Journal ofNeurology, Neurosurgery, and Psychiatty 1993;56:799-807

Smooth pursuit eye movement deficits afterpontine nuclei lesions in humans

B Gaymard, C Pierrot-Deseilligny, S Rivaud, S Velut

AbstractEye movements were recorded electro-oculographically in four patients withbasal pontine lesions, demonstrated byMRI. The most prominent eye move-ment abnormality observed was mild tosevere impairment of smooth pursuitand optokinetic nystagmus, mainly ipsi-lateral to the lesion. This abnormality isthought to result from damage to thepontine nuclei, which form a crucialrelay between the cerebral cortex and thecerebellum controlling smooth pursuit.Abnormalities of saccades and thevestibulo-ocular reflex in one patient arealso discussed.

(9Neurol Neurosurg Psychiatry 1993;56:799-807)

Clinique Neurologiqueand Unit6 INSERM289, Hopital de laSalpetriere, Paris, andService deNeurochirurgie,H6pital Bretonneau,Tours, FranceB GaymardC Pierrot-DeseillignyS RivaudS VelutCorrespondence to:B Gaymard, INSERM 289,H6pital de la Salpetriere, 47Bd de l'H6pital, 75651Paris, Cedex 13, France

Received 30 March 1992and in revised from11 August 1992.Accepted 25 September 1992

The pontine nuclei (PN) consist of severalgroups of neurons in the basis pontis relayingsignals from the cerebral cortex towards thecerebellum. Some of them, namely the dorso-lateral, the lateral, and the dorsomedian PN,could be specifically involved in smooth pur-suit eye movements, and represent a cruciallink in the corticopontine pathways mediatingthis eye movement.'23 However, the locationand function of the PN involved in smoothpursuit still have to be precisely determinedin humans. The first human case with a selec-tive PN lesion and including eye movementrecordings was recently reported.4 It provideddata consistent with the results of experimen-tal lesion studies involving the dorsolateralpontine nuclei (DLPN) in the monkey. Wereport four patients with diverse vascularlesions affecting the basis pontis, resulting invarious impairments of smooth pursuit andoptokinetic nystagnus (OKN). The relationbetween smooth pursuit impairment and thelocation of the lesions is discussed.

Case reportsPATENT 1A 73 year old woman had been complainingfor a year and a half of a right trigeminal neu-

ralgia despite carbamazepine therapy. Shethus agreed to a neurosurgical procedure, anda microvascular decompression of the fifthnerve was performed. After surgery, thepatient awoke with left hemiplegia. Therewas no cerebellar symptoms, no sensory loss,and no diplopia. MRI showed a right pontinelesion, compatible with a haematoma (fig 1).

This lesion was located along the lateral edgeof the basis pontis, and affected about twothirds of the rostrocaudal extent of the pons(fig 2). When eye movement recordings weremade, one week after surgery, the left hemi-plegia had not improved, though the patientwas alert and cooperative.

PATENT 2A 59 year old woman was hospitalised afterthe sudden onset of right hemiplegia. On ini-tial examination, severe right hemiplegia wasobserved. On the left side, strength was nor-mal but there was dysmetria in the finger tonose test. All sensory examination was nor-mal. MRI showed a left pontine lesion, com-patible with an infarct (fig 3). A transversesection showed that the lesion affected almostall the left basis pontis, and slightly crossedthe midline (fig 3A). The pontine tegmentumwas spared, excepc-for a limited part of themedian structures, on which a very narrowposterior extent of the lesion impinged (fig 2).Sagittal sections clearly showed that thelesion had a short rostrocaudal extent, andconsisted of a thin horizontal slice (about5 mm) at the mid-pons level (fig 3B). MRIdid not show any lesions in the superior orinferior cerebellar peduncles or in the cerebel-lum. Eye movement recordings were per-formed five months after the stroke. At thattime, the motor deficit and the cerebellarsyndrome persisted. The patient was alertand cooperative.

PATENT 3A 34 year old woman with no medical back-ground was hospitalised after the suddenonset of pure left hemiparesis. MRI showed alesion restricted to the basis pontis, compati-ble with an infarct. It was located just belowthe mid-pons level, along the midline, with alimited extent on the right side (fig 2). Onsagittal sections, it occupied approximately30% of the whole rostrocaudal extent of thepons. Eye movement recordings were per-formed one month after the stroke. At thattime, there was no improvement in the motordeficit, though the patient was alert andcooperative.

PATINT 4A 66 year old woman with a long history ofhypertension suddenly experienced isolatedleft hemiplegia. MRI showed a lesion com-patible with an infarct, located on the rightside of the brainstem, at the mid-pons level.The lesion was restricted to the basis pontis,

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Figure I MRI ofpatient 1 (T, weighted, TR = 500 ms, TE = 10 ms) shows a right pontine lesion, compatible with ahaematoma, located in the lateral part of the basis pontis, with a marked rostrocaudal extent. (A) pontomesencephalicjunction, (B) upper pons, (C) mid-pons, (D) lower pons.

except on the midline where it extendedslightly into the tegmentum (fig 2). On sagit-tal sections of the brainstem, it occupiedapproximately 40% of the rostrocaudal extentof the pons. Eye movements were recordedsix weeks after the stroke. By this time, themotor deficit had improved moderately, andthe patient was alert and cooperative.

Eye movementsFor all patients, eye movements were record-ed using direct current electro-oculography(EOG), with the head immobilised. Twotemporal electrodes were used for horizontaleye movements, and two others were locatedabove and below the right eye for vertical eyemovements.

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801Smooth pursuit eye movement deficits after pontine nuclei lesions in humans

E 1'atient 1

Z Patient 2

Patient 3

Patient 4

R

A

B

C

D

Figure 2 Drawing of the lesions of the four patients based on MRI scans (drawn by theauthors). (A) midbrain, (B) upper pons, (C) mid-pons, (D) lower pons, an = abducensnucleus, ml = medial lemniscus, mlf = medial longitudinalfasciculus, R = right. Thedorsoventral broken line passes through the peduncular PN and clearly separates theDMPN, laterally, and the DMPN, medially.

Saccades and smooth pursuit were elicitedin a dimmed room with a ramp of light emit-ting diodes (LED), located 80 cm in front ofthe subject. Horizontal visually guided sac-cades were studied by asking the subject tolook as fast as possible at a suddenly appear-ing 20° lateral target. Horizontal smooth pur-suit was induced by asking the subject totrack an LED moving sinusoidally with anamplitude of ±200, at various speeds (peakvelocities of 22-5, 29, and 45°/s for patient 1,and 14-5, 22-5, 29, and 45°/s for the otherpatients). For each speed, smooth pursuitgain (defined as the ratio of peak eye velocityto peak stimulus velocity), was calculated foreach lateral direction by averaging the gainobtained in 10 successive cycles. The calcula-tion of smooth pursuit gain was made fromthe chart (speed of the chart paper 10 mm/s).Furthermore, an index of asymmetry ofsmooth pursuit was defined as:

right gain - left gain x 100right gain + left gain

Vertical saccades and smooth pursuit wererecorded under the same conditions as forhorizontal eye movements, but only qualita-tively analysed.

Figure 3 MRI ofpatient 2 (T, weighted, TR = 600 ms,TE = 12 ms) shows a left pontine lesion, compatible withan infarct. (A) horizontal section at the mid-pons level.The lesion involved almost all of the left basis pontis, withslight extension, medially into the tegmentum andcontralaterally. (B) sagittal section. The lesion had alimited rostrocaudal extent.

For patient 1, horizontal OKN wasobtained by the manual displacement of alter-nate black and white stripes over a large partof the visual field. The horizontal vestibulo-ocular reflex (VOR) was studied in a dimmedroom on an armchair rotating with an ampli-tude of ± 200, without stimulation beingrecorded, and VOR suppression was tested byasking the patient to fixate a target rotatingwith the armchair. These different eye move-ments were analysed qualitatively.

For the other patients, OKN was elicitedby vertical black and white stripes, covering500 of the visual field and moving regularly at10, 20, and 300/s. The horizontal VOR wasstudied in complete darkness, using a chair

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isFigure 4 Horizontal eye movement recordings ofpatient 1. In figures 4, 5, and 6,rightward eye movements are represented by an upward trace, and leftward eye movementsby a downward trace. (A) Saccades, with normal latency, amplitude, and velocity. (B)Smooth pursuit, saccadic bilaterally though mainly rightwards. (C) OKN, asymmetrical,with slower rightward slow phase (horizontal arrows indicate the direction ofstimulation,and vertical arrows a change in the direction ofstimulation). (D) VOR, normal. (E)VOR suppression, impaired bilaterally, without visible asymmetry. e = eye, t = target.

Table 1 Horizontal saccades latencies and velocityLatncy (ms) Veloc4y (rIs)R L R L

Patient 1 300 270 402 399Patient 2 225 240 120* 144*Patient 3 180 200 335 340Patient 4 228 230 355 410First controlgroup 237 (47) 236 (59) 327 (72) 325 (72)Second controlgroup 197 (30) 192 (28) 346 (60) 331 (58)

In this and all subsequent tables patients 1, 2, and 4 are com-pared with the first control group and patient 3 is comparedwith the second control group. L = left, R = right; *Outsidethe normal range (mean (2 SD)).

rotating at 0-25 and 0 40 Hz with a 200amplitude on each side of the midline, undertwo conditions. Under the first condition, thepatient was asked to fixate an earth-fixedvisual target while being rotated, which testedboth the VOR and smooth pursuit. Under thesecond condition, the visual target was turnedoff, but the patient was asked to imagine itwhile being rotated, which tested only theVOR. Ability to suppress the VOR was alsostudied, the patient being asked to fixate atarget rotating with the armchair. Mean gainswere calculated for OKN, the VOR, andVOR suppression (ratio of peak eye velocityto peak head velocity).Two control groups, each of 10 normal

subjects, were used, because patient 3 wasmarkedly younger than the other three. Thefirst control group had a mean age of 60 years(range: 51-67 years), and the second a meanage of 35 years (range: 25-44 years). Theresults of patients 1, 2, and 4 were comparedwith those of the first control group, and theresults of patient 3 with those of the secondcontrol group.

ResultsPATIENT 1Horizontal saccades were accurate and hadlatency and velocity analogous to those of thefirst control group (fig 4A and table 1).Smooth pursuit gain was markedly decreasedbilaterally, even for a low stimulus velocity(fig 4B and table 2). Furthermore, there wasmarked asymmetry for each speed (fig 7) witha more severe deficit for rightward smoothpursuit (fig 4B and table 2). Therefore, manycatch up saccades were needed to follow thetarget. OKN slow phase was clearly asymmet-rical, with a slower rightward slow phase (fig4G).The VOR was symmetrical and qualitative-

ly normal (fig 4D). VOR suppression wasimpaired bilaterally, as shown by the presenceof a vestibular nystagmus, even for slow rota-tions, without obvious qualitative right-leftasymmetry (fig 4E).

Vertical saccades appeared normal, with nodysmetria. Both upward and downwardsmooth pursuit appeared severely impaired,being almost entirely replaced by catch upsaccades.

PATIENT 2Horizontal visually guided saccades wereaccurate, with latencies analogous to those ofthe first control group, but with markedlyreduced velocities, bilaterally (fig 5A andtable 1).Smooth pursuit was impaired bilaterally

(fig 5B and table 2), but predominantlytowards the left side, with marked asymmetryfor 145, 22-5 and 290/s target velocities (fig7). This asymmetry disappeared at higher tar-get velocities. The OKN slow phase gain wasdecreased bilaterally, though more markedlyleftwards (fig 5C and table 3).Under the first condition (the patient fixat-

ing an earth-fixed target), the VOR gain was

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Table 2 Horizontal smooth pursuit gain (SD)

Patient 1 Patient 2 Patient 3 Patient 4 First control group Second control groupGain Gain Gain Gain Mean gain Mean gain

Target (SD) (SD) (SD) (SD) (SD) (SD)peakvelocity R L R L R L R L R L R L

14 5°/s 0-69* 0.50* 0-71* 0-94 0-96 0-98 0-98 1.01 1 00 1 00(0-17) (0-15) (0-12) (0 10) (0 05) (0 05) (0 06) (0 07) (0 05) (0 07)

22-5°/s 0-13* 0-28* 0-62* 0-45* 0-68* 0-83* 0-78* 0-83* 1-02 0.99 1-05 1-06(0 10) (0 10) (0-12) (0-13) (0 11) (0-15) (0-08) (0-07) (0-05) (0-06) (0 06) (0-06)

29°/s 0.10* 0-28* 0-62* 0-26* 0-63* 0.75* 0.70* 0.73* 094 0-93 1 00 1-03(0-05) (0-09) (0-16) (0-07) (0-13) (0-13) (0 08) (0-08) (0 09) (0 09) (0 06) (0-04)

45°/s 0.05* 0-20* 0 19* 0-22* 0-56* 0-64* 0.53* 0-61 0-85 0-82 091 0-92(003) (007) (0 10) (0-13) (0 11) (0 11) (008) (006) (006) (0-13) (005) (004)

The side of the lesion is denoted in bold. (See also the legend of Table 1.)

I J tv I ;_

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aS

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E

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Figure S Horizontal eye movement recordings ofpatient 2. (A) Saccades, with nornallatency and amplitude, but bilateral decreased velocity. (B) Smooth pursuit, saccadicbilaterally, mainly leftwards. (C) OKN, asymmetrical with slower leftward slow phase(horizontal arrows indicate the direction ofstimulation, and the vertical arrow a change inthe direction ofstimulation). (D) VOR (a) under the first condition, with normal gain;(b) under the second condition, asymmetrical with normal leftward gain but increasedrightward gain. (E) VOR suppression, impaired bilaterally, though mainly rightwards.e = eye, s = stimulation, t = target.

analogous to that of the control group (fig 5Dand table 4). Under the second condition,rightward VOR gain increased, but leftwardVOR gain was normal, resulting in significantright left asymmetry (p < 0-001, Student'stest) (fig 5D and table 4). VOR suppressiongain was impaired bilaterally, though mainlyrightwards (fig 5E and table 4). The ratio ofleftward gain to rightward gain was approxi-mately 1 for the VOR under the first condi-tion, it was 0-36 for the VOR in the secondcondition, and 0 35 for VOR suppression.

Vertical saccades (200 amplitude) had nor-mal latency and accuracy. Their velocityseemed qualitatively normal (about 2400/supwards and 245°/s downwards). Smoothpursuit was almost entirely saccadic bothupwards and downwards, and velocity of ver-tical OKN slow phases was markedlyreduced.

PATENTS 3 AND 4Velocity and amplitude of horizontal saccadesof patient 3 (fig 6A) and patient 4 were analo-gous to those of the second and first controlgroups, respectively (table 1). Smooth pursuitwas impaired, mainly at higher target veloci-ties, slightly more ipsilaterally (fig 6B andtable 2). Asymmetry was slight for targetsmoving at 14 5°/s, 22-5°/s, and 45°/s forpatient 3, and the index of asymmetry waswithin the normal range for patient 4 (fig 7).Horizontal OKN was similarly impaired, withno (patient 3) (fig 6C and table 3) or slightasymmetry (patient 4) (table 3).

In both patients, the VOR was normalunder both conditions, and VOR suppressionwas impaired, with no asymmetry (fig 6 Dand E, and table 4). Vertical smooth pursuitwas qualitatively mildly impaired (that is,slightly saccadic), both upwards and down-wards.

DiscussionAll the patients had a limited vascular lesionlocated in the basis pontis. Two structures,therefore, were damaged, at least partially:the corticospinal tract and the PN. The pon-tine tegmentum was spared in patients 1 and3, and slightly damaged in patients 2 and 4,on the midline. The contralateral motordeficit existing in all four patients could easilybe ascribed to damage to the corticospinal

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Table 3 Horizontal optokinetic nystagmus (OKN) gain

Patient 2 Patient 3 Patient 4 First control group Second control groupGain Gain Gain Mean gain (SD) Mean gain (SD)

Stimulusvelocity R L R L R L R L R L

10°/s 0-69 0-46 0.40* 0 53 0-58 0-63 0 77 (0-17) 0-78 (0-19) 0-78 (0-11) 0 77 (0-14)20°/s 0.40* 0-15* 0-41* 0-43* 0 50* 0-68 0-74 (0-11) 0-73 (0-14) 0-69 (0 07) 0-71 (0-11)300/s 0.35* 0-12* 0-38* 0.39* 0-36* 0-68 0-72 (0-10) 0 75 (0-12) 0-71 (0 06) 0-69 (0 07)

The stated gain is that ofOKN slow phase. The side of the lesion is denoted in bold. (See also the legend of Table 1.)

Table 4 Horizontal VOR and VOR suppression gain

Patient 2 Patient 3 Patient 4 First control group Second control groupStimulus Gain Gain Gain Mean gain (SD) Mean gain (SD)frequency(Hz) R L R L R L R L R L

VOR, first condition0-25 0-81 0-79 0-91 0-82 0-67 0-70 0-81 (0-08) 0-81 (0-10) 0-73 (0-10) 0-71 (0-12)0-40 0-70 0-88 0-76 0-90 0-71 0-80 0-82 (0-18) 0-84 (0-18) 0-75 (0-19) 0-77 (0-19)VOR, second condition0-25 2-20* 0-80 0-66 0-79 0-84 0-99 0-85 (0-12) 0-80 (0-12) 0-80 (0-18) 0-78 (0-16)0-40 1-35* 0-85 0-71 0-72 0-90 0-85 0-76 (0-12) 0-76 (0-07) 0-79 (0-17) 0-77 (0-14)VOR suppression0-25 0-26* 0-09* 0-14* 0-12* 0-09* 0-09* 0-04 (0-02) 0-03 (0-02) 0-03 (0-02) 0-02 (0-01)The side of the lesion is denoted in bold. (See also the legend of Table 1.)

tract. Impairment of smooth pursuit wasprobably a result of the PN lesions. We willmainly deal with this point, but abnormalitiesconcerning the VOR and horizontal saccadesin patient 2 will also be discussed briefly.

SMOOTH PURSUIT AND OPTOKYNETICNYSTAGMUSThe precise location of the different PNgroups is unknown in humans. In the mon-key, the PN consist of several contiguoussubdivisions, classified using topographicalcriteria. The classification proposed by Nybyand Jansen,5 although obtained using oldanatomical techniques, is still used as a refer-ence by modern authors.678 They distinguishthe median PN, dorsal PN, lateral PN, ven-tral PN, and peduncular PN, all of which areintermingled with the corticospinal tract.These nuclei extend from the pontomedullaryjunction to the pontopeduncular junction.6The subdivisions involved in smooth pursuithave recently been investigated. The DLPNhave been extensively studied and appear tocontrol smooth pursuit. The DLPN receiveafferences from ipsilateral cortical areasinvolved in smooth pursuit: the middle tem-poral (MT) and medial superior temporal(MST) areas,6-9 and the frontal eye field(FEF).3"01 The DLPN project to the cere-bellar structures involved in smooth pursuit-that is, bilaterally to the oculomotor vermisand the fastigial nucleus, and also bilaterallybut mainly contralaterally to the floccu-lUS.' 12-18 Neurons in the DLPN dischargeduring ipsilateral or contralateral smooth pur-suit.19-22 Microstimulations applied within theDLPN increase ipsilateral smooth pursuitvelocity, but do not elicit slow eye move-ments if eyes are not already performingsmooth pursuit.2' It should be noted that thesame fact was observed for stimulations ofarea MST.24 Furthermore, it has been report-ed, in the monkey and in one patient, that aDLPN lesion results in a decrease in smooth

pursuit gain, mainly ipsilaterally.4 Other PNare also probably involved in smooth pursuit.The lateral PN (LPN) have largely similarconnections to those of the DLPN, althoughthey appear to project more heavily to thefloccular region than the DLPN. 81' A lesionrestricted to the LPN in the monkey results insevere impairment of ipsilateral smooth pur-suit.25 Recent experimental data suggest thatthe dorsomedian PN (DMPN) are also prob-ably involved in smooth pursuit.226 TheDMPN receive unilateral afferences fromareas MT and MST, and bilateral afferencesfrom the FEF.21' They send efferences main-ly to the vermis, bilaterally, and also to thecontralateral flocculus.21315 Cells in thesenuclei discharge during smooth pursuit and,in the monkey, a lesion in this area impairssmooth pursuit.2 Lastly, the nucleus reticu-laris tegmenti pontis (NRTP), located at theanterior part of the upper pontine tegmentumand difficult to differentiate anatomicallyfrom the nearby DMPN, also appears to beinvolved in smooth pursuit.2 Cells in the ros-tral NRTP discharge during smooth pursuit,27and stimulation of the NRTP elicits slow eyemovements (even if the eyes are not alreadyperforming smooth pursuit),28 as does stimu-lation of the FEF.29 The NRTP receives affer-ences from the FEF30 and projects heavily tothe flocculus and also to the vermis.13 14Lastly, a lesion affecting the NRTP in themonkey results in smooth pursuit impair-ment." Therefore, two parallel pathwayscould control smooth pursuit between thecerebral cortex and the pons: the first couldoriginate in the temporoparietal cortex (areasMT and MST), and project mainly to theDLPN and LPN, whereas the second couldoriginate in the FEF and project mainly tothe NRTP and/or the DMPN. The specificroles of these two parallel pathways in smoothpursuit remain, however, to be determined.

Smooth pursuit impairment differedbetween our four patients. Ipsilateral smooth

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t _

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Figure 6 Horizontal eye movement recordings ofpatient 3. (A) Saccades, normal. (B)Smooth pursuit, mildly impaired. (C) OKN, mildly impaired (horizontal arrows indicatethe direction ofstimulation, and the vertical arrow a change in the direction ofstimulation). (D) VOR (a) under the first condition, normal; (b) under the secondcondition, normal. (E) VOR suppression, slighdy impaired bilaterally. e = eye, s =

stimulation, t = target.

pursuit was severely impaired in patient 1,moderately impaired in patient 2, and onlyslightly impaired in patients 3 and 4. Smoothpursuit asymmetry was also pronounced inpatient 1, less marked in patient 2, and veryslight in patients 3 and 4. At first, a differencein the age of the lesions may account for dif-ferent rates of recovery between the patients,especially for patient 2, recorded 5 monthsafter the stroke. However, the differencescould also result from the diverse locations ofthe lesions. Although the exact topography ofthe PN is unknown in humans, it is possibleto distinguish the two groups of PN in whichwe are interested-that is, the LPN-DLPN

group and the DMPN group. According toSchmahmann and Pandya,6 these two groupsare separated by another PN group, thepeduncular PN, intermingled with the corti-cospinal tract. Therefore, the DLPN-LPNgroup and the DMPN group lie respectivelylaterally and medially to a virtual anteroposte-rior line crossing the pons through the centralpart of the peduncular PN (see fig 2). Thus,it is reasonable to assume that lesions locatedlaterally or medially to this line involve eitherthe DLPN-LPN group or the DMPN group,respectively. According to these anatomicalcriteria, the DLPN and the LPN were proba-bly extensively damaged in patient 1 (giventhe large rostrocaudal extent of this lesion),slightly damaged in patient 2, and intact inpatients 3 and 4.

Conversely, the DMPN were partly dam-aged unilaterally in patients 3 and 4, andbilaterally in patient 2, but spared in patient1. From a comparison of patient 1 andpatient 2, it may be suggested that the exten-sive impairment of the DLPN and the LPNwas responsible for the severe impairment ofipsilateral smooth pursuit in patient 1.Moreover, a comparison of patients 3 and 4with patient 2 suggests that the more pro-nounced impairment of ipsilateral smoothpursuit in patient 2 could be the consequenceof the involvement of the DLPN in thispatient, the DMPN being partly damaged inall these three patients. Lastly, impairment ofhorizontal OKN and vertical smooth pursuitin particular in patients 1 and 2, were consis-tent with results of experimental DLPNlesions.25

Smooth pursuit impairment was less asym-metrical in patient 2 than in patient 1, partlybecause of a relatively more marked con-tralateral smooth pursuit deficit in the former,especially for high target velocities (29 and45°/s). Patients 3 and 4, with DMPN lesions,had, respectively, slight and no asymmetry insmooth pursuit (fig 7). Slight asymmetry aftera DMPN lesion may be due to the mediallocation of these nuclei. Since the two groupsare located on either side of the midline, andtheir efferences decussate through the basispontis before projecting to the cerebellum, asingle medial lesion may affect both nuclei (asin patient 2) and their efferences. It shouldalso be noted that these nuclei receive bilater-al afferences from the FEF. The severeimpairment of contralateral smooth pursuit inpatients 1 and 2 appears to contradict experi-mental studies in the monkey, in whichDLPN lesions result in only slight or noimpairment of contralateral smooth pursuit.25However, these chemically induced lesions,performed by excitotoxic agents, such asibotenic acid, selectively damage cell somabut spare fibres of passage-that is, efferencesfrom the contralateral pontine nuclei.Therefore, this could explain the differencebetween the results of experimental and clini-cal studies.Our findings in patient 1 are consistent

with the results of Thier et al.4 These authorsreported the first case of selective smooth

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Target

velocity

(°/s)

0

00-

0

8

0

C

0

Target

velocity

(°/s)

*

291 - * *

*225},

14.5i v

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4.0 5.0Index of asymmetry

0

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* Patient I

* Patient 2

O Patient 3

V Patient 41--4 0

Figure 7 Index ofasymmetry ofsmooth pursuit. Valuesfor each control group are plotted as horizontal bars displayingmean index ofasymmetry ±SD. Note that patient 1, with a DLPN and LPN lesion, had the most marked asymmetry,whereas patients 3 and 4, with DMPN lesions, had slight and no asymmetry, respectively.

pursuit impairment after a PN lesion.According to MRI, the lesion probablyinvolved the LPN-DLPN group. Saccadeswere normal but smooth pursuit was marked-ly impaired, bilaterally although mostly ipsi-laterally, resulting in a high level ofasymmetry. To our knowledge, no previoussmooth pursuit study has been reported in apatient with a medially located pontinelesion, considered to involve the DMPN.

Therefore, our results appear to confirmthe involvement of the DLPN and LPN insmooth pursuit control, and suggest that theDMPN could be involved in this eye move-ment as well, though with a minor role. Asfor the NRTP, its role in smooth pursuit inhumans remains to be determined, since thisstructure was probably spared, either totallyor largely, in our four patients.

VESTIBULO-OCULAR REFLEXSince the VOR of patient 1 was not tested incomplete darkness and was analysed onlyqualitatively, a slight abnormality of this eyemovement cannot be ruled out. VOR sup-pression was impaired bilaterally in thispatient but, unlike smooth pursuit, was sym-metrical. A similar discrepancy betweensmooth pursuit and VOR suppression resultswas also observed in the patient previouslyreported.4 It has been suggested that VORsuppression does not result only from addi-tional mechanisms between the VOR andsmooth pursuit.

In patient 2, rightward gain was about2-20, whereas leftward VOR gain was normal.Increased VOR gain is uncommon. Inhumans, bilateral hyperactive VOR has been

observed in cerebellar degeneration,"-'4 andin the monkey, hyperactive VOR has beenproduced by a reversible lesion affecting theolivofloccular tracts or the inferior olivarynucleus.35 The lesion of patient 2 did notappear to involve the flocculus, the olivarynucleus, or the flocculovestibular and olivo-cerebellar tracts, both passing through theinferior cerebellar peduncle. Therefore, theexplanation for such a unilateral hyperactiveVOR is unclear. It may be that damage to theafferences of the inferior olivary nucleus wasresponsible for this abnormality. VOR sup-pression was likewise impaired bilaterally inpatient 2, but predominantly for the right-ward hyperactive VOR. However, as theindex of asymmetry of the VOR under thesecond condition and VOR suppression wereanalogous, it may be suggested that asym-metry observed in VOR suppression wasmainly the consequence of VOR asymmetry.In patients 3 and 4, the VOR tested underboth conditions was normal. VOR suppres-sion was mildly impaired bilaterally, withoutasymmetry.

SACCADESPatient 2 had reduced velocity of all horizon-tal saccades. As no lesions were visible onMRI in the cerebral hemispheres or in themidbrain, it may be suggested that thisabnormality was due to the pontine lesion. Inthe monkey,25 as well as in the previouslyreported case4 or in our patient 1, DLPN orLPN lesions did not result in a decrease insaccade velocity. Moreover, a lesion in theDMPN area does not seem to reduce saccadevelocity, as shown by patients 3 and 4.

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Smooth pursuit eye movement deficits after pontine nuclei lesions in humans

Therefore, it may be assumed that thissaccade abnormality was due to the smallmedian tegmental extent of the lesion,probably involving the pontine paramedianreticular formation (PPRF). The lesion ofpatient 4 impinged also slightly in the pontinetegmentum, but to a lesser extent than that ofpatient 2. Therefore, the PPRF was probablyspared in this patient, with saccades of nor-mal velocity.

This work was supported by the Direction de la RechercheClinique (N 91.2215).

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