of life outcomes in these premature infants.
Assuntos
Doenças do Prematuro , Qualidade de Vida , Hemorragia Cerebral/complicações , Hemorragia Cerebral/terapia , Ventrículos Cerebrais/diagnóstico por imagem , Ventrículos Cerebrais/cirurgia , Dilatação , Dilatação Patológica , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/terapiaRESUMO
PURPOSE: This retrospective cohort study aimed to investigate the surgical and neurodevelopmental outcomes (NDO) of infant hydrocephalus. We also sought to determine whether these outcomes are disproportionately poorer in post-haemorrhagic hydrocephalus (PHH) compared to other causes of infant hydrocephalus. METHODS: A review of all infants with hydrocephalus who had ventriculoperitoneal (VP) shunts inserted at Great Ormond Street Hospital (GOSH) from 2008 to 2018 was performed. Demographic, surgical, neurodevelopmental, and other clinical data extracted from electronic patient notes were analysed by aetiology. Shunt survival, NDO, cerebral palsy (CP), epilepsy, speech delay, education, behavioural disorders, endocrine dysfunction, and mortality were evaluated. RESULTS: A total of 323 infants with median gestational age of 37.0 (23.29-42.14) weeks and birthweight of 2640 g (525-4684 g) were evaluated. PHH was the most common aetiology (31.9%) and was associated with significantly higher 5-year shunt revision rates, revisions beyond a year, and median number of revisions than congenital or "other" hydrocephalus (all p < 0.02). Cox regression demonstrated poorest shunt survival in PHH, related to gestational age at birth and corrected age at shunt insertion. PHH also had the highest rate of severe disabilities, increasing with age to 65.0% at 10 years, as well as the highest CP rate; only genetic hydrocephalus had significantly higher endocrine dysfunction (p = 0.01) and mortality rates (p = 0.04). CONCLUSIONS: Infants with PHH have poorer surgical and NDO compared to all other aetiologies, except genetic hydrocephalus. Research into measures of reducing neurodisability following PHH is urgently required. Long-term follow-up is essential to optimise support and outcomes.
Assuntos
Hidrocefalia , Doenças do Prematuro , Idoso , Hemorragia Cerebral/cirurgia , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Doenças do Prematuro/cirurgia , Estudos Retrospectivos , Derivação VentriculoperitonealRESUMO
OBJECTIVE: This retrospective, cross-sectional study evaluated the feasibility and potential benefits of incorporating deep-learning on structural magnetic resonance imaging (MRI) into planning stereoelectroencephalography (sEEG) implantation in pediatric patients with diagnostically complex drug-resistant epilepsy. This study aimed to assess the degree of colocalization between automated lesion detection and the seizure onset zone (SOZ) as assessed by sEEG. METHODS: A neural network classifier was applied to cortical features from MRI data from three cohorts. (1) The network was trained and cross-validated using 34 patients with visible focal cortical dysplasias (FCDs). (2) Specificity was assessed in 20 pediatric healthy controls. (3) Feasibility of incorporation into sEEG implantation plans was evaluated in 34 sEEG patients. Coordinates of sEEG contacts were coregistered with classifier-predicted lesions. sEEG contacts in seizure onset and irritative tissue were identified by clinical neurophysiologists. A distance of <10 mm between SOZ contacts and classifier-predicted lesions was considered colocalization. RESULTS: In patients with radiologically defined lesions, classifier sensitivity was 74% (25/34 lesions detected). No clusters were detected in the controls (specificity = 100%). Of the total 34 sEEG patients, 21 patients had a focal cortical SOZ, of whom eight were histopathologically confirmed as having an FCD. The algorithm correctly detected seven of eight of these FCDs (86%). In patients with histopathologically heterogeneous focal cortical lesions, there was colocalization between classifier output and SOZ contacts in 62%. In three patients, the electroclinical profile was indicative of focal epilepsy, but no SOZ was localized on sEEG. In these patients, the classifier identified additional abnormalities that had not been implanted. SIGNIFICANCE: There was a high degree of colocalization between automated lesion detection and sEEG. We have created a framework for incorporation of deep-learning-based MRI lesion detection into sEEG implantation planning. Our findings support the prospective evaluation of automated MRI analysis to plan optimal electrode trajectories.
Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Técnicas Estereotáxicas , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos RetrospectivosRESUMO
Hinge craniotomy (HC) is a technique that allows for a degree of decompression whilst retaining the bone flap in situ, in a 'floating' or 'hinged' fashion. This provides expansion potential for ensuing cerebral oedema whilst obviating the need for cranioplasty in the future. The exact indications, technique and outcomes of this procedure have yet to be determined, but it is likely that HC provides an alternative technique to decompressive craniectomy (DC) in certain contexts. The primary objective was to collate and describe the current evidence base for HC, including perioperative parameters, functional outcomes and complications. The secondary objective was to identify current nomenclature, operative technique and operative decision-making. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Fifteen studies totalling 283 patients (mean age 45.1 and M:F 199:46) were included. There were 12 different terms for HC. The survival rate of the cohort was 74.6% (n = 211). Nine patients (3.2%) required subsequent formal DC. Six studies compared HC to DC following traumatic brain injury (TBI) and stroke, finding at least equivalent control of intracranial pressure (ICP). These studies also reported reduced rates of complications, including infection, in HC compared to DC. We have described the current evidence base of HC. There is no evidence of substantially worse outcomes compared to DC, although no randomised trials were identified. Eventually, a randomised trial will be useful to determine if HC should be offered as first-line treatment when indicated.