Preface

Demyelination disorders are among the most frequent neurological conditions that affect either the central or the peripheral structures of the nervous system or non-rarely both of them. These disorders have a multifactorial causative background and result in serious physical incapacity. They induce suffering, physical inability, and psychological and mental distress in millions of patients worldwide, increasing socioeconomic burden and negatively affecting patient quality of life. The most common type of central demyelination disease is multiple sclerosis (MS), which remains an unsolved problem in the field of neurosciences with a mosaic of clinical manifestations and a long labyrinth of therapeutic approach.

Many factors cause the complicated etiological pattern of demyelinating diseases, some of which are innate and some of which are exogenous. Among the innate causes, genetic factors play a dominant role in the majority of cases of central demyelination [1] as well as in a considerable number of peripheral ones. Among a large number of exogenous agents are viral infections, dietary habits, smoking, obesity, physical or psychological trauma, latitudinal gradient and climate of a country, and ultraviolet light exposure. Genetic predispositions affecting autoimmune reactions, which are mostly mediated by T and B cells, play the most substantial role in the dramatic course and conclusion of the disease. Current therapeutic protocols are scheduled based on the autoimmune character of MS, attempting to control the activation of lymphocytes and the many cellular interactions characteristic of the disease [2].

In this volume, the authors analyze many aspects of demyelination from clinical, diagnostic, and therapeutic points of view. They describe the role of Schwann cells in the periphery and that of pericytes in the brain using experimental models, which offer the possibility of close observation and detailed study of the morphological alterations and pathogenetic mechanisms of demyelination and remyelination.

The multiform clinical manifestations of MS have a global character involving the physical, psychological, and mental aspects of the patients' life. The first chapter [3], discusses depression in patients with demyelination disease [4]. Rarely in serious cases, depression may be associated with suicidal ideation [5], whereas in the majority of cases it is related to anxiety, phobic phenomena, or even panic disorders that are proportional to the physical inability of the patients. On the contrary, some patients show emotional inertia, apathy, or absence of interest for the course of the disease. Many patients neglect environmental conditions and show behavioral changes, including euphoria [6], which might be attributed to the gradual degeneration of the frontal or prefrontal areas of the brain.

In Chapter 2, the authors discuss the non-pharmacological treatment of MS. The authors suggest that physiotherapy is a crucial and effective measure for increasing neuroplasticity and thus enabling the patient to retain functional independence. Physical education and exercises [7] may generally increase the concentration

of neurotrophic factors in the brain, enhancing synaptogenesis and improving the physical condition of patients. Among the various types of physical therapy, Judo seems to have beneficial effects in cases of relapsing-remitting (RR) MS [8], especially when incorporated at the initial stages of the disease, given that it may improve the development of proprioception, motor coordination, endurance, and muscle strength.

Chapter 3, [9], analyzes the activity of the Schwann cell, concluding that it plays a preponderant role in recovering nerve fibers after Wallerian degeneration, forming bands of Büngner, which guide the centrifugal propagation of axonal sprouts, reforming the myelin sheath and providing support for axonal outgrowth by the initiation of a reciprocal dialogue between axon and Schwan cell basal lamina by the plastic potentiality of Schwann cell [10]. Unfortunately, human Schwan cells have a limited in-time regenerative capacity and their contribution in axonal regeneration and remyelination gradually declines [11]. The authors underline that the understanding of the "extraordinary plasticity" of Schwann cells may inspire the introduction of novel therapeutic methods for the healing of peripheral neuropathies and traumatic nerve injuries.

However, all Schwan cells do not participate in the formation of the myelin sheath and the remyelination of damaged nerve fibers. Some of them, the so-called Remak fibers, are non-myelinated Schwann cells (NMSCs). Nevertheless, they have an important contribution in axonal maintenance and neuronal survival and are essential for the normal development and function of the peripheral nerves [12]. Remak fibers also play an important role in the modulation of pain sensitivity in peripheral sensory neuropathies. Chapter 4 describes in detail the different functions of Remak fibers according to their distribution in the nervous system [13]. Thus, the chapter describes their role as immune-competent cells [14] in the modulation of pain sensitivity in peripheral sensory neuropathies as well as in the formation and function of the neuromuscular junction. The authors' of this chapter conclude that a better understanding of the function of Remak fibers could lead to potential new treatment approaches to sensory neuropathies and even spinal muscular atrophy.

It is unanimously accepted that acute demyelinating polyradiculoneuropathy or Guillain Barré syndrome (GBS) is among the most serious conditions of peripheral demyelination. It is one of the main causes of flaccid paralysis in previously healthy individuals, particularly children [15]. In a considerable number of cases, respiratory infection is noticed to occur before the initiation of clinical phenomena of the disease. Chapter 5, describes an unusual case of recurrent GBS in a child who suffered from the disease in two successive episodes: from the acute inflammatory demyelinating variant in the first episode and from the acute axonal motor variant in the second one [16]. Both appeared following an episode of respiratory infection. The authors underline the value of early diagnosis based on the clinical estimation of the patient, in correlation with neurophysiological data, which should be important for the prompt therapeutic intervention of intravenous immunoglobulins (IVIGs) [17, 18].

Peripheral neuropathies are substantial causes of motor, sensory, and even autonomic disabilities with an unfavorable impact on quality of life. Among the broad etiopathological spectrum of these neuropathies, diabetic peripheral neuropathy

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affects between 23% and 76% of the general population [19, 20]. Chapter 6 describes the various clinical and neuropathological types of diabetic neuropathies [21]. The authors emphasize the importance of the early clinical assessment of patients for

The vascular factor is an additional component in the broad pathogenetic background of central and peripheral demyelination. Anti-neutrophil cytoplasmic antibodies (ANCAs) may induce necrotizing vasculitis, which has polymorphic symptomatology including peripheral neuropathy in 50% of cases [23, 24]. In Chapter 7 [25] discusses the prevalence, clinical manifestations, prognosis, and treatment of peripheral neuropathies due to ANCAs, underlining that mononeuritis multiplex is the most common clinical form of peripheral neuropathy in antibodies-associated vasculitides (AAV), necessitating prompt treatment with

The mechanical lesions of the peripheral nerves are not a rare phenomenon. Compression on peripheral nerves may provoke serious functional deficits, particularly whenever it occurs for a long time at certain points along the nerves' anatomical pathways [27]. In Chapter 8, [28] the authors discuss the many types of entrapment neuropathies concerning the upper extremities. The authors present a detailed schematic topographic analysis of the vulnerable points of the nerves along their course. In addition, they offer a precise description of the clinical signs of diagnostic significance in each one of the syndromes of entrapment neuropathies, highlighting the substantial role that anatomical variations, trauma, metabolic diseases, tumors, synovitis, and vitamin B6 deficiency play, among others, in their

The main doctrine in medicine based on the Hippocratic aphorism οφελέειν ή μη βλάπτειν is the alleviation of human suffering and the improvement of the quality of life of patients. For the realization of this doctrine, according to Galen, experimental research is essential for further understanding of the pathogenetic mechanisms of diseases and subsequent tracing of new proper and efficient therapeutic approaches. In the field of demyelinating diseases, the development of experimental models of demyelination and remyelination in vitro and in vivo is a necessity [30]. Given that MS has a dominant place in the spectrum of demyelinating disorders, several models of experimental encephalomyelitis have been introduced, approximating the clinical and neuropathological phenomena of the disease [31]. Many of those models, such as experimental autoimmune encephalomyelitis (EAE), toxic, viral, and transgenic models, are described in Chapter 9 [32], which emphasize the value of understanding MS via patient data.

Finally, Chapter 10 discusses the role of pericytes in demyelination and remyelination in an experimental model of MS [33]. It is known that pericytes participate in the functional neurovascular unit [34], being a substantial component in the development and maintenance of the stability of the blood–brain barrier (BBB). In addition, pericytes cooperate with other cells in the autoimmune reactions of the central nervous system (CNS), having the capacity to interact with oligodendrocytes and astrocytes and even to generate other cell lines. The chapter describes the ultrastructural characteristics of pericytes in EAE, concluding that novel therapeutic regimes that protect pericytes at the initial stages of demyelination may open

proper management and treatment of the disease [22].

corticosteroids and immunosuppressants [26].

promising new horizons in the treatment of MS.

pathogenetic procedure [29].

affects between 23% and 76% of the general population [19, 20]. Chapter 6 describes the various clinical and neuropathological types of diabetic neuropathies [21]. The authors emphasize the importance of the early clinical assessment of patients for proper management and treatment of the disease [22].

The vascular factor is an additional component in the broad pathogenetic background of central and peripheral demyelination. Anti-neutrophil cytoplasmic antibodies (ANCAs) may induce necrotizing vasculitis, which has polymorphic symptomatology including peripheral neuropathy in 50% of cases [23, 24]. In Chapter 7 [25] discusses the prevalence, clinical manifestations, prognosis, and treatment of peripheral neuropathies due to ANCAs, underlining that mononeuritis multiplex is the most common clinical form of peripheral neuropathy in antibodies-associated vasculitides (AAV), necessitating prompt treatment with corticosteroids and immunosuppressants [26].

The mechanical lesions of the peripheral nerves are not a rare phenomenon. Compression on peripheral nerves may provoke serious functional deficits, particularly whenever it occurs for a long time at certain points along the nerves' anatomical pathways [27]. In Chapter 8, [28] the authors discuss the many types of entrapment neuropathies concerning the upper extremities. The authors present a detailed schematic topographic analysis of the vulnerable points of the nerves along their course. In addition, they offer a precise description of the clinical signs of diagnostic significance in each one of the syndromes of entrapment neuropathies, highlighting the substantial role that anatomical variations, trauma, metabolic diseases, tumors, synovitis, and vitamin B6 deficiency play, among others, in their pathogenetic procedure [29].

The main doctrine in medicine based on the Hippocratic aphorism οφελέειν ή μη βλάπτειν is the alleviation of human suffering and the improvement of the quality of life of patients. For the realization of this doctrine, according to Galen, experimental research is essential for further understanding of the pathogenetic mechanisms of diseases and subsequent tracing of new proper and efficient therapeutic approaches. In the field of demyelinating diseases, the development of experimental models of demyelination and remyelination in vitro and in vivo is a necessity [30]. Given that MS has a dominant place in the spectrum of demyelinating disorders, several models of experimental encephalomyelitis have been introduced, approximating the clinical and neuropathological phenomena of the disease [31]. Many of those models, such as experimental autoimmune encephalomyelitis (EAE), toxic, viral, and transgenic models, are described in Chapter 9 [32], which emphasize the value of understanding MS via patient data.

Finally, Chapter 10 discusses the role of pericytes in demyelination and remyelination in an experimental model of MS [33]. It is known that pericytes participate in the functional neurovascular unit [34], being a substantial component in the development and maintenance of the stability of the blood–brain barrier (BBB). In addition, pericytes cooperate with other cells in the autoimmune reactions of the central nervous system (CNS), having the capacity to interact with oligodendrocytes and astrocytes and even to generate other cell lines. The chapter describes the ultrastructural characteristics of pericytes in EAE, concluding that novel therapeutic regimes that protect pericytes at the initial stages of demyelination may open promising new horizons in the treatment of MS.

The editors wish to extend their gratitude to the authors for their valuable contributions as well as to the staff at IntechOpen for their assistance throughout the publication process.
