Oscillopsia: causes and management Caroline Tilikete a,b,c and Alain Vighetto a,b,c

Transcription

1 Oscillopsia: causes and management Caroline Tilikete a,b,c and Alain Vighetto a,b,c a Hospices Civils de Lyon, Unité de Neuroophtalmologie and Service de Neurologie D, Hôpital Neurologique, Bron, b Université Claude Bernard Lyon I, Lyon and c INSERM UMR-S 864 Espace et Action, Bron, France Correspondence to Caroline Tilikete, INSERM UMR-S 864 Espace et Action, Bron F-69677, France Tel: ; fax: ; [email protected] Current Opinion in Neurology 211, 24:38 43 Purpose of review Oscillopsia is an illusion of an unstable visual world. It is associated with poor visual acuity and is a disabling and distressing condition reported by numerous patients with neurological disorders. The goal of this study is to review the recent findings in the various pathophysiological mechanisms of oscillopsia and the potential treatments available. Recent findings Oscillopsia most often results from abnormal eye movements or from impaired vestibulo-ocular reflex. A special emphasis is provided on new hypotheses concerning the mechanisms of pendular nystagmus associated with oculopalatal tremor; on the clinical relevance of fixation instability in the diagnosis of degenerative disease; and on the causes of vestibular areflexia. Oscillopsia could also theoretically result from a deficit in mechanisms underpinning perceptual stability maintenance despite constant gaze displacement in the environment. The recent findings concerning the mechanisms and underlying neural network subserving this phenomenon of spatial constancy are developed. Summary Oscillopsia may result either from impaired ocular stability or impaired compensation or suppression of afferent visual information resulting from normal eye movements. Understanding the exact mechanisms of oscillopsia may lead to novel treatment. Keywords nystagmus, ocular fixation, spatial constancy, spatial updating, vestibulo-ocular reflex Curr Opin Neurol 24:38 43 ß 211 Wolters Kluwer Health Lippincott Williams & Wilkins Introduction Oscillopsia is an illusion of an unstable vision, made up of the perception of to-and-fro movement of the environment. The notion of oscillopsia refers to the interaction between the physiological mechanisms resulting in movements of the eyes and those keeping a stable visual perception [1]. Stable visual perception is conditioned by two factors. First, images of the seen world projected onto the retina have to be quite fixed for stable perception of the environment. The threshold perception of retinal drift is around.1 deg/s in normal individuals [2]. Oscillopsia may then be due to ocular instability, when exceeding this threshold. Congenital nystagmus represents an exception since despite important ocular instability, patients do not describe oscillopsia. This phenomenon can be explained by an elevated detection threshold of retinal drift but recent data also suggest the role of acquired suppression of the apparent visual motion at higher-order visual cortex level [3 ]. Optimal perception of an object also needs a quite stable retinal projection, onto or close to the fovea [4]. The visual acuity rapidly declines if the displacement of the image on the retina exceeds the threshold of a few (2. 4) deg/s []. Supra-threshold ocular instability may be consequently associated with decreased visual acuity. Oscillopsia may also result from excessive motion of images on the retina due to acquired abnormal functioning of central stabilizing ocular motor systems, leading to different types of nystagmus, saccadic intrusions or from impaired visuovestibular stabilizing reflexes. It may also result from abnormal hyperactivity in the peripheral ocular motor system, such as superior oblique myokimia or in the peripheral vestibular system, such as superior canal dehiscence syndrome. In the first part of this review, we develop the recent findings about mechanisms and causes of oscillopsia due to ocular instability and their treatment. Second, whereas moving our gaze within a stable environment could induce a visual instability due to retinal drift and a spatial disorientation due to changes in visual referential, our perception remains of a perfectly stable and well oriented environment, a phenomenon called spatial constancy [6]. The central nervous system is first able to anticipate retinal drift in capturing an expectation of the visual consequences of eye movements and suppress its perception. The accompanying issue is how the brain differentiates retinal drift produced by an eye movement from those produced by object displacement ß 211 Wolters Kluwer Health Lippincott Williams & Wilkins DOI:1.197/WCO.b13e328341e3b

2 Oscillopsia Tilikete and Vighetto 39 within a visual scene. Furthermore, the central nervous system is able to take into account the new positions of objects relative to our body after each change in gaze position, and induce a spatially oriented and continuous visual perception of the scene. This second phenomenon is mainly dependent on a remapping process and is called spatial updating [7]. Oscillopsia could theoretically result from an impairment of spatial constancy mechanisms but clinical data in this case are scarce. In the second part of the review we develop recent findings about the mechanisms and neural network computing spatial constancy. Oscillopsia due to ocular instability Eye instability may be observed in two main conditions: impairment of an ocular motor system that serves to maintain ocular stability, leading to permanent oscillopsia, or abnormal hyperactivity in the peripheral ocular motor or vestibular system, leading to paroxysmal oscillopsia. Permanent oscillopsia due to impairment of the ocular stabilizing systems Three different ocular motor systems serve to maintain the ocular stability: the fixation system, the visuo-vestibular stabilizing system and the neural integrator. The fixation system and its deficit In fixation condition, both visual and cerebellar ocular motor feedback loops [8] help to limit the physiological ocular motor noise made up of microsaccades, microtremor and slow drifts, which themselves serve important perceptual functions [9]. Fixation also requires accurate saccade and inhibition of unwanted saccades through a frontal-basal ganglia and cerebellar network [1]. Deficit in fixation systems results in ocular instability, which mainly comprises acquired pendular nystagmus and saccadic intrusions. Acquired pendular nystagmus is encountered in a variety of clinical conditions, the two most frequent being multiple sclerosis (MS) and oculopalatal tremor (OPT), both causes differing in clinical presentation and underlying mechanism (C. Tilikete, L. Jasse, D. Pelisson, et al., in revision) (Fig. 1). In MS, abnormal delay secondary to demyelination of either visual and/or motor central feedback loops represents the main hypothesis that can also explain the rare observation of eye-position-dependent monocular pendular nystagmus in some patients [11]. OPT is a peculiar condition that develops within a few weeks or months after a single brainstem or cerebellar lesion as part of the Guillain Mollaret triangle, a pathway originating in the dentate nucleus, passing through the superior cerebellar peduncle and looping caudally through the contralateral central tegmental tract down to the inferior olivary nucleus (ION) [12,13]. It results in synchronized low-frequency tremor of eyes and palate Key points Pendular nystagmus is the most disabling abnormal eye movement, on which specific therapeutics may be tested to alleviate oscillopsia. Fine analysis of saccadic intrusions during fixation may prove their usefulness as part of a differential oculomotor profile in degenerative disorders. Vestibular areflexia results in head movementinduced oscillopsia and may be clinically evaluated in measuring dynamic visual acuity. Following two centuries of specific research, the understanding of the underlying process of spatial constancy during and after eye movements remains complex, with the more recent notion of visual attentional focus and salience maps. and/or other oro-facial motor territories. This clinical condition is associated with anatomical changes, namely a hypertrophic degeneration with demonstrated immunohistochemical changes of the ION [14], leading to T2 hypersignal on MRI [12]. The more consistent recent model of OPT suggests that disruption of inhibitory cerebellar modulation of the ION results in the development of junction between neurons, generating periodic oscillations that are transmitted to the cerebellar cortex, which in turn would give a smoothing of the output signal leading to less periodic eye movements [1 ]. Finally, two recent controlled pharmacological studies confirmed the usefulness of gabapentin and memantine in the treatment of acquired pendular nystagmus in both MS [16 ] and, surprisingly, OPT [17]. Saccadic intrusions are defined by the abnormal occurrence of saccades and may reflect a dysfunction of the steady visual fixation system involving the frontal eye field, basal ganglia, superior colliculus and cerebellum. In cerebellar dysfunction, saccadic intrusion might be explained by disinhibition of the projection site of Purkinje neurons on the fastigial nucleus [18 ]. Saccadic intrusions are frequent in parkinsonian conditions but still have to prove their usefulness as part of a differential oculomotor profile [19]. Saccadic intrusions during fixation may also help to show up infraclinical frontal dysfunction such as demonstrated recently in patients with motor neuron disease without dementia [2]. The visuo-vestibular stabilizing systems and their deficits In head/body displacement condition, the vestibular and visual ocular stabilizing systems interact to maintain the image of the visual scene steady on the retina. The vestibular system, through the vestibulo-ocular reflex (VOR), induces a compensatory ocular movement that helps to maintain the eye stable in regard to the visual scene during head displacements. The visual stabilizing systems, through the smooth pursuit and the optokinetic

3 4 Neuro-ophthalmology and neuro-otology Figure 1 Acquired pendular nystagmus in oculopalatal tremor and multiple sclerosis OPT 1 1 Right eye 1 1 Left eye 1 MS s Eye position (in degrees) traces with time (in seconds) for right (left panels) and left (right panels) eye in one oculopalatal tremor (OPT) patient (upper panels) and one multiple sclerosis (MS) patient (lower panels). Dark line, horizontal position; mid-grey line, vertical position; light grey line, torsional position. reflex, induce following eye movements that maintain the images stable on the retina. Furthermore the fixation system may interact to inhibit unwanted VOR, for example during eye and head tracking of a moving object. Deficit in vestibular/visual ocular stabilizing systems may result in ocular instability due to pathological jerk nystagmus. VOR deficit, especially when bilateral, and deficit of VOR inhibition may result in oscillopsia and impaired visual acuity during head/body displacement. New findings in acquired jerk nystagmus are reported for downbeat and primary position upbeat nystagmus. Downbeat nystagmus, which is most often increased in lateral orbital position, is thought to result from floccular dysfunction and is attributed to either vestibular [21] or smooth pursuit [22] up down asymmetry. It is, for example, a frequent finding in spinocerebellar ataxia type 6 (SCA6) [23 ]. Orbital position-independent downbeat nystagmus can be observed either in uvula/nodulus [24] or the paramedian pontomedullary region [2] lesions. Downbeat nystagmus presents a decrease in intensity during daytime [26] and in idiopathic causes has demonstrated no change over a course of up to 6 years in some patients [27]. Positional downbeat nystagmus may be a clue for the diagnosis of multiple system atrophy in Parkinson disease [28]. Downbeat nystagmus and resulting oscillopsia are responsive to clonazepam, but the usefulness of 3, 4-diaminopyridine or 4-aminopyridine has been largely demonstrated in recent studies [29,3]. Primary position upbeat nystagmus (PPUN) is an uncommon form of central nystagmus. Its clinical importance usually lies in the fact that it results from a brainstem focal lesion at either the paramedian pars of caudal medulla or the paramedian rostral pons sites [31,32]. In many cases, PPUN is dampened in prone or supine head position, mainly in lesions involving the crossing ventral tegmental tract (CVTT) at the pontine level, suggesting a role for this pathway in counteracting the effect of gravity [33]. Rare cases of PPUN have been described secondary to bilateral involvement of vertical semi-circular canals [34,3]. Gabapentin, memantine and 4-aminopyridine have also demonstrated an effect on upbeat nystagmus in single case reports [17,29]. Vestibular areflexia, particularly when bilateral, results in oscillopsia during head and body displacement, associated with postural disturbances. In these cases, the measurement of dynamic visual acuity can be interesting for the evaluation of visual functional deficit [36 38]. Vestibular areflexia may be the consequence of multiple diseases involving either the peripheral vestibular end organ or vestibular nerve, including Creutzfeldt Jakob disease [39]. Vestibular deficit seems also to be a quite frequent consequence of cochlear implants [4]. It has recently been shown to be associated frequently to polyneuropathy, which should be a prompt for systematic vestibular tests in such patients in order to orient treatment toward specific physiotherapy [41 ]. Treatment in vestibular areflexia can rely on physiotherapy to help for compensation or different types of sensory feedbacks to develop substitutions [42,43], but these approaches only address the postural deficit. Promising animal studies are actually testing vestibular implant possibilities, notably on the adaptative aspect of the vestibulo-ocular reflex [44 ]. Deficit in VOR cancellation during gaze shift along with head motion, such as seen in some cerebellar patients, may also

4 Oscillopsia Tilikete and Vighetto 41 result in oscillopsia and visual impairment [4]. Two mechanisms have been proposed to explain VOR cancellation: a reduction of the VOR gain or cancellation using smooth pursuit. The observations of normal VOR cancellation despite impaired smooth pursuit in some cerebellar syndromes suggests that smooth pursuit is not the sole mechanism involved [46]. The neural integrator and its deficit In eccentric eye position in the orbit, the neural integrator helps to maintain a constant innervation of extra-ocular eye muscles to avoid backward drift of the eyes [47]. A deficit in the neural integrator may result in gaze-evoked nystagmus and oscillopsia in the eccentric eye position. This nystagmus can occur after different lesions involving the brainstem and cerebellum, most often in cases of metabolic, toxic, or degenerative diseases. It is even used by the US police officers to determine alcohol intoxication, the validity of which can be contested regarding the variability of physiological gaze-evoked nystagmus in sober individuals [48 ]. Gaze-evoked nystagmus still remains an important interictal diagnostic clue in episodic ataxia [49] and a quite constant finding in SCA6 [23 ], both diseases sharing overlapping phenotypes and calcium channel dysfunction. It can exceptionally be found in discrete lesions, specifically involving the nucleus prepositus hypoglossi or the paramedian tract at medullar or ponto-medullary levels []. Paroxysmal oscillopsia due to hyperactivity in the peripheral ocular motor or vestibular system When oscillopsia occurs in paroxysmal episodes, hyperactivity in the peripheral ocular motor or the vestibular system may be searched for. (1) Superior oblique myokymia is a rare disorder characterized by episodic monocular oscillopsia, following neurogenic hyperactivity in the trochlear nerve. Microvascular compression syndrome of the IVth nerve is thought to be the main mechanism. Whereas recurrent studies emphasize the efficacy of surgery for superior oblique myokymia [1,2], medical treatments based on carbamazepine, gabapentin or propanolol demonstrate potential benefits with less secondary effects [3]. (2) Superior canal dehiscence syndrome is another condition in which transient oscillopsia is triggered by loud sounds or maneuvers raising the intracranial pressure. The topic is reviewed elsewhere in this issue [4]. Oscillopsia in the context of impaired spatial constancy Spatial constancy processes anticipate and compensate for the two sensory consequences of gaze displacement, namely an oppositely directed retinal drift and a change in the relationship between retinal and spatial (or patientcentered) coordinates of the visual scene (spatial updating). The process of spatial constancy during eye movements It has been commonly thought for two centuries (see review in []) that the perception of a stable world during voluntary eye movement is achieved by subtracting a reference signal of the ongoing eye movement, that is the efference copy of the motor command, from the retinal motion signal induced by the eye movement. In this compensation theory, if the two signals cancel each other, stable visual objects will be perceived as nonmoving. The compensation theory could indeed explain the perceptual stability in the case of smooth pursuit. However, in normal individuals, a small illusory movement of the visual background can be perceived during smooth pursuit, known as Filehne illusion [6]. This illusion arises because the two signals would cancel only partially. However, the size of this phenomenon is too small to endanger our concept of visual stability. By modifying the background motion during pursuit of a small target in humans, one can demonstrate an inherent plasticity of the reference signal [6]. The experimental setup may be adapted to monkeys who have learned to provide a different motor response according to their perceived rightward vs. leftward background motion [7 ]. Combining those psychophysics experiments with neurophysiological recording of neurons helps to determine the underlying neuronal network subserving aspects of spatial constancy, including mainly the visual posterior sylvian area, just adjacent to the parieto-insular vestibular cortex (PIVC) [6]. In humans, the neural network would involve cerebellar crus I, supplementary eye field and PIVC [8]. The efference copy theory has, however, been challenged, and different or combining theories have recently emerged [9,6]. The major criticism is that efference copy is too slow, and its gain too low to support a perceptual compensation for saccades [9]. First, the term of reference signal would be a better way to implement the multiple neural signals that can be used to predict the sensory consequences of voluntary eye movements. In addition, suppression of perception of background motion during saccade may also involve a visual masking mechanism, which seems to be the dominant mechanism for normal high contrast environment (see review in [61]). The process of spatial updating Humans are constantly moving and this self-motion causes the visual representations of these stationary objects to move across our retinas [62]. If visual perception were based solely on the forward processing of sensory information, the position of objects in the world

5 42 Neuro-ophthalmology and neuro-otology would appear to shift with each eye movement. In reality, our perception is that objects in the world remain stationary. This reflects the fact that we use an internal representation of the visual world that is actively constructed and spatially updated to account for our eye movements. The reference signal used to compensate retinal drift during eye movement could also be used for spatial updating. However, this does not explain why in certain circumstances prominent objects may be perceived as unstable meanwhile the global background keeps stability (see review in [9]). More recent data indeed showed that neurons in the lateral intraparietal cortex (LIP) and several other cortical and subcortical areas may anticipate the perceptual consequence of the ongoing saccade, using remapping of objects in our visual environment [63]. In this way, we are able to keep track of position of relevant objects in the outside world [62]. Furthermore, different data suggest that LIP is providing a salience map of the visual scene, that allows shifting of visual attentional focus toward prominent objects that become saccade goals [64,6]. Consistency between the salience map and the eye movement made to acquire a salient target seems to be one of the fundamental requirements for keeping spatial constancy following saccades. Conclusion Oscillopsia is an illusion of an unstable vision, made up of the perception of to-and-fro movement of the environment. It may result either from impaired eye stability or impaired anticipation and compensation for the sensory consequences of gaze displacement, namely spatial constancy. Eye instability may be observed in either deficit of an ocular motor system that serves to maintain ocular stability or hyperactivity in the peripheral ocular motor or vestibular system. Spatial constancy involves anticipation and compensation of either the oppositely directed retinal drift during eye movement or the change in the relationship between retinal and spatial coordinates of the visual scene after eye movements. Acknowledgement The work was supported by Projet de Recherche Clinique des Hospices Civils de Lyon Grant n8 HCL/P/26.432/2. We do not disclose conflict of interest. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 9 91). 1 Tilikete C, Pisella L, Pelisson D, Vighetto A. Oscillopsia: pathophysiological mechanisms and treatment. Rev Neurol (Paris) 27; 163: Murakami I. Correlations between fixation stability and visual motion sensitivity. Vision Res 24; 44: Schlindwein P, Schreckenberger M, Dieterich M. Visual-motion suppression in congenital pendular nystagmus. Ann N Y Acad Sci 29; 1164: This is the first study of functional imaging in a patient with congenital pendular nystagmus demonstrating a decrease in metabolic activity in the network of visualmotion processing (MT/MST) correlated with the intensity of nystagmus. 4 Leigh RJ, Rushton DN, Thurston SE, et al. Effects of retinal image stabilization in acquired nystagmus due to neurologic disease. Neurology 1988; 38: Leigh RJ, Averbuch-Heller L, Tomsak RL, et al. Treatment of abnormal eye movements that impair vision: strategies based on current concepts of physiology and pharmacology. Ann Neurol 1994; 36: White RL 3rd, Snyder LH. Spatial constancy and the brain: insights from neural networks. Philos Trans R Soc Lond B Biol Sci 27; 362: Heiser LM, Colby CL. Spatial updating in area LIP is independent of saccade direction. J Neurophysiol 26; 9: Hotson JR. Cerebellar control of fixation eye movements. Neurology 1982; 32: Starzynski C, Engbert R. Noise-enhanced target discrimination under the influence of fixational eye movements and external noise. Chaos 29; 19: Wong-Lin K, Eckhoff P, Holmes P, Cohen JD. Optimal performance in a countermanding saccade task. Brain Res 21; 1318: Jasse L, Vukusic S, Pelisson D, et al. Unusual monocular pendular nystagmus in multiple sclerosis. J Neuro-ophthalmol 21 (in press). 12 Dincer A, Ozyurt O, Kaya D, et al. Diffusion tensor imaging of Guillain-Mollaret triangle in patients with hypertrophic olivary degeneration. J Neuroimag 29; Dec 16 [Epub ahead of print]. 13 Tilikete C, Hannoun S, Nighoghossian N, Sappey-Marinier D. Oculopalatal tremor and severe late-onset cerebellar ataxia. Neurology 28; 71: Ogawa K, Mizutani T, Uehara K, et al. Pathological study of pseudohypertrophy of the inferior olivary nucleus. Neuropathology 21; 3: Shaikh AG, Hong S, Liao K, et al. Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellarplasticity. Brain 21; 133: This article gives the more consistent model of OPT, suggesting the influence of a dual mechanism. First, disruption of inhibitory cerebellar modulation of the dendrodendritic gap junctions of the ION allows the development of somato-somatic gap junction between neurons, generating periodic oscillations that are transmitted to the cerebellar cortex. The second mechanism would be a superimposed cerebellar smoothing of the output signal leading to smoother and less periodic eye movements. 16 Starck M, Albrecht H, Pollmann W, et al. Acquired pendular nystagmus in multiple sclerosis: an examiner-blind cross-over treatment study of memantine and gabapentin. J Neurol 21; 27: This prospective examiner-blind, cross-over study comparing memantine and gabapentin in the treatment of pendular nystagmus in 11 patients with multiple sclerosis suggest that both are well tolerated and effective treatment options. 17 Thurtell MJ, Joshi AC, Leone AC, et al. Crossover trial of gabapentin and memantine as treatment for acquired nystagmus. Ann Neurol 21; 67: Shaikh AG, Marti S, Tarnutzer AA, et al. Gaze fixation deficits and their implication in ataxia-telangiectasia. J Neurol Neurosurg Psychiatry 29; 8: This study described precisely the fixation deficits in highlighting their potential pathophysiologic origin and visual implication in 13 patients with ataxia-telangiectasia. 19 Pinnock RA, McGivern RC, Forbes R, Gibson JM. An exploration of ocular fixation in Parkinson s disease, multiple system atrophy and progressive supranuclear palsy. J Neurol 21; 27: Donaghy C, Pinnock R, AbrahamsS, et al. Ocular fixation instabilities in motor neurone disease. A marker of frontal lobe dysfunction? J Neurol 29; 26: Pierrot-Deseilligny C, Tilikete C. New insights into the upward vestibulooculomotor pathways in the human brainstem. Prog Brain Res 28; 171: Glasauer S, Stephan T, Kalla R, et al. Up-down asymmetry of cerebellar activation during vertical pursuit eye movements. Cerebellum 29; 8: Yu-Wai-Man P, Gorman G, Bateman DE, et al. Vertigo and vestibular abnormalities in spinocerebellar ataxia type 6. J Neurol 29; 26: This clinical study focalizes on vertigo associated with SCA6. It suggests that a history of paroxysmal vertigo preceding the ataxia may be a useful feature discriminating SCA6 from other late-onset ataxia. 24 Walker MF, Tian J, Shan X, et al. Enhancement of the bias component of downbeat nystagmus after lesions of the nodulus and uvula. Ann N Y Acad Sci 29; 1164:

6 Oscillopsia Tilikete and Vighetto 43 2 Wagner J, Lehnen N, Glasauer S, et al. Downbeat nystagmus caused by a paramedian ponto-medullary lesion. J Neurol 29; 26: Spiegel R, Rettinger N, Kalla R, et al. The intensity of downbeat nystagmus during daytime. Ann N Y Acad Sci 29; 1164: Wagner J, Lehnen N, Glasauer S, et al. Prognosis of idiopathic downbeat nystagmus. Ann N Y Acad Sci 29; 1164: Lee JY, Lee WW, Kim JS, et al. Perverted head-shaking and positional downbeat nystagmus in patients with multiple system atrophy. Mov Disord 29; 24: Strupp M, Kalla R, Glasauer S, et al. Aminopyridines for the treatment of cerebellar and ocular motor disorders. Prog Brain Res 28; 171: Tsunemi T, Ishikawa K, Tsukui K, et al. The effect of 3,4-diaminopyridine on the patients with hereditary pure cerebellar ataxia. J Neurol Sci 21; 292: Lee SC, Lee SH, Lee KY, et al. Transient upbeat nystagmus due to unilateral focal pontine infarction. J Clin Neurosci 29; 16:63 6. This study, performed in a large group of patients with either multiple system atrophy (MSA) or Parkinson disease, shows that perverted head-shaking nystagmus more than positional downbeat nystagmus may help to differentiate the parkinsonian MSA from Parkinson disease. 32 Tilikete C, Milea D, Pierrot-Deseilligny C. Upbeat nystagmus from a demyelinating lesion in the caudal pons. J Neuro-ophthalmol 28; 28: Pierrot-Deseilligny C. Effect of gravity on vertical eye position. Ann N Y Acad Sci 29; 1164: Beyea JA, Parnes LS. Purely vertical upbeat nystagmus in bilateral posterior canal benign paroxysmal positional vertigo: a case report. Laryngoscope 21; 12: Tilikete C, Krolak-Salmon P, Truy E, Vighetto A. Pulse-synchronous eye oscillations revealing bone superior canal dehiscence. Ann Neurol 24; 6: Badaracco C, Labini FS, Meli A, Tufarelli D. Oscillopsia in labyrinthine defective patients: comparison of objective and subjective measures. Am J Otolaryngol 21; 31: Dannenbaum E, Paquet N, Chilingaryan G, Fung J. Clinical evaluation of dynamic visual acuity in subjects with unilateral vestibular hypofunction. Otol Neurotol 29; 3: Lambert S, Sigrist A, DelaspreO, et al. Measurement of dynamic visual acuity in patients with vestibular areflexia. Acta Otolaryngol 21; 13: Jahn K, Arbusow V, Zingler VC, et al. Bilateral vestibular failure as an early sign in Creutzfeldt-Jakob disease. Ann N Y Acad Sci 29; 1164: Melvin TA, Della Santina CC, Carey JP, Migliaccio AA. The effects of cochlear implantation on vestibular function. Otol Neurotol 29; 3: Palla A, Schmid-Priscoveanu A, Studer A, et al. Deficient high-acceleration vestibular function in patients with polyneuropathy. Neurology 29; 72: This important prospective study shows that more than 2/3 of patients with polyneuropathy exhibit an additional VOR deficit on head impulse test. This study has relevant implications regarding therapeutic strategies. 42 Barros CG, Bittar RS, Danilov Y. Effects of electrotactile vestibular substitution on rehabilitation of patients with bilateral vestibular loss. Neurosci Lett 21; 476: Janssen M, Stokroos R, Aarts J, et al. Salient and placebo vibrotactile feedback are equally effective in reducing sway in bilateral vestibular loss patients. Gait Posture 21; 31: Lewis RF, Haburcakova C, Gong W, et al. Vestibuloocular reflex adaptation investigated with chronic motion-modulated electrical stimulation of semicircular canal afferents. J Neurophysiol 21; 13: This study demonstrates in two monkeys the adaptive VOR capabilities to a canal prosthesis that senses angular head velocity and uses this information to modulate activity in vestibular afferents by direct electrical stimulation of canal ampullary nerves. It shows that the brain can modify the VOR gain, axis, and symmetry by using this canal prosthesis. There may be relevant clinical implications in patients with bilateral vestibular areflexia. 4 Kaeser PF, Borruat FX. Altered vision during motion: an unusual symptom of cerebellar dysfunction, quantifiable by a simple clinical test. Acta Ophthalmol 21; 88: Gordon CR, Caspi A, Levite R, Zivotofsky AZ. Mechanisms of vestibulo-ocular reflex (VOR) cancellation in spinocerebellar ataxia type 3 (SCA-3) and episodic ataxia type 2 (EA-2). Prog Brain Res 28; 171: Sparks DL, Mays LE. Signal transformations required for the generation of saccadic eye movements. Annu Rev Neurosci 199; 13: Whyte CA, Petrock AM, Rosenberg M. Occurrence of physiologic gazeevoked nystagmus at small angles of gaze. Invest Ophthalmol Vis Sci 21; 1: These authors looked for the presence of gaze evoked nystagmus (GEN) at different angle of gaze in 73 normal individuals. In addition to the known incidence of physiologic GEN at 38 of gaze angle, they found a high occurrence of GEN at 18 and 28 of gaze angle (respectively 21 and 34%). These results have important clinical implications. 49 Bertholon P, Chabrier S, Riant F, et al. Episodic ataxia type 2: unusual aspects in clinical and genetic presentation. Special emphasis in childhood. J Neurol Neurosurg Psychiatry 29; 8: Anagnostou E, Spengos K, Margeti S, et al. Vertical and horizontal integrator failure in a ponto-medullary infarction: a possible role for paramedian tract neurons. J Neurol Sci 29; 28: Agarwal S, Kushner BJ. Results of extraocular muscle surgery for superior oblique myokymia. J AAPOS 29; 13: Ruttum MS, Harris GJ. Superior oblique myectomy and trochlear resection for superior oblique myokymia. Am J Ophthalmol 29; 148: Williams PE, Purvin VA, Kawasaki A. Superior oblique myokymia: efficacy of medical treatment. J AAPOS 27; 11: Minor LB. Superior canal dehiscence syndrome. Am J Otol 2; 21:9 19. Abadi RV, Kulikowski JJ. Perceptual stability: going with the flow. Perception 28; 37: Dicke PW, Chakraborty S, Thier P. Neuronal correlates of perceptual stability during eye movements. Eur J Neurosci 28; 27: Dash S, Dicke PW, Chakraborty S, et al. Demonstration of an eye-movementinduced visual motion illusion (Filehne illusion) in Rhesus monkeys. J Vis 29; 9: This team developed a psychophysical experiment demonstrating capabilities of monkeys to perceive background motion during smooth pursuit. This percept would be correlated to the reference signal used for spatial constancy phenomenon. They nicely demonstrate a common process of spatial constancy in monkeys and humans that allows further proceeding to animal neurophysiological recording. 8 Lindner A, Haarmeier T, Erb M, et al. Cerebrocerebellar circuits for the perceptual cancellation of eye-movement-induced retinal image motion. J Cogn Neurosci 26; 18: Bridgeman B. Efference copy and its limitations. Comput Biol Med 27; 37: Feldman AG. New insights into action-perception coupling. Exp Brain Res 29; 194: Wurtz RH. Neuronal mechanisms of visual stability. Vision Res 28; 48: Klier EM, Angelaki DE. Spatial updating and the maintenance of visual constancy. Neuroscience 28; 16: Heiser LM, Berman RA, Saunders RC, Colby CL. Dynamic circuitry for updating spatial representations. II. Physiological evidence for interhemispheric transfer in area LIP of the split-brain macaque. J Neurophysiol 2; 94: Pisella L, Mattingley JB. The contribution of spatial remapping impairments to unilateral visual neglect. Neurosci Biobehav Rev 24; 28: Quaia C, Optican LM, Goldberg ME. The maintenance of spatial accuracy by the perisaccadic remapping of visual receptive fields. Neural Netw 1998; 11: