54 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 1 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 2 Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia Correspondence/ Korespondenca: Saba Battelino, e: saba. battelino@kclj.si Key words: benign paroxysmal postitional vertigo; central vestibular disorders; vertigo; Dix-Hallpike manoeuvre; calorimetry Ključne besede: benigna paroksizmalna vrtoglavica; centralne ravnotežne motnje; vrtoglavice; Dix-Hallpike-ov manever; kalorimetrija Received: 23. 9. 2019 Accepted: 5. 11. 2020 eng slo element en article-lang 10.6016/ZdravVestn.2985 doi 23.9.2019 date-received 5.11.2020 date-accepted Neurobiology Nevrobiologija discipline Review article Pregledni znanstveni članek article-type Functional tests for assessment of the vestibu- lar system – literature review and an example of our experience Funkcionalni testi za oceno ravnotežnega organa – pregled literature in primer naših izkušenj article-title Functional tests for assessment of the vestib- ular system Funkcionalni testi za oceno ravnotežnega organa alt-title benign paroxysmal postitional vertigo, central vestibular disorders, vertigo, Dix-Hallpike manoeuvre, calorimetry benigna paroksizmalna vrtoglavica, centralne ravnotežne motnje, vrtoglavice, Dix-Hallpike-ov manever, kalorimetrija kwd-group The authors declare that there are no conflicts of interest present. Avtorji so izjavili, da ne obstajajo nobeni konkurenčni interesi. conflict year volume first month last month first page last page 2021 90 1 2 54 73 name surname aff email Saba Battelino 1,2 saba.battelino@kclj.si name surname aff Metka Sluga 1 Manja Hribar 2 eng slo aff-id Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia Medicinska fakulteta, Univerza v Ljubljani, Ljubljana, Slovenija 1 Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia Klinika za otorinolaringologijo in cervikofacialno kirurgijo, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija 2 Functional tests for assessment of the vestibular system – literature review and an example of our experience Funkcionalni testi za oceno ravnotežnega organa – pregled literature in primer naših izkušenj Metka Sluga,1 Manja Hribar,2 Saba Battelino1,2 Abstract Vertigo and other balance disorders, which can have many different origins, are among the most common reasons for seeking medical care. The otorhinolaryngologist mostly deals with disorders of the inner ear and the vestibular nerve while, at the same time, identifying possible diseases of central origin as the cause of symptoms. To make a diagnosis, a combination of sev- eral different tests is usually required so that the impairment of different parts of the vestibular system can either be confirmed or excluded. In general, we distinguish between tests to exam- ine the semicircular canals and tests’ function to estimate the saccule and utricle’s function. We describe a clinical trial whereby we examined 1042 patients with a clear history of benign parox- ysmal positional vertigo, which was diagnosed in 36%. Further tests, described in the following article, had to be performed. To interpret the test results, we often rely on the observation and measurement of eye movements. This requires knowledge of mechanisms of certain reflexes responsible for maintaining balance. At the same time, we have to consider the patient’s symp- toms and complement the tests with other imaging examinations if necessary. Izvleček Težave z ravnotežjem sodijo med pogoste vzroke za obisk pri zdravniku, njihov izvor pa je lahko precej raznovrsten. Na področju otorinolaringologije se posvečamo predvsem okvaram notra- njega ušesa in ravnotežnega živca ter nakažemo morebitno centralno prizadetost ravnotežnega sistema. Za postavitev diagnoze pogosto ne zadostuje zgolj ena preiskava, pač pa je po navadi potrebna kombinacija različnih testov, s katerimi potrjujemo ali izključujemo prizadetost posa- meznih delov ravnotežnega sistema. V osnovi razlikujemo med testi, s katerimi ocenjujemo de- lovanje polkrožnih kanalčkov, in testi za oceno delovanja sakulusa in utrikulusa. Predstavljena je klinična raziskava, v kateri smo pri 1.042 bolnikih z jasno anamnezo za benigni paroksizmalni pozicijski vertigo le-tega dokazali v 36 %. Nujno je bilo opraviti še dodatna testiranja, ki jih pred- stavlja prispevek. Za razlago njihovih rezultatov se pogosto zanašamo na opazovanje in merje- nje gibanja očesnih zrkel, pri čemer je pomembno poznavanje določenih refleksov za ohranjanje ravnotežja. Ob tem moramo upoštevati tudi simptome, ki jih navaja bolnik, in teste po potrebi dopolniti s slikovnodiagnostičnimi preiskavami. Natančne računalniške meritve in grafični zapisi danes nadomeščajo opazovanje s prostim očesom in subjektivno razlaganje opažanj preiskoval- ca. Cite as/Citirajte kot: Sluga M, Hribar M, Battelino S. Functional tests for assessment of the vestibular system – literature review and an example of our experience. Zdrav Vestn. 2021;90(1–2):54–73. Slovenian Medical Journal 55 REVIEW ARTICLE Functional tests for assessment of the vestibular system 1 Introduction Vertigo and other balance disorders are among the most common reasons for seeking medical care. Patients de- scribe them as uncomfortable loss of orientation in space and a false feeling of movement of the body and/or the sur- roundings, such as spinning, wobbling, or inclining. Their prevalence in the gen- eral population is about 17%, and in the elderly above 80 years, it grows to 39% (1). Diseases of the vestibular part of the inner ear, together with the vestibuloco- chlear nerve form part of the peripheral vestibular system, are slightly more fre- quent than central nervous system dis- eases (2). In the strict sense, the human balance system includes the vestibuloco- chlear nerve and its ganglia, four vestib- ular nuclei in the brainstem, cerebellum, and parts of the cerebral cortex (3). The reasons for its malfunction have varied origins and pathogenesis. When facing balance issues, otorhinolaryngology pri- marily focuses on the inner ear and ves- tibular nerve disorders. Vestibular system dysfunction is gen- erally manifested as a combination of sensory, oculomotor, postural, and au- tonomous symptoms and signs: vertigo, gait abnormality (ataxia), nausea, and vomiting (1). The patient’s medical history is first used to define the type of symptom, its duration, trigger factors, and a possible concurrent hearing loss, as well as con- comitant chronic diseases, with systemic diseases often having a significant effect on balance. Next, we continue with an otoneurologic examination of the patient DOI: https://doi.org/10.6016/ZdravVestn.2985 Copyright (c) 2021 Slovenian Medical Journal. This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. and basic hearing tests. These are followed by assessing the balance function used to define disorders in individual structures responsible for maintaining balance. 2 Anatomy and physiology of the vestibular system The vestibular system in the inner ear consists of three semicircular canals and the otolith organs. The semicircular canals (superior, posterior, and lateral) lie perpendicular to one another, always functioning in pairs (posterior with the anterior of the opposite side and both lat- eral), and include cristas ampullae. These have gelatinous cups and detect angular acceleration through the changes in the endolymph current in the membranous part of the labyrinth with hair cells. In the inner ear’s vestibule, the otolith or- gan comprises the saccule, which lies on the vertical plane, and the utricle, which lies on the horizontal plane. Its sensory organs, the maculae, sense linear accel- eration and gravity (4). The vestibular system is connected to the eighth cranial nerve’s vestibular nerve through nuclei in the brain stem with the nuclei of some other cranial nerves, the cerebellum, and the cerebral cortex. The human brain does not contain a primary vestibular cerebral cortex area; however, it consists of sever- al separate areas. These regions combine the balance, aural, visual, and somato- sensory inputs (5). They demonstrate a strong right hemispheric dominance. The parieto-insular vestibular cortex (PIVC) was among the first areas to be defined 56 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 as vestibular, and after additional studies, the posterior insular cortex, the temporo- parietal junction, the anterior insula, the pre- and postcentral gyrus of the parietal lobe, the ventrolateral part of the occipital lobe, and the inferior frontal gyrus with the inferior part of the precentral sulcus (5). Understanding how the tests assess the vestibular system work is also essential to understand certain reflexes that ensure stabilization. The first among them is the vestibuloocular reflex, which stabilizes the image on the retina while the head moves by moving the eye bulb in the op- posite direction, thereby retaining the image in the central part of the field of vision. Stimuli for the reflex mainly orig- inate in the semicircular canals, then run through the vestibular nerve to the vestib- ular nuclei in the brainstem. From there, the neurons connect with the nuclei of cranial nerves that ensure the movement of the extraocular muscles, moving the eye bulb appropriately (6). In certain types of tests, the vestibu- lospinal reflex is also essential. This is a combination of reflexes whose objective is to stabilize the body. When tilting the head, the semicircular canals on both sides become stimulated. The stimulus is transferred through the vestibular nerve and the vestibular centres along the lat- eral and medial vestibulospinal tract, activating extensor muscles on the side towards which the head is tilted, and the flexor muscles on the other side. This en- sures that the position of the body and the head are stabilized (3). The most important indicator of the vestibular system function is spontaneous or evoked eye movements. By origin, we roughly divide them into ocular, periph- eral vestibular, and central vestibular nys- tagmus. Peripheral nystagmus is repeated, coordinated eye bulb movements around a horizontal or vertical axis, comprising a slow and fast phase, by which we also define its direction (7). Typical peripher- al nystagmus is horizontal, it may have a rotational component, and it intensifies when the gaze fixation is removed (e.g., with closed eyelids, in darkness, or when using high-powered Frenzel’s’ goggles). The first-degree nystagmus occurs when gazing towards the fast component’s di- rection, and the second degree also when gazing straight, while third-degree nys- tagmus is present when gazing in all di- rections (8). According to Alexander’s law, the amplitude of nystagmus increases when the eye moves towards the fast phase and decreases when viewing in the oppo- site direction (9). By nystagmus onset, we divide them into spontaneous nystagmus, which is always pathologic, except in the most eccentric positions and optokinetic, and evoked by the movements of the body or by vibration stimulation of the inner ear (10). Every nystagmus that onsets without proper physiological stimulation is treated as abnormal, or the absence of nystagmus with appropriate stimulation (8). Nystagmus can be observed with the naked eye, or we can use glasses or a CCD camera that follows the pupils and logs the eye movement on a computer. Because the vestibular system is not a single structure, every part must be test- ed with different stimulation frequencies when there are balance issues. First, we stimulate the semicircular canals; then, we assess the saccule and the utricle func- tion. The tests for assessing the vestibular system can be divided into the group of tests for assessing the function of semicir- cular canals and the group for assessing the saccule and the utricle. They are sum- marized in Table 1. 57 REVIEW ARTICLE Functional tests for assessment of the vestibular system 3 Test for the assessment of the vestibular system 3.1 Tests for the assessment of the semicircular canals The tests for assessing the function of semicircular canals are divided by the speed with which the canals are stimu- lated, as they have a different sensitivity to stimulation with low and high frequen- cies (11). Caloric testing is among the very low-frequency tests. Low-frequency tests include rotation testing, while high-fre- quency tests include the head impulse test. The medium-frequency dynamic vi- sual acuity test (DVAT), the very high-fre- quency vestibulo-collic reflex (VCR) test, and the vibration-induced nystagmus test (VIN) (11) are not performed at the Centre of Audiology and Vestibulology, Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Slovenia. 3.1.1 Caloric testing Caloric testing is primarily intended for assessing the function of the later- al semicircular canal. It is based on the principle that changes to the inner ear temperature trigger movement similar to turning the head. This results in the endolymph circulating within the lateral semicircular canal and, through the ves- tibulo-ocular reflex, induces the response in the form of nystagmus, based on which we can assess the function of the lateral semicircular canal (12). The examination procedure: the sub- ject is placed supine, with the head ele- vated at a 30-degree angle. Before we be- gin the ear irrigation, we check whether the patient has spontaneous nystagmus in a standing or a sitting position using Frenzel’s goggles. Then, we irrigate the left ear canal with 30 °C water for half a minute, and for the next half-minute, we count or electronically log the twitches of the subject’s eye bulbs. After a brief pause, we repeat the procedure on the opposite ear. When stimulating with cold water, the nystagmus generally occurs in the opposite direction of the stimulated ear. Then, we repeat the procedure on both ears with water heated to 44°C, initiating the nystagmus in the stimulated ear’s di- rection. If we do not initiate a response with ear irrigation in the first two tem- peratures, we repeat the procedure with 17°C water. When we cannot stimulate a response, even in this case, we can con- clude that the labyrinth is not calorically stimulable (11). This is one of the most frequently per- formed balance tests conducted for verti- go and instability, loss of hearing on one side, or any other suspicion of impaired function of the peripheral part of the ves- tibular system. When reading the results, it is import- ant to compare both sides and consider the nystagmographic response’s absolute values, comparing it with average, i.e., normal values. An example of a caloric test result is in Figure 1. When comparing both semicircular canals, we describe the paresis (labyrin- thine paresis/predominance) and prepon- derance (13). The semicircular canal’s pa- resis is defined as at least a 20% difference in nystagmography response between both canals and represents a reduced function of one labyrinth concerning the opposite labyrinth (14). This is frequent with vestibular neuritis, Menièr’s disease, and tumours of the eighth cranial nerve, and can also onset with migraines and cerebrovascular diseases. The directional preponderance describes the higher in- tensity of the nystagmus in a particular direction than the other side by at least 20–30%. Clinically, the preponderance 58 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 has several different implications. It may be present in entirely healthy people; it can reflect a single-side peripheral bal- ance impairment on the opposite side, a central impairment, or even damage to the cerebral cortex (13). Figure 1: Graphic display of caloric testing of the vestibular system. Less than 20% difference in the nystagmographic (i.e., paresis box) response between both sides indicates a normal response (A); a difference of more than 20% in the response between both sides indicates reduced function or paresis of one of the canals (B). R – right; L – left. Concerning the nystagmography re- sponse’s absolute values, we describe hy- per-, hypo-, and areflexia Hyperreflexia occurs when calorically stimulated nys- tagmus exceeds the standard value. With peripheral vestibular disorders, it may 59 REVIEW ARTICLE Functional tests for assessment of the vestibular system occur on the opposite side of the affected location. The reason can also be a change in the ear, e.g., after a mastoidectomy or an eardrum perforation. With central vestibular disorders, hyperreflexia can be bilateral. An example of this is an impair- ment of the cerebellum’s flocculus, which in its normal condition inhibits the neu- rons of the vestibular core, thereby inhib- iting the vestibulo-ocular reflex. When it is damaged, this inhibitory effect does not take place. Hyporeflexia can result from differ- ent causes, namely from drugs inhibit- ing the labyrinth function or their toxic effect on the ear to systemic infection diseases, hypertension, brain tumours, and degenerative diseases of the central nervous system anxiety, also possibly due to the abuse of psychoactive substanc- es. Areflexia, i.e., total unresponsiveness to caloric response, can be part of Usher syndrome resulting from bilateral periph- eral vestibular loss or ototoxicity. In 20% of patients, the reasons for it remain un- explained (15). However, it is not always related to a total loss of the balance func- tion (13). Despite frequent use, caloric testing has certain shortcomings. The effect that the ear irrigation has on the subject’s ear differs from person to person. This makes it difficult to compare the sensitivity of different people’s labyrinths concerning the absolute values of caloric stimulation responses. We can especially compare the sensitivity of both ears of the same sub- ject, and even this calls for a certain level of caution, as the stimuli received by the left and the right ear are not entirely the same. Also, the frequency with which we excite the semicircular canals in this test is reasonably low. The vestibular system re- sponds best to the head’s fast turns with a frequency of between 0.1 and 3 Hz. With caloric testing, we can only stimulate receptors up to a frequency of 0,003 Hz, which is significantly lower than the opti- mum. We also do not know the stimula- tion’s exact strength and must, therefore, be careful when interpreting results (16). Certain subjects find the tests especial- ly uncomfortable, as they can trigger ver- tigo and nausea. If the examiner assesses that testing could trigger significant dis- comfort in the examinee, testing should be stopped as soon as possible. Seldom is caloric testing performed on both sides simultaneously. Only with the onset of nystagmus, i.e., with a differ- ent stimulation results in one inner ear, is each ear tested separately (17). 3.1.2 Rotatory testing The rotary chair test is also aimed at assessing the sensitivity of simultaneous- ly stimulated lateral semicircular canals. The angular acceleration is used as a stim- ulus (when the rotation begins and after it ends) when rotating the whole body. It is generally used in combination with ca- loric testing, and if needed, the tests are supplemented with other vestibular sys- tem examinations. The rotary chair makes it possible to position the head at a 30-degree angle in which lateral semicircular canals are in a nearly horizontal position. The subject is then rotated ten times in one and ten times in the other direction, with a fre- quency of approximately one rotation per second. Using nystagmographic goggles, we can watch the nystagmus during the rotation (rotatory nystagmus) and when stopped (post-rotatory nystagmus) and its persistence for each side of rotation (18,19). Tests can consist of different protocols in which we rotate the subject in both directions with different frequencies and accelerations. The main indications for rotatory 60 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 testing are bilateral paresis of the lateral semicircular canals, unsatisfactory re- sults of the caloric testing, and the fact that small children being rotated in their parent’s lap can perform the test as well. The test assesses both vestibular systems at the same time. They provide the resid- ual function data in patients with signs of bilateral failure of the vestibular system measured with caloric testing and the da- ta on the central compensation of unilat- eral paresis of the vestibular system (19). 3.1.3 Head impulse test Unlike caloric and rotatory testing, where we stimulate and measure only the lateral semicircular canal function, all three canals are tested in the head im- pulse test (HIT). Also, the frequencies in this test are higher than with the caloric test. This is an examination in which the vestibulo-ocular reflex (VOR) of each semicircular canal is measured separately during passive, quick and unpredictable head movements by 10 to 20 degrees in different directions (20). First, the examiner merely monitored the subject’s eye movements by obser- vation. Later, eye bulb movements with special wires installed on an eye via lens were introduced. The latest HIT version is called vHIT (video head impulse test), where light-weight and tightly fitting gog- gles with a camera monitor the eye bulbs’ compensation movements during rapid head movements (impulses). The glasses are connected to software that marks the head and eye bulb movements, creating a graphic output from the data. After proper positioning of the gog- gles, the subject stares at a point approx- imately 1 meter away on the wall in front of them. The subject’s head is turned 35 degrees left or right, while their eyes re- main focused on the point. The examin- er then begins performing rapid sagittal head movements (up and down), stimu- lating both vertical semicircular canals. The head first faces straight ahead; then, the examiner rapidly turns it left and right. This stimulates canals in pairs – both lateral together, the right anterior and the left posterior (RALP – with the starting position of head-turning left) and the left anterior and the right poste- rior (LART – with the starting position of the head-turning right) at the same time. The examined person performs approxi- mately 7 to 10 unpredictable head move- ments individually in all directions. The whole procedure is called a head impulse paradigm (HIMP) (21). With healthy subjects, there is smooth, compensatory eye bulb movement, re- sulting from a well-functioning VOR. These maintain the focus on a fixed point (22) and are not visible to the examiner with the naked eye. Quite the opposite, patients with paresis of the semicircular canal exhibit corrective saccades at the Impulse’s end. When eye bulbs that had previously not been fixed on a point be- cause of the impacted VOR, these occur with head movements, making a com- pensatory move towards it. These are so-called overt saccades, which an exam- iner notices when performing the test. These are clinical signs of the paresis of the canal. When moving the head to the impacted side, the left semicircular canal is affected, occurring when moving the head rapidly to the left. Some patients are capable of performing corrective saccades when the head is being turned. These are covert saccades that the examiner cannot see with their naked eye. They are essen- tial for diagnosing impairments to the semicircular canal and can be measured with the vHIT test. The graphic outputs of the head and eye bulbs’ movements, as shown in Figure 2, are the same for healthy subjects, which 61 REVIEW ARTICLE Functional tests for assessment of the vestibular system means that eye bulbs with VOR appropri- ately follow head movements. The chart allows us to calculate the so-called gain, i.e., the ratio between the speed of the slow, compensatory phase of the eye bulb and the speed of head movements. The gain value for healthy people is approx- imately 1, i.e., sit should be above 0.79, meaning that the eye bulb movement’s speed follows head movements well (23). When there is the dysfunction of the semicircular canal, the VOR is impaired, and the graphic representation of eye bulb movement shows a record of com- pensatory saccades. The gain is character- istically lowered, generally much below 1. Figure 2: Video Head Impulse Test (vHIT) results. Impulse right graph indicates a subject’s results with a normal function of the vestibulo-ocular reflex, where eye bulb movements appropriately follow the head movements. The Impulse left graph indicates the results in a patient with an impaired, left vestibulo-ocular reflex. This patient produces overt saccades to attempt to compensate for the reduced gain (24) appropriately. There are numerous advantages of vHIT over caloric testing. With vHIT, we can measure the function of all six semi- circular canals, while with caloric test- ing we can only examine the function of the lateral ones. With caloric testing, we predominantly measure the asymmetry between the speeds of the slow phase of nystagmus with the same stimulation in both ears. The vHIT test also detects symmetrical, bilateral impairments of the vestibular system that appear as a normal, symmetric function of both canals in ca- loric testing. vHIT is quick, objective and repeatable, and can be performed even during acute vertigo attacks. It can assist 62 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 in differentiating between vertigo from a stroke, i.e., central nervous system lesion, where test results are often normal, ver- tigo resulting from peripheral vestibular neuritis, and vestibular dysfunction due to the Menière’s disease. The protocol version called the Suppression Head Impulse Paradigm (SHIMP) also must be mentioned. It al- so uses vHIT technology, but the subject does not fixate their gaze on a point on the wall during the test, instead of following a point that moves together with their head. Results of the SHIMP test are the oppo- site of those of HIMP. At the end of an impulse, a healthy subject makes a bigger anti-compensatory saccade, while with patients who suffer from loss of vestibular function, we do not see the saccade. The vestibulo-ocular reflex attempts to avert the gaze from the moving point. With healthy subjects, VOR is suppressed, but with a delay of a few tenths of a millisec- ond; therefore, VOR moves the gaze away from the point during this time. When the subject is instructed to follow the target, there is a conscious reflex suppression, causing an anti-compensatory saccade at the end of the Impulse (the SHIMPs sac- cade), a sign of a well-functioning VOR. With patients with an impairment of the semicircular canal, and therefore the loss of VOR, it does not avert their gaze from the point, and, therefore, there are no an- ti-compensatory saccades at the end of the Impulse (23). The Functional Head Impulse Test (fHIT) is a version of the test based on recognizing an optotype briefly flashed on a computer screen. It is a function- al measure of the vestibulo-ocular reflex function, mirrored with the ability to re- tain visual acuity and to read during fast, passive head movements (25). 3.1.4 Dynamic visual acuity test The dynamic visual acuity test (DVA) is a simpler version of the head impulse test. It is based on the fact that with the vestib- ular system’s peripheral impairments, the retinal slippage during head movements is higher than usual. When the slippage speed is greater than 2–4° per second, vi- sual acuity is reduced. By measuring visu- al acuity during head movements, we can directly conclude an impairment of the vestibulo-ocular reflex and semicircular canals; however, we must first exclude any impairments in the eye bulb motor func- tion that are not the result of an impair- ment of the vestibular system. Performing the test includes performing a version of quick passive and active head movements while simultaneously measuring visual acuity using a Snellen chart. This verifies the vestibulo-ocular reflex function and can lead to a conclusion regarding a uni- lateral or bilateral impairment of the ves- tibular system (26). 3.1.5 The Dix-Hallpike test This manoeuvre can confirm benign paroxysmal positional vertigo (BPPV), which is caused by free-floating otoliths in one or several semicircular canals. It can be performed on patients who feel short-term vertigo when changing their head position. At the start of the test, the patient sits on a bed, with the head tilt- ed towards the tested ear at a 45-degree angle. The examiner then lies the patient down with a quick movement so that the subject’s head gazes across the edge of the bed, and the examiner extends it by 20 to 30 degrees below the horizon. When performing this manoeuvre with a short pause, we can see the onset of typical nys- tagmus, which does not persist for more than a minute with BPPV; however, it 63 REVIEW ARTICLE Functional tests for assessment of the vestibular system may persist in a milder form sometime after the completion of the test. The test is then repeated on the opposite side. The impacted semicircular canal can be deter- mined according to the direction of the nystagmus (11). 3.1.6 Videonystagmography (VNG) The vestibular system function can be assessed with videonystagmography (VNG), where we analyze eye bulb move- ments in detail using nystagmography goggles. They follow the movements of the eye with an infra-red camera (27). VNG includes three standard tests: the oculomotor test, the optokinetic posi- tional test, and caloric testing. With the oculomotor test, we follow the eye mus- cle motor function independently from the vestibular function. Oculomotor abnormalities could affect the results of vestibular function test results, which are interpreted based on eye movements. First, we verify spontaneous nystagmus’s presence without fixation (in the dark), then while fixing the gaze at a 30° angle. These are followed by tracking a moving point (smooth and saccadic following) and forming the optokinetic nystagmus when viewing moving lines, vertical and horizontal, separately. The comput- er-generated results enable assessment of the nystagmus’ symmetry when rotating to the left and right, and we can compare the speed of eye bulb movement rela- tive to the head’s speed. We can compare measurements recorded in a dark room (preventing the gaze from fixing) and the measurements recorded with a fixed gaze. Nystagmus with a fixed gaze, abnormal- ities in gaze following, and optokinetic nystagmus generally occur in central ner- vous system impairment. This is followed by a position test, where we observe the onset of nystagmus when the head and the body are tilted into different positions. Persistent nystagmus is non-specific and is not particularly helpful for determining the location of the impairment in the ves- tibular system. We can also observe eye movements when performing the Dix- Hallpike manoeuvre. Delayed nystag- mus, rotational nystagmus, or weakened nystagmus in a particular position of the head point to BPPV, especially if the pa- tient also manifests corresponding symp- toms (28). This is followed by performing the ca- loric and rotational tests described above. 3.2 Tests for the assessment of the otolith organ 3.2.1 Vestibular-evoked myogenic potentials – VEMP Vestibular-evoked myogenic poten- tials (VEMP) are electromyographic re- sponses evoked by sound, vibrations, or electricity, of the stimulated vestibular system (29). In this test, there are two types of electromyographic respons- es. The cervical VEMP (cVEMP) runs through saccule stimulation, the inferior vestibular nerve (n. vestibularis inferior), the vestibular nuclei in the brain stem, and up to activating the vestibulospinal tract and the glossopharyngeal nerve nu- cleus (n. IX, n. glossopharyngeus) with an inhibition response of the sternoclei- domastoid muscle on the same side (the vestibulo-collic reflex). The ocular VEMP (oVEMP) runs through utricle stimu- lation and the superior vestibular nerve (n. vestibularis superior), the vestibular nuclei, and the medial longitudinal fasci- cle to the oculomotor nerve nucleus (n. oculomotorius) with excitation response to the opposite inferior oblique muscle (the otolith-ocular reflex). We measure the sternocleidomastoid muscle’s elec- tromyographic response or the external eye bulb muscles’ response to the aural 64 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 stimulation of the otolith organ. Both otolith organs respond to stim- ulation with loud, by air- or bone-trans- mitted low-frequency tone. However, cVEMP is generally more specific for measuring the saccule function, and oVEMP for the utricle (30). When cVEMP is performed using headphones, the saccule is stimulated, generally using 95–100 dB loud, short tones with a frequency of 500–1,000 Hz. Individual tones are played with 5-second pauses, and together approximately 200 repeats per ear are produced. It is recom- mended that one ear at a time is stimu- lated. We place an electrode on the mid- third of the sternocleidomastoid muscle to measure the muscle’s electromyo- graphic responses to the aural stimuli, and these are then displayed on the com- puter screen. Because the vestibulo-collic reflex causes an inhibition response of the sternocleidomastoid muscle, the subject must contract the muscle during the test. Via the same electrode, we also monitor the muscle contraction so that the sub- ject can maintain the proper contraction during the test. If the muscle contraction is insufficient during the test, the VEMP responses are not suitable for analysis (31). The most interesting parts of the test results depicted in Figure 3 are the char- acteristic waves P13 and N23. They enable an analysis of various parameters, such as the latency and amplitude of both waves, the latency between them, the difference in latencies and amplitudes between ears, and the difference between their values and their threshold values. oVEMP is conducted similarly, except the electrodes are placed beneath both eyes and on the forehead to measure the inferior oblique muscle’s electromyo- graphic response. The patient must keep the gaze upwards during the examination Fi gu re 3 : G ra ph ic d is pl ay o f t he re su lt of th e cV EM P te st . T he h ig hl ig ht ed w av es a re P 13 a nd N 23 o f t he m us cl e on th e rig ht si de o f t he n ec k aft er st im ul at io n of th e rig ht e ar . A fte r s tim ul at io n of th e le ft ea r, th er e is n o cV EM P re sp on se o n th e m us cl e. to retain the inferior oblique muscle con- tracted. The results show the frequency at which the response with the highest wave amplitude and latency occurs. The fre- quencies through which we stimulate the vestibular system in oVEMP are similar to cVEMP, and the results reflect mainly the stimulability of the utricle (32). A cVEMP test is used when diagnosing both peripheral and central lesions of the vestibular system (29). When diagnosing Menière’s disease or endolymphatic hy- drops, we can lose the VEMP response to stimulation. With Menière’s disease, we can also notice the highest amplitude re- sponse transition at usually 500–700 Hz to 1000 Hz. Comparing test results before and after an attack is especially crucial, as with endolymphatic hydrops, the cVEMP amplitude is restored at the impacted side after the attack. This also normalizes the frequency at which we get the response with the highest amplitude (33). With vestibular neuritis, cVEMP can significantly assist in diagnosing the af- fected location of the vestibular organ. The inferior vestibular nerve mainly sup- plies nerve fibres to the saccule and the posterior semicircular canal, while the su- perior vestibular nerve supplies nerve fib- bers mainly to the lateral and the anterior semicircular canal and the utricle. With a pathological cVEMP, which is more spe- cific for the saccule, in combination with normal results of the caloric test, specific for the lateral canal, we can conclude that the inferior vestibular nerve is affected (29). With migraine patients suffering from vertigo, the cVEMP results can change in the sense of lower amplitudes (34). With a vestibular migraine, cVEMP can show extended latency and increased frequen- cy at which the response with the high- est amplitude occurs (similar to Menièr’s disease), which points to the possibility of 65 REVIEW ARTICLE Functional tests for assessment of the vestibular system stimulation of the otolith organ. Both otolith organs respond to stim- ulation with loud, by air- or bone-trans- mitted low-frequency tone. However, cVEMP is generally more specific for measuring the saccule function, and oVEMP for the utricle (30). When cVEMP is performed using headphones, the saccule is stimulated, generally using 95–100 dB loud, short tones with a frequency of 500–1,000 Hz. Individual tones are played with 5-second pauses, and together approximately 200 repeats per ear are produced. It is recom- mended that one ear at a time is stimu- lated. We place an electrode on the mid- third of the sternocleidomastoid muscle to measure the muscle’s electromyo- graphic responses to the aural stimuli, and these are then displayed on the com- puter screen. Because the vestibulo-collic reflex causes an inhibition response of the sternocleidomastoid muscle, the subject must contract the muscle during the test. Via the same electrode, we also monitor the muscle contraction so that the sub- ject can maintain the proper contraction during the test. If the muscle contraction is insufficient during the test, the VEMP responses are not suitable for analysis (31). The most interesting parts of the test results depicted in Figure 3 are the char- acteristic waves P13 and N23. They enable an analysis of various parameters, such as the latency and amplitude of both waves, the latency between them, the difference in latencies and amplitudes between ears, and the difference between their values and their threshold values. oVEMP is conducted similarly, except the electrodes are placed beneath both eyes and on the forehead to measure the inferior oblique muscle’s electromyo- graphic response. The patient must keep the gaze upwards during the examination Fi gu re 3 : G ra ph ic d is pl ay o f t he re su lt of th e cV EM P te st . T he h ig hl ig ht ed w av es a re P 13 a nd N 23 o f t he m us cl e on th e rig ht si de o f t he n ec k aft er st im ul at io n of th e rig ht e ar . A fte r s tim ul at io n of th e le ft ea r, th er e is n o cV EM P re sp on se o n th e m us cl e. 66 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 the vestibular migraine originating both centrally and peripherally (35). There are also reports on normal val- ues of cVEMP and oVEMP with patients with a spinning feeling in the transversal or sagittal plane without rotational verti- go (so-called idiopathic otolithic vertigo). cVEMP results can also help diagnose lesions of the central nervous system that affect areas included in the vestibulo-col- lic or vestibulo-ocular reflex. The most often studied is multiple sclerosis which can be manifested with extended latency of P13 and N23 waves (36). In combination with computed to- mography (CT), oVEMP is most import- ant in diagnosing the superior semicir- cular canal’s dehiscence. It also plays an essential role in diagnosing BPPV. It can also be used for detecting other vestibu- lar impairments in the event of vestibular nerve lesions, otolith diseases, and central nervous system lesions (37). 3.2.2 Subjective visual vertical test (SVV) Patients with utricle impairment often do not have vertigo issues but instead de- scribe a general instability during move- ment, a feeling of swinging, and are more in danger of falling. In particular, the subjective visual vertical test (SVV) is in- tended to test the utricular function. It is based on the assessment of the patient’s ability to determine true vertical, i.e., de- termining how much the patient’s subjec- tive (i.e., visual) vertical differs from the real (i.e., gravitational) vertical (38). The patient inspects a straight line in front and aims to position it vertically. The an- gle between the subjective and the true verticality reflects the utricular function. This test’s simple version is the buck- et test, where the examiner encloses the subject’s whole visual field with a bucket. A straight line is drawn on the bottom of the bucket. In the beginning, the examin- er turns the bucket so that the line on the bottom is not aligned with true verticali- ty. Then the examiner slowly rotates the bucket, and the subject must say when the line is aligned vertically. There is an angle meter on the outside of the bucket that the examiner uses to measure how much the patient’s verticality differs from the gravitational. They can also use a weight- ed string, installed on the outside bottom of the bucket, aligned with 0° on the angle meter. They can use it to read the discrep- ancy of the subject’s verticality from true verticality (39). A newer, digitalized version of the SVV test is increasingly replacing the bucket test. It consists of digital goggles that block all light, and on the inside, the subject sees a straight line. Using a wire- less remote, they have to place the line into presumed true verticality. Setting the verticality occurs while the head is tilted at different angles, 0, 15, 30, and 45 de- grees left and right. A gyroscope located in the goggles supports measuring the head tilt angle, ensuring the correct head position during testing. The higher the head-tilt angle, the more difficult it is for the subject to determine true verticality. Results are measured using software, which records the angle of the tilt of the patient’s head and the angle of the dero- gation of their verticality from true verti- cality (Figure 4). Angle deviation beyond 2° is defined as pathological, and the di- rection of the deviation depends on the location of the vestibular system’s impair- ment. With unilateral peripheral or pon- tomedullary changes, the visual vertical is generally tilted to the affected side; with pontomesencephalic impairments, it is tilted to the opposite direction thalamic changes, it may be tilted to the affected or unaffected side. The test is described as especially useful in the literature when 67 REVIEW ARTICLE Functional tests for assessment of the vestibular system diagnosing certain peripheral vestibu- lar system lesions, such as BPPV and the unilateral vestibular loss, and in certain central nervous system lesions. It is also used as the follow-up instrument in the treatment of these diseases (39). 3.3 Balance assessment robot Besides the tests mentioned above, we should also focus on the balance assess- ment robot (BAR), developed by Slovenian researchers at University Rehabilitation Institute Soča (URI-Soča). This is a device for testing and enhancement the vestibular function of patients after a stroke. The pri- mary objective of training with the robot is to reduce the number of patients’ falls. The training is based on the fact that when unpredictable forces (i.e., perturbations) act on a body during walking, an individ- ual responds with a combination of ad- justing their centre of pressure (COP) in the leg that is currently on the ground and by redirecting the raised leg to a location where it will be able to support the body to counteract the unpredictable force appro- priately. With patients who have suffered a stroke, the mechanisms that provide such responses can be impaired. To learn how to perform the movements required to re- spond appropriately, their training must consist of realistic situations that make it possible to lose balance. Depending on their physical impairment, they can then develop a good balance response. The device is essentially a combination of a treadmill and a movable frame that supports the patient’s pelvis. It has embed- ded sensors for graphing the pelvis’s posi- tion on a screen, the length of the step, the duration of steps, and the COP in the foot. It supports comprehensive measurements of steps and provides pressure jolts to the pelvis and assessing the response to them (40). Fi gu re 4 : G ra ph ic d is pl ay o f t he re su lts o f t he su bj ec tiv e vi su al v er tic al te st (S VV ). Re co gn iz in g su bj ec tiv e ve rt ic al ity w ith in 2 ° a ng le fr om tr ue v er tic al ity is re co gn iz ed a s n or m al (l eft ), w hi le a ng le d ev ia tio ns a bo ve 2 ° a re p at ho lo gi ca l ( rig ht ). 68 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 Training on this device consists of three phases. During the first phase, the patient walks straight along the tread- mill while their position and movement are captured. The device exerts pressure on the pelvis when an abnormal gait is detected. This stimulates them to take all steps as equally as possible since they are otherwise asymmetric after a stroke. Meanwhile, the patient monitors their pelvis’s position on the monitor, striv- ing to maintain it in the correct position. In the second phase, the patient walks a “virtual terrain” with a screen’s aid. They see their path on the screen, e.g., uphill, while the BAR exerts forces to the body that simulates walking uphill. In the third phase, the BAR provides unpredictable jolts from all directions while the patient is walking, and they have to respond to them appropriately to correct their pos- ture and gait. Exercise on the BAR is entirely safe and makes it easier to develop the whole vestibular system’s effective responses to unpredictable events. 3.4 Vestibular evoked potentials Vestibular-evoked potentials (VsEPs) of the central nervous system are EEG responses, i.e., neurogenic potentials re- corded with electrodes placed on the scalp when stimulating the vestibular sys- tem. The vestibular system can be stim- ulated with numerous quick and short head turns. The average of electronic neu- ron responses and concurrent dissipation of background noise draws the curve of their path. The neurogenic response can- not be measured for patients with an im- pairment to the peripheral and/or central vestibular pathways. With these types of examinations, a frequent issue is the ar- tifacts in the results, which also hinders the interpretation of the results; therefore, Tests for the assessment of the semicircular canals Caloric testing By changing the liquid's temperature in the inner ear and observing the evoked nystagmus, we can assess the lateral semicircular canal dysfunction. Rotatory testing By rotating on a chair, we simultaneously stimulate both lateral semicircular canals. This provides the assessment of the residual function of the semicircular canals in a bilateral impairment of the vestibular system or provides an assessment of a central compensation of unilateral vestibular paresis. Head impulse test With rapid head movements in different directions, we stimulate all six semicircular canals in pairs. We monitor their function by changing vestibulo-ocular reflex, i.e., eye bulb compensation saccades during head movements. Functional head impulse test Using optotypes, we measure the ability to retain visual acuity during rapid head movements, thereby assessing the vestibulo-ocular reflex's function. A dynamic visual acuity test By measuring visual acuity during rapid head movements, we obtain the data on the impairment of the vestibulo-ocular reflex, i.e., the semicircular canals' function. The Dix-Hallpike test Using a special manoeuvre, we can evoke nystagmus in patients with suspected benign paroxysmal positional vertigo, and based on the result; we can assess the impairment of semicircular canals. Tests for the assessment of the otolith organ Vestibular-evoked myogenic potentials Using short, loud tones, we stimulate the saccule or utricle and measure characteristic electromyographic responses of the sternocleidomastoid muscle or external eye bulb muscles. Subjective Visual Vertical test (SVV) By measuring the difference between the subject’s subjective and true verticality, we measure the utricular function. Balance assessment robot The device makes it possible to measure exact steps and apply different forces to the body through the pelvis and is aimed at balance enhancement and practicing the steady gait for patients who have suffered a stroke. Vestibular-evoked potentials When stimulating the vestibular system with fast turns of the head, we measure the EEG of the cerebral cortex. Table 1: Classification of the vestibular system assessment test by the speed of stimulation and the inner ear’s anatomical location. this method is seldom used to assess ves- tibular system function (41). 4 Example of using several diagnostic tests 4.1 Patients and methods We performed a retrospective anal- ysis of the data for 1,042 patients who were treated for balance disorders at the Centre of Audiology and Vestibulology, Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Slovenia, between 2006 and 2015, and who reported a typical history for short-term benign paroxys- mal positional vertigo (BPPV). We per- formed the Dix-Hallpike manoeuvre for diagnosing BPPV (11). We continued with the therapeutic Epley repositioning manoeuvre with a positive manoeuvre (11), and the patients were scheduled for a check-up within three weeks. Because determining which semicircular canal or canals are impacted can be difficult in clinical practice, especially with bilater- al positive position tests, we divided all performed diagnostic maneuver results into positive (unilateral or bilateral) and negative. At the follow-up or even at the first examination, most patients had a caloric testing (i.e., bi-thermal frequency vestibulogram (VTG: Varitherm plus and Varioair)) performed, and in some vide- onystagmography (VNG: Interacoustics VN415/VO425) has been performed (11). The patients’ data for whom we confirmed BPPV was then analyzed in more detail by age, sex, side of the impairment, the treatment success, level of repeatability, history of head injury, and osteoporosis. To alleviate the results’ interpretation, we assumed that the repositioning manoeu- vre instructed at the first examination was successful for patients who did not attend 69 REVIEW ARTICLE Functional tests for assessment of the vestibular system Training on this device consists of three phases. During the first phase, the patient walks straight along the tread- mill while their position and movement are captured. The device exerts pressure on the pelvis when an abnormal gait is detected. This stimulates them to take all steps as equally as possible since they are otherwise asymmetric after a stroke. Meanwhile, the patient monitors their pelvis’s position on the monitor, striv- ing to maintain it in the correct position. In the second phase, the patient walks a “virtual terrain” with a screen’s aid. They see their path on the screen, e.g., uphill, while the BAR exerts forces to the body that simulates walking uphill. In the third phase, the BAR provides unpredictable jolts from all directions while the patient is walking, and they have to respond to them appropriately to correct their pos- ture and gait. Exercise on the BAR is entirely safe and makes it easier to develop the whole vestibular system’s effective responses to unpredictable events. 3.4 Vestibular evoked potentials Vestibular-evoked potentials (VsEPs) of the central nervous system are EEG responses, i.e., neurogenic potentials re- corded with electrodes placed on the scalp when stimulating the vestibular sys- tem. The vestibular system can be stim- ulated with numerous quick and short head turns. The average of electronic neu- ron responses and concurrent dissipation of background noise draws the curve of their path. The neurogenic response can- not be measured for patients with an im- pairment to the peripheral and/or central vestibular pathways. With these types of examinations, a frequent issue is the ar- tifacts in the results, which also hinders the interpretation of the results; therefore, Tests for the assessment of the semicircular canals Caloric testing By changing the liquid's temperature in the inner ear and observing the evoked nystagmus, we can assess the lateral semicircular canal dysfunction. Rotatory testing By rotating on a chair, we simultaneously stimulate both lateral semicircular canals. This provides the assessment of the residual function of the semicircular canals in a bilateral impairment of the vestibular system or provides an assessment of a central compensation of unilateral vestibular paresis. Head impulse test With rapid head movements in different directions, we stimulate all six semicircular canals in pairs. We monitor their function by changing vestibulo-ocular reflex, i.e., eye bulb compensation saccades during head movements. Functional head impulse test Using optotypes, we measure the ability to retain visual acuity during rapid head movements, thereby assessing the vestibulo-ocular reflex's function. A dynamic visual acuity test By measuring visual acuity during rapid head movements, we obtain the data on the impairment of the vestibulo-ocular reflex, i.e., the semicircular canals' function. The Dix-Hallpike test Using a special manoeuvre, we can evoke nystagmus in patients with suspected benign paroxysmal positional vertigo, and based on the result; we can assess the impairment of semicircular canals. Tests for the assessment of the otolith organ Vestibular-evoked myogenic potentials Using short, loud tones, we stimulate the saccule or utricle and measure characteristic electromyographic responses of the sternocleidomastoid muscle or external eye bulb muscles. Subjective Visual Vertical test (SVV) By measuring the difference between the subject’s subjective and true verticality, we measure the utricular function. Balance assessment robot The device makes it possible to measure exact steps and apply different forces to the body through the pelvis and is aimed at balance enhancement and practicing the steady gait for patients who have suffered a stroke. Vestibular-evoked potentials When stimulating the vestibular system with fast turns of the head, we measure the EEG of the cerebral cortex. Table 1: Classification of the vestibular system assessment test by the speed of stimulation and the inner ear’s anatomical location. their check-ups. In this retrospective, the National Medical Ethics Committee ap- proved the Republic of Slovenia’s clinical study (No. 0120-032/2016-2, March 21st, 2016). 4.2 Results We performed a diagnostic manoeu- vre for BPPV on our subjects, and the expected typically evoked nystagmus oc- curred in 376 (36%) of 1,042 patients, of whom 267 (71%) were women. Patients’ median age with a positive test was 58.5 years (± 15, with a range between 16-92). Manoeuvres on the right side were positive with 188 (50%), and on the left side with 145 (38.6%), bilaterally with 42 (11.1%) patients, while with one patient (0.23%), the only note is that the manoeuvre was positive, which can be interpreted as the presence of so-called subjective BPPV, i.e., the onset of vertigo without visible nystagmus. Repositioning manoeuvres were successful with 335 patients (89%). Improvements with occasional vertigo (with some depending on the position, with some not) or a feeling of instability 70 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 were mentioned by 20 (5.3%) patients, while with 21 (5.6%), there was no im- provement. Test results were divided into normal results, vestibular system paresis, and central impairment. 52 (13.8%) pa- tients had a recurrence of BPPV. With 40 (10.6%) patients, the onset of BPPV oc- curred after head trauma. 9 (2.4 %) pa- tients had osteoporosis. After performing appropriate thera- peutic manoeuvres, 217 (57.7%) patients had VTG done, and 51 (13.6%) VNG. Among the patients whose vertigo was successfully eliminated, 204 (60.9%) had normal VTG and VNG results. For 20 (6%), VTG proved vestibular system pa- resis, while for 4 (1.2%), VNG established central vestibular impairments, and with 2 (0.6%), there was a combination of ves- tibular system paresis and central impair- ment. With 105 (31.3%) patients without persistent vertigo, we could not perform the VTG or the VNG test. Among the patients who still had issues with BPPV after the therapeutic manoeuvres, VTG and VNG results were normal for 4 and 5, respectively, for a total of 9 (45%), while a total of 7 (35%), 2 with VTG and 5 with VNG, had paresis. For one patient (5%), VNG proved they had a central impair- ment. Neither VTG nor VNG was per- formed for 3 (15%) patients. Of the pa- tients with persisting vertigo, 8 (38.1%) had normal results of both tests, 6 (28.6%) had a paresis, which was proven with a VTG, 5 (23.8%) had central vestibular impairments, which were proven with VNG, while 1 (4.8%) had a combination of paresis and central vestibular impair- ments, also proven with a VNG test. We did not conduct additional tests on one (4.8%) patient from the group with per- sistent vertigo. The results of these tests are compiled in Table 2. 5 Conclusion The reason for short-term positional vertigo is not always BPPV, as we only diagnosed it in 36% of cases using di- agnostic manoeuvres on patients with related issues. We did not perform a de- tailed analysis on patients with negative diagnostics tests for BPPV in this study’s scope. Along with caloric testing and videonystagmography, the additional Diagnostic maneuver Therapeutic (repositioning) maneuver VTG VNG Positive/ pathologic right left bilateral 335 (89%) 28 (12.9%) 18 (35.3%) 188 (50%) 145 (38.6%) 42 (11.1%) Total 376 (36%) Negative/ normal 666 (64%) 41 (11%) 189 (87.1%) 33 (64.7%) Total 1.042 376 217 51 Table 2: The diagnostic manoeuvre was positive, i.e., pathological, for 376 patients (36%) of 1,042. Among these, repositioning manoeuvres were successful with 335 (89%) patients. Additional tests (VTG or VNG) were performed with 268 (71.3%) patients with a positive diagnostic manoeuvre, and using tests; we were able to additionally define the source of the problem with 46 (12.2%) patients. 71 REVIEW ARTICLE Functional tests for assessment of the vestibular system References 1. Brandt T, Strupp M. General vestibular testing. Clin Neurophysiol. 2005;116(2):406-26. DOI: 10.1016/j. clinph.2004.08.009 PMID: 15661119 2. Brandt T, Dieterich M. The dizzy patient: don’t forget disorders of the central vestibular system. Nat Rev Neurol. 2017;13(6):352-62. DOI: 10.1038/nrneurol.2017.58 PMID: 28429801 3. Khan S, Chang R. Anatomy of the vestibular system: a review. NeuroRehabilitation. 2013;32(3):437-43. DOI: 10.3233/NRE-130866 PMID: 23648598 4. Ekdale EG. Form and function of the mammalian inner ear. J Anat. 2016;228(2):324-37. DOI: 10.1111/ joa.12308 PMID: 25911945 5. Fasold O, von Brevern M, Kuhberg M, Ploner CJ, Villringer A, Lempert T, et al. Human vestibular cortex as identified with caloric stimulation in functional magnetic resonance imaging. Neuroimage. 2002;17(3):1384-93. DOI: 10.1006/nimg.2002.1241 PMID: 12414278 6. Cullen KE. The vestibular system: multimodal integration and encoding of self-motion for motor control. Trends Neurosci. 2012;35(3):185-96. DOI: 10.1016/j.tins.2011.12.001 PMID: 22245372 7. Probst R, Grevers G, Iro H. Basic Otorhinolaryngology. New York: Thieme; 2006. p. 277. 8. Kavanagh KT, Babin RW. Definitions and types of nystagmus and calculations. Ear Hear. 1986;7(3):157-66. DOI: 10.1097/00003446-198606000-00007 PMID: 3487475 9. Jeffcoat B, Shelukhin A, Fong A, Mustain W, Zhou W. Alexander’s Law revisited. J Neurophysiol. 2008;100(1):154-9. DOI: 10.1152/jn.00055.2008 PMID: 18450584 10. Newman-Toker DE. Symptoms and signs of neuro-otologic disorders. Continuum (Minneap Minn). 2012;18:1016-40. DOI: 10.1212/01.CON.0000421618.33654.8a PMID: 23042058 11. Jacobson GP, Shepard NT. Balance function assessment and management. San Diego (CA): Plural Publishing Inc; 2016. 12. Jacobson GP, Newman CW, Kartush JM. Handbook of balance function testing. St. Louis, MO: Mosby Year Book; 1997. 13. Gonçalves DU, Felipe L, Lima TM. Interpretation and use of caloric testing. Rev Bras Otorrinolaringol (Engl Ed). 2008;74(3):440-6. DOI: 10.1016/S1808-8694(15)30580-2 PMID: 18661020 14. Jongkees LB. Value of the Caloric Test of the Labyrinth. Arch Otolaryngol Head Neck Surg. 1948;48(4):402- 17. DOI: 10.1001/archotol.1948.00690040414003 15. Brandt T. Bilateral vestibulopathy revisited. Eur J Med Res. 1996;1(8):361-8. PMID: 9360934 16. Jacobson GP, Shepard NT. Balance function assessment and management. San Diego,CA: Pluras Publishing; 2008. definition of the origin of short-term positional vertigo would also be possible with newer tests described in this article, which can be used to more precisely con- firm or exclude impairment of an indi- vidual or several semicircular canals. For all patients for whom the periph- eral vestibular disorder has not been elu- cidated or excluded, we will perform all the described tests to assess the function of distinctive parts of the vestibular sys- tem. The results and the basic guidelines for treating patients whose medical his- tory points to BPPV are shown below. The significant progress in the devel- opment of balance assessment tests de- veloped over the past few years has made it possible to define the cause of the bal- ance disorder more clearly. Continued research of the vestibular system is re- quired to yield an even more detailed assessment of the results obtained from the existing tests. Regarding the patients we tested, we expect to increase the per- centage of etiologically explained bal- ance disorders through additional bal- ance assessment tests. At the same time, we are looking to develop new tests that will utilize computer technology and functional-magnetic imaging to improve treatment and the possibilities for the rehabilitation of patients with vestibular disorders. 72 NEUROBIOLOGY Zdrav Vestn | January – February 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.2985 17. Sataloff RT, Pavlick ML, McCaffrey JD, Davis JM, Stewart SM. Simultaneous binaural bithermal caloric testing: clinical value. 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