Ординатура / Офтальмология / Английские материалы / Advances in Understanding Mechanisms and Treatment of Infantile Forms of Nystagmus_Leigh, Devereaux_2008

vergence angle, but it may be more concerned with adjustment of the vestibulo-ocular reflex gain as a function of target distance, because monkeys with floccular lesions are able to adapt. In rabbits, the cerebellar flocculus has a projection to the medial, but not the lateral, rectus muscles, so a lesion of the flocculus could cause a convergence bias12; if this is the case in humans, such a lesion could cause the esotropia of DI. Further, experimental lesions of the flocculus and paraflocculus cause downbeat, gaze-evoked, and rebound nystagmus in primates.14 Lesions to the dorsal cerebellar vermis in monkeys cause a small-angle esotropia,15 probably because the dorsal vermis projects to the fastigial ocular motor area. Also, injury to the vermis and flocculonodular lobe causes midline ataxia.

All of our patients had gaze-evoked nystagmus, impaired balance, and gait ataxia, and one had downbeat nystagmus; because of these findings, we believe that their DI was associated with SCA as a result of flocculonodular lobe or midline cerebellar dysfunction. Thus, DI may be an early presenting feature of the midline dysfunction of SCA.

Most patients had deviations sufficiently small to be managed conservatively with prism therapy. One patient had a larger angle of deviation and responded well to medial rectus recession.

In conclusion, horizontal binocular distance diplopia caused by divergence insufficiency can be a presenting symptom of autosomal dominant spinocere-bellar ataxia. We strongly urge that patients with uncrossed diplopia greater at distance than at near undergo a detailed neurological history, family history, and examination. Neuroimaging and genetic testing may be helpful in the diagnosis, but normal studies do not exclude SCA.

ACKNOWLEDGMENT This research was funded in part by an unrestricted grant from Research to Prevent Blindness.

References

1.Duane A. Paralysis of divergence. Ophthalmology. 1905;2:1–19.

2.Ohyagi Y, Yamada T, Okayama A, et al. Vergence disorders in patients with spinocerebellar atoxia

3/Machado-Joseph disease: a synoptophore study.

J Neurol Sci. 2000;173:120–123.

3.Answers Corporation. Wikipedia. Answers.com Web site. http://www.answers.com/library/Wikipedia. Last accessed March 4, 2008.

4.Bruce GM. Ocular divergence: its physiology and pathology. Arch Ophthalmol. 1935;13:639–653.

5.Leigh RJ, Zee DS. The Neurology of Ocular Movements. 4th ed. Oxford, UK: Oxford University Press; 2006.

6.Kirkham TH, Bird AC, Sanders MD. Divergence paralysis with paired intracranial pressure. An electro-oculographic study. Brit J Ophthalmol. 1972;56:776–782.

7.Lewis AR, Kline LB, Sharpe JA. Acquired esotropia due to Arnold-Chiari I malformation. J Neuroophthalmol. 1996;16:49–54.

8.Lavin PJM, Donahue S. Neuro-ophthalmology: the efferent visual system. Gaze mechanisms and disorders. In: Daroff RB, Fenichel GM, Marsden CD, Bradley WG, eds. Neurology in Clinical Practice. 4th ed. Boston, MA: Butterworth-Heinemann; 2004.

9.Cunningham RD. Divergence paralysis. Am J Ophthalmol. 1972;74:630–635.

10.Lepore FE. Divergence paresis: a nonlocalizing cause of diplopia. J Neuro-ophthalmol. 1999;19: 242–245.

11.Jacobsen DM. Divergence insufficiency revisited: natural history of idiopathic cases and neurologic associations. Arch Ophthalmol. 2000;118:1237– 1241.

12.Versino M, Hurko O, Zee DS. Disorders of binocular control of eye movements in patients with cerebellar dysfunction. Brain. 1996;119:1933– 1950.

13.Schols L, Bauer P, Schmidt T, Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004; 3:291–304.

14.Leigh RJ, Zee DS. The Neurology of Ocular Movements. 4th ed. Oxford, UK: Oxford University Press; 2006.

15.Takagi M, Tamargo R, Zee DS. Effects of lesions of the cerebellar oculomotor vermis on eye movements in primate: binocular control. Progr Brain Res. 2003;142:19–33.

JANET C. RUCKER

ABSTRACT

Miller Fisher syndrome (MFS) consists of a triad that includes ophthalmoplegia, ataxia, and areflexia with a self-limited monophasic course. Anti-GQ1b antibodies are present in up to 90% of patients. It is considered a variant of GuillainBarré syndrome, with the primary pathology considered to be peripheral nerve demyelination. A 43-year-old man, who was given an acetylcholine receptor antibody–negative diagnosis of myasthenia gravis 15 years ago, presented with binocular diplopia. Electrophysiologic studies prior to neuro-ophthalmologic evaluation revealed a decremental response to repetitive stimulation. Relapse of myasthenia gravis was the working diagnosis. Examination revealed diffuse bilateral ophthalmoplegia, bilateral pupillary light-near dissociation, and areflexia. Cerebellar function and cerebrospinal fluid were normal. Anti-GQ1b antibodies were positive, and recurrent MFS was diagnosed. However, decremental response occurred with repetitive stimulation of the left orbicularis oculi and bilateral trapezius muscles. The patient recovered completely in three months. This case study highlights a developing recognition of neuromuscular dysfunction in MFS. Systematic evaluation of neuromuscular junction physiology should be performed in MFS patients to advance understanding of this process.

Miller Fisher syndrome (MFS) is considered a variant of acute inflammatory demyelinating polyneuropathy (AIDP), otherwise known as Guillain-Barré syndrome, and classically consists of a triad of bilateral ophthalmoplegia, ataxia, and areflexia.1 Anti-GQ1b antibodies are present in up to 90% of patients. The precise location, mechanism, and extent of neurological insult are not completely understood. Peripheral nerve demyelination is regarded as the hallmark of pathological involvement, given the clinical overlap of the syndrome with AIDP and direct pathological evidence,2 but extensive clinical and radiographic evidence of central nervous system involvement exists.3-6 In addition, evidence of direct neuromuscular junction (NMJxn) involvement is mounting in a mouse diaphragm/ phrenic nerve model and in human cases of MFS.7-10 A patient with recurrent MFS and a decremental response to repetitive stimulation on electromyography (EMG) in the absence of electrophysiological evidence of demyelinating peripheral neuropathy is described.

CASE REPORT

A 43-year-old Hispanic man presented with a chief complaint of binocular diplopia. Fifteen years prior, he had had an illness that began with vertigo and oscillopsia in right and left gaze and was followed by binocular oblique diplopia, bilateral ptosis, and gait difficulty. Records from that time were not available for review. Per patient report, the working diagnosis

was acetylcholine receptor antibody–negative myasthenia gravis. He was treated with pyridostigmine and had complete resolution of his symptoms over three months. He discontinued pyridostigmine and remained symptom free over the next 14 years.

The current illness began with binocular oblique diplopia and bilateral palm paresthesias. Ocular motor examination revealed significantly impaired bilateral elevation and abduction (5% to 10% of normal), moderately impaired adduction (60% to 70% of normal), and nearly normal depression (Fig. 23.1). Horizontal and vertical saccades were slow, and motility deficits were not overcome with vestibulo-ocular reflexes. There was minimal left ptosis. Orbicularis oculi strength was normal. Pupillary light-near dissociation was present bilaterally. Sensation and motor strength were normal. Reflexes were absent. There was no truncal or appendicular ataxia.

Gadolinium-enhanced brain MRI was normal. Acetylcholine receptor antibodies and MUSK antibodies were normal. EMG with repetitive stimulation revealed normal nerve conduction studies and needle examination but a pathological decremental response to repetitive stimulation in the left orbicularis oculi and bilateral trapezius muscles. Anti-GQ1b antibodies were elevated. Lumbar puncture was normal (protein 39). All symptoms and clinical findings resolved spontaneously within three months (Fig. 23.2). Anti-GQ1b antibody titer normalized, but a decremental response to EMG repetitive stimulation remained.

DISCUSSION

A decremental response on EMG repetitive stimulation typically represents impaired postsynaptic NMJxn transmission. It may also occur in the setting of severe peripheral neuropathy. However, in this patient, nerve conduction and needle studies were normal, with no evidence of demyelinating polyneuropathy. The NMJxn as an antigenic target and primary site of pathology in MFS is well established in a mouse diaphragm/phrenic nerve model.7,8 Application of serum from anti-GQ1b-positive patients to this model results in immediate, massive acetylcholine release at the NMJxn, followed by complete NMJxn blockade. The predominant effect is presynaptic, but there is some evidence to suggest a component of postsynaptic dysfunction as well.7 In addition to electrophysiological evidence of NMJxn pathology, electron microscopy reveals structural breakdown of the presynaptic NMJxn terminal with loss of synaptic vesicles and fragmentation the NMJxn by Schwann cell processes,11 and immunofluorescence studies reveal direct anti-GQ1b antibody binding to both presynaptic and postsynaptic NMJxn membranes.12 Direct evidence of primary NMJxn dysfunction is suggested in 7 human anti- GQ1b-positive patients with MFS and increased jitter on single-fiber EMG.9,10 In addition, 3 of these patients exhibited an incremental response to repetitive stimulation.10 The patient in this report provides additional support for the presence of NMJxn pathology in MFS.

Systematic evaluation of NMJxn physiology should be performed in MFS patients to advance understanding of the role of NMJxn pathology in the disease process of MFS. Supplementary information (video clips) is available at the Darof–Dell’Osso laboratory Web site (http://www.omlab.org).

References

1.Fisher M. An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia, and areflexia). N Engl J Med. 1956;255:57–65.

2.Phillips MS, Stewart S, Anderson JR. Neuropathological findings in Miller Fisher syndrome. J Neurol Neurosurg Psychiatry. 1984;47:492–495.

3.Ogawara K, Kuwabara S, Yuki N. Fisher syndrome or Bickerstaff brainstem encephalitis? Anti-GQ1b IgG antibody syndrome involving both the peripheral and central nervous systems. Muscle Nerve. 2002;26:845–849.

4.Tezer FI, Gurer G, Karatas H, Nurlu G, Saribas O. Involvement of the central nervous system in Miller Fisher syndrome: a case report. Clin Neurol Neurosurg. 2002;104:377–379.

5.Goldberg-Stern H, Melamed E, Gadoth N. Abnormal evoked potentials in Miller-Fisher syndrome: further evidence of combined peripheral and central demyelination. J Neurol Neurosurg Psychiatry. 1994;57:506.

6.Meienberg O, Ryffel E. Supranuclear eye movement disorders in Fisher’s syndrome of ophthalmplegia, ataxia, and areflexia. Report of a case and literature review. Arch Neurol. 1983;40: 402–405.

7.Buchwald B, Bufler J, Carpo M, et al. Combined preand postsynaptic action of IgG antibodies in Miller Fisher syndrome. Neurology. 2001;56:67–74.

8.Bullens RW, O’Hanlon GM, Goodyear CS, et al. Anti-GQ1b antibodies and evoked acetylcholine release at mouse motor endplates. Muscle Nerve. 2000;23:1035–1043.

9.LoYL, Chan LL, Pan A, Ratnagopal P. Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi. J Neurol Neurosurg Psychiatry. 2004;75:436–440.

10.Lo YL, Leoh TH, Dan YF, et al. Presynaptic neuromuscular transmission defect in the Miller Fisher syndrome. Neurology. 2006;66:148–149.

11.O’Hanlon GM, Plomp JJ, Chakrabarti M, et al. AntiGQ1b ganglioside antibodies mediate complementdependent destruction of the motor nerve terminal. Brain. 2001;124:893–906.

12.Wessig C, Buchwald B, Toyka KV, Martini R. Miller Fisher syndrome: immunofluorescence and immunoelectron microscopic localization of IgG at the mouse neuromuscular junction. Acta Neuropathol (Berl). 2001;101:239–244.

ABSTRACT

We used a new motion stimulus displayed on a computer monitor in the ground plane to induce involuntary version-vergence nystagmus. Eye movements were recorded with a search coil system. The involuntary version-vergence nystagmus had both vertical version and horizontal vergence components. Backward motion induced monophasic divergent quick phases and upward versional quick phases. Forward motion induced biphasic diver- gence-convergence quick phases and downward versional quick phases. Quick phases of both vergence and version components were analyzed. A time dissociation of about 20 milliseconds between version velocity peak and convergence velocity peak was observed. Dependence of vergence peak velocity on versional saccadic peak velocity was demonstrated. Our data support the hypothesis that the vergence system and the saccadic system can act separately but interact with each other whenever they occur simultaneously.

Saccades and vergence eye movements are commonly considered to be two separate subsystems with distinct characteristics in anatomy and neurophysiology. However, combined version-vergence movements are frequently made to shift binocular fixation between objects at different distances and directions under natural viewing conditions. When combined saccadevergence movements occur, vergence movements increase in velocity while versional saccades slow

down (saccade-vergence interactions).1-7 It has been suggested that activity of saccadic burst neurons and vergence neurons might be gated by the same group of neurons—omnipause neurons (OPN). During saccades, inhibition from OPN is lifted not only for saccades but also for vergence. Thus, vergence would be facilitated.3 However, recent evidence does not support this hypothesis. For example, it was found that vergence enhancement increases with saccadic peak velocity in monkeys.8 This cannot be explained with the OPN hypothesis. Another recent finding beyond the accountability of the OPN hypothesis is time dissociations between saccades and vergence, discovered by Kumar et al.9,10

Most earlier studies on saccade-vergence interaction used small visual targets to induce combined version and vergence eye movements.1-10 In the present study, we used large field motion stimuli in the ground plane to induce involuntary version-vergence nystagmus. The version-vergence nystagmus has quick and slow phases for both vertical version and horizontal vergence components. We will summarize dynamic properties of the nystagmus quick phases and analyze relationships between vertical saccadic and horizontal vergence peak velocity, and examine time dissociations between the vertical saccades and horizontal vergence.

METHODS

Methodological information is briefly presented in this chapter. Detailed information can be found in our previous paper.11

Subjects

Five subjects participated in this study (2 authors and 3 naive volunteers), aged 25 to 44 years, with normal ophthalmic and ocular motor evaluations as well as normal binocular vision. Each had best corrected visual acuity of 20/20 in each eye. All procedures observed the declaration of Helsinki, and informed consent was obtained from all subjects.

Stimuli

Motion in the Frontal Plane

For the purpose of comparison with experiments in the ground plane, a squarewave-grating pattern displayed on a computer monitor (ViewSonic, Walnut, CA) in the frontal plane was used to induce vertical optokinetic nystagmus (OKN).

Motion in the ground plane

The same grating pattern used for the frontal plane experiment was positioned face up and 9 cm below the eye level. The pattern moved forward or backward in the ground plane. Velocities of the motion on the surface were 4, 8, 12, 16, and 20 cm/s (approx. 10, 20, 30, 40, and 50 deg/s to the eyes).

Experimental Paradigms

Subjects were seated with their heads stabilized on a chin and forehead rest and performed calibration tasks by fixating on a 0.5° dot displayed at five different locations, with right eye and left eye viewing separately, before each experiment. After the calibration, the subject was instructed to look at the center of the stationary grating pattern and pressed a button to trigger the motion of the pattern, which lasted for 5 seconds in each trial. During the motion stimulus, subjects were instructed to obtain a clear image of the pattern and not to track any single bar. Ten trials (five different velocities in two directions) compose one block. Twenty blocks can be obtained in approximately 30 minutes.

Eye Movement Recording and Data Analysis

Horizontal and vertical eye movements of both eyes were recorded with an electromagnetic technique (Remmel Labs, Katy, TX) at 1 kHz.

The horizontal and vertical eye position data obtained during the calibration procedure were each fitted with a third-order polynomial that was then used to linearize the horizontal and vertical eye position data recorded during the experiment proper. The experimental data were then smoothed with a cubic

spline function with a weight of 107. The vergence position was computed by subtracting the position of the right eye from the position of the left eye. Vergence velocity was obtained by two-point backward differentiation of the vergence-position data. Version position was an average of the right and left eye positions.

Estimates of the amplitude of the versional responses were obtained by measuring the change in eye position from maximum point to minimum point using programs written in MATLAB (MathWorks, Natick, MA). A criterion of 3 deg/s was used to decide the beginning and end of version and vergence responses for the purpose of measuring the response duration.

RESULTS

Combined version-vergence eye movements showed ocular tracking slow phases and saccadic quick phases in both vertical and horizontal components. Eye movement traces of downward-convergent tracking slow phases and resetting upward-divergent quick phases induced with backward motion (toward subjects) and upward-divergent tracking slow phases and resetting downward-convergent quick phases induced with for- ward-motion stimuli (away from subjects) are displayed in Figure 24.1. The frontal plane stimuli did not induce any measurable horizontal vergence but did induce regular vertical versional nystagmus.

To demonstrate the dynamic properties of the version and vergence components, samples of velocity and position profiles for vertical saccades and horizontal vergence saccades are displayed in Figure 24.2. Divergent saccades and upward saccades induced by backward motion stimuli are displayed in Figure 24.2A, and biphasic divergence-convergence and downward saccades induced by forward motion stimuli are displayed in Figure 24.2B.

Amplitudes of the vertical versional saccades were about 5° on average but varied at different velocities. The amplitudes of saccadic divergences with backward motion were about 0.5° ± 0.3°. With forward-motion stimuli, amplitudes of divergence were 0.3° ± 0.13°, and amplitudes of convergence were 0.45° ± 0.16°.

The average peak velocities of the vertical saccades were about 70 to 110 deg/s, comparable to vertical OKN from frontal plane,12 and the average peak velocities of horizontal vergence quick phases were about 20 to 25 deg/s at various stimulus conditions, which is much higher than the slow-phase velocity of 2 to 4 deg/s.11

Time dissociation (TD) between version velocity peaks and vergence velocity peaks was examined. As shown in Figure 24.2A, the peak of the divergence velocity leads the velocity peak of the upward saccade

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response by a few milliseconds (TD1). In Figure 24.2B, the velocity peak of the divergence component of the biphasic vergence response leads the velocity peak of downward saccades by about 7 milliseconds (TD2). The velocity peak of the convergence followed the velocity peak of downward saccades by about 26 milliseconds (TD3). The mean of TD3 is about 20 milliseconds at varied stimulus velocities.

Relationships between peak velocities of horizontal vergence and vertical saccades were analyzed. With backward motion, divergence and upward saccades were induced (Fig. 24.2A). We correlated the peak velocity of divergence with peak velocity of upward saccades. Positive correlations were demonstrated for each of the subjects. The correlation coefficients of regression lines ranged from 0.13 to 0.59 (R2 = 0.13, 0.32, 0.43, 0.58, 0.59 for different subjects and p < 0.0001). With forward motion, biphasic diver- gence-convergence responses are associated with downward saccades (Fig. 24.2 B). Regression analysis for peak velocities of the divergent components of the biphasic vergence responses and peak velocity of downward saccades showed similar positive, weak correlations. Pooled data from all subjects showed a correlation coefficient of 0.07 (p < 0.0001). Positive correlations were also demonstrated between peak velocities of the convergent components and peak velocities of downward saccades. Pooled data for 5 subjects also showed a dependence of convergent peak velocity on peak velocity of downward saccades (R² = 0.26, p < 0.0001).

DISCUSSION

Using large field motion in the ground plane, we have induced version-vergence nystagmus. When backward motion stimuli were used, divergent quick phases occurred in association with upward saccades. The quick phases were generated to reset eye positions as required responses to refixate a distant target. When forward motion stimuli were used, we expected to see convergent quick phases and downward saccades. However, a transient divergence occurred prior to a convergence response. Similar transient divergences associated with both horizontal and vertical saccades were observed.3-6,9,13 In a recent study, the divergence occurred in association with upward saccades.9 However, we found that the divergence of the biphasic vergence responses occurred with downward saccades. It is believed that the divergence might be due to a central mechanism,9 although a peripheral mechanism in the ocular motor plant cannot be completely ruled out.14 Since the divergent responses occur independently of

the directions of accompanying saccades (upward, downward, and horizontal), it may be a stereotypical coordinated response with saccades.

One of the important observations from this study is the time dissociation between vergence and versional saccades, which has not received enough attention until recently.9-10 It is important to note that the TD3 is longer than that reported by Kumar9 under the “FarUpNearDown” condition, although the vergence (about 0.5°) and version eye movements (about 5°) in the present study were smaller than in the study by Kumar et al.9 We hypothesize that the larger TD3 in this study may be related to the involuntary nature of the nystagmus and less subjective inputs. The vergence and version may act more independently in involuntary version-vergence nystagmus than in voluntary ones. The observation of the time dissociation provides support to the model suggested by Kumar et al.10

The relationships between vergence and vertical saccades, including divergence with upward saccades and biphasic vergence with downward saccades, shows that there is a dependence of vergence peak velocity on vertical version peak velocity. Similar observations were reported by Maxwell et al.,15 Sylvestre et al.,6 and Busettini et al.16 These observations could be explained by the multiplicative model of Busettini et al.,17 but they could not be predicted using Zee’s3 omnipause model.

It has been known that saccades enhance other associated eye movements, including disparity and optic flow vergence,17-19 ocular following,20 smooth pursuits,21 accommodation,22 and vestibular ocular responses.23 The nonselective enhancements of saccades on other associated eye movements may play a role in the interaction of saccade and vergence.

It has been reported that brief radial optic flow stimuli induced vergence eye movements.17-18 We attribute the version-vergence nystagmus to optic flow inputs, because accommodation and proximal vergence cues may play only a minor role in generating the vergence in a naturalistic world24 and the motion stimuli did not have any horizontal disparity. The demonstration of version-vergence nystagmus responses to groundplane optic flow provides an approach for further study of saccade-vergence interactions.

In summary, our findings support the suggestion that the vergence system and the saccadic system can act separately but interact with each other whenever they occur simultaneously.4, 25

ACKNOWLEDGMENT This project was partly supported by a National Eye Institute grant and funding from Research to Prevent Blindness.

References

1.Ono H, Nakamizo S, Steinbach MJ. Nonadditivity of vergence and saccadic eye movement. Vision Res. 1978;18:735–739.

2.Enright JT. Changes in vergence mediated by saccades. J Physiol. 1984;350:9–31.

3.Zee DS, FitzGibbon EJ, Optican LM. Saccade– vergence interactions in humans. J Neurophysiol. 1992;68:1624–1641.

4.Collewijn H, Erkelens CJ, Steinman RM. Voluntary binocular gaze-shifts in the plane of regard: dynamics of version and vergence. Vision Res. 1995;35:3335–3358.

5.van Leeuwen AF, Collewijn H, Erkelens CJ. Dynamics of horizontal vergence movements: interaction with horizontal and vertical saccades and relation with monocular preferences. Vision Res. 1998;38:3943–3954.

6.Sylvestre PA, Galiana HL, Cullen KE. Conjugate and vergence oscillations during saccades and gaze shifts: implications for integrated control of binocular movement. J Neurophysiol. 2002;87(1):257–272.

7.Mays LE, Gamlin PDR. A neural mechanism subserving saccade-vergence interactions. In: Findlay JM, Walker R, Kentridge RW, eds. Eye Movement Research: Mechanism, Processes and Applications. Amsterdam, the Netherlands: Elsevier; 1995.

8.Busettini C, Mays LE. Saccade-vergence interactions in macaques. I. Test of the omnipause multiply model. J Neurophysiol. 2005;94:2295–2311.

9.Kumar AN, Han Y, Dell’Osso LF, Durand DM, Leigh RJ. Directional asymmetry during combined saccade-vergence movements. J Neurophysiol. 2005;93(5):2797–2808.

10.Kumar AN, Han YH, Kirsch RF, Dell’Osso LF, King WM, Leigh RJ. Tests of models for saccadevergence interaction using novel stimulus conditions. Biol Cybern. 2006;95(2):143–157.

11.Yang D-S, Zhu M, Kim CH, Hertle RW. Vergence nystagmus induced by motion in the ground plane: normal response characteristics. Vision Res. 2007; 47(9):1145–1152.

12.Garbutt S, Han Y, Kumar AN, Harwood M, Harris CM, Leigh RJ. Vertical optokinetic nystagmus and saccades in normal human subjects. Invest Ophthalmol Vis Sci. 2003;44(9):3833–3841.

13.Collewijn H, Erkelens CJ, Steinman RM. Trajectories of the human binocular fixation point during conjugate and non-conjugate gaze-shifts. Vision Res. 1997;37:1049–1069.

14.Enright JT. Convergence during human vertical saccades: probable causes and perceptual consequence. Br J Physiol. 1989;410:45–65.

15.Maxwell JS, King WM. Dynamics and efficacy of saccade-facilitated vergence eye movements in monkeys. J Neurophysiol. 1992;68(4):1248–1260.

16.Busettini C, Mays LE. Saccade-vergence interactions in macaques. II. Vergence enhancement as the product of a local feedback vergence motor error and a weighted saccadic burst. J Neurophysiol. 2005;94:2312–2330.

17.Busettini C, Masson GS, Miles FA. Radial optic flow induces vergence eye movements with ultrashort latencies. Nature. 1997;390:512–515.

18.Yang DS, Fitzgibbon EJ, Miles FA. Short-latency vergence eye movements induced by radial optic flow in humans: dependence on ambient vergence level. J Neurophysiol. 1999;81:945–949.

19.Yang DS, Fitzgibbon EJ, Miles FA. Short-latency disparity-vergence eye movements in humans: sensitivity to simulated orthogonal tropias. Vision Res. 2003;43(4):431–443.

20.Yang DS, Miles, FA. Short-latency ocular following in humans is dependent on absolute (rather than relative) binocular disparity. Vision Res. 2003;43:1387–1396.

21.Lisberger SG. Postsaccadic enhancement of initiation of smooth pursuit eye movements in monkeys. J Neurophysiol. 1998;79(4):1918–1930.

22.Schor CM, Lott LA, Pope D, Graham AD. Saccades reduce latency and increase velocity of ocular accommodation. Vision Res. 1999;39(22):3769– 3795.

23.Das VE, Dell’Osso LF, Leigh RJ. Enhancement of the vestibulo-ocular reflex by prior eye movements. J Neurophysiol. 1999;81(6):2884–2892.

24.Hung GK, Ciuffreda KJ, Rosenfield M. Proximal contribution to a linear static model of accommodation and vergence. Ophthalmic Physiol Opt. 1996;16(1):31–41.

25.Leigh RJ, Zee DS. The Neurology of Eye Movements. 4th ed. New York, NY: Oxford University Press; 2006.

MICHAEL W. DEVEREAUX

ABSTRACT

Cervical manipulation, specifically chiropractic manipulation, is an important cause of vertebral basilar and, rarely, carotid artery distribution strokes. The mechanism of action of vertebral artery distribution strokes is vertebral artery dissection at the level of the atlas as a result of rotation and extension of the head, which can occur in association with chiropractic manipulation. The vertebral arteries are tethered as they pass through the dura. Rotation of the atlas around the axis can lead to stretching of the vertebral artery on the side opposite the direction of head rotation, with a resultant intimal tear, and ultimately occlusion with thrombus formation and embolization. Neuro-ophthalmologic findings are a common, and at times relatively isolated, feature of strokes secondary to chiropractic manipulation. This is a more frequent occurrence than commonly recognized. A variety of neuro-ophthalmologic disturbances have been recognized, including visual field defects due to posterior cerebral artery distribution embolic strokes and oculomotor disturbances due to strokes anywhere in the brain stem, but most commonly in the medulla. Strokes induced by therapeutic manipulation of the neck are not rare. Patients, particularly young patients, with significant stroke risk factors presenting with vertebrobasilar strokes should be questioned as to whether they have undergone cervical manipulation. Patients should be routinely instructed to avoid chiropractic neck manipulation.

Neurological complications secondary to neck manipulation, specifically chiropractic neck manipulation, are known to neurologists but are not well known to the public. The major categories of injury include stroke, myelopathy, and cervical radiculopathy. The frequency, although debated, may be greater even than that stated in the literature.1-16 Neuro-ophthalmologic complications are almost always the result of ischemia/ infarction secondary to injury to one or both vertebral arteries, and far less frequently to a carotid artery.17-18 Most often the neuro-ophthalmologic findings are a part of a constellation of findings indicative of a brainstem stroke, usually in the lateral medulla, particularly the lateral medullary tegmentum (Wallenberg’s syn- drome).3-16 Occasionally, however, relatively isolated neuro-ophthalmologic symptoms and signs may occur after a chiropractic cervical manipulation, particularly visual field disturbances secondary to infarction in the distribution of one or both posterior cerebral arteries. The cause of the stroke may be overlooked unless the patient is carefully questioned. This is particularly true because the stroke may occur several days after the manipulation.16,19,20 The cases of two patients with past chiropractic manipulation strokes are presented below.

CASE REPORTS

Patient 1

A 34-year-old, healthy woman with a 2-week history of neck pain had three chiropractic treatments during that 2-week period. On the drive home from the third