Original Paper ORI. 1992:54:71-75
a Beijing Institute of Otorhinolaryngology and b Institute of Aviation Medicine. Beijing. China
KeyWords Human Electronystagmography Vestibular disorders Multiplc discriminant analysis
Electronystagmographic Features in Some Peripheral and Central Vestibular Disorders: Application of Multiple Discriminant Analysis of Electronystagmographic Parameters
Abstract In routine clinical electronystagmographic (ENG) tests (postrotatory, optokinetic, caloric and tracking tests), eye movement signals were analyzed and a multiple discriminant analysis was carried out with the aid of a microcomputcr. Six parameters were selected and, based on these, two functions for dis criminating between peripheral and central disorders were established. Dis crimination between 35 patients with peripheral lesions and 15 patients with central lesions was made with a correct classification rate of 97.1 and 86.7%, respectively. These rates are significantly higher than that of any single ENG test analysis. Our results indicate that the clinical application of ENG can be improved by searching for more sensitive ENG parameters and adopting the comprehensive analysis approach.
Introduction Although vertigo is frequently seen in the clinic, it is not easy to distinguish peripherally originating vertigo from centrally originating vertigo, which may lead to a misdiagnosis [1-4]. It has been hoped that electronystag mography (ENG) would be helpful in solving this prob lem. After several decades, systematic tests of the vestibu lar function have been established [5. 6], However, the currently applied methods of examination are often less helpful than originally thought. The conventional param eters and manual analysis methods are not sensitive enough to detect some abnormalities of the vcstibulo-oculomotor system, especially in the early stages of disease.
Received: July 25.1990 Accepted after revision: June 10.1991
Furthermore, the various ENG results from different tests are sometimes contradictory. In order to improve the status quo, many ENG experts are searching for effective methods to evaluate vestibular function accurately and objectively, and, furthermore, to distinguish the various kinds of vestibular diseases from each other by, for example, looking for more sensitive parameters [7-9] or by establishing vestibulo-oculomotor models [10-13]. The currently available methods, though having their own individual advantages, are all explora tory and focus on one particular aspect. Since the vestibu lar system is multileveled. it is worth trying to find com prehensive methods for evaluating vestibular function more accurately.
G. Wei Beijing Institute of Otorhinolaryngology Beijing (Peoples Republic of China)
© 1992 S. Karger AG. Basel 0301-1569/92/0542-0071 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 5:34:19 AM
G. Wei3 L.S. Yub C. L iua G.Q. L ih R. Zhangb S. H. Chenh
Table 1. Classification of subjects
Category
Cases
Normal group
253
Peripheral group
Meniere disease sudden deafness with vertigo ototoxiccsis acoustic neurinoma vestibular neuronitis
23 8 4 3 2
Central group
cerebellar diseases vertebrobasilar insufficiency brainstem encephalitis bulbar paralysis acute demyelinating disease
7 6 2 i i
Subjects and Methods Subjects There were three groups of subjects (table 1): a normal group (253 male, 18-48 years old); a peripheral group (23 male, 17 female, 2461 years old; 3 cases of acoustic neurinoma in this group had no sign of CNS damage), and a central group ( 10 male, 7 female. 25-72 years old). The lesions in the peripheral and central groups were confirmed clinically with solid diagnoses and/or by surgery or computed tomog raphy. ENG Examination Horizontal eye movements were recorded binocularly and verti cal eye movements of the left eye were recorded. The subjects under went the following tests. Pseudorandomly Numbered Eye Tracking Test. Saccadic and sinusoidal eye tracking tests were carried out using stimuli of one moving light dot on a wide screen, of which the velocity changed randomly in frequencies ranging from 0.1 to 1.2 Hz. The vision angle was 20°. Optokinetic Nystagmus Test. Velocities of the optokinetic stimuli were 20,40,60 and 807s, leftward and rightward, respectively. Each stimulus lasted 20 s. Postrotatory Test. The chair was rotated up to 907s at an acceler ation of 17 s2 and then rotated at constant speed for 1 min or until the postrotatory nystagmus disappeared. The chair was then stopped. This was carried out in the clockwise and counterclockwise direc tions. Caloric Test. The modified Hallpike's caloric test was used [14], The water temperatures were 30 and 44 °C, respectively, 50 ml and 20 s for each irrigation. The subjects were in a dark room during the tests with their eyes open and were instructed to do mental arithmetic during the postro tatory and caloric tests. For a variety of reasons, not every subject underwent all the tests; therefore, the numbers of cases were not the same for each different test. The subjects who had not undergone the whole series of the tests were not included in the comprehensive anal ysis. The ENG signals were fed into a computer for analysis as well as recorded on chart paper. The parameters describing the velocity, duration and amplitude of eye movements were analyzed by a com puter algorithm processing system that was set up in this laboratory. In this study, we set up 194 parameters altogether for the 4 ENG tests. There were 8, 77, 54 and 55 parameters in the eye tracking, optokinetic nystagmus, postrotatory and caloric tests, respectively. About 20% of the parameters were conventional, only describing
72
Table 2. Comprehensive analysis of the 4 ENG tests
Discriminatory classification
Clinical classification, case number
Discriminatory identification rate ,%
peripheral
central
Peripheral Central
34 1
2 13
97.1 86.7
Total
35
15
94.0
Table 3. Values of the 6 selected parameters
Parameter
Peripheral group
Central group
BN312 C0-FA-FV DPT DP60SPV C„-ST-FT SDT
39.4 ±13.1 0.66 ±0.17 20.6 ± 22.1 7.7 ±6.9 0.05 ±0.07 275 ±55
45.2 ±12.6 0.55±0.20 10.6 ± 12.6 10.2 ±7.0 0.25 ±0.21 410 ± 432
some features of the slow phase of eye movements, and the rest were newly built, describing features of the fast phase such as velocity, duration or latency. We also established some parameters to describe correlations between certain features, based on the assumption that there are some potential interactions between certain parameters. The MDA was carried out according to Bayes’s theorem [15,16], using a statistical program with the aid of a computer. The program was designed by statisticians. We took an F value = 4.5. which is greater than F (p = 0.05), as a criterion for the selection of para meters.
Wei/Y u/Liu/Li/Zhang/Chen
MDA of ENG Parameters in Vestibular Disorders
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 5:34:19 AM
Our study was aimed at searching for more sensitive parameters and employing a comprehensive analysis method - the multiple discriminant analysis (MDA) - in evaluating vestibular function from multiple perspec tives. Our goal was to find a better way of interactively analyzing the results of the presently used clinical ENG tests and, thereby, to improve the power of these tests for more accurately and objectively distinguishing central and peripheral disorders.
Table 4. Comparison between the results of each single test and of the 4 ENG tests combined
Central group
Total identified rate, %
case number
identified number
identified rate ,%
case number
identified number
identified rate, %
Postrotation Caloric Optokinetic Eye tracking
40 38 39 38
28 30 20 25
70.0 78.6 51.3 65.8
17 17 17 15
5 12 5 3
29.4 70.6 29.4 20.0
71.9 81.6 72.5 67.6
Four ENG tests combined
35
34
97.1
15
13
86.7
94.0
Results The data from the above-mentioned 4 ENG tests were combined in the analysis in which there were altogether 194 parameters. Table 2 shows the results. Six parameters (X1-X 6) were selected: X) = BN312 (beat number during 3-12 s in the postrotatory test); Xj = C0-FA-FV (correlation coefficient between the am plitude and velocity of the fast phase in the postrotatory test); X3 = DPT (asymmetric ratio between the time con stants of the clockwise and counterclockwise rotations in the postrotatory test); X4 = DP60SPV (asymmetric ratio between the leftward and rightward slow-phase velocities in the 60°/s optokinetic test); X5 = C0-ST-FT (correlation coefficient between the duration of the slow and fast phases in the caloric test), and X6 = SDT (delay time of square saccades in the tracking test). The values (mean ± SD) for each of the parameters are shown in table 3. Based on these selected parameters, the discriminant functions for distinguishing between the central and pe ripheral vestibular disorders were established as follows. Function for peripheral disorders: Y, = -1 3 .2 8 + 0.0475X, + 16.1360X2+ 0.1328X3 + 0.2490X4 + 1.3845X5 - 5.5975X6.
Function for central disorders: Y2 - -9.9148 + 0.1969X, + 6.9429X, + 0.0716X3 + 0.0742X4 + 5.4510X5+ 1.7879X6.
Y i and Y2 represent the discriminant score of the peripheral and central function, respectively, and X |-X 6 represent the respective discriminant variables (see ta ble 2 for results of the discriminatory analysis). The MDA was also carried out on the basis of each single test. The results from the different tests were com
pared (table 4). The x2 test detected a significant (p < 0.05) difference between the identification rates of the 4 ENG tests combined and the caloric test, as well as a highly significant (p < 0.01) difference between the iden tification rate of the 4 ENG tests combined and that of each of the 3 other single ENG tests (postrotatory, optoki netic and eye tracking test).
Discussion Multiple Discriminant Analysis In our study, MDA, which can process multiple vari ables, was used according to Bayes’s theorem. During the analysis, all the variables (parameters) were compared with each other step by step, such that variables having the greatest power of discrimination were selected, and then the discriminant functions were set up for distin guishing. The ordinary statistical methods, e.g. t test, only deal with one parameter in one single dimension. The dis criminant analysis we used in this study, however, can analyze comprehensively multiple variables. Hence, it is a more sensitive, reliable and accurate method. Comparison between the Results o f Each Single Test and o f the 4 ENG Tests Combined From table 4, it is obvious that the effect of the multi ple-test discrimination is better than that of any single test. This method takes into account that the nervous sys tem initiating and modulating the eye movements is multileveled, whereas one particular test mainly checks only one relevant aspect of the vestibulo-oculomotor function on the basis of the individually different mechanisms. Therefore, only by analyzing the information from the multiple tests can one obtain more accurate results, i.e. a higher rate of correct classification. This kind of analysis
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Peripheral group
Tests
Description o f the Selected Parameters in the MDA In the 4 routine ENG tests, altogether there were 194 parameters for analyzing the signals of the eye move ments. of which 6 parameters were selected. Based on the discriminant functions, these 6 parameters can reveal the intrinsic differences between central and peripheral disor ders. while the others have less or no significance in that sense in the present investigation. BN3I2 and DP60SPV. Both parameters showed no sig nificant difference between the peripheral and central groups only according to the t test (p > 0.05). However, the selection of these two parameters into the discrimi nant functions showed that MDA method has compre hensive analysis ability to evaluate vestibular function from the interrelationship between multiple parameters, not from one single parameter. Therefore, it is more sensi tive than the t test. It is generally considered that the beat numbers of the evoked nystagmus decrease with peripheral lesions, while the beat numbers increase with central ones. This is due to a loss of the central inhibitory function, thus lowering the threshold for initiating nystagmus in the fast phase [17. 18], Obvious asymmetric abnormalities in optokinetic nys tagmus frequently suggest disorders in the CNS. for instance, lesions of the parietal lobe [19], brainstem [5. 20] and cerebellum [21], or vertebrobasilar insufficiency [6], and this asymmetry cannot be compensated as it can be in peripheral cases. We also found that a certain inten sity of optokinetic stimulation is necessary to detect abnormalities sensitively but that overstimulation can weaken the response. In our laboratory, the appropriate optokinetic stimulation velocity is 60°/s [22], Cf-FA-FV and C„-ST-FT. Of all the parameters in cluded in the MDA, there were 4 individual parameters: FA (last-phase amplitude in postrotatory test): FV (fastphase velocity in postrotatory test): ST (slow-phase time in caloric test), and FT (fast-phase time in caloric test). All these 4. parameters were not selected into the functions. There were no significant differences between the mean values of these parameters in the peripheral and central groups according to the t test (p > 0.05). However. C0FA-FV and C0-ST-FT were selected into the functions, and the l test showed that both of them revealed a highly
74
significant difference between the peripheral and central groups (p < 0.01). This result suggests that, under patho logical conditions, the changes in the interrelations be tween certain parameters are more obvious than those of 1 single parameter, hence, being more sensitive in detect ing disorders. Pyykko and Dahlen [7] demonstrated that the integra tion of the velocity and amplitude of the nystagmus occurs in the CNS. most likely in the paramedian pontine reticular formation (PPRF) and the end point of the nys tagmus is determined by the velocity signals. Therefore, there is a close relationship between the velocity and amplitude of the nystagmus. Our result indicates that the relationship between the velocity and amplitude of the fast phase deteriorates when there is a damage in the CNS. According to our observations, no significant correla tion was found between ST and FT of the caloric nystag mus in either the normal or the peripheral groups. There w'as, however, a tendency towards a closer relationship between the two parameters in the central group. The rea son for this change is not clear and further research is needed to address its significance. SDT. SDT means the delay time of square saccades. The neurons that initiate saccadic eye movements arc located in the PPRF [23-25], The frontal cortex partici pates in the modulation of fast eye movements [26. 27]. Some authors reported that the normal SDT is 150-250 ms [5. 28]. Baloh et al. [29] found that SDT can be pro longed by lesions in the brainstem, basal ganglia, and frontal and parietal cortex, i.c. initiation of voluntary saccades can be delayed. We found a significant difference between the peripheral and central groups according to the t test (p < 0.05). suggesting that this parameter has an important value for distinguishing peripheral from cen tral diseases. Under the same degree of impairment due to a lesion in the CNS. the saccadic abnormalities appear more obvious than those of the fast phase of the nystag mus. The reason is that the saccadic movement requires longer neural pathways in which there is a larger number of synapses [30], DPT. DPT is the parameter showing the asymmetry of the time constants of postrotatory nystagmus decays be tween clockwise and counterclockwise rotations. After rotation, the intensity (slow-phase velocity) of the nystag mus decays exponentially. Under normal conditions, the time constants on both sices are actually equal. However, when there is a lesion in the peripheral vestibular system on one side, the nervous pulses emitted or transmitted do decrease, hence causing a decrease in nystagmus intensity.
Wei/Y u/Liu/Li/Zhang/Chen
MDA of ENG Parameters in Vestibular Disorders
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 5:34:19 AM
is neither an ‘or method nor the simple sum of each result, but a comprehensive method which evaluates ves tibular function from the interrelations of multiple pa rameters. So. it is an objective analysis, and the subjective factors can thereby be eliminated.
a shortening of the time constant on the lesion side and. thus, an asymmetry between the two sides. Our research revealed that there is a highly significant difference be tween the two groups (p < 0.01). The occurrence of time constant asymmetry in our patients with unilateral pe ripheral vestibular loss is in agreement with the observa tions of others [31, 32], In conclusion, routine ENG tests are helpful in the diagnosis of vestibular system disorders in the clinic, but the currently applied analysis methods make the use of ENG limited. Our study shows that the clinical applica tion of ENG can be improved by searching for more sensi tive ENG parameters and by using the comprehensive analysis approach. At present, we can only perform the
discriminant analysis in two general groups - central and peripheral - in some vestibular disorders, because of the relatively small population of subjects available. Once enough cases of some well-defined vestibular diseases have been obtained, it is expected that specific discrimi nant analysis functions will be established for each partic ular disorder.
Acknowledgments We gratefully acknowledge the technical assistance of Sen Liu. Kui-nian Wang and Rui-chun Xiao and the participation of our sub jects. Above all, we thank Drs. Neng-jing Lian and Yan Feng for their help in selecting the clinical cases.
References 12 Peterka RT. Black FO: Human vestibular re flex dynamics in patients with vestibular disor ders; in Grahma MD. Kemink JL(eds): Vestib ular System: Neurophysiologic and Clinical Research. New York. Raven Press, 1987. pp 437-447. 13 Harris CM: The ethology of saccades: A noncognitive model. Biol Cybern 1989:60:401 — 410. 14 Yu LS, Wang KN. Wang LT, Li LM, Xia XY, Zhao DC: The normal values of caloric nystag mus of normal Chinese male subjects. Natl Med J China 1980:60:6. 15 Xu SJ. Jin PH. Gu SY, Chen QM: Statistical Methods in Medicine (in Chinese). Shanghai, Shanghai Science and Technology Press. 1978. 16 Murphy EA: Biostatistics in Medicine. Balti more. Hopkins University Press. 1982. 17 Claussen CF, Schlachta IV: Butterfly chart for caloric nystagmus evaluation. Arch Otolaryn gol 1972:96:371. 18 Baloh RW: Electronystagmography; in Baloh RW (ed): Clinical Neurophysiology of the Ves tibular System. Philadelphia. Davis. 1979. chapt 5, p 125. 19 Baloh RW. Yee RD. Honrubia V: Optokinetic nystagmus and parietal lobe lesions. Ann Neu rol 1980;7:269-276. 20 Schalén L. Pyykkö I, Henriksson ND, Wenn mo C: Slow eye movements in patients with neurological disorders. Acta Otolaryngol (Stockh) I982(suppl 386):231-234. 21 Yee RD. Baloh RW, Honrubia V, Lau CGY, Jenkins HA: Slow build-up of optokinetic nys tagmus associated with downbeat nystagmus. Invest Opthalmol Vis Sei 1979:18:622-629. 22 Yu LS: The Basis of Electronystagmography (in Chinese). Aviat Milit Surg 1983 (suppl).
23 Cohen B. Feldman M: Relationship of elec trical geniculate body to rapid eye movements. J Neurophysiol 1968:31:806. 24 Keller EL: Participation of medial pontine reti cular formation in eye movement generation in monkey. J Neurophysiol 1974:37:316. 25 Geobel HH, Komatsuzaki A. Bender MB. Co hen B: Lesions of the pontine tegmentum and conjugate gaze paralysis. Arch Neurol 1971:24: 431. 26 Robinson DA, Fuchs AF: Eye movements evoked by stimulation of frontal eye field. J Neurophysiol 1969:32:637. 27 Raphan T, Cohen B: Brainstem mechanism for rapid and slwo eye movements. Annu Rev Physiol 1978:40:527. 28 Westheimer G: Mechanism of saccadic eye movement. AMA Arch Opthalmol 1954:52: 710. 29 Baloh RW, Honrubia V, Sills A: Eye-tracking and optokinetic nystagmus: Results o f qualita tive testing in patients with well-defined ner vous system lesions. Ann Otol 1977,86:108. 30 Wennmo C. Hindfelt B: Eye movement in brainstem lesions. Acta Otolaryngol 1980:90: 230. 31 Jenkins HA: Long-term adaptive changes of the vestibulo-ocular reflex in patients following acoustic neuroma surgery. Laryngoscope. 1985:95:1224-1234. 32 Olson JE. Wolfe JW. Engelken EJ: Responses to low-frequency harmonic acceleration in pa tients with acoustic neuromas. Laryngoscope 1981:91:1270-1277.
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1 Marshall J: A survey of occlusive diseases of the vertebrobasilar arterial system: in Vinken PJ, Bruyn GW (eds): Handbook of Clinical Neurology. New York, 1972, American Else vier, vol 12: Vascular Disease of Nervous Sys tem. part II, pp 1-6. 2 Rubenstcin RL. Normal DM, Schindler RA, Kaseff L: Cerebellar infarction: A presentation of vertigo. Laryngoscope 1980:90:505. 3 Wennmo C, Pyykko I: Vestibular neuronitis. Acta Otolaryngol 1982:94:507. 4 Corvera J. Benitez LD. Lopez-Rios G. Rabiela MT: Vestibular and oculomotor abnormalities in vertebrobasilar insufficiency. Ann Otol 1980:89:370. 5 Barber HO. Stockwell CW: Manual of Electro nystagmography. St. Louis, Mosby, 1980. 6 Krynycky IA: Electronystagmography in the examination of the dizzy patient. Ear Nose Throat J 1979:58:432. 7 Pyykko I. Daltlen AI: Intrabeat relationship of postrotatory nystagmus in normal subjects. Acta Otolaryngol (Stockh) 1985:99:74. 8 Collewijn H: The normal range of horizontal eye movements in the rabbit. Exp Neurol 1970: 28:132. 9 Chalabi Z: Cumulative slow-phase eye position of the caloric nystagmus. ORL 1984:46:270. 10 Honrubia V, Jenkins HA, Baloh RW. Lau CGY: Evaluation of rotatory vestibular tests in peripheral labyrinthine lesions; in Honrubia V, Brazier MAB (eds): Nystagmus and Vertigo: Clinical Approaches to the Patients with Dizzi ness. London. Academic Press, 1982. p 57. 11 Henn V: Models; in Henn V, Cohen B, Young I.R (eds): Visual-Vestibular Interaction in Mo tion Perception and the Generation of Nystag mus. Cambridge. MIT Press. 1980. pp 575— 617.
a Beijing Institute of Otorhinolaryngology and b Institute of Aviation Medicine. Beijing. China
KeyWords Human Electronystagmography Vestibular disorders Multiplc discriminant analysis
Electronystagmographic Features in Some Peripheral and Central Vestibular Disorders: Application of Multiple Discriminant Analysis of Electronystagmographic Parameters
Abstract In routine clinical electronystagmographic (ENG) tests (postrotatory, optokinetic, caloric and tracking tests), eye movement signals were analyzed and a multiple discriminant analysis was carried out with the aid of a microcomputcr. Six parameters were selected and, based on these, two functions for dis criminating between peripheral and central disorders were established. Dis crimination between 35 patients with peripheral lesions and 15 patients with central lesions was made with a correct classification rate of 97.1 and 86.7%, respectively. These rates are significantly higher than that of any single ENG test analysis. Our results indicate that the clinical application of ENG can be improved by searching for more sensitive ENG parameters and adopting the comprehensive analysis approach.
Introduction Although vertigo is frequently seen in the clinic, it is not easy to distinguish peripherally originating vertigo from centrally originating vertigo, which may lead to a misdiagnosis [1-4]. It has been hoped that electronystag mography (ENG) would be helpful in solving this prob lem. After several decades, systematic tests of the vestibu lar function have been established [5. 6], However, the currently applied methods of examination are often less helpful than originally thought. The conventional param eters and manual analysis methods are not sensitive enough to detect some abnormalities of the vcstibulo-oculomotor system, especially in the early stages of disease.
Received: July 25.1990 Accepted after revision: June 10.1991
Furthermore, the various ENG results from different tests are sometimes contradictory. In order to improve the status quo, many ENG experts are searching for effective methods to evaluate vestibular function accurately and objectively, and, furthermore, to distinguish the various kinds of vestibular diseases from each other by, for example, looking for more sensitive parameters [7-9] or by establishing vestibulo-oculomotor models [10-13]. The currently available methods, though having their own individual advantages, are all explora tory and focus on one particular aspect. Since the vestibu lar system is multileveled. it is worth trying to find com prehensive methods for evaluating vestibular function more accurately.
G. Wei Beijing Institute of Otorhinolaryngology Beijing (Peoples Republic of China)
© 1992 S. Karger AG. Basel 0301-1569/92/0542-0071 $2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 5:34:19 AM
G. Wei3 L.S. Yub C. L iua G.Q. L ih R. Zhangb S. H. Chenh
Table 1. Classification of subjects
Category
Cases
Normal group
253
Peripheral group
Meniere disease sudden deafness with vertigo ototoxiccsis acoustic neurinoma vestibular neuronitis
23 8 4 3 2
Central group
cerebellar diseases vertebrobasilar insufficiency brainstem encephalitis bulbar paralysis acute demyelinating disease
7 6 2 i i
Subjects and Methods Subjects There were three groups of subjects (table 1): a normal group (253 male, 18-48 years old); a peripheral group (23 male, 17 female, 2461 years old; 3 cases of acoustic neurinoma in this group had no sign of CNS damage), and a central group ( 10 male, 7 female. 25-72 years old). The lesions in the peripheral and central groups were confirmed clinically with solid diagnoses and/or by surgery or computed tomog raphy. ENG Examination Horizontal eye movements were recorded binocularly and verti cal eye movements of the left eye were recorded. The subjects under went the following tests. Pseudorandomly Numbered Eye Tracking Test. Saccadic and sinusoidal eye tracking tests were carried out using stimuli of one moving light dot on a wide screen, of which the velocity changed randomly in frequencies ranging from 0.1 to 1.2 Hz. The vision angle was 20°. Optokinetic Nystagmus Test. Velocities of the optokinetic stimuli were 20,40,60 and 807s, leftward and rightward, respectively. Each stimulus lasted 20 s. Postrotatory Test. The chair was rotated up to 907s at an acceler ation of 17 s2 and then rotated at constant speed for 1 min or until the postrotatory nystagmus disappeared. The chair was then stopped. This was carried out in the clockwise and counterclockwise direc tions. Caloric Test. The modified Hallpike's caloric test was used [14], The water temperatures were 30 and 44 °C, respectively, 50 ml and 20 s for each irrigation. The subjects were in a dark room during the tests with their eyes open and were instructed to do mental arithmetic during the postro tatory and caloric tests. For a variety of reasons, not every subject underwent all the tests; therefore, the numbers of cases were not the same for each different test. The subjects who had not undergone the whole series of the tests were not included in the comprehensive anal ysis. The ENG signals were fed into a computer for analysis as well as recorded on chart paper. The parameters describing the velocity, duration and amplitude of eye movements were analyzed by a com puter algorithm processing system that was set up in this laboratory. In this study, we set up 194 parameters altogether for the 4 ENG tests. There were 8, 77, 54 and 55 parameters in the eye tracking, optokinetic nystagmus, postrotatory and caloric tests, respectively. About 20% of the parameters were conventional, only describing
72
Table 2. Comprehensive analysis of the 4 ENG tests
Discriminatory classification
Clinical classification, case number
Discriminatory identification rate ,%
peripheral
central
Peripheral Central
34 1
2 13
97.1 86.7
Total
35
15
94.0
Table 3. Values of the 6 selected parameters
Parameter
Peripheral group
Central group
BN312 C0-FA-FV DPT DP60SPV C„-ST-FT SDT
39.4 ±13.1 0.66 ±0.17 20.6 ± 22.1 7.7 ±6.9 0.05 ±0.07 275 ±55
45.2 ±12.6 0.55±0.20 10.6 ± 12.6 10.2 ±7.0 0.25 ±0.21 410 ± 432
some features of the slow phase of eye movements, and the rest were newly built, describing features of the fast phase such as velocity, duration or latency. We also established some parameters to describe correlations between certain features, based on the assumption that there are some potential interactions between certain parameters. The MDA was carried out according to Bayes’s theorem [15,16], using a statistical program with the aid of a computer. The program was designed by statisticians. We took an F value = 4.5. which is greater than F (p = 0.05), as a criterion for the selection of para meters.
Wei/Y u/Liu/Li/Zhang/Chen
MDA of ENG Parameters in Vestibular Disorders
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 5:34:19 AM
Our study was aimed at searching for more sensitive parameters and employing a comprehensive analysis method - the multiple discriminant analysis (MDA) - in evaluating vestibular function from multiple perspec tives. Our goal was to find a better way of interactively analyzing the results of the presently used clinical ENG tests and, thereby, to improve the power of these tests for more accurately and objectively distinguishing central and peripheral disorders.
Table 4. Comparison between the results of each single test and of the 4 ENG tests combined
Central group
Total identified rate, %
case number
identified number
identified rate ,%
case number
identified number
identified rate, %
Postrotation Caloric Optokinetic Eye tracking
40 38 39 38
28 30 20 25
70.0 78.6 51.3 65.8
17 17 17 15
5 12 5 3
29.4 70.6 29.4 20.0
71.9 81.6 72.5 67.6
Four ENG tests combined
35
34
97.1
15
13
86.7
94.0
Results The data from the above-mentioned 4 ENG tests were combined in the analysis in which there were altogether 194 parameters. Table 2 shows the results. Six parameters (X1-X 6) were selected: X) = BN312 (beat number during 3-12 s in the postrotatory test); Xj = C0-FA-FV (correlation coefficient between the am plitude and velocity of the fast phase in the postrotatory test); X3 = DPT (asymmetric ratio between the time con stants of the clockwise and counterclockwise rotations in the postrotatory test); X4 = DP60SPV (asymmetric ratio between the leftward and rightward slow-phase velocities in the 60°/s optokinetic test); X5 = C0-ST-FT (correlation coefficient between the duration of the slow and fast phases in the caloric test), and X6 = SDT (delay time of square saccades in the tracking test). The values (mean ± SD) for each of the parameters are shown in table 3. Based on these selected parameters, the discriminant functions for distinguishing between the central and pe ripheral vestibular disorders were established as follows. Function for peripheral disorders: Y, = -1 3 .2 8 + 0.0475X, + 16.1360X2+ 0.1328X3 + 0.2490X4 + 1.3845X5 - 5.5975X6.
Function for central disorders: Y2 - -9.9148 + 0.1969X, + 6.9429X, + 0.0716X3 + 0.0742X4 + 5.4510X5+ 1.7879X6.
Y i and Y2 represent the discriminant score of the peripheral and central function, respectively, and X |-X 6 represent the respective discriminant variables (see ta ble 2 for results of the discriminatory analysis). The MDA was also carried out on the basis of each single test. The results from the different tests were com
pared (table 4). The x2 test detected a significant (p < 0.05) difference between the identification rates of the 4 ENG tests combined and the caloric test, as well as a highly significant (p < 0.01) difference between the iden tification rate of the 4 ENG tests combined and that of each of the 3 other single ENG tests (postrotatory, optoki netic and eye tracking test).
Discussion Multiple Discriminant Analysis In our study, MDA, which can process multiple vari ables, was used according to Bayes’s theorem. During the analysis, all the variables (parameters) were compared with each other step by step, such that variables having the greatest power of discrimination were selected, and then the discriminant functions were set up for distin guishing. The ordinary statistical methods, e.g. t test, only deal with one parameter in one single dimension. The dis criminant analysis we used in this study, however, can analyze comprehensively multiple variables. Hence, it is a more sensitive, reliable and accurate method. Comparison between the Results o f Each Single Test and o f the 4 ENG Tests Combined From table 4, it is obvious that the effect of the multi ple-test discrimination is better than that of any single test. This method takes into account that the nervous sys tem initiating and modulating the eye movements is multileveled, whereas one particular test mainly checks only one relevant aspect of the vestibulo-oculomotor function on the basis of the individually different mechanisms. Therefore, only by analyzing the information from the multiple tests can one obtain more accurate results, i.e. a higher rate of correct classification. This kind of analysis
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Peripheral group
Tests
Description o f the Selected Parameters in the MDA In the 4 routine ENG tests, altogether there were 194 parameters for analyzing the signals of the eye move ments. of which 6 parameters were selected. Based on the discriminant functions, these 6 parameters can reveal the intrinsic differences between central and peripheral disor ders. while the others have less or no significance in that sense in the present investigation. BN3I2 and DP60SPV. Both parameters showed no sig nificant difference between the peripheral and central groups only according to the t test (p > 0.05). However, the selection of these two parameters into the discrimi nant functions showed that MDA method has compre hensive analysis ability to evaluate vestibular function from the interrelationship between multiple parameters, not from one single parameter. Therefore, it is more sensi tive than the t test. It is generally considered that the beat numbers of the evoked nystagmus decrease with peripheral lesions, while the beat numbers increase with central ones. This is due to a loss of the central inhibitory function, thus lowering the threshold for initiating nystagmus in the fast phase [17. 18], Obvious asymmetric abnormalities in optokinetic nys tagmus frequently suggest disorders in the CNS. for instance, lesions of the parietal lobe [19], brainstem [5. 20] and cerebellum [21], or vertebrobasilar insufficiency [6], and this asymmetry cannot be compensated as it can be in peripheral cases. We also found that a certain inten sity of optokinetic stimulation is necessary to detect abnormalities sensitively but that overstimulation can weaken the response. In our laboratory, the appropriate optokinetic stimulation velocity is 60°/s [22], Cf-FA-FV and C„-ST-FT. Of all the parameters in cluded in the MDA, there were 4 individual parameters: FA (last-phase amplitude in postrotatory test): FV (fastphase velocity in postrotatory test): ST (slow-phase time in caloric test), and FT (fast-phase time in caloric test). All these 4. parameters were not selected into the functions. There were no significant differences between the mean values of these parameters in the peripheral and central groups according to the t test (p > 0.05). However. C0FA-FV and C0-ST-FT were selected into the functions, and the l test showed that both of them revealed a highly
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significant difference between the peripheral and central groups (p < 0.01). This result suggests that, under patho logical conditions, the changes in the interrelations be tween certain parameters are more obvious than those of 1 single parameter, hence, being more sensitive in detect ing disorders. Pyykko and Dahlen [7] demonstrated that the integra tion of the velocity and amplitude of the nystagmus occurs in the CNS. most likely in the paramedian pontine reticular formation (PPRF) and the end point of the nys tagmus is determined by the velocity signals. Therefore, there is a close relationship between the velocity and amplitude of the nystagmus. Our result indicates that the relationship between the velocity and amplitude of the fast phase deteriorates when there is a damage in the CNS. According to our observations, no significant correla tion was found between ST and FT of the caloric nystag mus in either the normal or the peripheral groups. There w'as, however, a tendency towards a closer relationship between the two parameters in the central group. The rea son for this change is not clear and further research is needed to address its significance. SDT. SDT means the delay time of square saccades. The neurons that initiate saccadic eye movements arc located in the PPRF [23-25], The frontal cortex partici pates in the modulation of fast eye movements [26. 27]. Some authors reported that the normal SDT is 150-250 ms [5. 28]. Baloh et al. [29] found that SDT can be pro longed by lesions in the brainstem, basal ganglia, and frontal and parietal cortex, i.c. initiation of voluntary saccades can be delayed. We found a significant difference between the peripheral and central groups according to the t test (p < 0.05). suggesting that this parameter has an important value for distinguishing peripheral from cen tral diseases. Under the same degree of impairment due to a lesion in the CNS. the saccadic abnormalities appear more obvious than those of the fast phase of the nystag mus. The reason is that the saccadic movement requires longer neural pathways in which there is a larger number of synapses [30], DPT. DPT is the parameter showing the asymmetry of the time constants of postrotatory nystagmus decays be tween clockwise and counterclockwise rotations. After rotation, the intensity (slow-phase velocity) of the nystag mus decays exponentially. Under normal conditions, the time constants on both sices are actually equal. However, when there is a lesion in the peripheral vestibular system on one side, the nervous pulses emitted or transmitted do decrease, hence causing a decrease in nystagmus intensity.
Wei/Y u/Liu/Li/Zhang/Chen
MDA of ENG Parameters in Vestibular Disorders
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is neither an ‘or method nor the simple sum of each result, but a comprehensive method which evaluates ves tibular function from the interrelations of multiple pa rameters. So. it is an objective analysis, and the subjective factors can thereby be eliminated.
a shortening of the time constant on the lesion side and. thus, an asymmetry between the two sides. Our research revealed that there is a highly significant difference be tween the two groups (p < 0.01). The occurrence of time constant asymmetry in our patients with unilateral pe ripheral vestibular loss is in agreement with the observa tions of others [31, 32], In conclusion, routine ENG tests are helpful in the diagnosis of vestibular system disorders in the clinic, but the currently applied analysis methods make the use of ENG limited. Our study shows that the clinical applica tion of ENG can be improved by searching for more sensi tive ENG parameters and by using the comprehensive analysis approach. At present, we can only perform the
discriminant analysis in two general groups - central and peripheral - in some vestibular disorders, because of the relatively small population of subjects available. Once enough cases of some well-defined vestibular diseases have been obtained, it is expected that specific discrimi nant analysis functions will be established for each partic ular disorder.
Acknowledgments We gratefully acknowledge the technical assistance of Sen Liu. Kui-nian Wang and Rui-chun Xiao and the participation of our sub jects. Above all, we thank Drs. Neng-jing Lian and Yan Feng for their help in selecting the clinical cases.
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