Is Mossy Fiber Sprouting a Potential Therapeutic Target for Epilepsy?

Mesial temporal lobe epilepsy (MTLE) caused by hippocampal sclerosis is one of the most frequent focal epilepsies in adults. It is characterized by focal seizures that begin in the hippocampus, sometimes spread to the insulo-perisylvian regions and may progress to secondary generalized seizures. Morphological alterations in hippocampal sclerosis are well defined. Among them, hippocampal sclerosis is characterized by prominent cell loss in the hilus and CA1, and abnormal mossy fiber sprouting (granular cell axons) into the dentate gyrus inner molecular layer. In this review, we highlight the role of mossy fiber sprouting in seizure generation and hippocampal excitability and discuss the response of alternative treatment strategies in terms of MFS and spontaneous recurrent seizures in models of TLE (temporal lobe epilepsy)

Peripheral leukocyte profile in people with temporal lobe epilepsy reflects the associated proinflammatory state

INTRODUCTION: Markers of low-grade peripheral inflammation have been reported amongst people with epilepsy. The mechanisms underlying this phenomenon are unknown. We attempted to characterize peripheral immune cells and their activation status in people with temporal lobe epilepsy (TLE) and healthy controls. METHODS AND RESULTS: Twenty people with TLE and 19 controls were recruited, and peripheral blood lymphocyte and monocyte subsets evaluated ex vivo by multi-color flow cytometry. People with TLE had higher expression of HLA-DR, CD69, CTLA-4, CD25, IL-23R, IFN-γ, TNF and IL-17 in CD4(+) lymphocytes than controls. Granzyme A, CTLA-4, IL-23R and IL-17 expression was also elevated in CD8(+) T cells from people with TLE. Frequency of HLA-DR in CD19(+) B cells and regulatory T cells CD4(+)CD25(+)Foxp3(+) producing IL-10 was higher in TLE when compared with controls. A negative correlation between CD4(+) expressing co-stimulatory molecules (CD69, CD25 and CTLA-4) with age at onset of seizures was found. The frequency of CD4(+)CD25(+)Foxp3(+) cells was also positively correlated with age at onset of seizures. CONCLUSION: Immune cells of people with TLE show an activation profile, mainly in effector T cells, in line with the low-grade peripheral inflammation

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and the brief but decorated clinical usage of chelated manganese compound mangafodipir in humans

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and the brief but decorated clinical usage of chelated manganese compound mangafodipir in humans

Underlying Mechanisms of Epilepsy

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

Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration

Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current in vivo investigative uses of MEMRI in CNS investigations and the brief but decorated clinical usage of chelated manganese compound mangafodipir in humans

Manganese Enhanced MRI for Use in Studying Neurodegenerative Diseases

MRI has been extensively used in neurodegenerative disorders, such as Alzheimer’s disease (AD), frontal-temporal dementia (FTD), mild cognitive impairment (MCI), Parkinson’s disease (PD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). MRI is important for monitoring the neurodegenerative components in other diseases such as epilepsy, stroke and multiple sclerosis (MS). Manganese enhanced MRI (MEMRI) has been used in many preclinical studies to image anatomy and cytoarchitecture, to obtain functional information in areas of the brain and to study neuronal connections. This is due to Mn2+ ability to enter excitable cells through voltage gated calcium channels and be actively transported in an anterograde manner along axons and across synapses. The broad range of information obtained from MEMRI has led to the use of Mn2+ in many animal models of neurodegeneration which has supplied important insight into brain degeneration in preclinical studies. Here we provide a brief review of MEMRI use in neurodegenerative diseases and in diseases with neurodegenerative components in animal studies and discuss the potential translation of MEMRI to clinical use in the future

Neuroimaging - Clinical Applications

Modern neuroimaging tools allow unprecedented opportunities for understanding brain neuroanatomy and function in health and disease. Each available technique carries with it a particular balance of strengths and limitations, such that converging evidence based on multiple methods provides the most powerful approach for advancing our knowledge in the fields of clinical and cognitive neuroscience. The scope of this book is not to provide a comprehensive overview of methods and their clinical applications but to provide a "snapshot" of current approaches using well established and newly emerging techniques

Imaging functional and structural networks in the human epileptic brain

Epileptic activity in the brain arises from dysfunctional neuronal networks involving cortical and subcortical grey matter as well as their connections via white matter fibres. Physiological brain networks can be affected by the structural abnormalities causing the epileptic activity, or by the epileptic activity itself. A better knowledge of physiological and pathological brain networks in patients with epilepsy is critical for a better understanding the patterns of seizure generation, propagation and termination as well as the alteration of physiological brain networks by a chronic neurological disorder. Moreover, the identification of pathological and physiological networks in an individual subject is critical for the planning of epilepsy surgery aiming at resection or at least interruption of the epileptic network while sparing physiological networks which have potentially been remodelled by the disease. This work describes the combination of neuroimaging methods to study the functional epileptic networks in the brain, structural connectivity changes of the motor networks in patients with localisation-related or generalised epilepsy and finally structural connectivity of the epileptic network. The combination between EEG source imaging and simultaneous EEG-fMRI recordings allowed to distinguish between regions of onset and propagation of interictal epileptic activity and to better map the epileptic network using the continuous activity of the epileptic source. These results are complemented by the first recordings of simultaneous intracranial EEG and fMRI in human. This whole-brain imaging technique revealed regional as well as distant haemodynamic changes related to very focal epileptic activity. The combination of fMRI and DTI tractography showed subtle changes in the structural connectivity of patients with Juvenile Myoclonic Epilepsy, a form of idiopathic generalised epilepsy. Finally, a combination of intracranial EEG and tractography was used to explore the structural connectivity of epileptic networks. Clinical relevance, methodological issues and future perspectives are discussed

Diseases of the Brain, Head and Neck, Spine 2020–2023

This open access book offers an essential overview of brain, head and neck, and spine imaging. Over the last few years, there have been considerable advances in this area, driven by both clinical and technological developments. Written by leading international experts and teachers, the chapters are disease-oriented and cover all relevant imaging modalities, with a focus on magnetic resonance imaging and computed tomography. The book also includes a synopsis of pediatric imaging. IDKD books are rewritten (not merely updated) every four years, which means they offer a comprehensive review of the state-of-the-art in imaging. The book is clearly structured and features learning objectives, abstracts, subheadings, tables and take-home points, supported by design elements to help readers navigate the text. It will particularly appeal to general radiologists, radiology residents, and interventional radiologists who want to update their diagnostic expertise, as well as clinicians from other specialties who are interested in imaging for their patient care