Journal of Neuro-Ophthalmology, December 1990, Volume 10, Issue 4

Periodic alternating oscillopsia: a symptom of alternating nystagmus abolished by baclofen.

We describe an unusual patient with periodic alternating oscillopsia caused by periodic alternating nystagmus. A dramatic cessation of her symptomatology and disappearance of periodic alternating nystagmus was achieved with baclofen and has been maintained for a period of over nine months. The importance of proper diagnosis and therapy of patients with oscillopsia is described.

Journal of Clinical Neuro- ophthalmology 10( 4): 273-- 277, 1990, © 1990 Raven Press, Ltd., New York Periodic Alternating Oscillopsia: A Symptom of Alternating Nystagmus Abolished by Baclofen B. Todd Troost, M. D., Francis Janton, M. D., and Richard Weaver, M. D. We describe an unusual patient with periodic alternating oscillopsia caused by periodic alternating nystagmus, A dramatic cessation of her symptomatology and dis­appearance of periodic alternating nystagmus was achieved with baclofen and has been maintained for a period of over nine months. The importance of proper diagnosis and therapy of patients with oscillopsia is de­scribed. Key Words: Oscillopsia- Periodic alternating nystag­mus- Baclofen. From the Departments of Neurology ( B. T. T., F.].), and Oph­thalmology ( B. T. T., R. W.), Wake Forest University Medical Center, Winston- Salem, North Carolina 27103, U. S. A. Address correspondence and reprint requests to Dr. B. Todd Troost at Department of Neurology, Bowman Gray School of Medicine, 300 S. Hawthorne Road, Winston- Salem, NC 27103, U. S. A. 273 Periodic alternating nystagmus ( PAN) is often accompanied by unusual ocular symptoms includ­ing oscillopsia. We present a patient with what we term periodic alternating oscillopsia. She had seen multiple ophthalmologic and neurologic consult­ants, some of whom had noted horizontal nystag­mus but had not realized she had a treatable form of ocular motor oscillation. Periodic alternating nystagmus and its accompanying symptomatology deserves further emphasis in the literature. CASE REPORT A 48- year- old woman was evaluated for an un­usual visual complaint that had begun two years earlier. She had first noticed that her head would turn unconsciously to the left or right as she was talking with someone or watching television. When she adjusted her head to regard an object of interest with her head straight, her visual environ­ment seemed to move rhythmically to the left or to the right. She described the sensation of move­ment as though she were watching close objects move from the window of a moving car. If she permitted her head to turn back to its original po­sition, the oscillation of the external environment ceased. She denied reduced vision, diplopia, sco­tomas, headache, or faintness, but occasionally felt a sensation of " self- movement" or imbalance in association with her visual disturbance. She had been seen by several neurologists, oph­thalmologists, and an otolaryngologist, who had diagnosed a perilymphatic fistula based on vertigo and an electronystagmogram showing nystagmus. ( The electronystagmogram- ENG- was unavail­able for review.) Surgery was performed for a peri­lymphatic fistula but no subjective improvement was noted by the patient. Her prior evaluation had included normal computed tomography ( CT) and 274 B. T. TROOST ET AI. magnetic resonance image of the head, erythrocyte sedimentation rate, electrolytes, and a complete blood count, all of which were normal. Various medications including beta- blocking drugs, halo­peridol, and meclizine, had failed to provide any relief of her symptoms. Her general physical and neurologic examina­tion, except for her eye movements, were normal. NEURO- OPHTHALMOLOGIC EVALUAnON Visual fields were normal, corrected visual acu­ity was 20/ 20 bilaterally, and there was no extraoc­ular limitation of motion upon gaze. Evaluation of Nystagmus The patient was observed to have periodic alter­nating nystagmus with the following characteris­tics: A variable total period of 5 to 10 minutes with approximately 80% of the nystagmus right beating in primary position. In primary position the eyes would remain free of nystagmus for 30 seconds to 1 minute ( Fig. lA) and then begin a nystagmus beating in a leftward direction with an increasing, then decreasing, amplitude over a duration of 2 to 3 minutes ( Fig. 18). After 30 seconds to 1 minute with no nystagmus ( Fig. lC) a nystagmus would begin with a fast phase to the right which would gradually increase in amplitude to 5° ( Fig. ID) and thereafter gradually diminish to a time of no nystagmus. When the patient had prominent primary posi­tion horizontal jerk right or jerk left nystagmus, the nystagmus remained horizontal on uJ:"' war~ gaze. When the patient had no nystagmus ill pn­mary position, a horizontal jerk nystagm~ s could be elicited by right gaze or leftward gaze wIth ~ fast component in the direction of gaze. The amplitude of such gazed- evoked nystagmus varied over time. Oscillopsia The patient described periodic alternating oscil­lopsia. When her head remained fixed in primary position and her eyes developed a right beating nystagmus, she reported a sensation of objects and her environment moving to the right in a " streaming" fashion. The direction of environ­mental movement was toward the nystagmus fast phase ( or in the direction opposite the nystagmus slow phase). The visual experience was similar to her subjective complaint in her usual visual envi­ronment, but more intense as head turning ( see below) was not permitted to lessen the intensity of her symptoms. Effect of Head Tum The patient's primary- position nystagmus could be extinguished or diminished by head turn in the direction of the nystagmus fast phase. For exam­ple, if the patient had a low amplitude primary position right beating nystagmus, turning her head a few degrees to the right, while she fixated straight ahead, would extinguish or " null" the nystagmus. As the nystagmus increased in ampli­tude it was necessary to turn the head further to A B C c: .~ Right ~ 5') 0- ~ E'" ( t E < f) : J E OJ V'" i >. Z (; - Q0) Left .~ 5° Ci E « I 0 2 4 6 o 8 10 Time ( minutes) FIG. 1. Typical cycle of periodic alternating nystagmus. The vertical shaded areas represent neutral period with no observable nystagmus in primary position. A: epoch of minimal or no nystagmus; B: epoch of leftward beating nystagmus; C: epoch of no nystagmus. [:: eroch of rightward beating nystagmus. PERIODIC ALTERNATING OSCILLOPSIA 275 the right to bring her eyes to a left orbital position where the nystagmus would disappear or be of lowest amplitude. In fact, when the nystagmus in­tensity was greatest in primary position, even with extreme head turn to the right, she continued to have a right beating nystagmus from the extreme left orbital position. When attention was not di­rected to her nystagmus it was clear that the pa­tient unconsciously turned her head to place her eyes in an orbital position with the minimum nystagmus. Therapy The patient was started on baclofen 10 mg two times a day and gradually titrated to a dose of 10 mg four times per day. She achieved complete res­olution of her symptoms at the 40 mg per day dos­age. When examined during her symptom- free pe­riods she had a variable gaze evoked nystagmus on extreme gaze left or right that disappeared when gaze was brought 10° toward the midline. With her permission the medication was gradually reduced to 10 mg per day after 2 months of therapy and she noted return of her symptoms and was noted to have her previously observed periodic al­ternating nystagmus and head turn. Her medica­tion was again gradually increased to a daily dose of 30 mg per day where she has been maintained for the past 9 months. She has minimal symptom­atology, virtually no nystagmus, and is fully able to carry out her activities, including television viewing and driving, without difficulty. DISCUSSION The disabling symptom of periodic alternating oscillopsia has not been previously emphasized as a symptom of periodic alternating nystagmus ( 1­6). In the patient described in this report symp­toms disabled her to the extent she was unable to carry out her usual activities of daily living, had seen a number of specialists and had even under­gone otolaryngologic surgery before a diagnosis was made. The usual cause of periodic alternating nystagmus is from structural abnormality in the brainstem including infarction, tumor, Arnold­Chiari malformation, and trauma. Periods of the alternating nystagmus may be quite asymmetric ( 4), may be " reset" with caloric stimulation, and may be easily missed during standard examina­tions. Daroff and Dell'Osso ( 1) have characterized PAN as being the result of an alternating null re­gion. In congenital nystagmus a " null region" is often found with the nystagmus fast phases being most apparent in directions away from the null region. For example, if a patient had a null region 20° to the right of primary position there might be little or minimal nystagmus when gaze were di­rected 20° to the right. There would be a left beat­ing nystagmus in a gaze direction to the left of the null region, however, including in the primary po­sition; through the entire range of leftward gaze, increasing in intensity as the gaze were directed further and further to the left. In gaze positions right of 20° ( for example 30°, 45°, and in extreme rightward gaze) there would be a rightward beat­ing nystagmus, again increasing in frequency and amplitude as gaze were directed further and fur­ther to the right. If the null region periodically alternated, as may happen in patients with congenital strabismus and nystagmus ( 7) over a 1 to 5- minute cycle, the pa­tient may change from having a left beating nystagmus in primary position ( Fig. 2A) to no nystagmus in primary position ( Fig. 2B- null re­gion in primary position) to right beating nystag­mus ( Fig. 2C- null region to the left of primary position). In a patient with acquired periodic alternating nystagmus from any etiology, oscillopsia may be a prominent complaint. If the null region were near primary position in leftward gaze evoked beating nystagmus, the external environment might be seen to move in an opposite direction during the slow phase. With left beating nystagmus, the slow phase is to the right and the patient might then experience a sensation of the visual world moving to the left, in fact in the direction of the fast phase. The patient we describe experienced periodic al­ternating oscillopsia: she noted often that objects to her left seemed to be moving horizontally in an oscillatory fashion in a leftward direction, but noted then in a few moments that this visual ap­parition was replaced by the illusion that objects to her right were moving regularly in a rightward di­rection. Why did she not report that objects in front of her were oscillating? Because she had periodic al­ternating head positions. She unconsciously ad­justed her head position, obvious even from her initial clinic visit, to have her line of sight or fixa­tion in an orbital position with minimum nystag­mus. For example, when her null region was 20° to her right ( when she would have had a left beating nystagmus in primary position) she turned her head 20° to the left and gazed at the examiners from an orbital position of 20° to the right. Thus, she was not noted by the majority of her examiners I Clin Neuro- ophthalmol, Vol. 10, No. 4, 1990 276 A B. T. TROOST ET AL. "-~:-_> 4 ..~~:-~=--~ B Right 40 20 0 20 40 40 20 0 20 40 C ~ ~ -------... < lep c(~ FIG. 2. Representation of alternating nystagmus with periodic alternating null region. The vertical shaded bars indicate the position of the null region in terms of orbital position. A: Null region 20° to the left. The right beating nystagmus in primary gaze. B: Null region in Right LeN primary position with no nystagmus. C: Null region 20° right. Left beating nystagmus in primary gaze. 40 20 o 20 40 to have a nystagmus during casual inspection. Confounding the difficulty in diagnosis was the fact that she had very irregular and long cycles of PAN. Her cycles of leftward beating alternating with rightward beating nystagmus often took a to­tal period of 10 minutes before the nystagmus di­rection in primary position ( with head straight ahead) would change direction. During many hours of observation she did not, when the null region was in the primary position, display pri­mary position upbeat or downbeat nystagmus as has been described in PAN ( 8). This might have given rise to periodic vertical oscillopsia further complicating her symptoms. In fact, when the pa­tient was made aware of this possibility through questioning, she began to observe that during for­ward or backward head tilt she experienced ob­lique oscillation of her external environment, which would periodically change moving ob­liquely upward and rightward with head tilt for­ward, alternating with objects moving upward and leftward, as she maintained her head in a forward position. PAN may be caused by a host of conditions in­cluding brainstem inf" rcti(~ n, intrinsic and extrin-sic brainstem tumors, cerebellar degeneration, en­cephalitis, drug intoxication on a congenital basis, and demyelinating disease ( 1,2,4,6). The patient's magnetic resonance imaging ( MRI) disclosed no brainstem abnormalities. There were no other neu­rologic abnormalities and no prior history to sug­gest other central or peripheral nervous system ab­normality. She was adamantly convinced that her symptoms did not start until 2 years before our examination and therefore we do not believe, par­ticularly with her complaint of oscillopsia, that her condition was on a congenital basis. Therapy of this type of nystagmus and oscillop­sia deserves emphasis. Halmagyi and others ( 2) first reported the response to baclofen in the neu­rologic literature. These authors speculated that the inhibitory action of baclofen on PAN is proba­bly not due to activation of gamma- aminobutyric acid responsive ( GABAergic) synapses in the cer­ebello vestibular or vestibulo- ocular pathway be­cause it is not believed that baclofen is a GABA­mimetic agent. It is believed that the principal ef­fect of baclofen is inhibition of release of the excitatory neurotransmitter glutamate ( 9) These authors also commented upon the fact tha r:' AN \ PERIODIC ALTERNATING OSCILLOPSIA 277 was not abolished in congenital cases. Others have reported on the success ( 6,10) or failure of long lasting therapy ( 11). An important clinical point is that there are only a few causes of primary position horizontal jerk nystagmus that tend to remain horizontal on ver­tical gaze. These are congenital jerk nystagmus, vestibular nystagmus, and periodic alternating nystagmus ( 3). Most acquired jerked nystagmus is gaze evoked with a fast phase in the direction of gaze including upbeating on upward gaze and downbeating on downward gaze. The most com­mon causes are drug intoxication, as with anticon­vulsants, and disease in the brainstem or cerebel­lum. We wish to emphasize that any patient with acquired horizontal jerk nystagmus must be ob­served over at least a 5- minute interval to deter­mine whether the nystagmus direction changes. It is further emphasized that the periodicity of PAN may be quite variable with uneven cycles of left­ward and rightward beating nystagmus. Careful observation for treatable forms of nystagmus should be sought in all patients with oscillopsia. REFERENCES 1. Daroff RB, Dell'Osso LF. Periodic alternating nystagmus and the shifting null. Can JOtolaryngol 1974; 3: 367- 371. 2. Halmagyi CM, Rudge P, Cresty MA, Leigh JR, Zee D5. Treatment of periodic alternating nystagmus. Ann Neurol 1980; 8: 609-- Q11. 3. Troost BT. Nystagmus: A clinical review. Rev Neurol 1989; 145: 417- 428. 4. Baloh RW, Honrubia V, Konad HR. Periodic alternating nystagmus. Brain 1976; 99: 11- 26. 5. Campbell WW. Periodic alternating nystagmus in phen­ytoin intoxication. Arch NeuroI1980; 37: 178- 180. 6. Isago H, Tsuboya R, Kataura A. A case of periodic alternat­ing nystagmus: with a special reference to the efficacy of baclofen treatment. Auris Nasus Larynx 1985; 12: 15-- 21. 7. Davis DC, 5mith JL. Periodic alternating nystagmus: A re­port of eight cases. Am JOphthalmol 1971; 72: 757- 762. 8. Keane JR. Periodic alternating nystagmus with downward beating nystagmus. Arch Neurol 1974; 30: 339- 402. 9. Potashner 5}. Effect on amino acid release and metabolism in slices of guinea pig cortex. JNeurochem 1979; 32: 103- 109. 10. Leigh RJ, Robinson DA, Zee DA. A hypothetical explana­tion for periodic alternating nystagmus: instability in the optokinetic- vestibular system. Ann NY Acad Sci 1981; 374: 619-- Q35. 11. Uemura T, Inoue H, Hirano T. The effects of baclofen on periodic alternating nystagmus and experimentally in­duced nystagmus. Adv Otorhinolaryngol 1988; 42: 254- 259. JClin Neuro- ophthalmol, Vol. 10, No. 4, 1990