Nuclei Lesions

83282ournal ofNeurology, Neurosurgery, and Psychiatry 1994;57:832-834

SHORT REPORT J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.832 on 1 July 1994. Downloaded from

Saccadic dysmetria and "intact" smooth pursuit eye movements after bilateral deep cerebellar nuclei lesions

U Buttner, A Straube, A Spuler

Abstract Case reports Two patients with well defined lesions of CASE 1 midline cerebeliar structures including A 29 year old woman suddenly developed a the fastigial nuclei on both sides pre- gait and postural ataxia pronounced on the sented with saccadic hypermetria but left side. A cerebellar a-v malformation had well preserved smooth pursuit eye move- been diagnosed on MRI. A neurological ments. This is a remarkable finding as examination revealed the ataxia for gait and the oculomotor vermis (lobules VI, VII) posture pronounced on the left side, along and the fastigial nucleus are known to with dysarthria, slight weakness of the left play a part in the control of smooth pur- extremities, and a stocking-like hypaesthesia suit eye movements and unilateral fasti- of the left leg. There was no positional or gial lesions lead to a smooth pursuit positioning nystagmus. For oculomotor deficit to the contralateral side (besides deficits see later. saccadic dysmetria). The results are dis- Before surgery, the angioma was partly cussed with regard to related deficits embolised by interventional angiography and seen in patients with Wallenberg's syn- was completely removed all the way through drome and after lesions of the pontine the cerebellum down to the roof of the fourth reticular formation. ventricle. After surgery, the lesion had a trian- gular shape in the sagittal plane on MRI with (7 Neurol Neurosurg Psychiatry 1994;57:832-834) the base destroying lobules III to VIII of the vermis and the apex extending to the fourth ventricle, destroying the fastigial nuclei on It recently became evident that the oculomo- both sides. In the coronal plane, the lesion tor vermis (lobules VI and VII)I and its major had an oval shape extending over the midline output structure, the caudal fastigial nucleus with a lateral diameter of 1-5 to 2-0 cm. The http://jnnp.bmj.com/ (fastigial oculomotor region,)2' are not only dentate nuclei and the floccular region were involved in the accuracy of saccades4 but also intact on both sides (fig 1). in the control of smooth pursuit eye move- ments.5 Experimental studies in monkeys CASE 2 showed a clear directional effect on saccade A 36 year old woman was admitted to hospi- accuracy and smooth pursuit eye movements tal after she had had several attacks of posi- for the fastigial oculomotor region. A unilat- tioning vertigo. On examination, there was

eral injection of the GABAergic-substance some central positioning vertigo with nystag- on September 26, 2021 by guest. Protected copyright. muscimol into the fastigial oculomotor region mus beating to the uppermost ear. Other ocu- leads to contralateral hypo and ipsilateral lomotor findings are described below. The hypermetric saccades4 and to a pronounced remaining cranial nerves were unremarkable. Department of decrease of smooth pursuit related optoki- The tendon reflexes were brisk and the Neurology and netic slow phase velocity6 and smooth pursuit Babinski sign negative. There was slight Neurosurgery A Spuler gain7 to the contralateral side. ataxia of posture and gait. The remaining Klinikum With this in mind, the question arises as to neurological examination was normal. Grosshadern, Ludwig what effect is to be expected from bilateral On MRI a large midline tumour was found Maxdmilians lesions in the fastigial oculomotor region. and diagnosed as a Lindau tumour. The University, 81377 This has been answered for circular lesion a Munich, Germany clearly saccades, large, nearly with diameter of U Buttner whereby a general hypermetria is found.4 The 4*3 cm extended over the midline with the A Straube effect that bilateral lesions in the fastigial centre 3-5 mm to the left. It extended from Correspondence to: oculomotor region have on smooth pursuit the fourth ventricle to the tentorium, totally Professor Dr U Buttner, Neurologische Klinik, performance has not been studied in humans. destroying lobules V-VII on the midline. All Klinikum Grosshadern, In this report we present two patients with the cerebellar nuclei were destroyed with D 81377 Munchen, Marchioninistrasse 15, well defined bilateral lesions of the deep cere- some possible sparing of lateral parts of Germany. bellar nuclei including the fastigial occulomo- dentate nucleus on the right side. The floccu- Received 21 June 1993 and tor region. Both of them had a pronounced lar region and most of its brainstem connec- in final revised form 27 October 1993. saccadic hypermetria but no smooth pursuit tions were intact. The patient underwent Accepted 1 November 1993 eye movement deficit. surgery after the eye movement recordings. Saccadic dysmetria and "intact" smooth pursuit eye movements after bilateral deep cerebellar nuclei lesions 833

Figure I MRI ofpatient 1 after surgery ofa J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.832 on 1 July 1994. Downloaded from cerebellar a-v malformation. Coronal (left) and sagittal (right) plane. The lesion extends over the midline and destroys the vermis (lobules III to VIII) and both fastigial nuclei. On the right some clip artefacts projections on to the medulla can be seen.

Histopathology verified the diagnosis of a saccadic dysmetria, the gain of the first (pri- hac-mangioblastoma (Lindau tumour). mary) saccade8 after the target step was deter- mined from at least 20 target steps of 200 around the midposition. Smooth pursuit gain Eye movement recordings was taken as the ratio of eye position/stimulus METHODS position for three to five cycles. Horizontal and vertical eye positions were recorded by DC-electro-oculography. The eye movement variables investigated were: Results spontaneous eye movements in light and CASE 1 darkness, fixation of small visual targets in Recordings were taken 11 days after surgery. 10° steps up to ±40° horizontally and ±200 There was no spontaneous nystagmus in light vertically, optokinetic nystagmus up to 90°/s or darkness. Saccades could be performed in stimulus velocity in the horizontal and 300/s all directions with a normal amplitude and in the vertical direction. Vestibular nystagmus velocity range. They were unremarkable dur- responses in the dark were determined after a ing spontaneous eye movements in light and sudden stop from 900/s whole body rotation. darkness. There was no horizontal or vertical The vestibulo-ocular reflex (VOR) was also gaze evoked nystagmus. Optokinetic nystag- tested during horizontal sinusoidal stimula- mus was within normal limits. Vestibular nys- tion (0-1 Hz, ±800) in the dark. To investi- tagmus after whole body rotation was slightly gate saccadic dysmetria, a small laser spot asymmetrical (duration right: 28 s, left: 23 s). was presented up to 40° laterally, in most The VOR in the dark was normal. The sac- instances stepping between the lateral and cadic dysmetria was severe (fig 2).8-10 All 200 http://jnnp.bmj.com/ midposition. For smooth pursuit eye move- target steps were followed by hypermetric pri- ments the target moved horizontally (± 250) in mary saccades with a gain of up to 2-0. On front of the patient at 0- 1-0-4 Hz, corre- average, the gain was 1 7 (SD 0.15). The sponding to ±16-63°/s. During visual sup- hypermetria was symmetrical for left and pression of the VOR, the patient fixated a rightward saccades. Centripetal saccades target moving with the head during sinusoidal were more hypermetric (average gain 1.82) vestibular stimulation (0 1 Hz, ± 800). All than centrifugal saccades (average gain 1.6). recordings were written out on paper charts Also vertical saccades were hypermetric, on September 26, 2021 by guest. Protected copyright. for evaluation and quantitative analysis. For more pronounced for upward (average gain 1 6) than for downward (average gain 1 3) saccades. By contrast, smooth pursuit eye movements were very well preserved. At 0-1 Figure 2 Eye movement Hz the gain was virtually 1-0 with long peri- recordings ofpatient 1 after ods of hardly any catch up saccades. The gain surgery. (A) horizontal at 0-3 Hz was still 0 9 (fig 2). Also, the visual saccades to visual target suppression of the VOR was within steps; (B) horizontal EH L 20 ,'t normal smooth pursuit eye limits. movements. = A EV vertical, R 20' EH = horizontal eye CASE 2 position, and TH = R 250' L horizontal target position. This patient also had neither spontaneous There is severe saccadic nystagmus in light or darkness nor gaze hypermetria, but no (O 1 Ev R20D2k 0 Hz left) or only little (0 3 evoked nystagmus. Horizontal and vertical Hz, right) smooth pursuit spontaneous saccades were normal. impairment. EH L 200 3 Vestibular nystagmus after whole body rota- tion was symmetrical (duration left 35 s, right 37 s). The VOR in the dark TH L 250 and the visual supression of the VOR were normal. During 2 s horizontal smooth pursuit, the gain was above 834 Biittner, Straube, Spuler

0O85 up to 0 3 Hz. Horizontal saccadic hyper- unilateral PPRF lesions, smooth pursuit to metria was symmetrical to the left and right. the ipsilateral side was also severely impaired, J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.57.7.832 on 1 July 1994. Downloaded from All saccades overshot the target up to 110 whereas smooth pursuit was possible in both corresponding to a gain of 1-55 (average gain directions after bilateral PPRF lesions.'4 1-32 (SD 0-14)). For this patient too, cen- Thus fastigial oculomotor region lesions tripetal saccades (average gain 1-36) were seem to have similar effects on saccades and more hypermetric than centrifugal saccades smooth pursuit eye movements. Unilateral (average gain 1-27). There was also some ver- lesions lead to hypometric saccades and cog- tical saccadic hypermetria but blink artefacts wheel smooth pursuit to the contralateral prevented detailed analysis here. side. Hypermetric saccades and "intact" smooth pursuit are found to the ipsilateral side after unilateral and bilateral lesions. As a Discussion general principle, a gain reduction is obvious Two patients are presented with large, well in both types of eye movements. An increased defined cerebellar lesions straddling the mid- gain only manifests itself, however, in the sac- line, and including deep cerebellar nuclei on cadic system. both sides, particularly the fastigial oculomo- The unusual finding that unilateral fastigial tor region. Both patients had a severe, sym- oculomotor region lesions cause a smooth metrical saccadic hypermetria with primary pursuit deficit, and that bilateral lesions do saccades overshooting a 20° target by nearly not can be best explained if it is assumed that 100%. As has been found experimentally,4 the fastigial oculomotor region affects smooth centripetal saccades were more hypermetric pursuit acceleration and deceleration. than centrifugal saccades. All other eye move- According to this hypothesis, a lack of accel- ments were normal. More specifically, there eration causes a pursuit deficit to the con- was no gaze evoked nystagmus and smooth tralateral side and a lack of deceleration to pursuit eye movements were well preserved. the ipsilateral side, which in this direction At first glance, knowing the effects of uni- does not produce an obvious eye movement lateral lesions in the fastigial oculomotor deficit. It has to be postulated that the com- region, this is a somewhat surprising finding. bined effect of a bilateral lesion is a net Experimentally, unilateral fastigial oculomo- decleration deficit on both sides. Potentially, tor region lesions have a severe effect both on this could lead to eye movements which are saccades as well as on smooth pursuit eye too fast (gain >1). This would cause a retinal movements6 7-with the smooth pursuit error in the opposite direction, however, deficit having a similar magnitude as that which apparently can still be prevented by the found after bilateral ablation of the floccular smooth pursuit system. region." Noticeably, no smooth pursuit deficit to We thank K Schuler for eye movement recordings. The work was supported by Deutsche Forschungsgemeinschaft (SFB the ipsilateral side has been found after uni- 220, D7). lateral lesions in the fastigial oculomotor region. 6 7 As both saccades and smooth pur- suit show a similar deficit (a decreased gain) 1 Yamada J, Noda H. Afferent and efferent connections of to the contralateral side, by analogy with the the oculomotor cerebellar vermis in the macaque mon- key. J Comp Neurol 1987;265:224-41. http://jnnp.bmj.com/ saccadic system an increased smooth pursuit 2 Noda H, Sugita S, Ikeda Y. Afferent and efferent connec- tions of the oculomotor region of the fastigial nucleus in gain to the ipsilateral side might be postu- the Macaque monkey. J Comp Neurol 1990;302:330-48. lated. As smooth pursuit eye movements are 3 Buttner U, Fuchs AF, Markert-Schwab G, Buckmaster P. Fastigial nucleus activity in the alert monkey during controlled in closed loop with continuous slow eye and head movements. Jf Neurophysiol 1991; feedback signals, this might be the reason that 65:1360-71. 4 Robinson FR, Straube A, Fuchs AF. Role of the caudal this is not the case. The specific mechanisms, fastigial nucleus in saccade generation. II. Effects of however, are not known. muscimol inactivation. J Neurophysiol 1993;70: 1741-58. 5 Amarenco Roullet Marteau Pierrot-Deseilligny Ch, P, E, on September 26, 2021 by guest. Protected copyright. The corresponding deficit of saccades and R. Vermal infarct with pursuit eye movement disorders. smooth pursuit is similar to that found J Neurol Neurosurg Psychiatry 1990;53:519-21. 6 Kurzan R, Straube A, Buttner U. The effect of Muscimol after lateral medulla oblongata lesions microinjections into the fastigial nucleus on the optoki- (Wallenberg's syndrome)."" In this syn- netic response and the vestibulo-ocular reflex in the alert monkey. Exp Brain Res 1993;94:252-60. drome too, hypometric saccades with a 7 Straube A. Uber die elektrophysiologischen Grundlagen und decreased smooth pursuit gain to the con- die pharmakologische Beeinflussung der Augenbewegungen beim Affen und ihre Bedeutung in der Therapie von tralateral side and hypermetric saccades with Augenbewegungsstorungen. Habilitationsschnft. Miinchen: a normal smooth pursuit gain to the ipsilat- Ludwig-Maximilians-Universitat, 1993. 8 Botzel K, Rottach K, Biittner U. Normal and pathological eral side are found. This deficit has been saccadic dysmetria. 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(Con- gial oculomotor region.46 temporary Neurology Series Vol 35.) 13 Waespe W, Wichmann W. Oculomotor disturbances dur- It is known that the fastigial oculomotor ing visual-vestibular interaction in Wallenberg's lateral region projects to the paramedian pontine medullary syndrome. Brain 1990;113:821-46. 14 Henn V, Lang W, Hepp K, Reisine H. Experimental gaze reticular formation (PPRF) in the brainstem. palsies in monkeys and their relation to human pathol- It fits very well with our findings that after ogy. Brain 1984;107:619-36.