Journal of Neuro-Ophthalmology, March 1999, Volume 19, Issue 1

Ocular Microtremor in Oculomotor Palsy

OBJECTIVES: Ocular microtremor (OMT) is a high frequency tremor of the eyes present in all individuals. Recent reports suggest that OMT may be a useful indicator of brainstem function. However, the actual origin of ocular microtremor remains controversial. This study aims to provide evidence that OMT has a neurogenic origin. MATERIALS AND METHODS: The OMT activity of five subjects with unilateral oculomotor nerve palsy and one subject with complete unilateral internal and external ophthalmoplegia were recorded from both eyes of each subject using the piezoelectric strain gauge technique, with the normal eye acting as a control. Five parameters of OMT activity were studied in each subject: the peak count, the power of the high frequency peak, the percentage power between 60 and 100 Hz, the percentage power between 70 and 80 Hz, and the 10 dB cut-off point. RESULTS: In the five subjects with oculomotor nerve palsy, the mean peak count in the normal eye was 88.4 Hz (SD+/-16.9) and in the affected eye was 59 Hz (SD+/-8.6), P < 0.0096. There was also a fall in the peak power, the power between 60 and 100 Hz, and the power between 70 and 80 Hz. In subject six, who had complete opthalmoplegia, there was no evidence of OMT activity in the denervated eye. CONCLUSIONS: These results suggest that innervation of the extraocular muscles is necessary for normal OMT activity, and OMT therefore has a neurogenic origin.

Journal of Neiim- Opllllmhiiohgy 19( 1): 42- 45, 1999. © 1999 Lippincotl Williams & Wilkins, Inc., Philadelphia Ocular Microtremor in Oculomotor Palsy Ciaran Bolger, F. R. C. S. I., Stana Bojanic, F. R. C. S., Noirin F. Sheahan, Ph. D., Davis Coakley, M. R. c. p. i., and James F. Malone, Ph. D. Objectives: Ocular microtremor ( OMT) is a high frequency tremor of the eyes present in all individuals. Recent reports suggest that OMT may be a useful indicator of brainstem func­tion. However, the actual origin of ocular microtremor remains controversial. This study aims to provide evidence that OMT has a neurogenic origin. Materials and Methods: The OMT activity of five subjects with unilateral oculomotor nerve palsy and one subject with complete unilateral internal and external ophthalmoplegia were recorded from both eyes of each subject using the piezoelectric strain gauge technique, with the normal eye acting as a control. Five parameters of OMT activity were studied in each subject: the peak count, the power of the high frequency peak, the percentage power between 60 and 100 Hz, the percentage power between 70 and 80 Hz, and the 10 dB cut- off point. Results: In the five subjects with oculomotor nerve palsy, the mean peak count in the normal eye was 88.4 Hz ( SD± 16.9) and in ( he affected eye was 59 Hz ( SD± 8.6), P < 0.0096. There was also a fall in the peak power, the power between 60 and 100 Hz, and the power between 70 and 80 Hz. In subject six, who had complete opthalmoplcgia, there was no evidence of OMT ac­tivity in the denervated eye. Conclusions: These results suggest that innervation of the ex­traocular muscles is necessary for normal OMT activity, and OMT therefore has a neurogenic origin. Key Words: Ocular microtremor- Piezoelectric strain gauge- Peak count- Oculomotor nerve palsy. Ocular microtremor ( OMT) is a small high frequency tremor of the eyes. It was first described in detail as one of the fixational eye movements in 1934 by Alder and Fliegelman ( 1). The most recent published estimate of ocular microtremor amplitude is that of Einzman ( 2), who puts the mean extent at 6 seconds of arc. The peak-to- peak rotation involves a displacement of the surface of the eye of between approximately 150 and 2000 nm ( 3). Ocular microtremor is believed to originate from con­stant oculomotor unit activity and is present in all indi­viduals ( 4). However, the actual origin of ocular mi­crotremor remains controversial. Manuscript received June 8, 1998; accepted October 30, 1998. From the Mercer's Institute for Research on Ageing, St. James's Hospital, Dublin, Ireland, and Department of Neurosurgery ( C. B., S. B.), Frenehay Hospital, Bristol. Address correspondence to Ciaran Bolger, Bsc, PhD, FRCSi, Room 1, Academic Centre, Frenehay Hospital, Frenehay Park Road, Bristol, BSI6 ILE, United Kingdom. Recent reviews dealing with ocular movement have expressed doubts about its having a neurogenic basis ( 5,6). It is increasingly being asserted that physiologic tremor of the extremities is caused by exogenous factors such as mechanical factors and cardiac activity. Work by Brumlick in 1962 ( 7) and Wachs in 1964 ( 8) involved the simultaneous recording of electrocardiogram, ballisto­cardiography, and tremor and established that at least some form of physiologic tremor are caused by cardiac activity. This was reaffirmed by work by Yap and Boshes in 1979 ( 9). Previous work has also suggested a nonneurogenic origin to ocular tremor. Marsden ( 10) has claimed that all resting tremor including ocular tremor is caused by cardiac activity. More recently, Freund and Dietz ( 11) could find no neuronal basis for " low ampli­tude (< 1 degree), irregular physiologic tremor." Other clinical studies have suggested that oculomicrotremor is a neurogenic phenomenon based on studies of patients with brainstem death and coma ( 12- 15). Patients with oculomotor palsy, i. e., dysfunction of one of the nerves innervating extraocular muscles, provide an ideal situation in which to investigate the neurogenic basis of OMT. If the palsy is unilateral, then the other eye provides the ideal control situation, being in the same individual under the same environ­mental conditions. The only difference between the two eyes is the presence of an oculomotor palsy in one of them. In 1983, Coakley ( 4) studied an 84- year- old woman with complete internal and external ophthalmoplegia. This patient had a cavernous sinus thrombosis of un­known etiology. This study found unilateral loss of OMT activity in the eye on the affected side and therefore provided strong evidence for the neurogenic basis of OMT. However, the objection may be raised that normal responses of the eye to cardiovascular pulsation and en­vironmental vibration may also be affected by cavernous sinus thrombosis as proptosis ( protrusion of the eye) and periorbital soft tissue edema may both affect the normal mechanical response of the eye to perturbation. Oculomotor palsy, however, remains a very convinc­ing model with which to study the neurogenic basis of OMT, particularly when the cause is not associated with changes in ocular mechanical properties. This study ex­amines the effects of unilateral oculomotor palsy in six patients. 42 OCULAR MICROTREMOR IN OCULOMOTOR PALSY 43 METHODS Five subjects with unilateral oculomotor nerve palsy and one subject with complete unilateral internal and external ophthalmoplegia were recruited. Studies were performed with the full written consent of each subject and with approval of the local ethics committee. Subject 1 was a 63- year- old male patient with a brain­stem infarct involving the third nerve fasciculus. Clini­cally, he had a complete left third nerve palsy. Subject 2 was a 34- year- old female patient with a complete right third nerve palsy caused by microvascular infarction of the third nerve. This patient was known to have insulin dependent diabetes mellitus ( IDDM). Subject 3 was a 33- year- old female patient ( known to have IDDM) with complete right third nerve palsy caused by microvascular infarction of the third nerve. Subject 4 was a 50- year- old female patient with com­plete left third nerve palsy caused by an aneurysm of the internal carotid artery compressing the third cranial nerve. Subject 5 was a 45- year- old female patient with com­plete left third nerve palsy secondary to a skull base fracture with direct trauma to the third nerve. Subject 6 was a 57- year- old man with complete inter­nal and external ophthalmoplegia caused by an aneurysm of the intracavernous portion of the internal carotid ar­tery. This man had complete loss of movement of the left eye. The aneurysm did not occlude the cavernous sinus totally, and venous drainage through the sinus was con­firmed on cerebral angiography. Recording Session Ocular microtremor was recorded using the piezoelec­tric transducer technique first developed by Bengi and Thomas in 1972 ( 16). This technique is described in detail elsewhere ( 3) and provides a reliable estimate of OMT activity ( 17). Briefly, the piezoelectric element ( pi­ezoelectric ceramic lead- Zirconium- PZT5BN) is con­structed as a cantilever with one end embedded in a solid mount and the other end free. The element is mounted in a Perspex rod ( Amari Plastics, Bristol, UK) with 1 cm of its tip protruding, which is coated with silicone rubber. The subject lies supine with the eyes in the primary position in a normally lit room. The subject is advised to keep his eyes fixating straight ahead at the same point throughout the recording. Movements of the head can represent a source of noise, and this problem is overcome by mounting the transducer onto the head by means of a headset. The subject is then asked to keep the head still throughout the recording, but no means of restraint are used. The subject's eyelids are retracted using adhesive tape. The Perspex rod is then lowered so that the rubber tip is just touching the scleral surface, which has been anesthetized with 0.5% proxymethacaine hydrochloride solution. Probe placement is judged by visual inspection and by listening to the signal being recorded, using audio cassette headphones. After a recording session, the probes are soaked in sodium hypochlorite ( concentration 500 ppm) for 10 minutes for sterilization purposes before being used again ( 18). The signal from each probe is passed to a conditioning unit and stored on audio tape using an adapted Sony Walkman ( London, UK). The conditioning unit consists of a differential amplifier with a 40 dB common mode rejection ratio. Amplification factor is 10. Between 20 and 150 Hz the frequency response deviates by less than - 2 dB from the peak response amplified. The system filters out inputs below 20 Hz; in particular, any drift movements are filtered. This system has a signal/ noise ratio of > 23 dB, and the resolution is less than I % of the dynamic range, or 12 nm. All records were obtained by one experienced opera­tor, and at least 30 seconds of OMT activity was re­corded from each eye ( 17). Once the signal is processed, it is passed by means of an analogue to a digital converter ( FPC- 011 DATA DESIGN TECHNIQUES) to an IBM compatible PC. The PC has an OMT processing package that compiles both fourier spectral and linear predictive analysis and performs peak counting as well. The param­eters measured were the peak count, the power of the high frequency peak, the percentage power between 60 and 100 Hz, the percentage power between 70 and 80 Hz, and the 10 dB cut- off point. RESULTS Figure 1 shows the records of OMT activity obtained from Subject 2 and illustrates the corresponding spectra. It is clear that the records provided in Figure 1 contrast with each other. The record from the eye with the third nerve palsy is slower and of an abnormal pattern. The same contrast was seen in all five patients between the OMT records from normal and abnormal eyes. Table 1 provides data on the mean values of OMT parameters for the five subjects with third nerve palsies and the corresponding paired t test analysis. The mean peak count frequency in the normal eye is 88.4 Hz ( SD± 16.9), compared with the mean value in the abnor­mal eye of 59 Hz ( SD± 8.6), t = 4.655, df = 5, P < 0.0096. There is also a fall in the peak power ( from 35.5% to 14.5%, P < 0.0096), the power between 60 and 100 Hz ( from 39% to 13.8%, P < 0.0053), and the power between 70 and 80 Hz ( from 14.5% to 4.7%, P < 0.0094) in the affected eye. These findings confirm the shift of the spectrum of OMT activity to the left, as demonstrated in Figure 1. The 10 dB cut- off point does not differ significantly between the eyes ( t = 0.402, P < 0.708). However, the absence of a true high frequency peak in the spectra from the eyes with third nerve palsies reduces the reliability of the measurement by the IBM software. In all cases, there was no true high frequency peak iden­tified in the eye with palsy. Figure 2 shows the records obtained from both eyes of subject six. Although there is some baseline oscillation corresponding to oscillations seen on the record from the good eye, there is no distinguishable tremor activity in the record from the good eye with complete denervation. The record in the subject was repeated with the eye probes reversed to exclude dysfunction of the recording apparatus. 44 C. BOLGER ET AL. LEFT EYE TIME: ' 1 . 5 p 0 W - E R - 28 dB FOURIER SPECTRUM \ v rW\' , v- FREQUENCY ^" YA v' *- 3. P - I 0 w - E R - 20' « B 150Hz 0 LINEAR PREDICTIVE SPECTRUM FIG. 1. Ocular microtremor record from the ab­normal eye in a patient with unilateral third nerve palsy. 150 Hz FREQUENCY DISCUSSION This study demonstrates abnormal OMT activity re­corded from the eyes of subjects with third nerve palsy when compared with the normal eye. The records show marked differences on visual inspection that are con­firmed on direct analysis of linear predictive spectral and statistical comparison of measured spectra parameters. This is much greater than any difference between the two eyes that have been documented in normal subjects ( 19). The third cranial nerve innervates the medial rectus muscle. If a neurogenic origin of OMT is postulated, then the medial and lateral recti are agonist and antago­nist pairs of the mechanism that transmits tremor move­ments to the eye, and we would expect this tremor to be reduced if palsy of one of these nerves was present. The only difference between each pair of eyes in these sub­jects is the lack of third nerve innervation and, in each case, OMT activity is reduced in the affected eye. None of the causes of third nerve palsy interfere with exog­enous effects on eye tremor. In subject six, there was no evidence of OMT in the denervated eye. The only difference between the two eyes of this patient was paralysis. There was no evidence of venous obstruction and no periorbital soft tissue edema that could interfere with ocular mechanical prop­erties. The study on this patient and the five patients with third nerve palsy provides contributing evidence as to the neurogenic basis of OMT. These cases clearly demon­strate that disruption of nerve impulses to the extraocular muscles, without affecting other possible sources of OMT activity, disrupt normal OMT activity. Innervation of the extraocular muscles is therefore necessary for normal OMT activity, and OMT has there­fore a neurogenic origin. This provides support for pre­vious clinical studies that proposed OMT as an indicator of brainstem function ( 4,12,14). These studies have shown that OMT activity is abnormal in coma patients and have proposed the use of OMT activity as an indi­cator of outcome in coma ( 4,13,14). Initial OMT mean peak count frequencies less than 50 Hz are associated with a grave prognosis in these patients ( 13). Ocular microtremor activity has been shown to be absent in patients with clinically confirmed brainstem death, which led Coakley ( 1977) to propose the ocular mi­crotremor record as a potential procedure for establishing brainstem death ( 20). Ocular microtremor activity is also affected by anesthetic agents such as thiopentone, and the ocular microtremor record may be useful in assessing depth of anesthesia ( 21). The 10 dB cut- off is the point at which the power has fallen 10 dB below the high frequency peak. The failure to identify changes in the 10 dB cut- off point by software analysis, when differences in spectra are clearly demon­strated on visual inspection, is interesting. It would seem likely that this is caused by the grossly abnormal nature of the spectra themselves and the failure to identify a true high frequency peak. It is unlikely that there was no true TABLE 1. Mean values for parameters of OMT actvily and paired t- test comparison from 5 subjects with third, nerve palsy Mean SD Range Mean t P difference Peak coun ( Hz) N 88.4 16.9 P 59 8.6 69- 84 50- 73 - 29.2 4.655 0.0096 Peak power (%) N 35.5 18.6 13- 69 - 21 4.656 0.0096 P 14.5 10.8 4- 34 Power 60- 100 Hz N 39 12.5 (%) P J3.8 4.9 15- 41.7 7.8- 19 - 25.2 5.516 0.0053 Power 70- 80 Hz N 14.5 5.8 5.8- (%) 21 - 9.86 4.688 0.0094 P 4.7 1.75 2.6- 7 10 dB point N 120.6 16.7 ( Hz) P 117 21.5 100- 150 95- 150 - 3.6 0.402 0.7085 N, normal eye; P, abnormal eye. ./ Neiiro- Ophllialiiiol, Vol. 19. No. 1, 1999 OCULAR MICROTREMOR IN OCULOMOTOR PALSY 45 FIG. 2. Ocular microtremor record from a sub­ject with complete right opthalmoplegia ( the re­cording from the left eye is included for compari­son). change in this parameter, given the abnormal spectra produced. The implication is that this parameter may not be reliably measured by the software in the presence of a grossly abnormal signal. Thus, a degree of caution must be employed when applying this parameter to ab­normal spectra in the clinical setting. It would be inter­esting to further evaluate the spectral parameters reliabil­ity and sensitivity to input frequency changes over a wider range than that employed by Sheahan ( 15). This should be evaluated before widespread clinical usage. Acknowledgment: The authors acknowledge The Health Research Board, Ireland. REFERENCES 1. Alder FH, Fleigclman F. The influence of fixation on the visual acuity. Arch Opthahnol 1934; 12: 475- 83. 2. Einzman M, Frccker RC, Hallelt PE. Power spectra for ocular drift and tremor. Vision Res 1985; 25: 1635- 40. 3. Sheahan NF, Coakley D, Hegarty F, Bolger C, Malone J. Ocular microtremor measurement system: design and performance. Med Biol Eng Comput 1993; 31: 205- 12. 4. Coakley D. Minute eye movement and brain stem function. Florida: CRC Press, I983; 23. 5. Carpenter RHS. Movements of the eyes. London: Pion Press, 1988. 6. Scott AB. Ocular mobility in physiology of the human eye and visual system. New York: Harper and Row, 1990. 7. Brumlick J. On the nature of normal tremor. Neurology 1962; 12: 159. 8. Wachs H. Studies of physiological tremor in the dog. Neurology 1964; 14: 50. 9. Yap CB, Boshes B. The frequency and pattern of normal tremor. Electroencephalogr Clin Neurophysiol 1979; 19: 325. 10. Marsden CD, Meadows JC, Lange GW, Watson RS. The role of the ballistocardiac impulse in the genesis of physiological tremor. Brain 1969; 92: 647- 62. I 1. Freund AJ, Diet/, V. The relationship between physiological and pathological tremor. In: Desmcdt JE, ed. Progress in clinical neu­rophysiology. Vol 5. Kanzcr: Beisel, 1975. 12. Shakhnovich AR, Thomas JG. OMT as an index of motor unit activity and of the functional stale of the brain slcm. ./ Physiol 1975; 283: 36P. 13. Coakley D, Thomas J. The ocular microtremor record and the prognosis of the unconscious patient. Lancet 1977; 1: 5 12. 14. Michalik M. Der okulare Mikrotrcmor- cin Indikator fur den functionellen Zustand des Hirnslammus, Psychiatr Neurol Med Psychol Beih 1983; 29: 196- 204. 15. Bolger C. Ocular microtremor: reliability of measurement, physi­ological variation and neurogenic origin [ PhD Thesis]. Trinity College Dublin, 1994. 16. Bengi H, Thomas JG. Three electronic methods for recording ocu­lar tremor. Med Biol Eng 1968; 6: 171- 8. 17. Bolger C, Sheahan N, Coakley D, Malone J. High frequency eye tremor: reliability of measurement. Clin Phys Physiol Meas 1992; 13: 151- 9. 18. Nagington J, Sutehall GM, Whipp P. Tonometer disinfection and viruses. Br J Ophthalmol 1983; 67: 674- 6. 19. Sheahan N. Ocular microtremor measurement technique and bio­physical analysis [ PhD Thesisf Trinity College Dublin, 1991. 20. Coakley D, Thomas J. The ocular microtremor record as a potential procedure for establishing brain death. ./ Neurol Sci I977; 31: 199- 205. 21. Coakley D, Thomas J, Lunn J. The effect of anaesthesia on ocular microtremor. Br .1 Anaesthesia 1981; Proceedings of the Anaes­thetic Research Society: 1122- 23. / A/„„[ v>-/ 0„/ J//,„/ Ill,,/ 1/,,/ 10 A/„