The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization, and Putative Roles

*Ramón Cobo, Yolanda García-Mesa, Jorge García-Piqueras, Jorge Feito, José Martín-Cruces, Olivía García-Suárez and José A. Vega*

## **Abstract**

Sensory corpuscles of human skin are structures located at the peripheral end of the mechanoreceptive neurons and function as low-threshold mechanoreceptors (LTMRs). In its structure, in addition to the axon, there are glial cells, not myelinating, that are organized in different ways according to the morphotype of sensitive corpuscle, forming the so-called laminar cells of Meissner's corpuscles, the laminar cells of the inner core of Pacinian corpuscles, or cells of the inner core in Ruffini's corpuscles. Classically the glial cells of sensory corpuscles have been considered support cells and passive in the process of mechanotransduction. However, the presence of ion channels and synapses-like systems between them and the axon suggests that corpuscular glial cells are actively involved in the transformation of mechanical into electrical impulses. This chapter is an update on the origin, development, cytoarchitecture, and protein profile of glial cells of sensitive corpuscles especially those of human glabrous skin.

**Keywords:** terminal glial cells, lamellar cells, Meissner corpuscles, Pacinian corpuscles, human

## **1. Introduction**

The human skin is supplied by sensory nerve fibers which form in the dermis complexes sensory structures known collectively as sensory corpuscles [1]. These sensory formations are connected to nerve fibers originating from intermediate- or large-sized neurons (see for a review [2]) that work as low-threshold mechanoreceptors (LTMRs). LTMRs are classified as Aβ, Aδ, or C based on their degree of myelination and action potential conduction velocities [2, 3] and functionally fall into two categories: rapidly adapting (RA) and slowly adapting (SA) mechanoreceptors, which each have two variants, type I and type II [4, 5]. RAI and RAII mechanoreceptors correspond to Meissner and Pacinian corpuscles, respectively; SAI mechanoreceptors are the Merkel cell-neurite complexes, and SAII mechanoreceptors are the dermal Ruffini's corpuscles [1]. This diversity of LTMRs suggests

differentiated ability to detect and discriminate diverse stimuli in relation to their connectivity to central nervous system nuclei [1, 2, 6, 7].

The peripheral processes of Aβ axons contact in the skin with specialized epithelial cells, i.e., Merkel cells to form Merkel cell-neurite complexes, or with glial Schwann-like cells to form a part of the sensory corpuscles, i.e., Meissner corpuscles, Ruffini's corpuscles, and Pacinian corpuscles [1, 3, 8, 9]. Structurally, the cutaneous sensory corpuscles consists of a dendritic zone (the extreme tip of the peripheral process of an Aβ LTMR), surrounded by nonmyelinating glial cells variably arranged, and both are surrounded by a more or less developed capsule of endoneurial/perineurial cells [9–13]. Filling the spaces among cells, there is a chemically complex extracellular matrix, sometimes organized as a basal lamina [14–17]. So, periaxonic cells that form sensory corpuscles are continuous with the cells of nerve trunks, demonstrating a close relationship between the components of nerves and sensory corpuscles [11].

The peripheral tip of the sensory Aβ axon is always coated by glial cells. These cells constitute a special population of peripheral glial cells denominated terminal glial cells or skin end-organ glia [18], but habitually they are a neglected entity in books and reviews in the topic and are not mentioned among peripheral glial cell types [19]. However, emerging data strongly suggest that glial cells of the sensory corpuscles play key roles in mechanotransduction.

In this review we summarize the current knowledge about the origin and development, cytoarchitecture, immunohistochemical profile, and putative roles of glial cells in sensory corpuscles especially in the genesis of mechanical potential action.

## **2. Origin of the sensory corpuscles glial cells**

The glial cells forming a part of the cutaneous sensory corpuscles are regarded as nonmyelinating Schwann-related cells and share some molecular markers. During embryonic development, peripheral glial progenitors originated in the neural crest (NC) cells contact the surface of developing axons and differentiate into Schwann cell precursors (SCPs) [20]. Subsequently, SCPs originate immature Schwann cells (ISCs) that later generate adult peripheral glial cells types, including the glia found in cutaneous sensory end organs [18].

Neural crest boundary cells (NC-BCs) can also generate peripheral glia during embryonic development [21] which in the presence of neuregulins (NRs) are able to differentiate into SCPs [22] and then into ISCs before maturing into myelinating and nonmyelinating Schwann cells [23]. The immediate progeny of NC-BCs, together with other nerve-associated SCPs, migrate along the sensory nerves toward the skin to give rise to highly specialized glial cells (denominated specific sensory nerve fiber-associated glia in the skin) associated to nerve endings in the epidermis although these cells are distinct to the specialized glial subtype found within the cutaneous sensory corpuscles [24]. But according to Etxaniz and coworkers [25], in the skin BC derivatives give rise to at least three glial populations: Schwann cells (mainly nonmyelinating) associated with subcutaneous and dermal nerves and two types of terminal Schwann cells, associated with lanceolate endings or free nerve endings. It can be speculated that the glial cells of sensory corpuscles can derivate of that first type.

Furthermore, NC-derived stem cells are retained postnatally in the skin and peripheral nerves after differentiation the SCPs cells and do not completely lost multipotentiality [26] retaining certain characteristics of NC cells and remaining multipotent [27, 28].

**21**

growth factor 2 [47].

signals [54].

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization…*

**3. Development of the sensory corpuscles glial cells**

in peripheral nerves upon axonal signals such as NRG-1 [30, 31].

In view of the diverse possible origins of the glial cells of sensory corpuscles, it is not possible to know exactly the cells from which they come. Probably these cells are a consequence of combinatory distinct molecular signatures and local factors

Sensory axons are critical inducing the development of sensory corpuscles, and reciprocal interactions between axons and target cells, especially peripheral glial cells, seem to initiate their morphogenesis [29]. SCPs comigrate with growing axons

Some of the molecules that interplay those axon-peripheral glial cells relationships in developing sensory corpuscles are now also known. The neurotrophin (NT) family of growth factors is involved in the development of mechanoreceptors controlling the development of mechanosensory neurons. Mice lacking TrkB and its ligand brain-derived neurotrophic factor (BDNF), but not NT-4, do not develop Meissner-like corpuscles [32–34], whereas overexpression of BDNF [35] and NT-4 [36] leads to an increase in the size and density of those corpuscles. The role of NTs in regulating development of Pacinian corpuscles is more complex and controversial since multiple NT-Trk signals participate, resulting in a reduction of the number of Pacinian corpuscles in mice deficient for BDNF and NT-3 and TrkA and TrkB [37]. However, Pacinian corpuscles of postnatal TrkB-deficient mice were found largely normal [33, 38]. ER81 is also present in developing murine Pacinian corpuscles [39], and in the absence of this transcription factor, Pacinian corpuscles do not form because their afferents do not survive. NRG-1 interacts with ErbB2/ErbB3 receptors on Schwann cell lineage and is broadly involved in Schwann cell development [40]. Recently, it has been demonstrated that a RET-ER81-NRG-1 signaling pathway promotes axon communication with nonmyelinating Schwann cells. The glial cells forming inner core of murine Pacinian corpuscles display NRG receptors erbB2, erbB3, and erbB4, whereas the central axon is immunoreactive for NRG-1 and ablating Ret and Nrg-1 in mechanosensory neurons results in the absence of Pacinian corpuscles, while Meissner's corpuscles were unaffected [41–43]. Interestingly, the dependence of the corpuscular glial cells from the axons continues during adult life at least for the expression of some antigens. After denervation, glial cells of Meissner-like corpuscles lack some specific markers [44, 45] and strongly decrease the expression of TrkA [46], and the glial cells forming the inner core of Pacinian corpuscles undergo apoptotic death that can be prevented by administration of glial

In addition to the axon-glial cells interactions, probably local molecules participate in the development of sensory corpuscles including growth factors [48, 49], β-arrestin-1 [50], semaphorins [49, 51, 52], ankyrin-B [53], and also mechanical

NC cells, SCPs, and ISCs share some markers (neuregulin receptors ErbB2 and ErbB3, L1, nestin, vimentin). Two markers used for labeling of mature Schwann cells, i.e., S100 protein and vimentin, are also present in ISCs but are absent or expressed at much lower levels in PSCs [30, 55]. Using these proteins as ISCs or mature Schwann and Schwann-related cell markers, we have determined the timetable of the development of sensory corpuscles. In murine Meissner-like corpuscles start to express immunoreactivity for S100 protein by postnatal day 7 (Pd7), vimentin by Pd12, and p75LNGFR (a marker for peripheral glia too) transitory from Pd7 to Pd19. Pacinian corpuscles show S100 protein in the inner core at Pd7, whereas vimentin starts expression at Pd19 and later [56]. In human, the first evidence

*DOI: http://dx.doi.org/10.5772/intechopen.91815*

during development [18].

In view of the diverse possible origins of the glial cells of sensory corpuscles, it is not possible to know exactly the cells from which they come. Probably these cells are a consequence of combinatory distinct molecular signatures and local factors during development [18].

## **3. Development of the sensory corpuscles glial cells**

Sensory axons are critical inducing the development of sensory corpuscles, and reciprocal interactions between axons and target cells, especially peripheral glial cells, seem to initiate their morphogenesis [29]. SCPs comigrate with growing axons in peripheral nerves upon axonal signals such as NRG-1 [30, 31].

Some of the molecules that interplay those axon-peripheral glial cells relationships in developing sensory corpuscles are now also known. The neurotrophin (NT) family of growth factors is involved in the development of mechanoreceptors controlling the development of mechanosensory neurons. Mice lacking TrkB and its ligand brain-derived neurotrophic factor (BDNF), but not NT-4, do not develop Meissner-like corpuscles [32–34], whereas overexpression of BDNF [35] and NT-4 [36] leads to an increase in the size and density of those corpuscles. The role of NTs in regulating development of Pacinian corpuscles is more complex and controversial since multiple NT-Trk signals participate, resulting in a reduction of the number of Pacinian corpuscles in mice deficient for BDNF and NT-3 and TrkA and TrkB [37]. However, Pacinian corpuscles of postnatal TrkB-deficient mice were found largely normal [33, 38]. ER81 is also present in developing murine Pacinian corpuscles [39], and in the absence of this transcription factor, Pacinian corpuscles do not form because their afferents do not survive. NRG-1 interacts with ErbB2/ErbB3 receptors on Schwann cell lineage and is broadly involved in Schwann cell development [40]. Recently, it has been demonstrated that a RET-ER81-NRG-1 signaling pathway promotes axon communication with nonmyelinating Schwann cells. The glial cells forming inner core of murine Pacinian corpuscles display NRG receptors erbB2, erbB3, and erbB4, whereas the central axon is immunoreactive for NRG-1 and ablating Ret and Nrg-1 in mechanosensory neurons results in the absence of Pacinian corpuscles, while Meissner's corpuscles were unaffected [41–43]. Interestingly, the dependence of the corpuscular glial cells from the axons continues during adult life at least for the expression of some antigens. After denervation, glial cells of Meissner-like corpuscles lack some specific markers [44, 45] and strongly decrease the expression of TrkA [46], and the glial cells forming the inner core of Pacinian corpuscles undergo apoptotic death that can be prevented by administration of glial growth factor 2 [47].

In addition to the axon-glial cells interactions, probably local molecules participate in the development of sensory corpuscles including growth factors [48, 49], β-arrestin-1 [50], semaphorins [49, 51, 52], ankyrin-B [53], and also mechanical signals [54].

NC cells, SCPs, and ISCs share some markers (neuregulin receptors ErbB2 and ErbB3, L1, nestin, vimentin). Two markers used for labeling of mature Schwann cells, i.e., S100 protein and vimentin, are also present in ISCs but are absent or expressed at much lower levels in PSCs [30, 55]. Using these proteins as ISCs or mature Schwann and Schwann-related cell markers, we have determined the timetable of the development of sensory corpuscles. In murine Meissner-like corpuscles start to express immunoreactivity for S100 protein by postnatal day 7 (Pd7), vimentin by Pd12, and p75LNGFR (a marker for peripheral glia too) transitory from Pd7 to Pd19. Pacinian corpuscles show S100 protein in the inner core at Pd7, whereas vimentin starts expression at Pd19 and later [56]. In human, the first evidence

*Somatosensory and Motor Research*

of nerves and sensory corpuscles [11].

tial action.

corpuscles play key roles in mechanotransduction.

**2. Origin of the sensory corpuscles glial cells**

in cutaneous sensory end organs [18].

can derivate of that first type.

multipotent [27, 28].

differentiated ability to detect and discriminate diverse stimuli in relation to their

The peripheral processes of Aβ axons contact in the skin with specialized epithelial cells, i.e., Merkel cells to form Merkel cell-neurite complexes, or with glial Schwann-like cells to form a part of the sensory corpuscles, i.e., Meissner corpuscles, Ruffini's corpuscles, and Pacinian corpuscles [1, 3, 8, 9]. Structurally, the cutaneous sensory corpuscles consists of a dendritic zone (the extreme tip of the peripheral process of an Aβ LTMR), surrounded by nonmyelinating glial cells variably arranged, and both are surrounded by a more or less developed capsule of endoneurial/perineurial cells [9–13]. Filling the spaces among cells, there is a chemically complex extracellular matrix, sometimes organized as a basal lamina [14–17]. So, periaxonic cells that form sensory corpuscles are continuous with the cells of nerve trunks, demonstrating a close relationship between the components

The peripheral tip of the sensory Aβ axon is always coated by glial cells. These cells constitute a special population of peripheral glial cells denominated terminal glial cells or skin end-organ glia [18], but habitually they are a neglected entity in books and reviews in the topic and are not mentioned among peripheral glial cell types [19]. However, emerging data strongly suggest that glial cells of the sensory

In this review we summarize the current knowledge about the origin and development, cytoarchitecture, immunohistochemical profile, and putative roles of glial cells in sensory corpuscles especially in the genesis of mechanical poten-

The glial cells forming a part of the cutaneous sensory corpuscles are regarded as nonmyelinating Schwann-related cells and share some molecular markers. During embryonic development, peripheral glial progenitors originated in the neural crest (NC) cells contact the surface of developing axons and differentiate into Schwann cell precursors (SCPs) [20]. Subsequently, SCPs originate immature Schwann cells (ISCs) that later generate adult peripheral glial cells types, including the glia found

Neural crest boundary cells (NC-BCs) can also generate peripheral glia during embryonic development [21] which in the presence of neuregulins (NRs) are able to differentiate into SCPs [22] and then into ISCs before maturing into myelinating and nonmyelinating Schwann cells [23]. The immediate progeny of NC-BCs, together with other nerve-associated SCPs, migrate along the sensory nerves toward the skin to give rise to highly specialized glial cells (denominated specific sensory nerve fiber-associated glia in the skin) associated to nerve endings in the epidermis although these cells are distinct to the specialized glial subtype found within the cutaneous sensory corpuscles [24]. But according to Etxaniz and coworkers [25], in the skin BC derivatives give rise to at least three glial populations: Schwann cells (mainly nonmyelinating) associated with subcutaneous and dermal nerves and two types of terminal Schwann cells, associated with lanceolate endings or free nerve endings. It can be speculated that the glial cells of sensory corpuscles

Furthermore, NC-derived stem cells are retained postnatally in the skin and peripheral nerves after differentiation the SCPs cells and do not completely lost multipotentiality [26] retaining certain characteristics of NC cells and remaining

connectivity to central nervous system nuclei [1, 2, 6, 7].

**20**

of Pacinian corpuscles was at 13 weeks of estimated gestational age (wega). At this time, and until 16 wega, the S100 protein positive from one or two layers of rounded cells then (16–18 wega) become flattened and show lamellar organization, thus originating a primitive inner core. Thereafter, between 20 and 24 wega, the S100 protein-positive cells emitted cytoplasmic expansions that invaded the outer region of the corpuscle forming a network. In the period between 24 and 36 wega, the edge of the inner core was still not totally defined until the fourth month of life, when the lamellae forming it become strongly packed and the inner core clefts are clearly distinguished. During development of Pacinian corpuscles, expression of vimentin started shortly later than that of S100P and did not vary along lifespan. On the other hand, at 23 wega hook-shaped axonal profiles are identified in the dermal papillae, but S100P-positive cells reach this place at 33 wega. By 36–40 wega, the S100 protein-positive lamellar cells of incipient Meissner's corpuscles can become progressively flattened, and around these cells also express vimentin, but their definite and typical arrangement occurs in the first weeks of life. Along the first semester of life, the S100P-positive cells become definitively flattened, reaching the adult morphology around 8 months [57].

## **4. Cytoarchitecture of glial cells in the different morphotypes of cutaneous sensory corpuscles**

The arrangement of terminal glial cells in the different morphotypes of sensory corpuscles varies from one to another, either irregularly (Krause and Ruffini's corpuscles), regularly (Meissner corpuscles), or forming the lamellar system of the inner core (Pacinian corpuscles) [8, 9].

In Meissner's corpuscles, the terminal glial cells are currently denominated lamellar cells.

The organization of the lamellar has a typical flattened appearance due to the horizontal lamelation that form stacks of lamellae separated by axon branches [8, 58]. Habitually the nuclei of the cells are at the periphery of the corpuscle and are total or partially covered by a CD34-positive capsule of endoneurial origin [13] (**Figure 1**).

The inner core is the zone of Pacinian corpuscles that lies between the axon and the intermediate layer and consists of tightly packed lamellae of peripheral glial cells which are diversely organized in the preterminal, terminal, and ultraterminal zones of the corpuscle. In the preterminal zone, the axon is still covered by the myelin sheath; the terminal zone characteristically has a bilateral symmetric organization; and in the ultraterminal zone, glial cells lose bilaterally. The flattened lamellar cells forming the terminal zone of the inner core have the nuclei lying in the outer core of the inner core itself. The lamellar cells project processes from the outer margin into the inner core, and flattening give the appearance of concentric layers of lamellae arranged in bilateral symmetry, hemilamellae, and the tips of the lamellae are separated by two clefs that run along the entire length of the axon until the ultraterminal zone. Interestingly the lamellae of the inner core have numerous gap (tight) junctions as well as desmosome-like junctions (see for a review [8, 9, 59]) (**Figure 2**).

Regarding Ruffini's corpuscles, the glial cells forming the inner core have an irregular distribution within the capsule with variable relationship with the dendritic zone of the axon tip [8] (**Figure 3**).

The terminal glial cells forming the inner core of Pacinian corpuscles and the lamellar cells of the Meissner ones are covered by a basal lamina, and around there is a complex extracellular matrix, whose composition in now rather well known [14–17, 60].

**23**

**Figure 1.**

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization…*

*DOI: http://dx.doi.org/10.5772/intechopen.91815*

**5. Immunohistochemical profile**

**5.1 Cytoskeletal proteins and general markers**

Glial fibrillary acidic protein (GFAP) is theoretically the intermediate filament

*Immunohistochemical localizacion of S100 protein (S100P; a, b, g, h), vimentin (VIM; c, e, i), neurofilament proteins (red in g) and CD34 (red in h, i) in Meissner'w corpuscles. The lamellar cells display intense and selective cytoplasmic S100P and VIM which are colocalized (d-f). The lamellar are in close contact with the* 

*axon (red fluorescence in g) and an endoeneurial capsule (red fluorescence in h and i).*

protein filling the cytoplasm of Schwann and Schwann-related cells forming cutaneous sensory corpuscles. However, most authors consider that peripheral glial cells express vimentin as the main intermediate filament protein [61]. In agreement with this assumption, GFAP was always absent from rat [62] and human [63] cutaneous sensory corpuscles. In contrast, the cytoplasm of the peripheral glial cells of sensory corpuscles expresses vimentin [62–64]. However, GFAP immunoreactivity was detected in the innermost lamellae of the inner core of feline Pacinian corpuscles [65] and human pancreatic Pacinian corpuscles [66]. The Ca2+-binding proteins represent one of the physiological mechanisms for maintaining intracellular Ca2+ homeostasis [67]. Some of these proteins have been

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization… DOI: http://dx.doi.org/10.5772/intechopen.91815*

#### **Figure 1.**

*Somatosensory and Motor Research*

ing the adult morphology around 8 months [57].

**cutaneous sensory corpuscles**

inner core (Pacinian corpuscles) [8, 9].

dritic zone of the axon tip [8] (**Figure 3**).

lamellar cells.

(**Figure 1**).

of Pacinian corpuscles was at 13 weeks of estimated gestational age (wega). At this time, and until 16 wega, the S100 protein positive from one or two layers of rounded cells then (16–18 wega) become flattened and show lamellar organization, thus originating a primitive inner core. Thereafter, between 20 and 24 wega, the S100 protein-positive cells emitted cytoplasmic expansions that invaded the outer region of the corpuscle forming a network. In the period between 24 and 36 wega, the edge of the inner core was still not totally defined until the fourth month of life, when the lamellae forming it become strongly packed and the inner core clefts are clearly distinguished. During development of Pacinian corpuscles, expression of vimentin started shortly later than that of S100P and did not vary along lifespan. On the other hand, at 23 wega hook-shaped axonal profiles are identified in the dermal papillae, but S100P-positive cells reach this place at 33 wega. By 36–40 wega, the S100 protein-positive lamellar cells of incipient Meissner's corpuscles can become progressively flattened, and around these cells also express vimentin, but their definite and typical arrangement occurs in the first weeks of life. Along the first semester of life, the S100P-positive cells become definitively flattened, reach-

**4. Cytoarchitecture of glial cells in the different morphotypes of** 

corpuscles varies from one to another, either irregularly (Krause and Ruffini's corpuscles), regularly (Meissner corpuscles), or forming the lamellar system of the

In Meissner's corpuscles, the terminal glial cells are currently denominated

The organization of the lamellar has a typical flattened appearance due to the horizontal lamelation that form stacks of lamellae separated by axon branches [8, 58]. Habitually the nuclei of the cells are at the periphery of the corpuscle and are total or partially covered by a CD34-positive capsule of endoneurial origin [13]

The inner core is the zone of Pacinian corpuscles that lies between the axon and the intermediate layer and consists of tightly packed lamellae of peripheral glial cells which are diversely organized in the preterminal, terminal, and ultraterminal zones of the corpuscle. In the preterminal zone, the axon is still covered by the myelin sheath; the terminal zone characteristically has a bilateral symmetric organization; and in the ultraterminal zone, glial cells lose bilaterally. The flattened lamellar cells forming the terminal zone of the inner core have the nuclei lying in the outer core of the inner core itself. The lamellar cells project processes from the outer margin into the inner core, and flattening give the appearance of concentric layers of lamellae arranged in bilateral symmetry, hemilamellae, and the tips of the lamellae are separated by two clefs that run along the entire length of the axon until the ultraterminal zone. Interestingly the lamellae of the inner core have numerous gap (tight) junctions as well as desmosome-like junctions (see for a review [8, 9, 59]) (**Figure 2**). Regarding Ruffini's corpuscles, the glial cells forming the inner core have an irregular distribution within the capsule with variable relationship with the den-

The terminal glial cells forming the inner core of Pacinian corpuscles and the lamellar cells of the Meissner ones are covered by a basal lamina, and around there is a complex extracellular matrix, whose composition in now rather well known [14–17, 60].

The arrangement of terminal glial cells in the different morphotypes of sensory

**22**

*Immunohistochemical localizacion of S100 protein (S100P; a, b, g, h), vimentin (VIM; c, e, i), neurofilament proteins (red in g) and CD34 (red in h, i) in Meissner'w corpuscles. The lamellar cells display intense and selective cytoplasmic S100P and VIM which are colocalized (d-f). The lamellar are in close contact with the axon (red fluorescence in g) and an endoeneurial capsule (red fluorescence in h and i).*

### **5. Immunohistochemical profile**

#### **5.1 Cytoskeletal proteins and general markers**

Glial fibrillary acidic protein (GFAP) is theoretically the intermediate filament protein filling the cytoplasm of Schwann and Schwann-related cells forming cutaneous sensory corpuscles. However, most authors consider that peripheral glial cells express vimentin as the main intermediate filament protein [61]. In agreement with this assumption, GFAP was always absent from rat [62] and human [63] cutaneous sensory corpuscles. In contrast, the cytoplasm of the peripheral glial cells of sensory corpuscles expresses vimentin [62–64]. However, GFAP immunoreactivity was detected in the innermost lamellae of the inner core of feline Pacinian corpuscles [65] and human pancreatic Pacinian corpuscles [66].

The Ca2+-binding proteins represent one of the physiological mechanisms for maintaining intracellular Ca2+ homeostasis [67]. Some of these proteins have been

#### **Figure 2.**

*Immunohistochemical localization of S100 protein (S100; a-e), neurofilament protein (NFP; red fluorescence in e) and CD34 (red fluorescence in f). The glial cells forming the central zone of the inner core are characteristically arranged into two symmetrical hemilamellar systems separated by clefts (arrows in c-e) whereas in the ultraterminal zone of the inner core are irregularly disposed (a, b). The inner most lamellae of the inner core is in close contact with the axon (e) while de outer most lamellae is closely related with the so-called intermediate layer. ic: inner core; il: intermediate layer; asterisks indicate the zone occupied by the axon.*

#### **Figure 3.**

*Immunohistochemical localization of S100 protein (a-c) and CD34 in human cutaneous Ruffini's corpuscles. The glial cells are irregularly arranged and display a strong S100P immunofluorescence (a-c). The capsule of these corpuscles is CD34 positive suggesting and endoneurial origin (b, c). c: capsule; ic: inner core.*

found in the glial cells of cutaneous sensory corpuscles, most of them belonging to the so-called "EF-hand" family. They include S100 protein, calbindin D28k, parvalbumin, and calretinin (sensory corpuscles) [10, 68, 69].

#### **5.2 Growth factors and growth factor receptors**

As far as we know, the only growth factors detected in the glial cells of sensory corpuscles are TGF-β in the lamellar cells of rat Meissner corpuscles [70] and BDNF in the inner core cells of digital Pacinian corpuscles of *Macaca fascicularis* [71]. However, the glial cells of sensory corpuscles display a wide range of receptors for different growth factors. Epidermal growth factor receptor was detected in the lamellar and the inner core cells of human Meissner and Pacinian corpuscles,

**25**

epithelial Na+

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization…*

**6. Are the corpuscular glial cells accessory cells or active cells?**

**6.1 The GABA-ergic/glutamatergic system in Pacinian corpuscles**

respectively [72], as well as low- and high-affinity receptors for NTs including p75NNR [73–76], TrkA [77], and TrkB [78, 79]. TGF-β receptors RI and RII are also present in the inner core lamellar cells of cat Pacinian corpuscles and the lamellar

The inner core of Pacinian corpuscles expresses immunoreactivity for glutamate

In the past, investigators proposed that the response of sensory corpuscles could

Numerous types of mechanically gated ion channels were found in vertebrate sensory corpuscles, but most of them were localized in the axon. Nevertheless, evidence exists that some of them are also present in the glial cells. The inner core of murine [89] and human [90] Pacinian corpuscles displays immunoreactivity for ASIC2, a member of the acid-sensing ion channels included in the degenerin/

puscles, the lamellar cells also show ASIC2 immunoreactivity [91]. Some members of the superfamily of the transient receptor potential (TRP) ion channels have been

channel superfamily. In a subpopulation of human Meissner cor-

be explained entirely by the mechanical properties periaxonic cells, especially the capsule. Then the discovery that some ion channels are gated by mechanical forces (mechanosensitive ion channels) suggests that mechanotransduction occurs through the activation of ion channels along the somatosensory neurons that reach the skin. The opening of these channels consent the entry of ions within the axon to produce the mechanotransduction [82–86]. Thus, deformations in the membrane of different cells that form the mechanoreceptors (i.e., axon, glial cells, and endoneurial and/or perineurial fibroblast) trigger the opening of mechanosensitive ion channels that transduce mechanical energy into electrical activity. Consistently, the cells forming the mechanoreceptors are thought to express ion channels activated by force or displacement to act as mechanodetectors and/or mechanotransducers. Thus, mechanotransduction can be defined as the conversion of a mechanical stimulus into an electrical signal, and in the sensory corpuscles, the first step of

receptors, vesicular-glutamate transporters, and the synaptic proteins synaptobrevin (VAMP2) and SNAP-23. Moreover, inner core cells release neurotransmitters (glutamate, GABA) when they are stimulated by glutamate, ATP, or even by mechanical motion [80]. This implies "synaptic-like" interaction between the axon and the glial cells of Pacinian corpuscles. This hypothesis, postulated by Pawson and co-workers [80, 81], argues that: "action potentials in response to dynamic stimuli are due to depolarization of the axon by cations entering mechano-gated channels that are opened due to mechanical motion; however, action potentials in the static portion of the Pacinian corpuscle rapidly adapting response are due to glutamatergic excitation, which are then inhibited by GABA released from the modified Schwann cells of the inner core." These results suggest that in the Pacinian corpuscles, GABA emanating from the capsule inhibits glutamate excitation (stemming either from the neurite itself or from the capsule), leading to a glial-neuronal "mechanochemical," rather than solely mechanical, RA response to sustained pressure. These elegant and attractive results should be confirmed in other mecha-

*DOI: http://dx.doi.org/10.5772/intechopen.91815*

noreceptors and in different vertebrate species.

mechanotransduction takes place [87, 88].

**6.2 Ion channels**

cells of Meissner corpuscles [70].

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization… DOI: http://dx.doi.org/10.5772/intechopen.91815*

respectively [72], as well as low- and high-affinity receptors for NTs including p75NNR [73–76], TrkA [77], and TrkB [78, 79]. TGF-β receptors RI and RII are also present in the inner core lamellar cells of cat Pacinian corpuscles and the lamellar cells of Meissner corpuscles [70].

## **6. Are the corpuscular glial cells accessory cells or active cells?**

#### **6.1 The GABA-ergic/glutamatergic system in Pacinian corpuscles**

The inner core of Pacinian corpuscles expresses immunoreactivity for glutamate receptors, vesicular-glutamate transporters, and the synaptic proteins synaptobrevin (VAMP2) and SNAP-23. Moreover, inner core cells release neurotransmitters (glutamate, GABA) when they are stimulated by glutamate, ATP, or even by mechanical motion [80]. This implies "synaptic-like" interaction between the axon and the glial cells of Pacinian corpuscles. This hypothesis, postulated by Pawson and co-workers [80, 81], argues that: "action potentials in response to dynamic stimuli are due to depolarization of the axon by cations entering mechano-gated channels that are opened due to mechanical motion; however, action potentials in the static portion of the Pacinian corpuscle rapidly adapting response are due to glutamatergic excitation, which are then inhibited by GABA released from the modified Schwann cells of the inner core." These results suggest that in the Pacinian corpuscles, GABA emanating from the capsule inhibits glutamate excitation (stemming either from the neurite itself or from the capsule), leading to a glial-neuronal "mechanochemical," rather than solely mechanical, RA response to sustained pressure. These elegant and attractive results should be confirmed in other mechanoreceptors and in different vertebrate species.

#### **6.2 Ion channels**

*Somatosensory and Motor Research*

**24**

**Figure 2.**

**Figure 3.**

found in the glial cells of cutaneous sensory corpuscles, most of them belonging to the so-called "EF-hand" family. They include S100 protein, calbindin D28k, parval-

*Immunohistochemical localization of S100 protein (a-c) and CD34 in human cutaneous Ruffini's corpuscles. The glial cells are irregularly arranged and display a strong S100P immunofluorescence (a-c). The capsule of these corpuscles is CD34 positive suggesting and endoneurial origin (b, c). c: capsule; ic: inner core.*

*Immunohistochemical localization of S100 protein (S100; a-e), neurofilament protein (NFP; red fluorescence in e) and CD34 (red fluorescence in f). The glial cells forming the central zone of the inner core are characteristically arranged into two symmetrical hemilamellar systems separated by clefts (arrows in c-e) whereas in the ultraterminal zone of the inner core are irregularly disposed (a, b). The inner most lamellae of the inner core is in close contact with the axon (e) while de outer most lamellae is closely related with the so-called intermediate layer.* 

*ic: inner core; il: intermediate layer; asterisks indicate the zone occupied by the axon.*

As far as we know, the only growth factors detected in the glial cells of sensory corpuscles are TGF-β in the lamellar cells of rat Meissner corpuscles [70] and BDNF in the inner core cells of digital Pacinian corpuscles of *Macaca fascicularis* [71]. However, the glial cells of sensory corpuscles display a wide range of receptors for different growth factors. Epidermal growth factor receptor was detected in the lamellar and the inner core cells of human Meissner and Pacinian corpuscles,

bumin, and calretinin (sensory corpuscles) [10, 68, 69].

**5.2 Growth factors and growth factor receptors**

In the past, investigators proposed that the response of sensory corpuscles could be explained entirely by the mechanical properties periaxonic cells, especially the capsule. Then the discovery that some ion channels are gated by mechanical forces (mechanosensitive ion channels) suggests that mechanotransduction occurs through the activation of ion channels along the somatosensory neurons that reach the skin. The opening of these channels consent the entry of ions within the axon to produce the mechanotransduction [82–86]. Thus, deformations in the membrane of different cells that form the mechanoreceptors (i.e., axon, glial cells, and endoneurial and/or perineurial fibroblast) trigger the opening of mechanosensitive ion channels that transduce mechanical energy into electrical activity. Consistently, the cells forming the mechanoreceptors are thought to express ion channels activated by force or displacement to act as mechanodetectors and/or mechanotransducers. Thus, mechanotransduction can be defined as the conversion of a mechanical stimulus into an electrical signal, and in the sensory corpuscles, the first step of mechanotransduction takes place [87, 88].

Numerous types of mechanically gated ion channels were found in vertebrate sensory corpuscles, but most of them were localized in the axon. Nevertheless, evidence exists that some of them are also present in the glial cells. The inner core of murine [89] and human [90] Pacinian corpuscles displays immunoreactivity for ASIC2, a member of the acid-sensing ion channels included in the degenerin/ epithelial Na+ channel superfamily. In a subpopulation of human Meissner corpuscles, the lamellar cells also show ASIC2 immunoreactivity [91]. Some members of the superfamily of the transient receptor potential (TRP) ion channels have been detected in glial cells of sensory corpuscles. TRPV4 was detected in the lamellar cells of human Meissner corpuscles [92]. On the other hand, voltage-sensitive Na<sup>+</sup> channels (α-subunit type I and type II voltage-gated Na<sup>+</sup> channel) present in the inner core lamellae and the axon might participate in both transduction and action potential generation [93].

Based on the above data in addition to the hypothesis of voltage-gated and nonvoltage-gated channels, a possible classical neurotransmission cannot be excluded for the genesis of the action potential in sensory corpuscles. In the process of touch sensation, a mechanical stimulus is converted into electrical activity in peripheral sensory neurons, and this conversion may occur through the activation of ion channels that gate in response to mechanical stimuli.

## **7. Concluding remarks**

The glial cells of the sensory corpuscles form a glial subpopulation, highly differentiated and with important functions in the mechanotransduction process that has been repeatedly forgotten in studies on peripheral glia. Its origin is not known exactly, and they could come from cells of the neural crest or the boundary cap cells. However, the chronology of its arrival and organization within the corpuscles has recently been established, as well as their interdependence with sensory axons. In the last decade, some mechano-gated ion channels have been discovered in corpuscular glial cells. This fact associated with the demonstration of a GABA-ergic/ glutamatergic neurotransmission system in the Pacinian corpuscles suggests that the glial cells of the sensory corpuscles are not support cells but have an active role in the mechanotransduction process. Nevertheless, whether or not this occurs only in Pacinian corpuscles or in all sensory corpuscles remains to be demonstrated.

## **Acknowledgements**

This study was supported in part by a grant from Gerencia Regional de Salud de Castilla y León (GRS 1615/A/17). YG-M was supported by a grant "Severo Ochoa" from the Government of the Principality of Asturias (Ref. BP17-044). The authors thank Dr. Marta Guervos (Servicios Comunes de Investigación, Microscopia Confocal, Universidad de Oviedo) and Marta Sánchez-Pitiot (Grupo de Histopatología Molecular, Instituto Universitario de Oncología del Principado de Asturias) for their technical assistance.

**27**

**Author details**

José Martín-Cruces1

Oviedo, Oviedo, Spain

Salamanca, Salamanca, Spain

, Yolanda García-Mesa1

\*Address all correspondence to: javega@uniovi.es

provided the original work is properly cited.

, Olivía García-Suárez1

, Jorge García-Piqueras1

1 Departamento de Morfología y Biología Celular, Grupo SINPOS, Universidad de

2 Departamento de Anatomía e Histología Humanas, Universidad de Salamanca,

3 Servicio de Anatomía Patológica, Complejo Hospitalario, Universitario de

4 Facultad de Ciencias de la Salud, Universidad Autónoma, Santiago, Chile

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and José A. Vega1,4\*

, Jorge Feito1,2,3,

Ramón Cobo1

Spain

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization…*

*DOI: http://dx.doi.org/10.5772/intechopen.91815*

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization… DOI: http://dx.doi.org/10.5772/intechopen.91815*

## **Author details**

*Somatosensory and Motor Research*

potential generation [93].

**7. Concluding remarks**

**Acknowledgements**

Asturias) for their technical assistance.

detected in glial cells of sensory corpuscles. TRPV4 was detected in the lamellar cells of human Meissner corpuscles [92]. On the other hand, voltage-sensitive Na<sup>+</sup>

inner core lamellae and the axon might participate in both transduction and action

Based on the above data in addition to the hypothesis of voltage-gated and nonvoltage-gated channels, a possible classical neurotransmission cannot be excluded for the genesis of the action potential in sensory corpuscles. In the process of touch sensation, a mechanical stimulus is converted into electrical activity in peripheral sensory neurons, and this conversion may occur through the activation of ion chan-

The glial cells of the sensory corpuscles form a glial subpopulation, highly differentiated and with important functions in the mechanotransduction process that has been repeatedly forgotten in studies on peripheral glia. Its origin is not known exactly, and they could come from cells of the neural crest or the boundary cap cells. However, the chronology of its arrival and organization within the corpuscles has recently been established, as well as their interdependence with sensory axons. In the last decade, some mechano-gated ion channels have been discovered in corpuscular glial cells. This fact associated with the demonstration of a GABA-ergic/ glutamatergic neurotransmission system in the Pacinian corpuscles suggests that the glial cells of the sensory corpuscles are not support cells but have an active role in the mechanotransduction process. Nevertheless, whether or not this occurs only in Pacinian corpuscles or in all sensory corpuscles remains to be demonstrated.

This study was supported in part by a grant from Gerencia Regional de Salud de Castilla y León (GRS 1615/A/17). YG-M was supported by a grant "Severo Ochoa" from the Government of the Principality of Asturias (Ref. BP17-044). The authors thank Dr. Marta Guervos (Servicios Comunes de Investigación, Microscopia Confocal, Universidad de Oviedo) and Marta Sánchez-Pitiot (Grupo de Histopatología Molecular, Instituto Universitario de Oncología del Principado de

channel) present in the

channels (α-subunit type I and type II voltage-gated Na<sup>+</sup>

nels that gate in response to mechanical stimuli.

**26**

Ramón Cobo1 , Yolanda García-Mesa1 , Jorge García-Piqueras1 , Jorge Feito1,2,3, José Martín-Cruces1 , Olivía García-Suárez1 and José A. Vega1,4\*

1 Departamento de Morfología y Biología Celular, Grupo SINPOS, Universidad de Oviedo, Oviedo, Spain

2 Departamento de Anatomía e Histología Humanas, Universidad de Salamanca, Spain

3 Servicio de Anatomía Patológica, Complejo Hospitalario, Universitario de Salamanca, Salamanca, Spain

4 Facultad de Ciencias de la Salud, Universidad Autónoma, Santiago, Chile

\*Address all correspondence to: javega@uniovi.es

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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**28**

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*Somatosensory and Motor Research*

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[52] McCormick AM, Jarmusik NA, Leipzig ND. Co-immobilization of semaphorin3A and nerve growth factor to guide and pattern axons. Acta

Biomaterialia. 2015;**28**:33-44

[53] Engelhardt M, Vorwald S, Sobotzik JM, Bennett V, Schultz C. Ankyrin-B structurally defines terminal

microdomains of peripheral

Function. 2013;**218**:1005-1016

somatosensory axons. Brain Structure &

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[55] Aquino JB, Sierra R. Schwann cell precursors in health and disease. Glia.

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**30**

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[51] Curley JL, Catig GC, Horn-Ranney EL, Moore MJ. Sensory axon guidance with semaphorin 6A and nerve growth factor in a biomimetic choice point model. Biofabrication. 2014;**6**:035026

[52] McCormick AM, Jarmusik NA, Leipzig ND. Co-immobilization of semaphorin3A and nerve growth factor to guide and pattern axons. Acta Biomaterialia. 2015;**28**:33-44

[53] Engelhardt M, Vorwald S, Sobotzik JM, Bennett V, Schultz C. Ankyrin-B structurally defines terminal microdomains of peripheral somatosensory axons. Brain Structure & Function. 2013;**218**:1005-1016

[54] Koser DE, Thompson AJ, Foster SK, Dwivedy A, Pillai EK, Sheridan GK, et al. Mechanosensing is critical for axon growth in the developing brain. Nature Neuroscience. 2016;**19**:1592-1598

[55] Aquino JB, Sierra R. Schwann cell precursors in health and disease. Glia. 2018;**66**:465-476

[56] Albuerne M, De Lavallina J, Esteban I, Naves FJ, Silos-Santiago I, Vega JA. Development of Meissnerlike and Pacinian sensory corpuscles in the mouse demonstrated with specific markers for corpuscular constituents. The Anatomical Record. 2000;**258**:235-242

[57] Feito J, García-Suárez O, García-Piqueras J, García-Mesa Y, Pérez-Sánchez A, Suazo I, et al. The development of human digital Meissner's and Pacinian corpuscles. Annals of Anatomy. 2018;**219**:8-24

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[65] Vega JA, Dubovy P, del Valle-Soto ME, Hernandez LC, Perez-Casas A, Malinovsky L. Immunohistochemical study of Pacinian corpuscles using monoclonal antibodies for neurofilament protein, glial fibrillary acidic protein and S-100 protein. Cellular and Molecular Biology. 1989;**35**:627-633

[66] García-Suárez O, Calavia MG, Pérez-Moltó FJ, Alvarez-Abad C, Pérez-Piñera P, Cobo JM, et al. Immunohistochemical profile of human pancreatic pacinian corpuscles. Pancreas. 2010;**39**:403-410

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[68] Del Valle ME, Vazquez E, Naves FJ, Represa JJ, Malinovsky L, Vega JA. Immunohistochemical localization of calcium-binding proteins in the human cutaneous sensory corpuscles. Neuroscience Letters. 1994;**168**:247-250

[69] Gonzalez-Martinez T, Perez-Piñera P, Díaz-Esnal B, Vega JA. S-100 proteins in the human peripheral nervous system. Microscopy Research and Technique. 2003;**60**:633-638

[70] Stark B, Carlstedt T, Risling M. Distribution of TGF-β, the TGF-β type I receptor and the R-II receptor in peripheral nerves and mechanoreceptors; observations on changes after traumatic injury. Brain Research. 2001;**913**:47-56

[71] Cabo R, Alonso P, San José I, Vázquez G, Pastor JF, Germanà A, et al. Brain-derived neurotrophic factor and its receptor TrkB are present, but segregated, within mature cutaneous Pacinian corpuscles of Macaca fascicularis. Anatomical record (Hoboken, N.J.). 2015;**298**:624-629

[72] Vega JA, Vazquez E, Naves FJ, Calzada B, Del Valle ME, Represa JJ. Expression of epidermal growth factor receptor (EGFr) immunoreactivity in human cutaneous nerves and sensory corpuscles. The Anatomical Record. 1994;**240**:125-130

[73] Ribeiro da Silva A, Kenigsberg RL, Cuello AC. Light and electron microscopic distribution of nerve growth factor receptor-like immunoreactivity in the skin of the rat lower lip. Neuroscience. 1991;**43**:631-646

[74] Vega JA, Del Valle ME, Haro JJ, Calzada B, Suarez-Garnacho S, Malinovsky L. Nerve growth factor receptor immunoreactivity in Meissner and Pacinian corpuscles of the human digital skin. The Anatomical Record. 1993;**236**:730-736

[75] Vega JA, Haro JJ, De Lamo A, Ordieres M, Del Valle ME, Calzada B. Distribution of low affinity nerve growth factor receptors (NGFr) immunoreactivity in the human digital skin. European Journal of Dermatology. 1993;**2**:509-516

[76] Schatteman GC, Langer T, Lanahn AA, Bothwell MA. Distribution of 75-kD low affinity nerve growth factor receptor in the primate peripheral nervous system. Somatosensory & Motor Research. 1993;**10**:415-432

[77] Vega JA, Vazquez E, Naves FJ, Del Valle ME, Calzada B, Represa JJ. Immunohistochemical localization of the high affinity NGF receptor (p140kDa-trkA) in adult dorsal root and sympathetic ganglia, and in the nerves and sensory corpuscles supplying digital skin. The Anatomical Record. 1994;**240**:579-588

[78] Stark B, Risling M, Carlstedt T. Distribution of the neurotrophin receptors p75 and trkB in peripheral

**33**

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization…*

determinants of mechanosensitive receptors. Channels (Austin).

anatomy, function, and development of mammalian Aβ low-threshold mechanoreceptors. Frontiers in Biology (Beijing). 2013;**8**(4). DOI: 10.1007/

[89] Montaño JA, Calavia MG, García-Suárez O, Suarez-Quintanilla JA, Gálvez A, Pérez-Piñera P, et al. The expresssssion of ENa(+)C and ASIC2 proteins in Pacinian corpuscles is differently regulated by TrkB and its ligands BDNF and NT-4. Neuroscience

[88] Fleming MS, Luo W. The

2012;**6**:234-245

s11515-013-1271-1

Letters. 2009;**463**:114-118

[90] Calavia MG, Montaño JA, García-Suárez O, Feito J, Guervós MA, Germanà A, et al. Differential localization of acidsensing ion channels 1 and 2 in human

cutaneus pacinian corpuscles.

[91] Cabo R, Alonso P, Viña E,

[92] Alonso-González P, Cabo R, San José I, Gago A, Suazo IC,

Meissner corpuscles display immunoreactivity for the

and Trpv4. Anatomical Record (Hoboken, N.J.). 2016.

2016;**300**:1022-1031

García-Suárez O, et al. Human digital

multifunctional ion channels Trpc6

[93] Pawson L, Bolanowski SJ. Voltagegated sodium channels are present on both the neural and capsular structures of Pacinian corpuscles. Somatosensory & Motor Research. 2002;**19**:231-237

2010;**30**:841-848

2015;**143**:267-276

Cellular and Molecular Neurobiology.

Vázquez G, Gago A, Feito J, et al. ASIC2 is present in human mechanosensory neurons of the dorsal root ganglia and in mechanoreceptors of the glabrous skin. Histochemistry and Cell Biology.

*DOI: http://dx.doi.org/10.5772/intechopen.91815*

Iglesias L, de Carlos F, García-Suárez O, Pérez-Piñera P, et al. The lamellar cells in human Meissner corpuscles express TrkB. Neuroscience Letters.

[80] Pawson L, Pack AK, Bolanowski SJ. Possible glutaminergic interaction between the capsule and neurite of Pacinian corpuscles. Somatosensory &

[81] Pawson L, Prestia LT, Mahoney GK, Güçlü B, Cox PJ, Pack AK. GABAergic/ glutamatergic-glial/neuronal interaction contributes to rapid adaptation in pacinian corpuscles. The Journal of Neuroscience. 2009;**29**:2695-2705

mechanotransduction. Current Opinion in Neurobiology. 2009;**19**:362-369

mechanoreceptors; observations on changes after injury. Experimental Brain

Research. 2001;**136**:101-107

2010;**468**:106-109

[79] Calavia MG, Feito J, López-

Motor Research. 2007;**24**:85-95

[82] Tsunozaki M, Bautista DM. Mammalian somatosensory

[83] Lumpkin EA, Marshall KL, Nelson AM. The cell biology of touch. The Journal of Cell Biology.

[84] Gu Y, Gu C. Physiological and pathological functions of mechanosensitive ion channels. Molecular Neurobiology.

[85] Paluch EK, Nelson CM, Biais N, Fabry B, Moeller J, Pruitt BL, et al. Mechanotransduction: Use the force(s).

[86] Ranade SS, Syeda R, Patapoutian A. Mechanically activated ion channels.

[87] Roudaut Y, Lonigro A, Coste B, Hao J, Delmas P, Crest M. Touch sense: Functional organization and molecular

2010;**191**:237-248

2014;**50**:339-347

BMC Biology. 2015;**13**:47

Neuron. 2015;**87**:1162-1179

*The Glial Cell of Human Cutaneous Sensory Corpuscles: Origin, Characterization… DOI: http://dx.doi.org/10.5772/intechopen.91815*

mechanoreceptors; observations on changes after injury. Experimental Brain Research. 2001;**136**:101-107

*Somatosensory and Motor Research*

study of Pacinian corpuscles using monoclonal antibodies for neurofilament protein, glial fibrillary acidic protein and S-100 protein. Cellular and Molecular Biology.

1989;**35**:627-633

[65] Vega JA, Dubovy P, del Valle-

[66] García-Suárez O, Calavia MG, Pérez-Moltó FJ, Alvarez-Abad C, Pérez-Piñera P, Cobo JM, et al. Immunohistochemical profile of human pancreatic pacinian corpuscles.

[67] Andressen C, Bliimke I, Celio MR. Calcium-binding proteins: Selective markers of nerve cells. Cell and Tissue

[68] Del Valle ME, Vazquez E, Naves FJ, Represa JJ, Malinovsky L, Vega JA. Immunohistochemical localization of calcium-binding proteins in the human cutaneous sensory corpuscles. Neuroscience Letters.

[69] Gonzalez-Martinez T, Perez-Piñera P, Díaz-Esnal B, Vega JA. S-100 proteins in the human peripheral nervous system. Microscopy Research and Technique. 2003;**60**:633-638

[70] Stark B, Carlstedt T, Risling M. Distribution of TGF-β, the TGF-β type I receptor and the R-II receptor in peripheral nerves and mechanoreceptors; observations on changes after traumatic injury. Brain

Research. 2001;**913**:47-56

[71] Cabo R, Alonso P, San José I, Vázquez G, Pastor JF, Germanà A, et al. Brain-derived neurotrophic factor and its receptor TrkB are present, but segregated, within mature cutaneous Pacinian corpuscles of Macaca fascicularis. Anatomical record (Hoboken, N.J.). 2015;**298**:624-629

Pancreas. 2010;**39**:403-410

Research. 1993;**271**:181-208

1994;**168**:247-250

Soto ME, Hernandez LC, Perez-Casas A, Malinovsky L. Immunohistochemical

[72] Vega JA, Vazquez E, Naves FJ, Calzada B, Del Valle ME, Represa JJ. Expression of epidermal growth factor receptor (EGFr) immunoreactivity in human cutaneous nerves and sensory corpuscles. The Anatomical Record.

[73] Ribeiro da Silva A, Kenigsberg RL,

[74] Vega JA, Del Valle ME, Haro JJ, Calzada B, Suarez-Garnacho S, Malinovsky L. Nerve growth factor receptor immunoreactivity in Meissner and Pacinian corpuscles of the human digital skin. The Anatomical Record.

[75] Vega JA, Haro JJ, De Lamo A, Ordieres M, Del Valle ME, Calzada B. Distribution of low affinity nerve growth factor receptors (NGFr) immunoreactivity in the human digital skin. European Journal of Dermatology.

[76] Schatteman GC, Langer T,

[77] Vega JA, Vazquez E, Naves FJ, Del Valle ME, Calzada B, Represa JJ. Immunohistochemical localization of the high affinity NGF receptor (p140kDa-trkA) in adult dorsal root and sympathetic ganglia, and in the nerves and sensory corpuscles supplying digital skin. The Anatomical Record.

[78] Stark B, Risling M, Carlstedt T. Distribution of the neurotrophin receptors p75 and trkB in peripheral

Lanahn AA, Bothwell MA. Distribution of 75-kD low affinity nerve growth factor receptor in the primate peripheral nervous system. Somatosensory & Motor Research. 1993;**10**:415-432

Cuello AC. Light and electron microscopic distribution of nerve growth factor receptor-like immunoreactivity in the skin of the rat lower lip. Neuroscience.

1994;**240**:125-130

1991;**43**:631-646

1993;**236**:730-736

1993;**2**:509-516

1994;**240**:579-588

**32**

[79] Calavia MG, Feito J, López-Iglesias L, de Carlos F, García-Suárez O, Pérez-Piñera P, et al. The lamellar cells in human Meissner corpuscles express TrkB. Neuroscience Letters. 2010;**468**:106-109

[80] Pawson L, Pack AK, Bolanowski SJ. Possible glutaminergic interaction between the capsule and neurite of Pacinian corpuscles. Somatosensory & Motor Research. 2007;**24**:85-95

[81] Pawson L, Prestia LT, Mahoney GK, Güçlü B, Cox PJ, Pack AK. GABAergic/ glutamatergic-glial/neuronal interaction contributes to rapid adaptation in pacinian corpuscles. The Journal of Neuroscience. 2009;**29**:2695-2705

[82] Tsunozaki M, Bautista DM. Mammalian somatosensory mechanotransduction. Current Opinion in Neurobiology. 2009;**19**:362-369

[83] Lumpkin EA, Marshall KL, Nelson AM. The cell biology of touch. The Journal of Cell Biology. 2010;**191**:237-248

[84] Gu Y, Gu C. Physiological and pathological functions of mechanosensitive ion channels. Molecular Neurobiology. 2014;**50**:339-347

[85] Paluch EK, Nelson CM, Biais N, Fabry B, Moeller J, Pruitt BL, et al. Mechanotransduction: Use the force(s). BMC Biology. 2015;**13**:47

[86] Ranade SS, Syeda R, Patapoutian A. Mechanically activated ion channels. Neuron. 2015;**87**:1162-1179

[87] Roudaut Y, Lonigro A, Coste B, Hao J, Delmas P, Crest M. Touch sense: Functional organization and molecular determinants of mechanosensitive receptors. Channels (Austin). 2012;**6**:234-245

[88] Fleming MS, Luo W. The anatomy, function, and development of mammalian Aβ low-threshold mechanoreceptors. Frontiers in Biology (Beijing). 2013;**8**(4). DOI: 10.1007/ s11515-013-1271-1

[89] Montaño JA, Calavia MG, García-Suárez O, Suarez-Quintanilla JA, Gálvez A, Pérez-Piñera P, et al. The expresssssion of ENa(+)C and ASIC2 proteins in Pacinian corpuscles is differently regulated by TrkB and its ligands BDNF and NT-4. Neuroscience Letters. 2009;**463**:114-118

[90] Calavia MG, Montaño JA, García-Suárez O, Feito J, Guervós MA, Germanà A, et al. Differential localization of acidsensing ion channels 1 and 2 in human cutaneus pacinian corpuscles. Cellular and Molecular Neurobiology. 2010;**30**:841-848

[91] Cabo R, Alonso P, Viña E, Vázquez G, Gago A, Feito J, et al. ASIC2 is present in human mechanosensory neurons of the dorsal root ganglia and in mechanoreceptors of the glabrous skin. Histochemistry and Cell Biology. 2015;**143**:267-276

[92] Alonso-González P, Cabo R, San José I, Gago A, Suazo IC, García-Suárez O, et al. Human digital Meissner corpuscles display immunoreactivity for the multifunctional ion channels Trpc6 and Trpv4. Anatomical Record (Hoboken, N.J.). 2016. 2016;**300**:1022-1031

[93] Pawson L, Bolanowski SJ. Voltagegated sodium channels are present on both the neural and capsular structures of Pacinian corpuscles. Somatosensory & Motor Research. 2002;**19**:231-237

**35**

**Chapter 3**

**Abstract**

accident is also given.

**1. Introduction**

and working capacity.

any disorders in the body.

Evaluation

Vestibular System: Anatomy,

*Dmytro Illich Zabolotnyi and Nina Serhiivna Mishchanchuk*

Аbstract Studies on vestibular system have brought new experimental studies, clinical examinations, and the development of effective treatment for a number of diseases of this system. In particular, vestibular paroxysmal positional disorders of peripheral and central origin have been studied. The main criteria for differential diagnosis of these disorders have been determined. Vestibular dysfunction in canalolithiasis and cupololithiasis has been investigated clinically and histologically. Effective therapeutic and prophylactic positional maneuvers of three types have been introduced into clinical practice. They were developed taking into account the anatomical and physiological features of the vestibular system. Currently only 20% of vestibular reactions, in particular, using electronystagmography test (ENG), are estimated in the horizontal plane. Videonystagmography (VNG) gives the possibility of video recording of nystagmus in the directions of semicircular channels (vertical, diagonal, horizontal). The vestibular evoked myogenic potential test (VEMP) is being widely used in clinical practice. Magnetic coils and scanning laser ophthalmoscopes are gaining increasing significance in examining patients. A brief information on vestibular disorders after the Chornobyl nuclear power plant

**Keywords:** vestibular dysfunction, vertigo, postural balance and control,

Sensory functions, in particular, vestibular and auditory ones, represent a reliable criterion for assessing human health, social adequacy, professional suitability,

Symmetry of the anatomical-topographical localization of these systems and proper space orientation provided by them are important regarding all social life aspects. The vestibular system plays a crucial role in space orientation, both at rest and in movement, as well as in professional activity of the person. Its effect onto the motor memory mechanisms, underlying all human motor activity forms, including the professional ones, is extremely important. The vestibular system, with its extremely keen sensitivity, dynamism, and high informativeness of symptoms of the ear labyrinth diseases, as well as different parts of the brain, significantly exceeds the informativeness of all other analyzers. It is the first system to respond to

spontaneous, positional, and experimental nystagmus

Physiology, and Clinical

## **Chapter 3**

## Vestibular System: Anatomy, Physiology, and Clinical Evaluation

*Dmytro Illich Zabolotnyi and Nina Serhiivna Mishchanchuk*

## **Abstract**

Аbstract Studies on vestibular system have brought new experimental studies, clinical examinations, and the development of effective treatment for a number of diseases of this system. In particular, vestibular paroxysmal positional disorders of peripheral and central origin have been studied. The main criteria for differential diagnosis of these disorders have been determined. Vestibular dysfunction in canalolithiasis and cupololithiasis has been investigated clinically and histologically. Effective therapeutic and prophylactic positional maneuvers of three types have been introduced into clinical practice. They were developed taking into account the anatomical and physiological features of the vestibular system. Currently only 20% of vestibular reactions, in particular, using electronystagmography test (ENG), are estimated in the horizontal plane. Videonystagmography (VNG) gives the possibility of video recording of nystagmus in the directions of semicircular channels (vertical, diagonal, horizontal). The vestibular evoked myogenic potential test (VEMP) is being widely used in clinical practice. Magnetic coils and scanning laser ophthalmoscopes are gaining increasing significance in examining patients. A brief information on vestibular disorders after the Chornobyl nuclear power plant accident is also given.

**Keywords:** vestibular dysfunction, vertigo, postural balance and control, spontaneous, positional, and experimental nystagmus

## **1. Introduction**

Sensory functions, in particular, vestibular and auditory ones, represent a reliable criterion for assessing human health, social adequacy, professional suitability, and working capacity.

Symmetry of the anatomical-topographical localization of these systems and proper space orientation provided by them are important regarding all social life aspects. The vestibular system plays a crucial role in space orientation, both at rest and in movement, as well as in professional activity of the person. Its effect onto the motor memory mechanisms, underlying all human motor activity forms, including the professional ones, is extremely important. The vestibular system, with its extremely keen sensitivity, dynamism, and high informativeness of symptoms of the ear labyrinth diseases, as well as different parts of the brain, significantly exceeds the informativeness of all other analyzers. It is the first system to respond to any disorders in the body.

Auditory system provides for social communication function. Binaural hearing impairment leads to spatial orientation disorders. Vestibular and auditory sensory systems stimulate cortical processes, being responsible for various activities, postural balance and control, emotions, and creative thought. Therefore, the need for a comprehensive clinical study of vestibular and auditory disorders in order to increase the effectiveness of prevention and treatment, correction and rehabilitation, identification of issues of professional suitability, and work capacity is very important.

## **2. Overview and anatomy of the vestibular system**

Vestibular system (VS) is the most mysterious biological system. It was the first to develop during the embryogenesis. The vestibular system consists of the peripheral and central components, which have a complex structure that has not been fully understood. Its peripheral components are located in the paired ear labyrinth of the pyramid of the temporal bone. Its central components are composed of the conductive part, vestibular nuclei in the brain stem and cortical representation [1, 2].

Bony labyrinth is located in the temporal bone. The membranous labyrinth is located in the middle of the bony labyrinth, resembling the shape of its small cavities. Membranous labyrinth is fixed to the inner wall of the bony labyrinth by means of helical formations acting as shock absorbers. Due to this, it is held in relation to the bony labyrinth, being suspended. Membranous labyrinth consists of the peripheral acoustic section of the cochlea, where the auditory receptor organ of Corti is located, as well as the peripheral component of the vestibular system. The peripheral component of the vestibular system is represented by the vestibulum containing spherical (saccule) and elliptical (utricle) sacs that form the receptor otolith organ. Another three semicircular canals of the peripheral vestibular system are located in the membranous labyrinth [3].

Each canal is thickened and enlarged at one side, resembling ampoules by shape (ampullary receptor organ), and it has a smooth terminal region that connects to the vestibulum on the other side. The three semicircular canals are located approximately at straight angle to each other. Therefore, they may sense angular motion, conducted in any plane or direction. One canal is horizontal and the other two (front and back) are vertical. The perception of head movement is provided by activation of the right and left semicircular canals, which are located within the movement plane, thus forming functional pairs.

The membranous labyrinth is washed by perilymph fluid, which in chemical composition is similar to the cerebrospinal fluid. The middle of membranous labyrinth contains endolymph. It is intracellular fluid that provides the helix, otolith, and ampullar apparatus with oxygen, nutrients, and hormones. The potassium concentration in it is high (144 mmol/L), and the concentration of sodium is low (5 mmol/L). The mechanisms of endolymph formation and its circulation in the membranous labyrinth have not been yet well understood. The membranous labyrinth is elastic, and its size can increase by 2–3 times, filling all the "cavities" of the bony labyrinth, for example, in the case of ascites and other pathological conditions [4].

In the receptor otolithic apparatus, spherical (saccule) and elliptic (utricle) sacs contain hairy receptor cells covered by supporting dense layers of cells called overhead covers. These receptor cells are sensitive to linear acceleration. They flex in response to appropriate irritation. The clusters of the neuroepithelial receptor cells of the otolith apparatus, which are located between the supporting cells in elliptical and spherical sacs, interweave, forming loops. Calcium salt microcrystals are located in these loops; they are called otoliths [5].

**37**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

The receptor structures of the ampullar apparatus, three semicircular canals (anterior, posterior, and horizontal), are located in mutually perpendicular planes. The smooth terminal parts of two semicircular canals (anterior and posterior) are joined into a single canal that enters the utricle. It is connected to the receptive auditory structures of the Corti organ. Endolymph, which is produced by the vascular strip of the helix, passes through this canal into the vestibular endolymphatic canals. This important fact, as the authors emphasize [4], is significant for various ear diseases and pathological changes of the temporal bone, as well as the brain,

The hair cells of the vestibulum and the ampoules of three semicircular canals

The vestibular nerve fibers originate in the vestibular ganglion. It is located deep in the internal auditory canal. This node consists of bipolar cells. The dendrites of these cells penetrate into the bony labyrinth through the internal auditory canal opening, approaching the saccule and utricle receptor structures, as well as the ampullar semicircular canal receptor structures. Axons of these cells, joining the helix nerve, represent the vestibulocochlear (auditory vestibular) nerve—the VIII cranial nerve. In the internal auditory canal, this nerve meets facial nerve—the VII cranial nerve—proceeding into the cavity of the skull; then in the thickness of the rhombic fossa of the medulla oblongata, four-paired vestibular nuclei enter: upper

Reflex pathways originate in the vestibular nuclei, and these pathways are in various ways related to different systems and organs in the body. There are five

1.Tractus vestibulo-spinalis, through which impulses from the vestibular nuclei

2.Tractus vestibulo-longitudinalis joins vestibular nuclei with nuclei of the III, IV, and VI cranial nerves, resulting in responses produced by the oculomotor

4.Tractus vestibulо-reticularis joins vestibular nuclei with the vagus nerve nuclei in the reticular formation, producing reflexes in the internal organ smooth

5.Tractus vestibulo-соrtikalis joins the vestibular nuclei with the temporal lobes of the cerebral cortex through multisynaptic connections, with the midbrain

It should be noted that disorders of the vestibular system occur at any of its levels from the receptor structures of the ear maze to the cortical representation. When leaving the internal auditory canal, V, VI, and VII pairs of cranial nerves are located near the VIII pair of cranial nerve as well as a group of pairs of caudal (ІX–XII) cranial nerves. They reflect the lesions of structures located near the

It should be emphasized that in the cases of disorders in the area of the labyrinth, temporal bone, and cerebellar angle, vestibular disorders are often accompanied by unilateral auditory disorders. Central vestibular disorders are less

reach the voluntary muscles of the spinal cord anterior horns.

3.Tractus vestibulo-сеrebellaris joins the nuclei with the cerebellum.

generate a receptor potential, which through the synapses (by production of acetylcholine) transmits signals to the terminal regions of the vestibular nerve

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

accompanied by vestibular disorders.

and lower and lateral and medial [6].

nerves—varieties of nystagmus.

fibers.

pathways:

muscles.

crossway.

vestibular system.

#### *Vestibular System: Anatomy, Physiology, and Clinical Evaluation DOI: http://dx.doi.org/10.5772/intechopen.90538*

*Somatosensory and Motor Research*

Auditory system provides for social communication function. Binaural hearing impairment leads to spatial orientation disorders. Vestibular and auditory sensory systems stimulate cortical processes, being responsible for various activities, postural balance and control, emotions, and creative thought. Therefore, the need for a comprehensive clinical study of vestibular and auditory disorders in order to increase the effectiveness of prevention and treatment, correction and rehabilitation, identification of issues of professional suitability, and work capacity is very important.

Vestibular system (VS) is the most mysterious biological system. It was the first to develop during the embryogenesis. The vestibular system consists of the peripheral and central components, which have a complex structure that has not been fully understood. Its peripheral components are located in the paired ear labyrinth of the pyramid of the temporal bone. Its central components are composed of the conductive part, vestibular nuclei in the brain stem and cortical representation [1, 2]. Bony labyrinth is located in the temporal bone. The membranous labyrinth is located in the middle of the bony labyrinth, resembling the shape of its small cavities. Membranous labyrinth is fixed to the inner wall of the bony labyrinth by means of helical formations acting as shock absorbers. Due to this, it is held in relation to the bony labyrinth, being suspended. Membranous labyrinth consists of the peripheral acoustic section of the cochlea, where the auditory receptor organ of Corti is located, as well as the peripheral component of the vestibular system. The peripheral component of the vestibular system is represented by the vestibulum containing spherical (saccule) and elliptical (utricle) sacs that form the receptor otolith organ. Another three semicircular canals of the peripheral vestibular system

Each canal is thickened and enlarged at one side, resembling ampoules by shape (ampullary receptor organ), and it has a smooth terminal region that connects to the vestibulum on the other side. The three semicircular canals are located approximately at straight angle to each other. Therefore, they may sense angular motion, conducted in any plane or direction. One canal is horizontal and the other two (front and back) are vertical. The perception of head movement is provided by activation of the right and left semicircular canals, which are located within the

The membranous labyrinth is washed by perilymph fluid, which in chemical composition is similar to the cerebrospinal fluid. The middle of membranous labyrinth contains endolymph. It is intracellular fluid that provides the helix, otolith, and ampullar apparatus with oxygen, nutrients, and hormones. The potassium concentration in it is high (144 mmol/L), and the concentration of sodium is low (5 mmol/L). The mechanisms of endolymph formation and its circulation in the membranous labyrinth have not been yet well understood. The membranous labyrinth is elastic, and its size can increase by 2–3 times, filling all the "cavities" of the bony labyrinth, for example, in the case of ascites and other pathological

In the receptor otolithic apparatus, spherical (saccule) and elliptic (utricle) sacs contain hairy receptor cells covered by supporting dense layers of cells called overhead covers. These receptor cells are sensitive to linear acceleration. They flex in response to appropriate irritation. The clusters of the neuroepithelial receptor cells of the otolith apparatus, which are located between the supporting cells in elliptical and spherical sacs, interweave, forming loops. Calcium salt microcrystals

**2. Overview and anatomy of the vestibular system**

are located in the membranous labyrinth [3].

movement plane, thus forming functional pairs.

are located in these loops; they are called otoliths [5].

**36**

conditions [4].

The receptor structures of the ampullar apparatus, three semicircular canals (anterior, posterior, and horizontal), are located in mutually perpendicular planes. The smooth terminal parts of two semicircular canals (anterior and posterior) are joined into a single canal that enters the utricle. It is connected to the receptive auditory structures of the Corti organ. Endolymph, which is produced by the vascular strip of the helix, passes through this canal into the vestibular endolymphatic canals. This important fact, as the authors emphasize [4], is significant for various ear diseases and pathological changes of the temporal bone, as well as the brain, accompanied by vestibular disorders.

The hair cells of the vestibulum and the ampoules of three semicircular canals generate a receptor potential, which through the synapses (by production of acetylcholine) transmits signals to the terminal regions of the vestibular nerve fibers.

The vestibular nerve fibers originate in the vestibular ganglion. It is located deep in the internal auditory canal. This node consists of bipolar cells. The dendrites of these cells penetrate into the bony labyrinth through the internal auditory canal opening, approaching the saccule and utricle receptor structures, as well as the ampullar semicircular canal receptor structures. Axons of these cells, joining the helix nerve, represent the vestibulocochlear (auditory vestibular) nerve—the VIII cranial nerve. In the internal auditory canal, this nerve meets facial nerve—the VII cranial nerve—proceeding into the cavity of the skull; then in the thickness of the rhombic fossa of the medulla oblongata, four-paired vestibular nuclei enter: upper and lower and lateral and medial [6].

Reflex pathways originate in the vestibular nuclei, and these pathways are in various ways related to different systems and organs in the body. There are five pathways:


It should be noted that disorders of the vestibular system occur at any of its levels from the receptor structures of the ear maze to the cortical representation. When leaving the internal auditory canal, V, VI, and VII pairs of cranial nerves are located near the VIII pair of cranial nerve as well as a group of pairs of caudal (ІX–XII) cranial nerves. They reflect the lesions of structures located near the vestibular system.

It should be emphasized that in the cases of disorders in the area of the labyrinth, temporal bone, and cerebellar angle, vestibular disorders are often accompanied by unilateral auditory disorders. Central vestibular disorders are less often combined with auditory disorders. In the brain stem, four pairs of vestibular nuclei are located in a relatively small anatomical space. The presence of these nuclei indicates the great importance of the vestibular system in evolutionary terms [2, 3, 5].

Vestibular disorders very often occur in patients with brainstem pathology. The nuclei of the III, IV, and VI cranial nerves are located with the vestibular conduction pathways, the damage of which is accompanied by diplopia. Pathology of the V cranial nerve is manifested by a decrease in the sensitivity of the skin of the face. Facial (VII) nerve disorders lead to facial distortion, speech disorders, pathology of the IX–X cranial nerves, and disorders of swallowing and articulation. Vestibular disorders through close anatomical connection with the cerebellum can contribute to the development of cerebellar ataxia [4].

## **3. Physiology of the vestibular system**

Researchers have been studying functions of the ear labyrinth for centuries. Describing the feelings during self-spinning, the symptoms of responses occurring in this case were reported: vertigo, balance problems, sweating, nausea, vomiting, changes in heart rate and blood pressure, and respiratory disorders. In the study on birds, destroying semicircular canal of the ear labyrinth, it was first found that sensory perception is based on stimulation of ampullary receptors. In further experiments it was reported that semicircular canals are receptor organs that perceive rotational motions. These movements cause shifting of the endolymph, which causes irritation of receptor neuroepithelial cells in the semicircular canal ampoules, producing nerve impulse [6].

Purkyně [7], reporting on his feelings in the rotation, first described the symptoms of the reactions that occur in this case: vertigo, imbalance, sweating, nausea, vomiting, changes in heart rate and blood pressure, and breathing.

Florens [8] in the experiment on birds, destroying the semicircular canals of the ear labyrinth, first established that the stimulation described by J. Purkiunje was based on the irritation of the ampullary receptors of these canals. These observations initiated the experimental study of the vestibular labyrinth. It was defined that semicircular canals are receptive organs that perceive rotational movements. These movements cause displacement of the endolymph, leading to irritation of receptor neuroepithelial cells in ampoules of semicircular canals, resulting in a nerve impulse.

Evald [9] conducted unique experimental studies and discovered the patterns of functioning of vestibular semicircular canals, which are known as the three laws of Evald:


**39**

labyrinthopathies.

movements.

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

If vestibular system is affected, three types of pathological responses may occur:

**I. The vestibulo-sensory subjective pathological responses** are caused by the processes that occur in the cerebral cortex. These structures analyze and synthesize obtained stimuli. The disorder here may be manifested as a pathological subjective sensation of continuous or periodic vertigo of different direction and intensity, as well as orientation disorders with the reflex action. Vertigo is the most widespread specific sensation after pain, which indicates a disease. The vestibulo-sensory subjective pathological responses originate in the vestibulo-cortical tract.

**II. The vestibulo-somatic objective pathological responses** are manifested

**III. The vestibulo-vegetative objective pathological responses** arise in the receptor vestibular apparatus, as a response onto the smooth muscle of the internal organs' irritation (overpronounced response, hyperreflexia; suppressed response, hyporeflexia) with symmetric or asymmetric sensitivity due to vestibular pathologies, as well as intense and prolonged vestibular loads. These responses occur via tractus vestibulo-reticularis. They often lead to, combined with other vestibular responses, the development of various symptom complexes, including various forms of kinetosis, formerly called motion sickness (marine, air) [6, 10, 11].

These responses are differently significant for human life. As for professional activity, the vestibular vegetative and vestibular sensory responses are the most important. The first ones cause vegetative discomfort, in which a person feels bad and his/her workability is reduced. Others disorient a person in space and can cause serious danger when performing work that involves precise and coordinated

According to the literature [12], up to 20% of the professionals whose jobs are related to the effect of prolonged or elevated vestibular system stimuli may become disabled due to vestibular disorders. Such professionals, as a result of movement discoordination or space disorientation, can make professional mistakes, which may

In anatomical, physiological, and functional relationship between the vestibular and auditory systems, the relation between the nuclear areas and different central nervous system formations and cerebral circulation contributed to the development of otoneurology. Progress in otosurgery and neurosurgery has identified a separate

Pressure changes and various pathological changes associated with purulent and non-purulent processes in the tympanic cavity cause impaired middle-ear sounding function. These changes reach the window of the helix and vestibulum, causing

The structural, vascular, toxic, allergic disorders of the labyrinth may lead to hyperfunction of the endolymph and various vestibulopathies and

Vestibular system, as a system consisting of paired organs, functions by the lever principle. The receptor hairy cells in each of the semicircular canals are located so that shift of the cupula into one side increases afferent input along the vestibular nerve directed toward that side and decreases toward the opposite side.

as muscle reflexes, accompanied by objective spontaneous static and kinetic equilibrium disturbance, as well as pathological objective vestibulo-oculomotor reflexes: spontaneous or positional nystagmus of various direction and intensity (horizontal, rotating, vertical, diagonal, multiple). They are an objective feature of the vestibulo-sensory subjective sensation vertigo of appropriate orientation. These reflexes are provided via tractus vestibulo-spinalis, tractus vestibulo-longitudinalis,

vestibular sensory, vestibular somatic, and vestibular vegetative, with different

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

levels of manifestation.

and tractus vestibulo-сеrebellaris.

cause man-made accidents or even catastrophes.

sensory and neural hearing loss and vestibular dysfunction.

medical specialty: otoneurosurgery.

*Somatosensory and Motor Research*

to the development of cerebellar ataxia [4].

**3. Physiology of the vestibular system**

ampoules, producing nerve impulse [6].

terms [2, 3, 5].

often combined with auditory disorders. In the brain stem, four pairs of vestibular nuclei are located in a relatively small anatomical space. The presence of these nuclei indicates the great importance of the vestibular system in evolutionary

Vestibular disorders very often occur in patients with brainstem pathology. The nuclei of the III, IV, and VI cranial nerves are located with the vestibular conduction pathways, the damage of which is accompanied by diplopia. Pathology of the V cranial nerve is manifested by a decrease in the sensitivity of the skin of the face. Facial (VII) nerve disorders lead to facial distortion, speech disorders, pathology of the IX–X cranial nerves, and disorders of swallowing and articulation. Vestibular disorders through close anatomical connection with the cerebellum can contribute

Researchers have been studying functions of the ear labyrinth for centuries. Describing the feelings during self-spinning, the symptoms of responses occurring in this case were reported: vertigo, balance problems, sweating, nausea, vomiting, changes in heart rate and blood pressure, and respiratory disorders. In the study on birds, destroying semicircular canal of the ear labyrinth, it was first found that sensory perception is based on stimulation of ampullary receptors. In further experiments it was reported that semicircular canals are receptor organs that perceive rotational motions. These movements cause shifting of the endolymph, which causes irritation of receptor neuroepithelial cells in the semicircular canal

Purkyně [7], reporting on his feelings in the rotation, first described the symptoms of the reactions that occur in this case: vertigo, imbalance, sweating, nausea,

Florens [8] in the experiment on birds, destroying the semicircular canals of the ear labyrinth, first established that the stimulation described by J. Purkiunje was based on the irritation of the ampullary receptors of these canals. These observations initiated the experimental study of the vestibular labyrinth. It was defined that semicircular canals are receptive organs that perceive rotational movements. These movements cause displacement of the endolymph, leading to irritation of receptor neuroepithelial cells in ampoules of semicircular canals, resulting in a

Evald [9] conducted unique experimental studies and discovered the patterns of functioning of vestibular semicircular canals, which are known as the three laws of

2.Ampullopetal (toward the canal ampulla) movement of the endolymph causes richer response than the ampullofugal (toward the smooth terminal part of the

4.Prominent scientists of the last century presented clinical and experimental evidence of the vestibular system connection with other body systems and organs, the dependence of response on both strength of the stimulus and func-

1.Nystagmus always occurs in the plane of the semicircular canal irritation.

3.Nystagmus is always directed toward more active semicircular canal.

vomiting, changes in heart rate and blood pressure, and breathing.

**38**

nerve impulse.

canal) one.

tional state of the CNS (cited by [6]).

Evald:

If vestibular system is affected, three types of pathological responses may occur: vestibular sensory, vestibular somatic, and vestibular vegetative, with different levels of manifestation.

**I. The vestibulo-sensory subjective pathological responses** are caused by the processes that occur in the cerebral cortex. These structures analyze and synthesize obtained stimuli. The disorder here may be manifested as a pathological subjective sensation of continuous or periodic vertigo of different direction and intensity, as well as orientation disorders with the reflex action. Vertigo is the most widespread specific sensation after pain, which indicates a disease. The vestibulo-sensory subjective pathological responses originate in the vestibulo-cortical tract.

**II. The vestibulo-somatic objective pathological responses** are manifested as muscle reflexes, accompanied by objective spontaneous static and kinetic equilibrium disturbance, as well as pathological objective vestibulo-oculomotor reflexes: spontaneous or positional nystagmus of various direction and intensity (horizontal, rotating, vertical, diagonal, multiple). They are an objective feature of the vestibulo-sensory subjective sensation vertigo of appropriate orientation. These reflexes are provided via tractus vestibulo-spinalis, tractus vestibulo-longitudinalis, and tractus vestibulo-сеrebellaris.

**III. The vestibulo-vegetative objective pathological responses** arise in the receptor vestibular apparatus, as a response onto the smooth muscle of the internal organs' irritation (overpronounced response, hyperreflexia; suppressed response, hyporeflexia) with symmetric or asymmetric sensitivity due to vestibular pathologies, as well as intense and prolonged vestibular loads. These responses occur via tractus vestibulo-reticularis. They often lead to, combined with other vestibular responses, the development of various symptom complexes, including various forms of kinetosis, formerly called motion sickness (marine, air) [6, 10, 11].

These responses are differently significant for human life. As for professional activity, the vestibular vegetative and vestibular sensory responses are the most important. The first ones cause vegetative discomfort, in which a person feels bad and his/her workability is reduced. Others disorient a person in space and can cause serious danger when performing work that involves precise and coordinated movements.

According to the literature [12], up to 20% of the professionals whose jobs are related to the effect of prolonged or elevated vestibular system stimuli may become disabled due to vestibular disorders. Such professionals, as a result of movement discoordination or space disorientation, can make professional mistakes, which may cause man-made accidents or even catastrophes.

In anatomical, physiological, and functional relationship between the vestibular and auditory systems, the relation between the nuclear areas and different central nervous system formations and cerebral circulation contributed to the development of otoneurology. Progress in otosurgery and neurosurgery has identified a separate medical specialty: otoneurosurgery.

Pressure changes and various pathological changes associated with purulent and non-purulent processes in the tympanic cavity cause impaired middle-ear sounding function. These changes reach the window of the helix and vestibulum, causing sensory and neural hearing loss and vestibular dysfunction.

The structural, vascular, toxic, allergic disorders of the labyrinth may lead to hyperfunction of the endolymph and various vestibulopathies and labyrinthopathies.

Vestibular system, as a system consisting of paired organs, functions by the lever principle. The receptor hairy cells in each of the semicircular canals are located so that shift of the cupula into one side increases afferent input along the vestibular nerve directed toward that side and decreases toward the opposite side. For example, turning the head to the right will increase afferent input of the right lateral semicircular canal and decrease afferent input of the left one. As a result, two conclusions can be made, based on the above mentioned: (1) vertigo may develop at unilateral hypofunction state, even at rest; (2) in the case of complete dysfunction of the semicircular canal on one side, the functioning semicircular canal on the opposite side may perceive head movements in both directions of appropriate plane (by decreased or increased afferent input perception). This ability of the preserved labyrinth to perceive head movements represents the basis of vestibular compensation, providing for restored vestibular functions with unilateral vestibular dysfunction (VD) [12].

The adequate stimulus of the three semicircular canal ampulla apparatus receptor structures is acceleration and slowing during rotation movements. The receptor cells may shift due to the endolymph inertia shift. At the movement acceleration stage, it will be the maximum one. While rotating the head with steady speed, the endolymph shift gradually decreases, and in 15–20 s of rotation it attains the background properties. If to stop movement, the cupula shift turns the cupula toward the opposite side. This phenomenon represents the "stop-stimulus" while conducting classical rotation test using Barany rotational chair. If to compare duration of the caloric test, or the bilateral caloric cold and heat stimulation as well as the post-rotation nystagmus after rotating to the left and right, we should assess the symmetry or asymmetry of vestibular functions [1].

An adequate stimulus of the otolith organ results in acceleration or slowing down at the straight-line movements. As the gravity force is a linear acceleration, the otolith receptors perceive head inclination movements regarding the earth gravity force vector. Absent action of the gravity force onto the otolith organ at null gravity causes significant disturbance in the body, which are thoroughly studied by cosmic medicine. The sensitivity of otolith hairy cells to linear acceleration is determined by the mass of heavy calcium crystals—otoliths. Elliptic sacs of the otolith organ, situated close to horizontal plane, are more sensitive to acceleration within this plane. Spheric sacs are located in almost vertical plane, so they are more sensitive to acceleration and slowing down within a vertical plane. It is necessary to stress that the head movements are the combined ones, i.e., they are accompanied with linear and angular acceleration within various planes and directions. Due to joint functioning of four otolith organs and six semicircular canals, it is possible to perceive complex movements in space [11, 13, 14].

The nystagmus subtypes are the most valuable specific and objective characteristics of acute peripheral, chronic, or acute progressing central VD. The nature of these nystagmuses has not been understood completely. It is supposed that the standard tone of the eye-moving muscles is supported by the impulses of similar symmetric force which derive from the both labyrinths. When we irritate the labyrinth, there appears reflex asymmetry from the eye-moving muscles, expressed as a gradual turning away of the eyes toward the muscle hypertonia side, with gradual nystagmus component developing. Gradual turning away of the eyes causes instant response from the central (cortex) parts, so the eyes turn to the previous position. This is how a quick component of the spontaneous or other nystagmus may appear. The confirmation of cortex genesis of quick nystagmus component is its absence in the case of unconsciousness or narcosis. The slow nystagmus component is preserved in these cases. The nystagmus direction is determined by its quick component [12].

There are three stages of spontaneous nystagmus: in the first phase, when the nystagmus is manifested when the eyes turn away toward the quick component side; in the second phase, when the eyes move toward the quick component or when a person looks straightforward; in the third phase, when the eyes look toward the quick component, straightforward and to the opposite side [13].

**41**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

The studies established that the peripheral or labyrinth-borne spontaneous nystagmus, as a rule, by its intensity is a small- or medium-swinging; by its direction the nystagmus may be horizontal or horizontal-rotating and rhythmical, with

The acute vestibular syndrome requires urgent medical aid. As the authors observe [14–16], the peripheral vestibular syndrome is characterized by high capacity for compensating the affected functions due to central regulating mechanisms. In 2–4 weeks the spontaneous nystagmus decreases in intensity and then disappears completely. At the same time, vertigo decreases; kinetic and then static equilibrium

The pressure changes and pathological disorders in purulent and non-purulent processes in the external ear and tympanic membranes cause problems with the sound-conducting function of the middle ear. These pathological changes through the helix window and vestibule may migrate onto the ear labyrinth. In the labyrinth, under the effect of these conditions, the content and shift of endolymph movement may be changed. These endolymph changes lead to the VS receptor structure impairment, and finally they result in sensorineural deafness and vestibular

In the case of the acute central vestibular syndrome (pathology of the cerebellopontine angle or the pons bodies), there may be other characteristics of spontaneous nystagmus observed. It may be large-swinging or medium-swinging. It may develop within various planes: the vertical, diagonal, horizontal, or multiple. In some cases, spontaneous nystagmus is defined as a tonic-clonic or tonic (with prolonged average angular speed of the slow stage of nystagmus or decrease of its frequency). Spontaneous nystagmus in the case of the central vestibular syndrome

Benign paroxysmal positional vertigo (BPPV) is the most frequent cause of light-headedness. Its treatment has become possible due to application of the original correction methods. The main sign of the BPPV is short-lasting vertigo attacks, which appear when a person abruptly changes his head position related to the gravity vector, for example, changing from the vertical onto the horizontal position, when a

Peripheral nystagmus in the acute stage lasts from the first 2–3 hours to 2–3 days, being directed toward acute stimulation of the labyrinth receptor structures. With gradual labyrinth depression, the nystagmus changes its direction toward the healthy side. In the case of the VD acute stage of peripheral syndrome type, the spontaneous horizontal or horizontal-rotating nystagmus is accompanied with sensory subjective sensation, horizontal vertigo toward labyrinth hyperreflexia side and, in the case of depression, toward the opposite intact side. So, shifts in statics and movement coordination, keeping to the vector laws, are observed the same, directed toward stimulation side or toward the healthy side in depression. The specific acute vestibular symptoms are accompanied by considerable general discomfort, manifested dually; its first manifestation is characterized by nausea, vomiting, and vascular disorders associated with sympatho-adrenergic crisis. Here we may observe increased arterial pressure, tachycardia, hyperemia, and skin dryness, as well as dry oral mucosa. Its second manifestation is characterized by decreased arterial pressure, bradycardia, pale skin and mucosa, extreme

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

sweating, and salivation [13, 14].

is continuous and may progress in intensity [12].

**4. Clinical disorders of the vestibular system**

**4.1 Benign paroxysmal positional vertigo (BPPV)**

functions are restored.

dysfunction.

distinctly changing quick and slow phases [12].

*Somatosensory and Motor Research*

tion (VD) [12].

For example, turning the head to the right will increase afferent input of the right lateral semicircular canal and decrease afferent input of the left one. As a result, two conclusions can be made, based on the above mentioned: (1) vertigo may develop at unilateral hypofunction state, even at rest; (2) in the case of complete dysfunction of the semicircular canal on one side, the functioning semicircular canal on the opposite side may perceive head movements in both directions of appropriate plane (by decreased or increased afferent input perception). This ability of the preserved labyrinth to perceive head movements represents the basis of vestibular compensation, providing for restored vestibular functions with unilateral vestibular dysfunc-

The adequate stimulus of the three semicircular canal ampulla apparatus receptor structures is acceleration and slowing during rotation movements. The receptor cells may shift due to the endolymph inertia shift. At the movement acceleration stage, it will be the maximum one. While rotating the head with steady speed, the endolymph shift gradually decreases, and in 15–20 s of rotation it attains the background properties. If to stop movement, the cupula shift turns the cupula toward the opposite side. This phenomenon represents the "stop-stimulus" while conducting classical rotation test using Barany rotational chair. If to compare duration of the caloric test, or the bilateral caloric cold and heat stimulation as well as the post-rotation nystagmus after rotating to the left and right, we should assess the

An adequate stimulus of the otolith organ results in acceleration or slowing down at the straight-line movements. As the gravity force is a linear acceleration, the otolith receptors perceive head inclination movements regarding the earth gravity force vector. Absent action of the gravity force onto the otolith organ at null gravity causes significant disturbance in the body, which are thoroughly studied by cosmic medicine. The sensitivity of otolith hairy cells to linear acceleration is determined by the mass of heavy calcium crystals—otoliths. Elliptic sacs of the otolith organ, situated close to horizontal plane, are more sensitive to acceleration within this plane. Spheric sacs are located in almost vertical plane, so they are more sensitive to acceleration and slowing down within a vertical plane. It is necessary to stress that the head movements are the combined ones, i.e., they are accompanied with linear and angular acceleration within various planes and directions. Due to joint functioning of four otolith organs and six semicircular canals, it is possible to

The nystagmus subtypes are the most valuable specific and objective characteristics of acute peripheral, chronic, or acute progressing central VD. The nature of these nystagmuses has not been understood completely. It is supposed that the standard tone of the eye-moving muscles is supported by the impulses of similar symmetric force which derive from the both labyrinths. When we irritate the labyrinth, there appears reflex asymmetry from the eye-moving muscles, expressed as a gradual turning away of the eyes toward the muscle hypertonia side, with gradual nystagmus component developing. Gradual turning away of the eyes causes instant response from the central (cortex) parts, so the eyes turn to the previous position. This is how a quick component of the spontaneous or other nystagmus may appear. The confirmation of cortex genesis of quick nystagmus component is its absence in the case of unconsciousness or narcosis. The slow nystagmus component is preserved in these

cases. The nystagmus direction is determined by its quick component [12].

quick component, straightforward and to the opposite side [13].

There are three stages of spontaneous nystagmus: in the first phase, when the nystagmus is manifested when the eyes turn away toward the quick component side; in the second phase, when the eyes move toward the quick component or when a person looks straightforward; in the third phase, when the eyes look toward the

symmetry or asymmetry of vestibular functions [1].

perceive complex movements in space [11, 13, 14].

**40**

The studies established that the peripheral or labyrinth-borne spontaneous nystagmus, as a rule, by its intensity is a small- or medium-swinging; by its direction the nystagmus may be horizontal or horizontal-rotating and rhythmical, with distinctly changing quick and slow phases [12].

Peripheral nystagmus in the acute stage lasts from the first 2–3 hours to 2–3 days, being directed toward acute stimulation of the labyrinth receptor structures. With gradual labyrinth depression, the nystagmus changes its direction toward the healthy side. In the case of the VD acute stage of peripheral syndrome type, the spontaneous horizontal or horizontal-rotating nystagmus is accompanied with sensory subjective sensation, horizontal vertigo toward labyrinth hyperreflexia side and, in the case of depression, toward the opposite intact side. So, shifts in statics and movement coordination, keeping to the vector laws, are observed the same, directed toward stimulation side or toward the healthy side in depression.

The specific acute vestibular symptoms are accompanied by considerable general discomfort, manifested dually; its first manifestation is characterized by nausea, vomiting, and vascular disorders associated with sympatho-adrenergic crisis. Here we may observe increased arterial pressure, tachycardia, hyperemia, and skin dryness, as well as dry oral mucosa. Its second manifestation is characterized by decreased arterial pressure, bradycardia, pale skin and mucosa, extreme sweating, and salivation [13, 14].

The acute vestibular syndrome requires urgent medical aid. As the authors observe [14–16], the peripheral vestibular syndrome is characterized by high capacity for compensating the affected functions due to central regulating mechanisms. In 2–4 weeks the spontaneous nystagmus decreases in intensity and then disappears completely. At the same time, vertigo decreases; kinetic and then static equilibrium functions are restored.

The pressure changes and pathological disorders in purulent and non-purulent processes in the external ear and tympanic membranes cause problems with the sound-conducting function of the middle ear. These pathological changes through the helix window and vestibule may migrate onto the ear labyrinth. In the labyrinth, under the effect of these conditions, the content and shift of endolymph movement may be changed. These endolymph changes lead to the VS receptor structure impairment, and finally they result in sensorineural deafness and vestibular dysfunction.

In the case of the acute central vestibular syndrome (pathology of the cerebellopontine angle or the pons bodies), there may be other characteristics of spontaneous nystagmus observed. It may be large-swinging or medium-swinging. It may develop within various planes: the vertical, diagonal, horizontal, or multiple. In some cases, spontaneous nystagmus is defined as a tonic-clonic or tonic (with prolonged average angular speed of the slow stage of nystagmus or decrease of its frequency). Spontaneous nystagmus in the case of the central vestibular syndrome is continuous and may progress in intensity [12].

## **4. Clinical disorders of the vestibular system**

## **4.1 Benign paroxysmal positional vertigo (BPPV)**

Benign paroxysmal positional vertigo (BPPV) is the most frequent cause of light-headedness. Its treatment has become possible due to application of the original correction methods. The main sign of the BPPV is short-lasting vertigo attacks, which appear when a person abruptly changes his head position related to the gravity vector, for example, changing from the vertical onto the horizontal position, when a

person lies down, or vice versa, when he gets up, or upturns in the bed, or abruptly throws his head back. These attacks of vertigo more often appear in the morning after sleep. They are mostly manifested when the person first changes body position after sleep. They are weakened with repeated head movements. The patients' complaints are very characteristics, quite often basing on the complaints it is possible to diagnose the condition and define the affected side. The patient quite often shows himself, from what side vertigo appears [1, 4, 10, 12].

If the vertigo and nystagmus are horizontally or horizontally rotating directed, this shows us that the horizontal (lateral) semicircular canal is affected. The provoking moment may be when a patient inclines his head toward the affected ear side. The vertigo may be accompanied with nausea and vomiting. The attack appears after a person moves his head, in 1–2 s and lasts for 30–60 s.Vertigo and nystagmus depend on the head movement. If a person looks upward, vertigo and nystagmus are vertical. Vertical nystagmus in this case evidences about excitement of receptors of the posterior semicircular canal. BPPV may develop at any age, most often from 50 to 70 years, affecting women twice as often as men. It may develop after prolonged bed stay, particularly after craniocerebral traumas [11, 14, 16, 17].

The diagnosis is established due to position tests. The position tests should be conducted with all patients complaining of the vertigo even if a patient's complaint is typical for the other vestibular disorders (Meniere's disease, vestibular neuronitis, migraine, and various etiology labyrinth diseases). When there are no effective method of the primary disease treatment, it is always possible to relieve the vertigo, related to the BPPV [12, 15].

According to the cupulolothiasis theory, which was histologically confirmed, in the ampulla of the posterior canal, which is located lower than the other canals, otoliths may deposit more frequently. They, due to various reasons, leave the otolith membrane and stick to the cupula walls. The cupula walls with otoliths become heavy. They become a sensor of linear acceleration instead of the sensor of the angular one though this theory cannot explain many peculiarities of nystagmus [4].

The canalolithiasis theory explains the positional nystagmus signs. Otoliths, according to this theory, do not stick but freely float in the endolymph. As they narrow or obstruct the canal diameter, they cause positional vertigo. As they travel along the canal, otoliths disrupt free shift of the endolymph from the utricle or to the utricle. This theory allows predicting the direction, latent period, and duration of the nystagmus, as well as the changes of its characteristics at various positional maneuvers [4].

In 10–20% of patients suffering from BPPV, lateral semicircular canals have been affected. There are two types of them: related to canalolithiasis (more widespread) and a rarer one, cupulolithiasis. Identification of the lateral semicircular canal BPPV is characterized by some features which were earlier considered to be characteristics of the central positional vertigo. In the case of the lateral semicircular canal canalolithiasis, the patient experiences vertigo when he turns his head to sides, being supine. Changing the position from the supine onto the sitting one and vice versa is not accompanied with significant symptoms. Exacerbations with the lateral canal BPPV are less prolonged than those with the posterior canal affected. The cause of lateral canal BPPV as a canalithiasis type is the invasion of aggressive otoliths in this canal. Remissions are often observed in patients with lateral canal BPPV as otoliths can easily leave the lateral canal during head movements. On the contrary, otoliths do not move from the posterior canal independently due to the anatomical position (it is located below all other canals). A quick result from the maneuvers testifies to the lateral canal BPPV. BPPV anterior canal is used very rarely [4, 6, 17].

The Dix-Hallpike test is the technique used to diagnose posterior semicircular canal BPPV. A patient is brought from sitting to a supine position, with the head

**43**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

turned 45° to one side and extended over the end of the stretcher. In the case of left posterior semicircular canal dysfunction, the test will first cause an increased and then decreased nystagmus that occurs after a short latent period. After returning to

A number of positional maneuvers have been developed to treat BPPV. They are aimed at removing conglomerates of otoliths from semicircular canals. At present, maneuvers developed by Brandt and Daroff and Semont and Epley maneuvers are used. Within the theory of canalolithiasis, Brandt and Daroff were the first to come up with a set of exercises, including head movements that destroy the otolith conglomerates. Their fragments move to the other sections of the labyrinth, where they may be stationary. Therefore, they do not affect the function of

These maneuvers, when applied correctly, are always effective but 50% relapse. In case of relapses, it is recommended to repeat the maneuver that was more effec-

Vestibular neuronitis is a common cause after BPPV peripheral vestibular disease. Clinically, it is manifested by vertigo in the direction of a healthy ear, by spontaneous nystagmus of a horizontally rotary direction to a healthy ear. Functional tests check various degrees of hyporeflexia to the affected ear and postural abnormalities toward a healthy ear. It is considered that vestibular neuronitis is of viral etiology. It is recommended to prescribe glucocorticoids at first as they effectively reduce functional disorders and have a strong anti-inflammatory effect. In addition, they accelerate the central mechanisms of vestibular compensation for

Meniere's disease refers to the peripheral diseases of both vestibular and auditory systems. During an acute attack in the excitation phase in the affected labyrinth, there occurs a strong vertigo of the horizontal direction with horizontal nystagmus, postural disorders, and significant vestibulo-vegetative pathological reactions. At the same time, there is a strong noise in the affected ear, hearing loss, feeling of pawning and fullness in it, and the phenomena of sound discomfort on enhanced sound stimuli. In the phase of inhibition of the labyrinth, vertigo and nystagmus change the direction toward a healthy labyrinth. Postural disorders gradually settle, and vestibulo-vegetative pathological reactions disappear. Within functional stimulation, hyporeflection of the nystagmus is fixed from the side of the affected labyrinth. At the same time, noise, stuffiness, and fullness in the ear decrease, and the effects of sound discomfort are reduced. These facts indicate a common mechanism of the processes of excitation and inhibition in both sensory systems in this

It was histologically confirmed that the basis for Meniere's disease is the periodic accumulation of endolymphatic dropsy (endolymphatic hydrops). An acute attack of vestibular dysfunction lasts from 30 minutes to 3–4 hours and recurs at different intervals. One of the effective treatment methods for Meniere's disease is shunting of a damaged labyrinth, vestibular gymnastics, and salt restriction. Long-term betahistine treatment is often prescribed to prevent attacks and reduce their manifestation. However, the causes of its occurrence have not been fully

postural disorders. Antiviral drugs are less effective [10].

the starting position, the nystagmus will change the direction [15–17].

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

semicircular canals [4].

tive at the first attack [12, 14].

**4.2 Vestibular neuronitis**

**4.3 Meniere's disease**

disease [6, 10, 18, 19].

understood [11, 12, 18].

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation DOI: http://dx.doi.org/10.5772/intechopen.90538*

turned 45° to one side and extended over the end of the stretcher. In the case of left posterior semicircular canal dysfunction, the test will first cause an increased and then decreased nystagmus that occurs after a short latent period. After returning to the starting position, the nystagmus will change the direction [15–17].

A number of positional maneuvers have been developed to treat BPPV. They are aimed at removing conglomerates of otoliths from semicircular canals. At present, maneuvers developed by Brandt and Daroff and Semont and Epley maneuvers are used. Within the theory of canalolithiasis, Brandt and Daroff were the first to come up with a set of exercises, including head movements that destroy the otolith conglomerates. Their fragments move to the other sections of the labyrinth, where they may be stationary. Therefore, they do not affect the function of semicircular canals [4].

These maneuvers, when applied correctly, are always effective but 50% relapse. In case of relapses, it is recommended to repeat the maneuver that was more effective at the first attack [12, 14].

### **4.2 Vestibular neuronitis**

*Somatosensory and Motor Research*

related to the BPPV [12, 15].

himself, from what side vertigo appears [1, 4, 10, 12].

person lies down, or vice versa, when he gets up, or upturns in the bed, or abruptly throws his head back. These attacks of vertigo more often appear in the morning after sleep. They are mostly manifested when the person first changes body position after sleep. They are weakened with repeated head movements. The patients' complaints are very characteristics, quite often basing on the complaints it is possible to diagnose the condition and define the affected side. The patient quite often shows

If the vertigo and nystagmus are horizontally or horizontally rotating directed,

According to the cupulolothiasis theory, which was histologically confirmed, in the ampulla of the posterior canal, which is located lower than the other canals, otoliths may deposit more frequently. They, due to various reasons, leave the otolith membrane and stick to the cupula walls. The cupula walls with otoliths become heavy. They become a sensor of linear acceleration instead of the sensor of the angular one though this theory cannot explain many peculiarities of nystagmus [4]. The canalolithiasis theory explains the positional nystagmus signs. Otoliths, according to this theory, do not stick but freely float in the endolymph. As they narrow or obstruct the canal diameter, they cause positional vertigo. As they travel along the canal, otoliths disrupt free shift of the endolymph from the utricle or to the utricle. This theory allows predicting the direction, latent period, and duration of the nystagmus, as well as the changes of its characteristics at various positional maneuvers [4]. In 10–20% of patients suffering from BPPV, lateral semicircular canals have been affected. There are two types of them: related to canalolithiasis (more widespread) and a rarer one, cupulolithiasis. Identification of the lateral semicircular canal BPPV is characterized by some features which were earlier considered to be characteristics of the central positional vertigo. In the case of the lateral semicircular canal canalolithiasis, the patient experiences vertigo when he turns his head to sides, being supine. Changing the position from the supine onto the sitting one and vice versa is not accompanied with significant symptoms. Exacerbations with the lateral canal BPPV are less prolonged than those with the posterior canal affected. The cause of lateral canal BPPV as a canalithiasis type is the invasion of aggressive otoliths in this canal. Remissions are often observed in patients with lateral canal BPPV as otoliths can easily leave the lateral canal during head movements. On the contrary, otoliths do not move from the posterior canal independently due to the anatomical position (it is located below all other canals). A quick result from the maneuvers testifies to

the lateral canal BPPV. BPPV anterior canal is used very rarely [4, 6, 17].

The Dix-Hallpike test is the technique used to diagnose posterior semicircular canal BPPV. A patient is brought from sitting to a supine position, with the head

this shows us that the horizontal (lateral) semicircular canal is affected. The provoking moment may be when a patient inclines his head toward the affected ear side. The vertigo may be accompanied with nausea and vomiting. The attack appears after a person moves his head, in 1–2 s and lasts for 30–60 s.Vertigo and nystagmus depend on the head movement. If a person looks upward, vertigo and nystagmus are vertical. Vertical nystagmus in this case evidences about excitement of receptors of the posterior semicircular canal. BPPV may develop at any age, most often from 50 to 70 years, affecting women twice as often as men. It may develop after prolonged bed stay, particularly after craniocerebral traumas [11, 14, 16, 17]. The diagnosis is established due to position tests. The position tests should be conducted with all patients complaining of the vertigo even if a patient's complaint is typical for the other vestibular disorders (Meniere's disease, vestibular neuronitis, migraine, and various etiology labyrinth diseases). When there are no effective method of the primary disease treatment, it is always possible to relieve the vertigo,

**42**

Vestibular neuronitis is a common cause after BPPV peripheral vestibular disease. Clinically, it is manifested by vertigo in the direction of a healthy ear, by spontaneous nystagmus of a horizontally rotary direction to a healthy ear. Functional tests check various degrees of hyporeflexia to the affected ear and postural abnormalities toward a healthy ear. It is considered that vestibular neuronitis is of viral etiology. It is recommended to prescribe glucocorticoids at first as they effectively reduce functional disorders and have a strong anti-inflammatory effect. In addition, they accelerate the central mechanisms of vestibular compensation for postural disorders. Antiviral drugs are less effective [10].

#### **4.3 Meniere's disease**

Meniere's disease refers to the peripheral diseases of both vestibular and auditory systems. During an acute attack in the excitation phase in the affected labyrinth, there occurs a strong vertigo of the horizontal direction with horizontal nystagmus, postural disorders, and significant vestibulo-vegetative pathological reactions. At the same time, there is a strong noise in the affected ear, hearing loss, feeling of pawning and fullness in it, and the phenomena of sound discomfort on enhanced sound stimuli. In the phase of inhibition of the labyrinth, vertigo and nystagmus change the direction toward a healthy labyrinth. Postural disorders gradually settle, and vestibulo-vegetative pathological reactions disappear. Within functional stimulation, hyporeflection of the nystagmus is fixed from the side of the affected labyrinth. At the same time, noise, stuffiness, and fullness in the ear decrease, and the effects of sound discomfort are reduced. These facts indicate a common mechanism of the processes of excitation and inhibition in both sensory systems in this disease [6, 10, 18, 19].

It was histologically confirmed that the basis for Meniere's disease is the periodic accumulation of endolymphatic dropsy (endolymphatic hydrops). An acute attack of vestibular dysfunction lasts from 30 minutes to 3–4 hours and recurs at different intervals. One of the effective treatment methods for Meniere's disease is shunting of a damaged labyrinth, vestibular gymnastics, and salt restriction. Long-term betahistine treatment is often prescribed to prevent attacks and reduce their manifestation. However, the causes of its occurrence have not been fully understood [11, 12, 18].

#### **4.4 Migrainous vertigo**

Migrainous vertigo is the most common form of spontaneous recurrent systemic vertigo. It occurs at any age, from preschoolers to older adults. Family history is often noted, indicating the contribution of genetic factors. It occurs with an aura less often than without an aura. During the attack, transient symptoms occur, such as atrial fibrillation, unilateral paresthesia, and aphasia. These symptoms are often preceded by headaches. Migraine-associated vertigo increases when the position of the head changes. The duration of symptomatic episodes when positional nystagmus can be detected may take several days. Relapses occur more frequently than BPPV. Migrainous vertigo is referred to as central positional vertigo [2, 3, 5, 19].

#### **4.5 Central positional vertigo**

Central positional vertigo occurs not frequently, in less than 5% of patients with vertigo. But it is a sign of a serious disease that is associated with structural damage of central divisions of the vestibular system and lobes of the cerebellum. Therefore, central lesion should be excluded first of all in patients with positional vertigo. The most reliable differential feature of BPPV and central positional vertigo is the direction of positional nystagmus. In the case of BPPV, by stimulation in the plane of a certain canal, positional nystagmus characteristic for this canal is typical. When stimulating horizontal (lateral) canalis semicircularis, horizontal positional nystagmus always occurs. The direction of the central positional nystagmus is often not correlated with the stimulating canal. Pure vertical or rotary nystagmus is a sign of central vestibular disorder. In patients with central vertigo, in the absence of changes in MRI, it is possible to suspect a migrainous or other vertigo [14, 16, 19].

#### **4.6 The effect of Chornobyl nuclear power plant accident on vestibular system**

Our own experience [20, 21] of vestibular examinations for more than three decades of 8136 participants of Chornobyl nuclear power plant accident indicates that the patients had vestibular and sensorineural dysfunction. These two dysfunctions are characterized by a predominant disorder in the central (brain stem and subcortical) structures. The priority of changes (preclinical and early clinical) in the central departments of the vestibular and auditory systems, the dependence of the degree of manifestation on the dose, and duration of radiation exposure indicate the parallelism of the common mechanism under the influence of the radiation factor.

The occurrence of deterministic radiation effects of these dysfunctions by the type of central syndrome in radiation doses greater than 0.20 Gy has been investigated. Mathematical modeling determined the dependence of these effects on the age, magnitude of the dose, and duration of stay in the exclusion zone of the Chornobyl power plant, both by clinical electrophysiological and audiometric psychoacoustic and electroacoustic methods. Elongation of magnitudes of the latent periods of the components P-2 and N-2 of auditory evoked long latency or cortical potentials (AEP) in patients with progressive sensorineural hearing loss (SHL) is characterized by slowing the intelligibility of speech and its paradoxical decrease in the conditions of high loads of noise. These features alongside with рresbyacuzis praecoх indicate common inhibitory processes of subcortical and cortical structures of the auditory system [20, 21].

At the same time, there was a decrease in the parameters of the induced nystagmus reaction and a decrease in the postural balance, as well as changes in the manifestation of pathological vestibulo-vegetative reflexes inpatients with VD in

**45**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

tion measures to improve quality and life expectancy [21].

**5. Clinical tests for the vestibular system**

diseases [12, 14].

tion includes:

for further study of a sick person.

ized card or survey.

registration.

registration.

late post-accident period. It has been proven on the basis of epidemiological studies that the inhibition processes in these systems can be regarded as a symptomocomplex of premature aging, with the development of cognitive, emotional, and volitional responses. They require regular treatment and prevention and rehabilita-

Determination of vestibular dysfunction of peripheral, central, or combined (mixed) character requires timely vestibulometric examination for differential diagnosis. This is necessary for the clinical needs of ENT specialists in the treatment of ear diseases (non-purulent and purulent otitis media, otosclerosis, sensory and neural deafness of different genesis, Meniere's disease, neoplasms of the ear). Varieties of vestibular and acoustic dysfunctions may be detected by the physicians of other specialties to provide optimal medical care for neoplasms and traumas of the skull (including the temporal bone, brain), cardiovascular, neuropsychic, infectious, noise-vibrating, radiation-induced, endocrine, toxic, and other

According to the clinical data [13, 15–17], vestibular test methods should be economical, informative, and adequate to the patient's condition and the task of diagnostics and include the study of the functional state of other cranial nerves which may be required to provide a qualified advisory opinion. ENT examination, as well as voice and speech audiometry, is mandatory for vestibular examination. In the case of unilateral or asymmetric bilateral disorder of sound-conducting or sound processing functions, or their combined disorder, it is necessary to carry out one of the following procedures: pure tone audiometry, impedancemetry, otoacoustic emission, registration of short-latent (brain stem) and long-latent (cortex) auditory evoked potentials. The results of the state of auditory function permit making certain focuses during vestibular examination and determining directions

Schemes of vestibular surveys which include vestibular card surveys and a certain sequence of procedures were developed [6]. Scheme of vestibular examina-

1.The study of complaints, medical history, and past diseases using a standard-

2.Investigation of spontaneous vestibular reactions (equilibrium functions, varieties of spontaneous, positional and pressor nystagmuses) and their

3.Conducting vestibular experimental loads (functional stimulations) and their

4.Analysis and evaluation of vestibular test results, making conclusions about

Special vestibular test cards or surveys include a list of general and specific complaints. The sensory subjective reaction—vertigo (the nature of the rotation of objects or their floating or self-rotation, the sense of failing, etc.)—is explained in detail. The direction of vertigo (left, right, up, down, chaotic) and postural disorders (while walking, in the darkness, in fatigue, during transport loads) should

the status of vestibular function and recommendations.

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

*Somatosensory and Motor Research*

**4.5 Central positional vertigo**

Migrainous vertigo is the most common form of spontaneous recurrent systemic

Central positional vertigo occurs not frequently, in less than 5% of patients with vertigo. But it is a sign of a serious disease that is associated with structural damage of central divisions of the vestibular system and lobes of the cerebellum. Therefore, central lesion should be excluded first of all in patients with positional vertigo. The most reliable differential feature of BPPV and central positional vertigo is the direction of positional nystagmus. In the case of BPPV, by stimulation in the plane of a certain canal, positional nystagmus characteristic for this canal is typical. When stimulating horizontal (lateral) canalis semicircularis, horizontal positional nystagmus always occurs. The direction of the central positional nystagmus is often not correlated with the stimulating canal. Pure vertical or rotary nystagmus is a sign of central vestibular disorder. In patients with central vertigo, in the absence of changes in MRI, it is possible to suspect a migrainous or other vertigo [14, 16, 19].

**4.6 The effect of Chornobyl nuclear power plant accident on vestibular system**

Our own experience [20, 21] of vestibular examinations for more than three decades of 8136 participants of Chornobyl nuclear power plant accident indicates that the patients had vestibular and sensorineural dysfunction. These two dysfunctions are characterized by a predominant disorder in the central (brain stem and subcortical) structures. The priority of changes (preclinical and early clinical) in the central departments of the vestibular and auditory systems, the dependence of the degree of manifestation on the dose, and duration of radiation exposure indicate the parallelism of the common mechanism under the influence of the radiation

The occurrence of deterministic radiation effects of these dysfunctions by the type of central syndrome in radiation doses greater than 0.20 Gy has been investigated. Mathematical modeling determined the dependence of these effects on the age, magnitude of the dose, and duration of stay in the exclusion zone of the Chornobyl power plant, both by clinical electrophysiological and audiometric psychoacoustic and electroacoustic methods. Elongation of magnitudes of the latent periods of the components P-2 and N-2 of auditory evoked long latency or cortical potentials (AEP) in patients with progressive sensorineural hearing loss (SHL) is characterized by slowing the intelligibility of speech and its paradoxical decrease in the conditions of high loads of noise. These features alongside with рresbyacuzis praecoх indicate common inhibitory processes of subcortical and cortical structures

At the same time, there was a decrease in the parameters of the induced nystagmus reaction and a decrease in the postural balance, as well as changes in the manifestation of pathological vestibulo-vegetative reflexes inpatients with VD in

vertigo. It occurs at any age, from preschoolers to older adults. Family history is often noted, indicating the contribution of genetic factors. It occurs with an aura less often than without an aura. During the attack, transient symptoms occur, such as atrial fibrillation, unilateral paresthesia, and aphasia. These symptoms are often preceded by headaches. Migraine-associated vertigo increases when the position of the head changes. The duration of symptomatic episodes when positional nystagmus can be detected may take several days. Relapses occur more frequently than BPPV. Migrainous vertigo is referred to as central positional vertigo [2, 3, 5, 19].

**4.4 Migrainous vertigo**

**44**

of the auditory system [20, 21].

factor.

late post-accident period. It has been proven on the basis of epidemiological studies that the inhibition processes in these systems can be regarded as a symptomocomplex of premature aging, with the development of cognitive, emotional, and volitional responses. They require regular treatment and prevention and rehabilitation measures to improve quality and life expectancy [21].

## **5. Clinical tests for the vestibular system**

Determination of vestibular dysfunction of peripheral, central, or combined (mixed) character requires timely vestibulometric examination for differential diagnosis. This is necessary for the clinical needs of ENT specialists in the treatment of ear diseases (non-purulent and purulent otitis media, otosclerosis, sensory and neural deafness of different genesis, Meniere's disease, neoplasms of the ear).

Varieties of vestibular and acoustic dysfunctions may be detected by the physicians of other specialties to provide optimal medical care for neoplasms and traumas of the skull (including the temporal bone, brain), cardiovascular, neuropsychic, infectious, noise-vibrating, radiation-induced, endocrine, toxic, and other diseases [12, 14].

According to the clinical data [13, 15–17], vestibular test methods should be economical, informative, and adequate to the patient's condition and the task of diagnostics and include the study of the functional state of other cranial nerves which may be required to provide a qualified advisory opinion. ENT examination, as well as voice and speech audiometry, is mandatory for vestibular examination.

In the case of unilateral or asymmetric bilateral disorder of sound-conducting or sound processing functions, or their combined disorder, it is necessary to carry out one of the following procedures: pure tone audiometry, impedancemetry, otoacoustic emission, registration of short-latent (brain stem) and long-latent (cortex) auditory evoked potentials. The results of the state of auditory function permit making certain focuses during vestibular examination and determining directions for further study of a sick person.

Schemes of vestibular surveys which include vestibular card surveys and a certain sequence of procedures were developed [6]. Scheme of vestibular examination includes:


Special vestibular test cards or surveys include a list of general and specific complaints. The sensory subjective reaction—vertigo (the nature of the rotation of objects or their floating or self-rotation, the sense of failing, etc.)—is explained in detail. The direction of vertigo (left, right, up, down, chaotic) and postural disorders (while walking, in the darkness, in fatigue, during transport loads) should be determined as well as the presence of autonomic disorders (nausea, vomiting, changes in heart rhythm, changes in skin color, sweating). In cases of complaints about vertigo and postural disorders, attention is focused on the possibility of detecting specific objective spontaneous symptoms—registration of types of nystagmus and posturographic control of these complaints. Some patients pay attention to the fact that they have impaired vision fixation in vertigo. Visual performance is reduced, and fatigue occurs when using a personal computer or mobile phone. In the inter-onset, when there is no vertigo, vision fixation and visual acuity are restored.

The history of the disease is collected in detail: the sequence of its development and the combination with signs of disorders in other systems and organs (cardiovascular, neuro-psychiatric, endocrine, digestive, and musculoskeletal) and past diseases. Attention is paid to the presence of noise, its nature, the acuity, and asymmetry of hearing. Also the asymmetry of the pair of cranial nerves of V, VII, IX, and XII must be examined. Allergic or toxic manifestations are recorded during the survey.

In the course of clinical vestibular test, a large number of trials and tests have been accumulated for postural control. Some of them are of historical importance, and some are still in use, particularly, walking in a straight line, flank walking by steps to the right and left—for differential diagnosis of vestibular and cerebellar disorders.

Romberg's test (classical and sensitized) is the basis for determining the static and kinetic equilibrium in modern types of postural test techniques (in particular, stabilography—a mobile platform with processing of the center of "gravity" and Fourier oscillation analysis.). The speed of movement of the center of gravity in three directions (back and forth, left-right, up-down) is calculated quickly and accurately by a computer. Deviations in the performance of these methods are taken into account when assessing the degree of manifestation of disturbances of the equilibrium function. Postural tests are widely used in the differential diagnosis of peripheral and central balance disorders, for postural control during rehabilitation measures, for postural balance before and after cochlear implantation, for expert and prognostic purposes.

The next step in vestibular examination is the detection of spontaneous, positional, and pressor nystagmuses and registration of their characteristics [13, 14]. At first, nystagmuses can be evaluated visually as well as using Frenzel glasses (+10–12 diopters, which have the backlight inside). A type of spontaneous nystagmus is a positional nystagmus that occurs in one of the head positions and can change its parameters depending on its change. The positional nystagmus is of peripheral or central origin.

Applying pressure, fistula test is of great importance in vestibular field in cases when fistula, prefistula, or dyskinesia in the bony labyrinth is suspected. As a rule, its presence is associated with the destruction of the capsule of bony labyrinth in the purulent process in the middle ear and in the temporal bone. Pressor nystagmus occurs most frequently in the lateral semicircular canal but can often occur in the anterior and posterior semicircular canals. In the presence of a fistula, the pressor nystagmus is directed in the direction of thickening of the air, and in the case of rarefaction (decompression)—in the opposite direction. Tullio phenomenon is characterized by under acoustic loads with vertigo and nystagmus. The Tullio phenomenon is often a barrier to the use of sound-enhancing equipment and hearing aids. The presence of a fistula in the dynamics of clinical observation and surgery is specified at the MSCT.

Barany tests [22] continue to be the most common methods of functional stimulation in clinical practice for the study of the characteristics of induced nystagmus. They are called classic caloric and rotating. The essence of the induced nystagmus reaction

**47**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

examinations and the accepted schemes in certain clinics.

in caloric stimulation according to Barany is explained by the different movements of the endolymph during its cooling or heating of the liquid. In the caloric test, the patient bends his head back at 60°. In this location, the lateral and semicircular canals occupy a position when their ampoules are on top and the smooth end is below [22]. The caloric test is generally well tolerated. It can be performed in the case of the integrity of the eardrum, even in the state of unconsciousness, but in the absence of other obstacles. Temperature regimes can be changed depending on the tasks of the

Barany rotary test causes angular acceleration. In this test, the subject with the eyes closed and the head tilted forward 30° rotates according to the program in a chair 10 times for 20 s. in the lateral plane of the semicircular canals. These channels are of particular importance in people's life, because most frequently they make

During the rotating test to the right, after stopping the chair the movement of the endolymph in the left semicircular duct will be ampullopetal, that is, the postlateral nystagmus reaction will be directed to the left according to Ewald's laws, and during the rotating test to the left, it will be directed to the right. The disadvantage of the probe is that each labyrinth cannot be inspected separately in isolation.

The Fitzgerald-Hallpike caloric test estimates the function of each of the lateral

When infused with hot water 44°C in the same amount, the endolymph molecules rise up, causing the ampullopetal movement of the endolymph, which causes a caloric nystagmus reaction toward the irritated ear. The main advantage of caloric stimulation is monaurality, which allows surveying each labyrinth separately. This advantage is especially important for otoneurology. The disadvantages are limited possibilities for perforated ear drums, traumas, and neoplasms of the outer, middle

Electronystagmography (ENG) and videonystagmography (VNG) record varieties of spontaneous nystagmus and experimental nystagmus reaction to functional stimulation using special mass-produced instruments, with computer-aided

ENG is the first noninvasive quantitative and qualitative method of recording the difference of the corneo-retinal potential for the evaluation of spontaneous and induced nystagmuses in cold and warm caloric stimulation, as well as in rotational and optokinetic tests in the horizontal plane. ENG ensures accurate recording of results in patients with known vestibular disorders not only for clinical but for

In caloric and rotational tests, the induced nystagmus reaction in the case of central vestibular syndrome is arrhythmic or dysrhythmic, with the presence of "silent fields," which indicates a violation of the central regulatory mechanisms of nystagmus

At the same time, illusory sensory sensations—vertigo and autonomic reactions—arise, the degree of manifestation of which is taken into account when assessing the reactivity of the vestibular system. The more excitable it is, the greater

analysis of their quantitative and qualitative characteristics [1, 6, 10].

semicircular canals separately [1, 2]. Before examination, the pathology of the tympanic membrane is excluded, and the head is raised up to 30° forward, so that the lateral semicircular canals take a strictly vertical position, which will maximize the sensitivity of canals to thermal stimulation. Water at a temperature of 30 and 44°C is infused bilaterally (after 5–10 minutes) to the external auditory canal each time for 40 s. Electronystagmography (ENG) records horizontal and vertical nystagmus, which occurs during cold calorization toward irritation and during hot calorization, in the opposite direction. A difference of more than 25% indicates an

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

movements in the horizontal plane [22].

asymmetric lesion.

ear, and ear labyrinth.

forensic and insurance medicine.

(see dysrhythmic nystagmus in **Figure 1**).

and longer the illusory reactions will be.

#### *Vestibular System: Anatomy, Physiology, and Clinical Evaluation DOI: http://dx.doi.org/10.5772/intechopen.90538*

*Somatosensory and Motor Research*

are restored.

the survey.

disorders.

and prognostic purposes.

specified at the MSCT.

be determined as well as the presence of autonomic disorders (nausea, vomiting, changes in heart rhythm, changes in skin color, sweating). In cases of complaints about vertigo and postural disorders, attention is focused on the possibility of detecting specific objective spontaneous symptoms—registration of types of nystagmus and posturographic control of these complaints. Some patients pay attention to the fact that they have impaired vision fixation in vertigo. Visual performance is reduced, and fatigue occurs when using a personal computer or mobile phone. In the inter-onset, when there is no vertigo, vision fixation and visual acuity

The history of the disease is collected in detail: the sequence of its development and the combination with signs of disorders in other systems and organs (cardiovascular, neuro-psychiatric, endocrine, digestive, and musculoskeletal) and past diseases. Attention is paid to the presence of noise, its nature, the acuity, and asymmetry of hearing. Also the asymmetry of the pair of cranial nerves of V, VII, IX, and XII must be examined. Allergic or toxic manifestations are recorded during

In the course of clinical vestibular test, a large number of trials and tests have been accumulated for postural control. Some of them are of historical importance, and some are still in use, particularly, walking in a straight line, flank walking by steps to the right and left—for differential diagnosis of vestibular and cerebellar

Romberg's test (classical and sensitized) is the basis for determining the static and kinetic equilibrium in modern types of postural test techniques (in particular, stabilography—a mobile platform with processing of the center of "gravity" and Fourier oscillation analysis.). The speed of movement of the center of gravity in three directions (back and forth, left-right, up-down) is calculated quickly and accurately by a computer. Deviations in the performance of these methods are taken into account when assessing the degree of manifestation of disturbances of the equilibrium function. Postural tests are widely used in the differential diagnosis of peripheral and central balance disorders, for postural control during rehabilitation measures, for postural balance before and after cochlear implantation, for expert

The next step in vestibular examination is the detection of spontaneous, positional,

Barany tests [22] continue to be the most common methods of functional stimulation in clinical practice for the study of the characteristics of induced nystagmus. They are called classic caloric and rotating. The essence of the induced nystagmus reaction

and pressor nystagmuses and registration of their characteristics [13, 14]. At first, nystagmuses can be evaluated visually as well as using Frenzel glasses (+10–12 diopters, which have the backlight inside). A type of spontaneous nystagmus is a positional nystagmus that occurs in one of the head positions and can change its parameters depending on its change. The positional nystagmus is of peripheral or central origin. Applying pressure, fistula test is of great importance in vestibular field in cases when fistula, prefistula, or dyskinesia in the bony labyrinth is suspected. As a rule, its presence is associated with the destruction of the capsule of bony labyrinth in the purulent process in the middle ear and in the temporal bone. Pressor nystagmus occurs most frequently in the lateral semicircular canal but can often occur in the anterior and posterior semicircular canals. In the presence of a fistula, the pressor nystagmus is directed in the direction of thickening of the air, and in the case of rarefaction (decompression)—in the opposite direction. Tullio phenomenon is characterized by under acoustic loads with vertigo and nystagmus. The Tullio phenomenon is often a barrier to the use of sound-enhancing equipment and hearing aids. The presence of a fistula in the dynamics of clinical observation and surgery is

**46**

in caloric stimulation according to Barany is explained by the different movements of the endolymph during its cooling or heating of the liquid. In the caloric test, the patient bends his head back at 60°. In this location, the lateral and semicircular canals occupy a position when their ampoules are on top and the smooth end is below [22].

The caloric test is generally well tolerated. It can be performed in the case of the integrity of the eardrum, even in the state of unconsciousness, but in the absence of other obstacles. Temperature regimes can be changed depending on the tasks of the examinations and the accepted schemes in certain clinics.

Barany rotary test causes angular acceleration. In this test, the subject with the eyes closed and the head tilted forward 30° rotates according to the program in a chair 10 times for 20 s. in the lateral plane of the semicircular canals. These channels are of particular importance in people's life, because most frequently they make movements in the horizontal plane [22].

During the rotating test to the right, after stopping the chair the movement of the endolymph in the left semicircular duct will be ampullopetal, that is, the postlateral nystagmus reaction will be directed to the left according to Ewald's laws, and during the rotating test to the left, it will be directed to the right. The disadvantage of the probe is that each labyrinth cannot be inspected separately in isolation.

The Fitzgerald-Hallpike caloric test estimates the function of each of the lateral semicircular canals separately [1, 2]. Before examination, the pathology of the tympanic membrane is excluded, and the head is raised up to 30° forward, so that the lateral semicircular canals take a strictly vertical position, which will maximize the sensitivity of canals to thermal stimulation. Water at a temperature of 30 and 44°C is infused bilaterally (after 5–10 minutes) to the external auditory canal each time for 40 s. Electronystagmography (ENG) records horizontal and vertical nystagmus, which occurs during cold calorization toward irritation and during hot calorization, in the opposite direction. A difference of more than 25% indicates an asymmetric lesion.

When infused with hot water 44°C in the same amount, the endolymph molecules rise up, causing the ampullopetal movement of the endolymph, which causes a caloric nystagmus reaction toward the irritated ear. The main advantage of caloric stimulation is monaurality, which allows surveying each labyrinth separately. This advantage is especially important for otoneurology. The disadvantages are limited possibilities for perforated ear drums, traumas, and neoplasms of the outer, middle ear, and ear labyrinth.

Electronystagmography (ENG) and videonystagmography (VNG) record varieties of spontaneous nystagmus and experimental nystagmus reaction to functional stimulation using special mass-produced instruments, with computer-aided analysis of their quantitative and qualitative characteristics [1, 6, 10].

ENG is the first noninvasive quantitative and qualitative method of recording the difference of the corneo-retinal potential for the evaluation of spontaneous and induced nystagmuses in cold and warm caloric stimulation, as well as in rotational and optokinetic tests in the horizontal plane. ENG ensures accurate recording of results in patients with known vestibular disorders not only for clinical but for forensic and insurance medicine.

In caloric and rotational tests, the induced nystagmus reaction in the case of central vestibular syndrome is arrhythmic or dysrhythmic, with the presence of "silent fields," which indicates a violation of the central regulatory mechanisms of nystagmus (see dysrhythmic nystagmus in **Figure 1**).

At the same time, illusory sensory sensations—vertigo and autonomic reactions—arise, the degree of manifestation of which is taken into account when assessing the reactivity of the vestibular system. The more excitable it is, the greater and longer the illusory reactions will be.

#### **Figure 1.**

*ENG in caloric stimulation: (1) normoreflexia, (2) hyperreflexia, (3) hyporeflexia, and (4) dysrhythmia (obtained with permission from [6]).*

Computer analysis of induced nystagmus responses to calorific and rotational stimulations can be performed every 10 s from the onset to attenuation, as also the duration of the induced and sensory responses can be determined and their changes tracked in the dynamics of the process and control of the treatment.

We would like to emphasize that caloric and rotational stimulations are based on the study of the functions of horizontal semicircular canal. It is considered that this is only an estimation of 20% of the functions of the vestibular system. However, the ability to capture the functions of horizontal semicircular canal is clinically important for otology and labyrinthology [2, 4].

The following variants of the state of the induced nystagmus reaction to functional loads are distinguished by ENG:


**49**

**Figure 2.**

*our own archive).*

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

There are three types of vestibular dysfunction: (1) peripheral, (2) central,

These examinations are now possible with the help of videonystagmography (VNG). VNG is the second noninvasive method which is increasingly used in clinical practice. On VNG, which is based on the principle of video telemetry of the eyeball movements, a video photo of spontaneous or positional nystagmuses is performed in different directions (vertical, horizontal, diagonal). It quickly and accurately captures horizontal and vertical eye movements, without artifacts (motion blinks or electrical noise when recording). VNG is performed with the eyes wide open. Eye movement is recorded with a camera recorder using a monocular and binocular mask. The resolution of the method is limited by the speed of the camera recorder shot (the most common currently available is the camcorder capacity of 100 frames per second). Computer processing of video of pupil movements and light reflexes on the cornea are carried out, and two-dimensional image of eye movements is obtained. VNG registers Fitzgerald-Hallpike bithermal caloric stimulation with graphical image and digital computer analysis of its indices in relation to each other, which is important for clear determination of asymmetries in otoneurology (**Figure 2**).

Vestibular evoked myogenic potential (VEMP) testing has been studied in recent decades. In conducting this test, intense sound is used to stimulate one of the receptor otolith organs, the spherical sac. This stimulus elicits an electrophysiological

The vestibulospinal reaction with relaxation in the ipsilateral sternocleidomastoid (SCM) muscle is measured by changing its activity. It is recorded using electromyography (EMG). SCM muscle is used because the response to this muscle is considered reliable due to the availability of EMG technology with electrodes on the skin surface. Initially, VEMP is recorded with a background muscle contraction and

*(A) Equipment for videonystagmography. (B) Examination of a patient with a videonystagmograph (from* 

response through the lower branch of the vestibular nerve.

There are three stages of manifestation of vestibular dysfunction and three stages of development—compensation, subcompensation, and decompensation [6, 11]. ENG has some limitations. It is important to emphasize that ENG records the function of the lateral semicircular canals and does not capture information about the anterior and posterior semicircular canals and spherical and elliptical sacs. ENG testing is not sensitive to rotary, vertical, and other types of spontaneous and

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

and (3) mixed.

induced nystagmuses.

In addition to assessment of the condition of the vestibular function, the type of lesion, the degree of its manifestation, and stage of development will be determined.

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation DOI: http://dx.doi.org/10.5772/intechopen.90538*

*Somatosensory and Motor Research*

*(obtained with permission from [6]).*

Computer analysis of induced nystagmus responses to calorific and rotational stimulations can be performed every 10 s from the onset to attenuation, as also the duration of the induced and sensory responses can be determined and their changes

*ENG in caloric stimulation: (1) normoreflexia, (2) hyperreflexia, (3) hyporeflexia, and (4) dysrhythmia* 

We would like to emphasize that caloric and rotational stimulations are based on the study of the functions of horizontal semicircular canal. It is considered that this is only an estimation of 20% of the functions of the vestibular system. However, the ability to capture the functions of horizontal semicircular canal is clinically impor-

The following variants of the state of the induced nystagmus reaction to func-

2.Hyperreflexia, characterized by an increase in the qualitative and quantitative parameters of the induced nystagmus reaction on one side or on two sides. It indicates unilateral asymmetric or bilateral symmetric state of excitement of vestibular function; the symmetrical state of excitement of vestibular function

3.Hyporeflexia, which is characterized by a decrease in the qualitative and quantitative parameters of the induced nystagmus reaction on one side or on two sides. It indicates a one-way asymmetric or two-way symmetrical state of decrease in sensitivity of vestibular function. Symmetrical state of decrease in sensitivity in the absence of disturbances of the functions of equilibrium oc-

4.Areflexia is the complete absence of experimental nystagmus reaction on one side or two sides. It is confirmed by two stimuli—caloric and rotational.

5.Dissociated vestibular reactions are marked by dysrhythmia of experimental nystagmus with disharmony of all constituent reactions (vestibulo-sensory, vestibulo-vegetative, and vestibulo-somatic). This condition is observed in the

In addition to assessment of the condition of the vestibular function, the type of lesion, the degree of its manifestation, and stage of development will be

tracked in the dynamics of the process and control of the treatment.

is often registered at congenital and acquired kinetoses.

curs in trained people of certain professions (pilots, athletes).

central disorders of the vestibular function [6].

tant for otology and labyrinthology [2, 4].

tional loads are distinguished by ENG:

1.Normoreflexia.

**Figure 1.**

**48**

determined.

There are three types of vestibular dysfunction: (1) peripheral, (2) central, and (3) mixed.

There are three stages of manifestation of vestibular dysfunction and three stages of development—compensation, subcompensation, and decompensation [6, 11].

ENG has some limitations. It is important to emphasize that ENG records the function of the lateral semicircular canals and does not capture information about the anterior and posterior semicircular canals and spherical and elliptical sacs. ENG testing is not sensitive to rotary, vertical, and other types of spontaneous and induced nystagmuses.

These examinations are now possible with the help of videonystagmography (VNG). VNG is the second noninvasive method which is increasingly used in clinical practice. On VNG, which is based on the principle of video telemetry of the eyeball movements, a video photo of spontaneous or positional nystagmuses is performed in different directions (vertical, horizontal, diagonal). It quickly and accurately captures horizontal and vertical eye movements, without artifacts (motion blinks or electrical noise when recording). VNG is performed with the eyes wide open. Eye movement is recorded with a camera recorder using a monocular and binocular mask. The resolution of the method is limited by the speed of the camera recorder shot (the most common currently available is the camcorder capacity of 100 frames per second).

Computer processing of video of pupil movements and light reflexes on the cornea are carried out, and two-dimensional image of eye movements is obtained. VNG registers Fitzgerald-Hallpike bithermal caloric stimulation with graphical image and digital computer analysis of its indices in relation to each other, which is important for clear determination of asymmetries in otoneurology (**Figure 2**).

Vestibular evoked myogenic potential (VEMP) testing has been studied in recent decades. In conducting this test, intense sound is used to stimulate one of the receptor otolith organs, the spherical sac. This stimulus elicits an electrophysiological response through the lower branch of the vestibular nerve.

The vestibulospinal reaction with relaxation in the ipsilateral sternocleidomastoid (SCM) muscle is measured by changing its activity. It is recorded using electromyography (EMG). SCM muscle is used because the response to this muscle is considered reliable due to the availability of EMG technology with electrodes on the skin surface. Initially, VEMP is recorded with a background muscle contraction and

**Figure 2.**

*(A) Equipment for videonystagmography. (B) Examination of a patient with a videonystagmograph (from our own archive).*

then with a 90–100 dB acoustic click stimulation for 30 s from the ear to which the acoustic stimulus is applied. The VEMP test is considered promising for the assessment of labyrinth in norm and pathology [23].

Recently, methods of examination with the use of magnetic coils and scanning laser ophthalmoscopes have become increasingly important. The main purpose of these methods is differential diagnosis of peripheral and central vestibular and oculomotor disorders.

In patients with acute pathology of the external, middle, and inner ears of inflammatory nature and other genesis, functional loads at vestibulometry are performed with the implementation of rotational stimulation. Caloric stimulation is limited. With purulent chronic otitis media, complicated by cholesteatoma, retraction pockets, and other pathology, fistula (pressor) tests and rotational stimulation with mandatory appointment of MSCT with contrast are required.

In bilateral or asymmetric sensorineural hearing loss of different genesis, vestibulometric examination is performed using caloric and rotational stimulations, with consultations of psycho-neurologists, hematologists, vertebrologists, endocrinologists, and toxicologists.

The otoneurologic examination should necessarily include the studies which make it possible to detect structural changes in the state of the auditory and vestibular systems in the ear labyrinth, temporal bone, cervical spine, skull, and brain. They are performed using multispiral computed tomography (MSCT) and magnetic resonance imaging (MRI) with contrast.

Data on the functional status of sensory systems are needed for clinical physicians to obtain expanded information on diseases with consideration of morphological, etiological, and pathogenetic factors for nosological diagnosis.

To make conclusions the most commonly used classification of vestibular syndromes is used according to the syndromotopic scheme:

Peripheral and central syndromes are distinguished by this scheme. The peripheral syndrome includes labyrinthine and radicular ones. Central syndromes are divided into subtentorial and supratentorial. Subtentorial syndromes are subdivided into subnuclear, nuclear, and super-nuclear. Supratentorial syndromes include diencephalic-hypothalamic, subcortical, and cortical. Often combined vestibular syndromes are identified.

This classification is not universal. However, in the creation of a universal one, as emphasized by researchers [3–5], the obstacle is the "ubiquity" of the vestibular representation in the CNS. In addition, the subtle sensitivity to various changes in the internal and external environment and the globality of the vestibular symptom complex with similar symptoms, known as "vestibular triad," complicate the development of the principle of classifications of vestibular disorders according to the nosological principle.

Due to the anatomical, physiological, and functional closeness of the receptor structures of the auditory and vestibular systems, given the specificity of their disorders in the ear labyrinth, it is rational to isolate the peripheral cochleovestibular syndrome. Specific changes in the central departments of the vestibular and auditory systems are the bases for the formation of the central audio-vestibular syndrome and their combination—for mixed audio-vestibular syndrome.

### **6. Conclusions**

1.The presented anatomical and physiological bases of the vestibular system indicate the structural and functional interrelation of its peripheral and central departments in normal and pathological conditions.

**51**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

and cortical stimulation of their activity.

under the influence of radiation has been proven.

cognitive and emotional-volitional reactions.

vertigo of peripheral and central origins.

system peripheral and central components.

of vestibular functions in normal and pathological conditions.

modern technological advancements, is of high priority.

2.The parity and symmetry of the anatomical and physiological localizations of the vestibular and auditory systems play a crucial role in the spatial orientation in the state of motion and rest, in the formation of motor, sensory memory,

3.The vestibular system is closely linked to the departments of the central nervous system, cerebral circulation, organs, and other systems of the body, so before others, it responds to the smallest changes in the internal and external

4.The priority of changes in the central departments of the vestibular system

5.It is established that the inhibitory processes in the vestibular and auditory systems as a result of radiation from the Chornobyl accident can be regarded as a symptomocomplex of premature aging of the organism with a decrease in

6.Along with the widespread use of objective electrophysiological methods of registration, in particular, electronystagmography, new diagnostic tests have been developed. The method of videonystagmography, scanning laser ophthalmoscopes, and magnetic coil examinations are gaining popularity. They contributed to the study of vestibular dysfunction in the positional paroxysmal

7.Three types of effective therapeutic and prophylactic positional provocative maneuvers have been implemented in clinical practice. They were developed by taking into account the anatomical and physiological features of vestibular

Further experimental and clinical studies are needed to explore regarding the receptor functions of three semicircular canals and the otolith apparatus of the vestibular system. Developing new and refining existing objective methods for examining and recording varieties of spontaneous and experimental nystagmus not only in horizontal but also in other planes are necessary to enhance the assessment

The solutions to the important problems of vocational guidance; professional selection and career aptitude in sports, arts, maritime, aviation, and space technologies; and jobs related to ground and underground transportations are extremely needed. These professions are associated with heavy loads on the vestibular system. Particularly high demands are placed not only on vestibulo-vegetative and postural stability but also on vestibulo-sensory reactions. The development of preventive measures for safety and high endurance of the vestibular system, along with

*DOI: http://dx.doi.org/10.5772/intechopen.90538*

environment.

*Somatosensory and Motor Research*

oculomotor disorders.

nologists, and toxicologists.

ment of labyrinth in norm and pathology [23].

netic resonance imaging (MRI) with contrast.

vestibular syndromes are identified.

the nosological principle.

**6. Conclusions**

then with a 90–100 dB acoustic click stimulation for 30 s from the ear to which the acoustic stimulus is applied. The VEMP test is considered promising for the assess-

Recently, methods of examination with the use of magnetic coils and scanning laser ophthalmoscopes have become increasingly important. The main purpose of these methods is differential diagnosis of peripheral and central vestibular and

In patients with acute pathology of the external, middle, and inner ears of inflammatory nature and other genesis, functional loads at vestibulometry are performed with the implementation of rotational stimulation. Caloric stimulation is limited. With purulent chronic otitis media, complicated by cholesteatoma, retraction pockets, and other pathology, fistula (pressor) tests and rotational stimulation

In bilateral or asymmetric sensorineural hearing loss of different genesis, vestibulometric examination is performed using caloric and rotational stimulations, with consultations of psycho-neurologists, hematologists, vertebrologists, endocri-

The otoneurologic examination should necessarily include the studies which make it possible to detect structural changes in the state of the auditory and vestibular systems in the ear labyrinth, temporal bone, cervical spine, skull, and brain. They are performed using multispiral computed tomography (MSCT) and mag-

Data on the functional status of sensory systems are needed for clinical physicians to obtain expanded information on diseases with consideration of morpho-

To make conclusions the most commonly used classification of vestibular

Peripheral and central syndromes are distinguished by this scheme. The peripheral syndrome includes labyrinthine and radicular ones. Central syndromes are divided into subtentorial and supratentorial. Subtentorial syndromes are subdivided into subnuclear, nuclear, and super-nuclear. Supratentorial syndromes include diencephalic-hypothalamic, subcortical, and cortical. Often combined

This classification is not universal. However, in the creation of a universal one, as emphasized by researchers [3–5], the obstacle is the "ubiquity" of the vestibular representation in the CNS. In addition, the subtle sensitivity to various changes in the internal and external environment and the globality of the vestibular symptom complex with similar symptoms, known as "vestibular triad," complicate the development of the principle of classifications of vestibular disorders according to

Due to the anatomical, physiological, and functional closeness of the receptor structures of the auditory and vestibular systems, given the specificity of their disorders in the ear labyrinth, it is rational to isolate the peripheral cochleovestibular syndrome. Specific changes in the central departments of the vestibular and auditory systems are the bases for the formation of the central audio-vestibular syndrome and their combination—for mixed audio-vestibular syndrome.

1.The presented anatomical and physiological bases of the vestibular system indicate the structural and functional interrelation of its peripheral and central

departments in normal and pathological conditions.

logical, etiological, and pathogenetic factors for nosological diagnosis.

syndromes is used according to the syndromotopic scheme:

with mandatory appointment of MSCT with contrast are required.

**50**


Further experimental and clinical studies are needed to explore regarding the receptor functions of three semicircular canals and the otolith apparatus of the vestibular system. Developing new and refining existing objective methods for examining and recording varieties of spontaneous and experimental nystagmus not only in horizontal but also in other planes are necessary to enhance the assessment of vestibular functions in normal and pathological conditions.

The solutions to the important problems of vocational guidance; professional selection and career aptitude in sports, arts, maritime, aviation, and space technologies; and jobs related to ground and underground transportations are extremely needed. These professions are associated with heavy loads on the vestibular system. Particularly high demands are placed not only on vestibulo-vegetative and postural stability but also on vestibulo-sensory reactions. The development of preventive measures for safety and high endurance of the vestibular system, along with modern technological advancements, is of high priority.

*Somatosensory and Motor Research*

## **Author details**

Dmytro Illich Zabolotnyi and Nina Serhiivna Mishchanchuk\* O.S. Kolomiychenko Institute of Otolaryngology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine

\*Address all correspondence to: nsmisch@i.ua; nsmishch@gmail.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**53**

*Vestibular System: Anatomy, Physiology, and Clinical Evaluation*

Des Nervus Octavus Wiesbaden.

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*Somatosensory and Motor Research*

**52**

**Author details**

Sciences of Ukraine, Kyiv, Ukraine

provided the original work is properly cited.

Dmytro Illich Zabolotnyi and Nina Serhiivna Mishchanchuk\*

\*Address all correspondence to: nsmisch@i.ua; nsmishch@gmail.com

O.S. Kolomiychenko Institute of Otolaryngology, National Academy of Medical

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

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Section 2

Motor Research
