98 research outputs found

    Movement correction and clinical implementation of wearable magnetoencephalography (MEG)

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    Magnetoencephalography (MEG) is the non-invasive measurement of magnetic fields due to neuronal current flow. The magnitude of the magnetic fields (10 fT to 1000 fT) is millions of times smaller than the Earth’s static field. Consequently, highly sensitive magnetic sensors are required for MEG. Until recently, MEG systems have been based on sensors requiring cryogenic cooling. Hardware limitations from this cooling have made MEG systems large, immobile and expensive. In recent years, Optically Pumped Magnetometers (OPMs) have become viable sensors with which to measure neuromagnetic fields. These can be placed directly on the scalp. This wearability means that the participant is no longer required to remain still and the cost of the system, both financial and in terms of space, is generally lower. The freedom of movement opens up new neuroscientific and clinical applications. However, this new system is not without limitations. Movement in particular leads to artefacts unlike those previously seen in MEG; the OPM properties (gain, sensitive axis orientation, phase) are dependent on the ambient magnetic field at the sensor, which changes with position. In this thesis, we look at the impact of movement on OPM based MEG (OP-MEG) and how it can be reduced. In Chapter 2, we look into the cause of movement artefacts in OP-MEG, by mapping the spatial variation in the background magnetic field in our OP-MEG system. We show that the field varies both spatially and temporally, and that by modelling it we can reduce the interference in an OP-MEG recording. In Chapters 3 and 4, we correct for this changing field in real-time, first in simulation and then empirically. Based on the simulation results, we updated our empirical method to remove reliance on recording the position of the participant and to minimise time delays in providing the correction. Finally, in Chapters 5 and 6, we record interictal (between seizure) and ictal (seizure) OP-MEG in patients with epilepsy, while considering the impact movement has on the recordings and interictal event detection

    Surgical treatment of drug-resistant focal epilepsy: selection, economic considerations and long-term outcomes

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    Epilepsy surgery can be an effective treatment for drug-resistant focal epilepsy, but requires careful selection of appropriate candidates to achieve optimal results and minimise the chance of adverse outcomes, including seizure recurrence. Long-term data on multimodal outcomes and a better appreciation of various factors influencing surgical suitability will help facilitate informed discussions between clinicians and prospective surgical candidates. This thesis includes a comprehensive analysis of a cohort of individuals who had epilepsy surgery at a tertiary neurosciences centre over the last 30 years, supplemented by data on individuals who completed presurgical evaluation at the same centre but did not proceed to surgical resection. An inability to localise the epileptogenic zone (EZ), multifocal epilepsy, or an individual choice not to have either intracranial electroencephalography or surgery were the most common reasons why people referred for presurgical evaluation did not proceed to a definitive resection. A predictive model based on demographic, imaging and electroclinical data was constructed to assist early discussions about surgical suitability. Those with normal MRI, extratemporal epilepsy and evidence of bilateral seizure onsets on video telemetry had an estimated 2.9% chance of proceeding to surgery, and people with a normal MRI brain invariably required intracranial EEG. Frontal lobe epilepsy surgery was safe and effective, with a long-term (median seven years) seizure freedom rate of 27%, and another 11% having auras only. Psychiatric comorbidity frequently improved postoperatively and paralleled seizure freedom. Focal MRI abnormality and fewer anti-seizure medications at the time of surgery could help predict a good outcome. In contrast, the site of resection and intracranial monitoring were not independently significant. Localisation of the EZ should rely on clinical features and multimodal investigation, as in our cohort frontal lobe semiology alone could correctly lateralise the EZ in only 77% and localise to a sublobar level in 52%. For those who completed presurgical evaluation but did not have surgery, under 5% had >12 months of seizure-freedom following the decision not to proceed, although a quarter had substantial improvement with further anti-seizure medication (ASM) or neurostimulation. Evaluation for epilepsy surgery was lengthy for individuals and costly for the public health system. Both duration and cost depended on what investigations were required and varied according to different routes through the presurgical pathway, especially the need for intracranial EEG. The median duration of evaluation was 29.7 months (IQR 18.6-44.1 months), with a median cost per person of £9,138 (IQR £6,984-£14,868). Approximately £123,500 was spent per additional person seizure-free

    Nuclear imaging for localization and surgical outcome prediction in epilepsy: A review of latest discoveries and future perspectives

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    BackgroundEpilepsy is one of the most common neurological disorders. Approximately, one-third of patients with epilepsy have seizures refractory to antiepileptic drugs and further require surgical removal of the epileptogenic region. In the last decade, there have been many recent developments in radiopharmaceuticals, novel image analysis techniques, and new software for an epileptogenic zone (EZ) localization.ObjectivesRecently, we provided the latest discoveries, current challenges, and future perspectives in the field of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) in epilepsy.MethodsWe searched for relevant articles published in MEDLINE and CENTRAL from July 2012 to July 2022. A systematic literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis was conducted using the keywords “Epilepsy” and “PET or SPECT.” We included both prospective and retrospective studies. Studies with preclinical subjects or not focusing on EZ localization or surgical outcome prediction using recently developed PET radiopharmaceuticals, novel image analysis techniques, and new software were excluded from the review. The remaining 162 articles were reviewed.ResultsWe first present recent findings and developments in PET radiopharmaceuticals. Second, we present novel image analysis techniques and new software in the last decade for EZ localization. Finally, we summarize the overall findings and discuss future perspectives in the field of PET and SPECT in epilepsy.ConclusionCombining new radiopharmaceutical development, new indications, new techniques, and software improves EZ localization and provides a better understanding of epilepsy. These have proven not to only predict prognosis but also to improve the outcome of epilepsy surgery

    RNA, the Epicenter of Genetic Information

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    The origin story and emergence of molecular biology is muddled. The early triumphs in bacterial genetics and the complexity of animal and plant genomes complicate an intricate history. This book documents the many advances, as well as the prejudices and founder fallacies. It highlights the premature relegation of RNA to simply an intermediate between gene and protein, the underestimation of the amount of information required to program the development of multicellular organisms, and the dawning realization that RNA is the cornerstone of cell biology, development, brain function and probably evolution itself. Key personalities, their hubris as well as prescient predictions are richly illustrated with quotes, archival material, photographs, diagrams and references to bring the people, ideas and discoveries to life, from the conceptual cradles of molecular biology to the current revolution in the understanding of genetic information. Key Features Documents the confused early history of DNA, RNA and proteins - a transformative history of molecular biology like no other. Integrates the influences of biochemistry and genetics on the landscape of molecular biology. Chronicles the important discoveries, preconceptions and misconceptions that retarded or misdirected progress. Highlights major pioneers and contributors to molecular biology, with a focus on RNA and noncoding DNA. Summarizes the mounting evidence for the central roles of non-protein-coding RNA in cell and developmental biology. Provides a thought-provoking retrospective and forward-looking perspective for advanced students and professional researchers

    Drug development progress in duchenne muscular dystrophy

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    Duchenne muscular dystrophy (DMD) is a severe, progressive, and incurable X-linked disorder caused by mutations in the dystrophin gene. Patients with DMD have an absence of functional dystrophin protein, which results in chronic damage of muscle fibers during contraction, thus leading to deterioration of muscle quality and loss of muscle mass over time. Although there is currently no cure for DMD, improvements in treatment care and management could delay disease progression and improve quality of life, thereby prolonging life expectancy for these patients. Furthermore, active research efforts are ongoing to develop therapeutic strategies that target dystrophin deficiency, such as gene replacement therapies, exon skipping, and readthrough therapy, as well as strategies that target secondary pathology of DMD, such as novel anti-inflammatory compounds, myostatin inhibitors, and cardioprotective compounds. Furthermore, longitudinal modeling approaches have been used to characterize the progression of MRI and functional endpoints for predictive purposes to inform Go/No Go decisions in drug development. This review showcases approved drugs or drug candidates along their development paths and also provides information on primary endpoints and enrollment size of Ph2/3 and Ph3 trials in the DMD space

    Molecular Targets of CNS Tumors

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    Molecular Targets of CNS Tumors is a selected review of Central Nervous System (CNS) tumors with particular emphasis on signaling pathway of the most common CNS tumor types. To develop drugs which specifically attack the cancer cells requires an understanding of the distinct characteristics of those cells. Additional detailed information is provided on selected signal pathways in CNS tumors

    Underlying Mechanisms of Epilepsy

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    This book is a very provocative and interesting addition to the literature on Epilepsy. It offers a lot of appealing and stimulating work to offer food of thought to the readers from different disciplines. Around 5% of the total world population have seizures but only 0.9% is diagnosed with epilepsy, so it is very important to understand the differences between seizures and epilepsy, and also to identify the factors responsible for its etiology so as to have more effective therapeutic regime. In this book we have twenty chapters ranging from causes and underlying mechanisms to the treatment and side effects of epilepsy. This book contains a variety of chapters which will stimulate the readers to think about the complex interplay of epigenetics and epilepsy

    Clinical Management and Evolving Novel Therapeutic Strategies for Patients with Brain Tumors

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    A dramatic increase in knowledge regarding the molecular biology of brain tumors has been established over the past few years, and this has lead to the development of novel therapeutic strategies for these patients. In this book a review of the options available for the clinical management of patients with these tumors are outlined. In addition advances in radiology both for pre-operative diagnostic purposes along with surgical planning are described. Furthermore a review of newer developments in chemotherapy along with the evolving field of photodynamic therapy both for intra-operative management and subsequent therapy is provided. A discussion of certain surgical management issues along with tumor induced epilepsy is included. Finally a discussion of the management of certain unique problems including brain metastases, brainstem glioma, central nervous system lymphoma along with issues involving patients with a brain tumor and pregnancy is provided
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