H. Rambold

Cerebellar activation in opsoclonus An fMRI study

It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose opsoclonus largely disappeared on eye closure underwent fMRI. A comparison of these two states revealed neither vermal nor brainstem activation but rather a bilateral activation in the deep cerebellar nuclei in excess of what the authors found in healthy subjects. The results support a crucial role of the fastigial nucleus in opsoclonus.

Localizing value of torsional nystagmus in small midbrain lesions.

Background: The topodiagnostic value and specificity of nystagmus in patients with mesencephalic lesions and its relation to tonic torsional deficits and vertical saccade deficits is controversial and anecdotal. Methods: The authors examined 11 patients with vascular MRI-identified mesencephalic lesions and clinical evidence of vertical-torsional nystagmus on gaze straight ahead, focusing on the three-dimensional nystagmus components recorded with the three-dimensional search coil technique. Results: Combined lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (iC) are much more frequent than riMLF and, in particular, iC lesions alone. Eight patients showed contralesional torsional nystagmus with a conjugate vertical component on gaze straight ahead and had anatomic (MRI) and clinical evidence (slowing of vertical saccades) for riMLF involvement. Tonic ocular torsion and the subjective visual vertical were shifted to the contralesional side (n = 7). Torsional nystagmus to the ipsilesional side was uncommon (n = 3) and found in patients with midbrain lesions involving the iC, all of whom also had decreased time constants of the slow phases of gaze-evoked nystagmus. Conclusions: Contrary to previous proposals, contralesional torsional nystagmus was the most frequent direction and is probably not compensatory for contralesional tonic ocular torsion. Small amplitude vertical saccades with normal velocities in association with ipsilesional torsional nystagmus may indicate isolated iC lesions. Torsional nystagmus following mesencephalic lesions may last for years and may help to distinguish rostral (riMLF) from caudal (iC) midbrain lesions.

Vergence deficits in patients with cerebellar lesions.

The cerebellum is part of the cortico-ponto-cerebellar circuit for conjugate eye movements. Recent animal data suggest an additional role of the cerebellum for the control of binocular alignment and disconjugate, i.e. vergence eye movements. The latter is separated into two different components: fast vergence (to step targets) and slow vergence (to ramp and sinusoidal targets). The aim of this study was to investigate whether circumscribed cerebellar lesions affect these dynamic vergence eye movements. Disconjugate fast and slow vergence, conjugate smooth pursuit and saccades were binocularly recorded by a scleral search coil system in 20 patients with acute cerebellar lesions (all ischemic strokes except for one) and 20 age-matched healthy controls. Patients showed impairment of slow vergence while fast vergence was unaffected. Slow vergence gain to sinusoidal targets was significantly reduced, both in convergence and divergence direction. Divergence but not convergence velocity to ramp targets was reduced. Conjugate smooth pursuit eye movements to sinusoidal and to step-ramp targets were impaired. Patients had saccadic hypometria. All defects were particularly expressed in patients with vermis lesions. In contrast to recent animal data fast vergence was not impaired in any of our patient subgroups. We conclude that (i) the human cerebellum, in particular the vermis, is involved in the processing of dynamic vergence eye movements and (ii) cerebellar lesions elicit dissociable effects on fast and slow vergence.

Vergence deficits in pontine lesions

Eye movements were recorded with the search coil system in two patients to determine whether lesions of the pontine nuclei selectively impair vergence to ramp targets (slow vergence) or step targets (fast vergence). Whereas conjugate saccades were not different from healthy control subjects, conjugate smooth pursuit eye movements had a reduced gain in horizontal and vertical directions. Slow convergence and divergence were impaired, whereas fast vergence did not differ from that of control subjects. Pontine nuclei appear to be involved in the slow vergence control.

Age-related changes of vergence under natural viewing conditions

Vergence eye movements were recorded with the scleral search-coil system in 32 healthy subjects (ages 19-73 years) to characterize the age-related effects on the dynamic parameters of vergence responses to step (transient components) and ramp or sinusoidal targets (sustained components) under natural viewing conditions. Transient vergence showed an age-related increase in latency and decreases in peak velocity and acceleration in the binocular stimulus condition but not in accommodative vergence. Sustained vergence showed no age-related effect in the binocular condition, but there was an age-related decrease in accommodative vergence steady-state velocity and an increase in latency. Age-related changes of the transient and sustained components were very similar to those reported for saccades and smooth pursuit; they thus might support a distinction between a sustained and transient vergence system. Furthermore, such age-related effects have to be taken into account when assessing eye movement disorders in neurodegenerative and cerebrovascular diseases.

Structural Changes in the Human Brain following Vestibular Neuritis Indicate Central Vestibular Compensation

Vestibular neuritis (VN) is a sudden unilateral vestibular failure (UVF) with a variable course. Caloric hyporesponsiveness often persists, and it is largely unknown why patients with the same degree of hyporesponsiveness show different functional recovery. As the peripheral vestibular deficit alone does not seem to determine functional recovery, it was the aim of this study to elucidate whether structural (morphological) brain changes (1) contribute to central vestibular compensation, and (2) account for the variability of clinical recovery in VN. Structural global gray‐matter volume (GMV) changes in 15 VN patients were compared with age‐matched controls. Morphometric changes in multisensory vestibular cortices, which may be related to functional disability scores, were hypothesized. Patients were examined with neuro‐otological tests and clinical scores to assess vestibular disability. Using voxel‐based morphometry (VBM, SPM2), categorical comparison revealed GMV increase in patients’ multisensory vestibular cortices [insula, inferior parietal lobe (IPL), superior temporal gyrus (STG)], cerebellum, and motion‐sensitive areas in the middle temporal area (MT). GMV decrease was found in the midline pontomedullary junction. Simple regression analysis revealed (1) GMV increase in insula and retroinsular vestibular cortex and STG with improving clinically assessed vestibular deficits, and (2) GMV increase in insula vestibular cortex and STG with improving self‐assessed vestibular impairment. For the first time, these data suggest structural cortical plasticity in multisensory vestibular‐cortex areas in VN that are related to clinical vestibular function and vertigo. As increase of GMV was related to an improvement of vestibular function, structural alterations may be related to central vestibular compensation.

Effect of 3,4‐Diaminopyridine on the Postural Control in Patients with Downbeat Nystagmus

Abstract: Downbeat nystagmus (DBN) is a common, usually persistent ocular motor sign in vestibulocerebellar midline lesions. Postural imbalance in DBN may increase on lateral gaze when downbeat nystagmus increases. 3,4‐Diaminopyridine (3,4‐DAP) has been shown to suppress the slow‐phase velocity component of downbeat nystagmus and its gravity‐dependent component with concomitant improvement of oscillopsia. Because the pharmacological effect is thought to be caused by improvement of the vestibulocerebellar Purkinje cell activity, the effect of 3,4‐DAP on the postural control of patients with downbeat nystagmus syndrome was examined. Eye movements were recorded with the video‐based Eyelink II system. Postural sway and pathway were assessed by posturography in lateral gaze in the light and on eye closure. Two out of four patients showed an improvement of the area of postural sway by 57% of control (baseline) on eye closure. In contrast, downbeat nystagmus in gaze straight ahead and on lateral gaze did not benefit in these two patients, implying a specific influence of 3,4‐DAP on the vestibulocerebellar control of posture. It was concluded that 3,4‐DAP may particularly influence the postural performance in patients with downbeat nystagmus.

Convergence retraction nystagmus: a disorder of vergence?

The pathological mechanism of convergence retraction nystagmus (CRN) is not known. To determine whether CRN is a disorder of vergence or of the saccadic system, the scleral search coil technique was used to record binocularly the three‐dimensional components of CRN in a patient with a left mesencephalic infarction involving the nucleus of the posterior commissure and the rostral interstitial nucleus of the medial longitudinal fascicle. CRN had disconjugate horizontal and torsional components. The horizontal amplitude/velocity relationship of CRN aligned with the main sequence of vergence responses of normal control subjects but not with that of saccades. Vergence responses of the right eye and left eye were not asynchronous. The slow phases of CRN showed an exponential decay with a time constant of 70 milliseconds. Thus, CRN is probably a disorder of vergence rather than of opposing adducting saccades.

Treatment of the gravity dependence of downbeat nystagmus with 3,4-diaminopyridine

The authors examined the effect of 3,4-diaminopyridine (DAP) on the gravity-dependent (GD) vertical ocular drift component of downbeat nystagmus in 11 patients with idiopathic cerebellar ataxia. With the head tilted downward (45°), DAP reduced slow phase velocity (SPV) in 7 of 11 patients by 36%. Its efficacy correlated with the GD modulation. DAP minimizes the gravity-independent velocity bias and may improve deficient inhibitory cerebellar control on overacting otolith–ocular reflexes.

Palsy of “fast” and “slow” vergence by pontine lesions

The role of pontine nuclei in vergence eye movements to “step” targets (“fast” vergence) is unknown. Eye movements were recorded in two patients with unilateral pontine infarctions and in 11 healthy controls. In addition to the deficit of “slow” vergence, “fast” vergence was particularly impaired. However, conjugate saccades did not differ from controls, but smooth pursuit eye movements did. The authors conclude that “fast” vergence palsy is not only caused by midbrain but also upper pontine lesions.