Smooth pursuit eye movements and otolith-ocular responses are differently impaired in cerebellar ataxia.

Brain (1998), 121, 1497–1505 Smooth pursuit eye movements and otolith–ocular responses are differently impaired in cerebellar ataxia Dimitri Anastasopoulos,1, 2 Thomas Haslwanter,1 Michael Fetter1 and Johannes Dichgans1 1Departments of Neurology, Eberhard-Karls-University, Tübingen, Germany and 2Departments of Neurology, University of Ioannina, Ioannina, Greece Correspondence to: M. Fetter, Department of Neurology, Eberhard-Karls-University Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. E-mail: Summary Horizontal and vertical smooth pursuit was compared with otolith–ocular responses in 11 patients with cerebellar ataxia and 21 normal subjects using three-dimensional magnetic search coil eye movement recordings. Otolith– ocular responses were investigated during off-vertical axis rotation. This stimulus induces nystagmus consisting of the exponentially decaying canalicular response, and an eye-velocity modulation and offset which arise from the excitation of the otoliths by the gravity vector, which lasts as long as the rotation continues. Otolith–ocular reflexes are intimately interrelated with visual tracking when real targets are viewed during linear motion. The responses of both the translational vestibulo-ocular reflex and the pursuit system have been shown to be linearly dependent on the inverse of the viewing distance, so that a common central pathway for the two systems has been suggested, probably travelling through the cerebellum. Thus, the aim of the study was to evaluate to what extent these reflexes are disturbed in cerebellar disease. The results confirm the earlier notion that in normal subjects pursuit performance is better for horizontal than for vertical tracking, and that it is better for upward than for downward tracking. This pattern is also found in patients. In addition, smooth pursuit performance is clearly degraded in patients, but the modulation of eye-velocity during off-vertical axis rotation is enhanced. Since the amount of this enhancement does not correlate with the amount of pursuit impairment, degradation of smooth pursuit and pathological enhancement of otolith–ocular responses seem to be independent effects of cerebellar degeneration. Thus, the increase in the otolith–ocular response in patients cannot be attributed to adaptational mechanisms trying to overcome the smooth pursuit deficiency; it is more likely to represent pathological disinhibition of otolith derived responses. The absence of compensatory eye-velocity offset during off-vertical axis rotation may reflect the fact that in patients the otolith signals are not utilized in computations thought to be important for spatial orientation mechanisms arising from the interaction of vestibular, visual and somatosensory signals. Keywords: cerebellar ataxia; otolith–canal interaction; smooth pursuit; off-vertical axis rotation; three-dimensional eye movements Abbreviations: ADCA 5 autosomal dominant cerebellar ataxia; ANOVA 5 analysis of variance; EOCA5 early onset cerebellar ataxia; IDCA 5 idiopathic late onset ataxia; IDCA-C 5 cerebellar IDCA; MSA-C 5 cerebellar type of multiple system atrophy; SCA 5 spinocerebellar ataxia; VOR 5 vestibulo-ocular reflex Introduction Cerebellar dysfunction can result in specific abnormalities of ocular motor control (see Leigh and Zee, 1991). Disturbances of ocular following reflexes, of gaze holding and saccadic pulse-step mismatch can be produced by lesions of the flocculus and paraflocculus, while lesions of the dorsal vermis and the underlying fastigial nuclei cause mainly saccadic dysmetria. The nodulus and uvula appear to control the time constant of the vestibulo-ocular reflex (VOR) and seem to © Oxford University Press 1998 be involved in otolith mediated responses. Furthermore, long-term adaptive functions have been attributed to the cerebellum, which help to keep eye movements appropriate to the visual stimuli. There are several lines of evidence that cerebellar dysfunction can afflict otolith mediated responses. Downbeat, upbeat and positional nystagmus of central origin have been frequently associated with cerebellar disease. Their 1498 D. Anastasopoulos et al. dependency on head position in the gravitational field implies the possibility of abnormal otolith function in cerebellar disease (Halmagyi et al., 1983). Although there are major quantitative differences in otolith-derived ocular responses between monkey and man (Darlot et al., 1988; Fetter et al., 1996), some further evidence for a cerebellar involvement in otolith–ocular reflexes comes from primate experiments. Lesions of cerebellar nodulus and ventral uvula in primates produce oscillatory vestibular responses (periodic alternating nystagmus), abolish the capability of ‘dumping’ post-rotatory vestibular nystagmus by reorientation of the head relative to gravity (Waespe et al., 1985), and abolish the ability of the otolith system to generate steady-state nystagmus during offvertical axis rotation (Angelaki and Hess, 1995a). It was assumed that the periodic alternating nystagmus reflects disinhibition of otolith-controlled inhibitory effects on central vestibular processes, and that these structures may comprise part of the neural substrate involved in the computation of head angular velocity from rotation of a linear acceleration vector. This function is thought to be related to the central velocity storage mechanism (Cohen et al., 1983; Angelaki and Hess, 1995b), which prolongs the time constant of the peripheral vestibular signal and generates optokinetic afternystagmus following a period of optokinetic stimulation. While the angular VOR, which serves to stabilize gaze during rotational head movements, has been extensively described in patients with cerebellar dysfunction (Zee et al., 1976; Thurston et al., 1987; Fetter et al., 1994; Moschner et al., 1994), there is only limited information on the otolith– ocular reflexes in cerebellar patients (Baloh et al., 1995). Otolithic-ocular reflexes have been studied in normal human subjects by applying translations along the interaural axis (Niven et al., 1966; Buizza et al., 1980; Baloh et al., 1988a, b) and by using constant speed rotations around an axis tilted relative to the vertical (off-vertical axis rotation: Guedry, 1965; Benson and Bodin, 1966; Harris and Barnes, 1987; Darlot et al., 1988). In the study presented here we used the latter stimulus, off-vertical axis rotation, to investigate the otolith–ocular responses in patients with cerebellar ataxia. Off-vertical axis rotation in darkness induces nystagmus consisting of the exponentially decaying canalicular response and a component arising from the stimulation of the otoliths by the continuously changing orientation with respect to gravity, which lasts as long as the rotation continues. Otolith– ocular reflexes interact synergistically with the angular VOR during combined canal-otolithic stimulation in the horizontal plane (Anastasopoulos et al., 1996). Fu (...truncated)