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While inflammatory diseases affecting the CNS can produce a huge range of symptoms, depending on the exact nature of the disease process, the range of therapeutic options in these conditions is rather limited. Almost all the available treatments depend on some form of suppression of immunological function. These have been explored to the greatest extent in the treatment of multiple sclerosis, so the present account focuses on this disease, and it mentions other inflammatory conditions under the headings of the various types of available therapies.

This chapter discusses axonal regeneration in the adult mammalian central nervous system (CNS). In contrast to the situation in the peripheral nervous system (PNS), where injured axons often regenerate successfully over long distances, axonal regeneration is minimal or absent in the adult mammalian CNS. Therefore, CNS trauma often results in severe and permanent deficits.

This chapter shows the disease-specific, individual, and finely tuned reaction pattern of astrocytes and microglia during central nervous system (CNS) infections and their contribution to the intracerebral immune response. While both soluble mediators and the induction and/or upregulation of immunologically relevant cell surface molecules contribute to elimination of offending pathogens, microglia also serve an immunoregulatory function in order to minimize damage and destruction of vulnerable brain tissue. However, while these various components of the immune reaction serve a protective function, it is also evident that, depending on the underlying pathology, reactions of microglia and astrocytes may also be detrimental, as antibacterial effector molecules may also be neurotoxic and thereby contribute to neuronal damage, apoptosis, and, ultimately, long-term neurological sequelae.

This chapter presents an autobiography of Leslie L. Iversen. Iversen has been at the forefront of research on neurotransmitters and neuropeptides and understanding the mode of action of CNS drugs. He was among the first to describe the detailed properties and pharmacological specificity of the noradrenaline transporter (NAT) in sympathetic nerves and brain, and he helped to strengthen the concept of antipsychotic drugs as dopamine receptor antagonists. He participated in the first demonstration of the release of GABA on activation of an inhibitory synapse, and was the first to describe GABA uptake into inhibitory nerve endings in mammalian brain. His early years, career and achievements are discussed.

This chapter describes the efforts that have been made to date to persuade axons in the CNS to regrow, and the resulting re-innervation of terminal structures and behavioural recovery. The success or failure of axon regeneration depends on a balance of positive and negative factors. On the one hand, the CNS environment produces several molecules that are inhibitory to growth, many of which increase following injury, and on the other hand, CNS axons are attempting with variable vigour to regrow through this inhibitory environment. It follows that if one wishes to encourage axon regeneration, one might do so either by making the CNS environment less inhibitory, or by making the axons better able to regrow.

This chapter discusses the central nervous system (CNS) and the malignant tumours prevalent in this region of the body. Primary tumours of the central nervous system are rare, but they are more common than primary intracerebral tumours. Cerebral metastases account for 30 per cent in children. And overall, 80 per cent of the tumours in the CNS occur within the brain, while the remaining 20 per cent occur within the spinal cord. The common intracranial tumours in children are low-grade astrocytomas, medulablastoma, and ependymoma, while in adults the common tumours are high-grade astrocytomas. CNS tumours are usually non-metastatic; however, they can impose a threat by the localized seedling via cerebrospinal fluid circulation. The prognosis of CNS tumours heavily depends on their type and extent. In general, they can be excised; however, neurological deficits pose limitations. Some types of CNS malignancy, such as gliomas, medullablastomas, and ependymoma, have a cure rate of 50 per cent, while high-grade gliomas are universally fatal.

This chapter is concerned with how dendritic trees may contribute to the information-processing functions of individual nerve cells in the CNS. After reviewing the history of ideas about dendritic integration, beginning with several influential modeling studies of the 1980s, it focuses on the pyramidal neuron of the cerebral cortex and hippocampus. It describes a sequence of models of increasing complexity, beginning with the classical “point neuron” model, and ending with a highly articulated single-neuron abstraction consisting of multiple integrative subunits organized into multiple processing layers.

This chapter looks at potential common underlying factors linking MMN/MMNm deficiency to the broad range of heterogeneous clinical conditions outlined in the book. Several promising clinical applications of MMN/MMNm are summarized, including the prediction of conversion to psychosis among clinically at-risk individuals, the prediction of the recovery of consciousness and cognitive capabilities in patients in a comatose or persistent vegetative state, the early detection of perceptual deficits in developmental brain disorders, and the early identification of the presence of Mild Cognitive Impairment (MCI). Furthermore, the evaluation of the cognitive decline occurring in different brain disorders, as well as the prediction of cognitive recovery after the occurrence of a stroke or other brain injury, and the objective monitoring of age-related cognitive brain change and potential countermeasures to slow down this age-related cognitive decline are discussed.

This chapter begins by describing neural coding systems (the ‘messages’) thought to take part in information processing in the brain. It then discusses the possible roles played by neurotransmitters in transferring or integrating signals at synapses. Particular emphasis is placed on the complex interplay that can occur between messages and messengers even at the simplest synapses involving a single transmitter and a single receptor subtype. An argument is also made that transmitters are relatively poor indicators of signaling function. It is more appropriate to regard receptors and their associated cellular effects as the primary mediators of information processing in the CNS. Finally, the importance of these interactions are discussed in the context of neurotransmission and neuromodulation.

Many conditions can cause metabolic damage to the CNS, and they do so through a variety of mechanisms. Stroke, for instance, causes anoxic damage to a region of the brain, the actual cell death being due to excitotoxicity, release of free radicals, release of nitric oxide, and other mechanisms. This chapter therefore describes some of the major mechanisms causing metabolic damage in CNS pathology, and then some of the more common conditions.

Although the CNS has conventionally been viewed as an immunologically privileged site, the importance of immunological responses in the pathogenesis of CNS disease has become increasingly apparent over the last few decades. Indeed, the concept of CNS isolation from the immune system is hard to reconcile with the favourable outcome of encephalitides commonly complicating some exanthemata, such as mumps, and with the brisk cerebrospinal fluid pleocytosis, which almost invariably accompanies brain infection; neither observation suggests that CNS invasion by infective agents proceeds unhindered by immune response. However, whilst absolute immune privilege can no longer be sustained, is has become clear that there are fundamental differences between the mechanisms of immunity in the CNS and those elsewhere in the body. In order to understand the part inflammation plays in both pathogenesis and repair, it is necessary to consider briefly both the principles of the systemic immune response and the blood–brain barrier, which protects nervous tissues from the systemic circulation.

Axons in the mammalian peripheral nervous system (PNS) regenerate well. Axons in the adult mammalian central nervous system (CNS), however, do not spontaneously regenerate, with the result that any injury that cuts axons, such as spinal-cord injury, will not recover. Clearly a central feature of CNS repair will have to be the induction of axon regeneration. In principle, axon growth is a collaborative process that involves a dialogue between the axon and the environment it is trying to penetrate. Whether an axon will regenerate or not, therefore, depends on the regenerative efforts made by the axon, on the inhibitory or permissive molecules in the environment, and on the receptors for these molecules on the axonal surface. This chapter examines these various factors and their effects on CNS axon regeneration.

In mammals, after damage to major axon tracts or large areas of neuronal tissue, there is permanent loss of function. Axons will not regenerate, and killed neurones are not replaced. This is in contrast to animals below the evolutionary level of the primitive amphibia, in which there is eventually an almost complete recovery of function, and early mammalian embryos have similar abilities. This is made possible by the regeneration of cut axons, and the replacement of lost neurones. The ability to regenerate central nervous system (CNS) axons over long distances and to replace large numbers of lost neurons is lost in evolutionary terms round the level of the primitive frogs, and in developmental terms around late limb-bud stages in mammalian embryos. However, even the mammalian CNS does have a considerable ability to readjust to functional loss. Thus, immediately after a stroke, patients will often have complete paralysis down one side of the body, but in the ensuing months a large proportion of the lost function may return.

Neuro-oncology is the most difficult area for patients, family, and staff. Of all cancers, gliomas are one of the most devastating cancers, and which posit unique problems and challenges. Primary central nervous system (CNS) tumours affect people of all ages. They are prevalent in children, and the secondmost leading cause of death in children. CNSs are the third death-causing disease in adolescents and in adults. Compared to other solid tumours such as lung, breast, or prostate cancer, primary CNS tumours cause greater incidence of mortality. This chapter does not discuss the management of patients with brain metastases, but focuses on the problems unique to patients with brain tumours and the different types of primary CNS tumours. The succeeding sections of the chapter concentrate on the major problem of patients with malignant gliomas. Discussed as well are the symptoms prevalent in patients with brain primary CNS tumours and the general management issues concerning such patients.

This chapter introduces the core concepts of neural dynamics on which dynamic field theory (DFT) is based. Behavior is generated by the central nervous system (CNS). From this observation, the argument is made that the inner state of the CNS must be described by continuous variables that evolve continuously over time. The concept of activation is introduced to characterize the inner state of the CNS; activation evolves over time as described by a dynamical system. The form this neural dynamics takes is based on the need for states of the CNS to be stable—for behaviorally significant states to resist perturbations. Stability means that the system coheres around special states called attractors where the rate of change of activation is balanced. This might occur under the influence of sensory input, or when neurons are coupled together, passing excitatory or inhibitory activation back and forth. Also discussed is the movement of the CNS into and out of attractor states, which are formally called instabilities. Such instabilities arise in the CNS due to the nonlinear way in which neurons interact.

The concept of central nervous system manifestations of rheumatologic disease is a well-recognized clinical phenomenon. Complications in Sjögren’s can include stroke, seizures, movement disorders, encephalopathy, meningoencephalitis, neuropsychiatric symptoms, inflammatory spinal cord disease, optic neuropathy and multiple sclerosis (MS)-like conditions. Central nervous system manifestations of Sjögren’s require multidisciplinary management and investigation while also highlighting the difficulties inherent with biomedical research in an era of changing definitions of disease. Sjögren’s was initially defined by a constellation of symptoms that were recognizable to the expert clinician. As underlying autoimmune disease mechanisms are uncovered, it is our challenge to continuously consider how we categorize disease such that groupings remain clinically relevant and allow us to take care of our patients.

The frequency of central nervous system involvement in patients with Sjögren’s disease varies widely, but it is less common than involvement of the peripheral nervous system. Even though it is less common, patients and medical professionals should be aware of potential central nervous system manifestations. There can be considerable overlap between autoimmune disorders; therefore, central nervous system involvement can include neuromyelitis optica or multiple sclerosis as part of a patient’s Sjögren’s disease or may be considered separate comorbidities. Cognitive dysfunction and mood disorders, including anxiety and depression, also can be rooted in Sjögren’s that impacts the central nervous system, or they may appear as comorbidities.

In some patients with Sjögren’s, the central nervous system is compromised. Depending on the area of the brain affected, pathophysiologic changes may affect physical, cognitive, and/or psychological functions. Since a multitude of factors, such as pain, fatigue, medication side effects, psychological factors, and normal aging, can mimic the deficits associated with brain damage, it is important that the patient undergo a comprehensive assessment in order to determine the exact underlying etiology of any neurologic or neuropsychological changes and to assist in the development of the most efficacious treatment program. Sjögren’s patients who present with cognitive problems and complaints should be referred for a neurologic evaluation, imaging studies, and a comprehensive neuropsychological evaluation. Although the treatment of the neurologic and neuropsychological sequelae of these disorders is still in the early stages, a well-informed treatment program can help to reverse some of the areas of impairment or at least help the patient better cope with the neuropsychological sequelae of the illness.