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Fax +41 61 306 12 34 E-Mail [email protected] www.karger.com Original Paper Eur Neurol 2005;54:186–190 DOI: 10.1159/000090295 Upbeat Nystagmus due to a Small Pontine Lesion: Evidence for the Existence of a Crossing Ventral Tegmental Tract C. Pierrot-Deseilligny a D. Milea b J. Sirmai c C. Papeix a S. Rivaud-Péchoux a a INSERM 679 et Service de Neurologie 1 et b Service d’Ophtalmologie, Hôpital de la Salpêtrière, AP-HP, Paris, et c Service de Médecine Interne, Hôpital de Lagny, Lagny, France ‘Primary-position’ upbeat nystagmus (UBN) exists not only in the primary position of gaze, but also in the other positions [1]. Such nystagmus should be distin- guished from the more common gaze-evoked nystagmus observed only in upgaze. The pathophysiology of UBN is incompletely understood. Its causes are diverse, compris- ing intoxications, diffuse damage to the brainstem and/or cerebellum (e.g. encephalitis, degenerative diseases) and also focal brainstem lesions [1]. Lesions of the latter cat- egory are relatively rare with about 30 cases reported so far [2]. Among them, two main brainstem locations pre- dominate, namely the caudal medulla and the upper pons. In the pons, the lesions were large and bilateral [3–5], resulting in a coarse UBN of about 10° amplitude in the primary position [5]. It has been hypothesized that these pontine lesions interrupt the excitatory ‘crossing ventral tegmental tract’ (CVTT) connecting the superior vestibular nucleus, involved in the transmission of ante- rior canal inputs, to the superior rectus and inferior oblique motoneurons in the third nerve nucleus [6]. We report a case of UBN resulting from a small unilateral pontine lesion, which supports the above hypothesis and improves our knowledge of the brainstem upward ves- tibular pathways. Some preliminary data of this case ap- peared in two recently published general reviews [2, 7] . Key Words Upbeat nystagmus Vertical nystagmus Ventral tegmental tract Vestibulo-ocular reflex Abstract We report a patient with an isolated large upbeat nystag- mus (UBN) in the primary position of gaze. Eye move- ments were filmed and recorded using electro-oculogra- phy. The upward vestibulo-ocular reflex gain, evaluated by pitching the head forward, was markedly reduced compared to when pitching the head back. The lesion was a probable lacunar infarction located in the parame- dian and posterior part of the basis pontis, at the upper pons level. This UBN case, with one of the smallest brain- stem lesions reported so far, supports the existence in humans of the crossing ventral tegmental tract, de- scribed in the cat and transmitting excitatory upward vestibular signals to the third nerve nucleus. It is also suggested that the decussation of this tract lies at the same upper pons level as in the cat but in a slightly more ventral location, i.e. in the posterior basis pontis. Copyright © 2005 S. Karger AG, Basel Received: July 14, 2005 Accepted: October 19, 2005 Published online: December 13, 2005 Prof. C. Pierrot-Deseilligny Service de Neurologie 1, Hôpital de la Salpêtrière 47, boulevard de l’Hôpital FR–75651 Paris Cedex 13 (France) Tel. +33 1 4216 1828, Fax +33 1 4424 5247, E-Mail [email protected] © 2005 S. Karger AG, Basel 0014–3022/05/0544–0186$22.00/0 Accessible online at: www.karger.com/ene

Upbeat Nystagmus due to a Small Pontine Lesion: Evidence for the Existence of a Crossing Ventral Tegmental Tract

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Page 1: Upbeat Nystagmus due to a Small Pontine Lesion: Evidence for the Existence of a Crossing Ventral Tegmental Tract

Fax +41 61 306 12 34E-Mail [email protected]

Original Paper

Eur Neurol 2005;54:186–190 DOI: 10.1159/000090295

Upbeat Nystagmus due to a Small Pontine Lesion: Evidence for the Existence of a Crossing Ventral Tegmental Tract

C. Pierrot-Deseilligny

a D. Milea

b J. Sirmai

c C. Papeix

a S. Rivaud-Péchoux

a

a INSERM 679 et Service de Neurologie 1 et b

Service d’Ophtalmologie, Hôpital de la Salpêtrière, AP-HP, Paris , et c

Service de Médecine Interne, Hôpital de Lagny, Lagny , France

‘Primary-position’ upbeat nystagmus (UBN) exists not only in the primary position of gaze, but also in the other positions [1] . Such nystagmus should be distin-guished from the more common gaze-evoked nystagmus observed only in upgaze. The pathophysiology of UBN is incompletely understood. Its causes are diverse, compris-ing intoxications, diffuse damage to the brainstem and/or cerebellum (e.g. encephalitis, degenerative diseases) and also focal brainstem lesions [1] . Lesions of the latter cat-egory are relatively rare with about 30 cases reported so far [2] . Among them, two main brainstem locations pre-dominate, namely the caudal medulla and the upper pons. In the pons, the lesions were large and bilateral [3–5] , resulting in a coarse UBN of about 10° amplitude in the primary position [5] . It has been hypothesized that these pontine lesions interrupt the excitatory ‘crossing ventral tegmental tract’ (CVTT) connecting the superior vestibular nucleus, involved in the transmission of ante-rior canal inputs, to the superior rectus and inferior oblique motoneurons in the third nerve nucleus [6] . We report a case of UBN resulting from a small unilateral pontine lesion, which supports the above hypothesis and improves our knowledge of the brainstem upward ves-tibular pathways. Some preliminary data of this case ap-peared in two recently published general reviews [2, 7] .

Key Words Upbeat nystagmus � Vertical nystagmus � Ventral tegmental tract � Vestibulo-ocular refl ex

Abstract We report a patient with an isolated large upbeat nystag-mus (UBN) in the primary position of gaze. Eye move-ments were fi lmed and recorded using electro-oculogra-phy. The upward vestibulo-ocular refl ex gain, evaluated by pitching the head forward, was markedly reduced compared to when pitching the head back. The lesion was a probable lacunar infarction located in the parame-dian and posterior part of the basis pontis, at the upper pons level. This UBN case, with one of the smallest brain-stem lesions reported so far, supports the existence in humans of the crossing ventral tegmental tract, de-scribed in the cat and transmitting excitatory upward vestibular signals to the third nerve nucleus. It is also suggested that the decussation of this tract lies at the same upper pons level as in the cat but in a slightly more ventral location, i.e. in the posterior basis pontis.

Copyright © 2005 S. Karger AG, Basel

Received: July 14, 2005 Accepted: October 19, 2005 Published online: December 13, 2005

Prof. C. Pierrot-DeseillignyService de Neurologie 1, Hôpital de la Salpêtrière47, boulevard de l’HôpitalFR–75651 Paris Cedex 13 (France)Tel. +33 1 4216 1828, Fax +33 1 4424 5247, E-Mail [email protected]

© 2005 S. Karger AG, Basel0014–3022/05/0544–0186$22.00/0

Accessible online at:www.karger.com/ene

Page 2: Upbeat Nystagmus due to a Small Pontine Lesion: Evidence for the Existence of a Crossing Ventral Tegmental Tract

Upbeat Nystagmus Eur Neurol 2005;54:186–190 187

Case Report

A 47-year-old man, without any history of neurological or vas-cular disturbances, suddenly experienced marked oscillopsia asso-ciated with gait disturbances. Six days later, his gait had improved and was almost normal, but oscillopsia persisted. Neurological ex-amination performed at that time revealed an isolated large UBN. A video recording was made and eye movements were recorded using direct-current electro-oculography in the light. Although elec-tro-oculography is not the best technique for recording vertical eye movements, in particular for a precise quantifi cation, it may nev-ertheless be considered informative when there are marked abnor-malities as in the present case. In the primary position of gaze, the UBN had a mean frequency of 2.9 Hz, a mean amplitude (eye po-sition) of 10° and a mean slow phase velocity of 39°/s ( fi g. 1 ). The UBN was also studied in the four cardinal positions, at about 25° eccentricity. In upgaze, the mean amplitude of UBN was increased (17°), with a mean frequency of 1.7 Hz and a mean slow phase ve-locity of 30°/s ( fi g. 1 ). The amplitude was decreased in downgaze (9°), in right gaze (7°) and in left gaze (4°). It should be noted that the UBN was markedly attenuated when the eyes were fi xating in the extreme upgaze (i.e. in the upper part of the orbits, at about 45° eccentricity): in this extreme position, the nystagmus unexpectedly even disappeared intermittently for 1 or 2 s and reappeared with a small amplitude (not exceeding a few degrees). In the extreme downgaze (i.e. at about 45°), the nystagmus was analogous to that observed in the intermediate down position (i.e. at 25°) and did not disappear, even when the patient attempted to block his eyes against the lower part of the orbits. Furthermore, the nystagmus had an obvious torsional component in right gaze (with a clockwise direc-tion of the quick phase, from the point of view of the patient) and left gaze (with a counterclockwise direction of the quick phase), without apparent torsion in the primary position, in downgaze or in upgaze. Occasionally, the slow phase had an exponentially de-

creasing-velocity waveform ( fi g. 1 ). During convergence (only fi lmed), which was preserved, the nystagmus appeared to be at-tenuated compared to that existing in the primary position. Given the extent of the spontaneous vertical nystagmus, it was impossible to analyze horizontal and vertical smooth pursuit, and the optoki-netic nystagmus was not tested. However, the vertical oculocephal-ic refl ex (OCR), which is a good refl ection of the vestibulo-ocular refl ex (VOR), could be studied, but only at a relatively high head velocity. The OCR was tested in the light. The subject was instruct-ed to look at a stationary target located straight ahead at a distance of 1 m, while the examiner moved the subject’s head with his hands. This was a pseudo-sinusoidal stimulation of 0.66 Hz with an am-plitude of 8 30° around the erect position of the head, displaced in the pitch plane, resulting in a peak head velocity of 160°/s. Such relatively high head velocities are recommended to detect asym-metries in pathological vestibular eye movement mechanisms [1] . Furthermore, with such a peak head velocity, the UBN was no lon-ger visible in our patient during the OCR, at least in the zone of evaluation of the peak eye velocity (i.e. close to the midline). A quantifi cation of the OCR velocity gain (peak eye velocity over peak head velocity) was thus performed: the results were 0.48 for the upward eye movement (pitching the head forward) and 0.94 for the downward eye movement (pitching the head back). Therefore, the upward eye movement gain was almost half that of the down-ward eye movement, despite the measuring method being the same for both vertical directions. Horizontal and vertical saccades were normal. General examination was normal.

A CT scan performed 2 days after the onset showed a lacunar lesion (not enhanced by the contrast medium) located in the left paramedian part of the upper pons. Ten days later, the lesion was confi rmed by magnetic resonance imaging (MRI; 1.5 T), which showed a small pontine lesion, with a hypointense signal in T 1 -weighted imaging (not enhanced by the contrast medium) and a hyperintense signal in the T 2 -weighted image ( fi g. 2 ). The rest of

Fig. 1. Upbeat nystagmus. D = Down; M = midline; U = up.

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Eur Neurol 2005;54:186–190 188

the brain and in particular the cerebellum, midbrain and medulla were normal. The lesion, which was probably vascular, was unilat-eral and located in the left paramedian part of the upper pons, be-ing visible on only one horizontal section (5 mm thick) passing 7 mm above the midpons level. In the anteroposterior axis, the le-sion was located in the posterior part of the basis pontis, appar-ently not reaching the ventral limit of the tegmentum. The fi nal clinical diagnosis was a probable lacunar infarction, without known mechanism. The UBN progressively improved and disappeared after 3 months.

Discussion

This patient had a probable lacunar infarction in the pons which, to the best of our knowledge, appears to be the smallest focal pontine lesion reported so far with a (primary-position) UBN. Indeed, the previously reported cases of pontine lesions with UBN involved extensive bi-lateral damage to the ventral tegmentum and the poste-rior part of the basis pontis [3–5] . Thus, the location of this lesion would appear to support the hypothesis that the CVTT, transmitting upward vestibular signals to the third nucleus, also exists in humans [6] . The medial longitudinal fasciculus (MLF) and the brachium conjunctivum (BC), which are also involved in upward slow eye movement transmission [1, 2] , were not affected here since they are located in the paramedian and lateral parts, respectively, of the posterior pontine tegmentum, and thus at a distance from the lesion. Furthermore, adduction of both eyes was

normal in our patient, thus ruling out the existence of an associated internuclear ophthalmoplegia. We will fi rst dis-cuss the course of the CVTT and its physiological role, and then briefl y review the other pathways involved in upward vestibular eye movements.

Course of the CVTT The CVTT has been described in the cat [8–10] and

probably also exists in the monkey [11] . This tract orig-inates in the superior vestibular nucleus, with an initial rostral course passing laterally and ventrally to the BC in the lateral tegmentum of the lower pons, arching a fi rst time at the midpons level, then coursing almost hor-izontally towards the midline near the limit between the tegmentum and the basis pontis, crossing the midline close to the upper part of the nucleus reticularis tegmen-ti pontis, slightly above the midpons level ( fi g. 3 ). After decussation, the tract arches a second time and contin-

Fig. 2. T 2 -weighted MRI: note the lesion (arrow) in the left para-median part of the pons, 7 mm above the midpons level, affecting the posterior part of the basis pontis. L = Left.

Lowerpons

MVN

Medulla

SVN

Upperpons

Midbrain

CVTT CVTTMLF

Lesion

Midpons

SR SR

III

M

Fig. 3. Excitatory upward vestibular tracts. Only the excitatory up-ward vestibular tracts are shown (brachium conjunctivum and in-ferior oblique motoneurons not shown). Note how a small unilat-eral paramedian lesion located just above the midpons level may involve both CVTTs, at the point where they decussate. CVTT = Crossing ventral tegmental tract; MLF = medial longitudinal fas-ciculus; M = midline; MVN = medial vestibular nucleus; SVN = superior vestibular nucleus; SR = superior rectus; III = third nerve nucleus.

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Upbeat Nystagmus Eur Neurol 2005;54:186–190 189

ues with a rostral course through the upper pons, near the medial part of the medial lemniscus in the parame-dian ventral tegmentum. It arches a third time in the midbrain tegmentum near the inferior pole of the red nucleus, with a fi nal medial and slightly caudal course towards the inferior pole of the third nucleus, before reaching in this nucleus the superior rectus and inferior oblique motoneurons, probably on both sides [10] . In our patient, the lesion was located slightly above the midpons level, very close to the midline, in the poste-rior part of the left basis pontis, not reaching the ante-rior limit of the tegmentum. This location of the lesion raises two points. First, it cannot be ruled out that a more dorsal extension of the lesion, not visible on MRI, ex-isted in our patient and in fact reached the ventral teg-mentum. However, this appears to be unlikely since MRI was performed 10 days after the onset, namely at a time when this probably vascular lesion was no longer evolving. Moreover, the limits of the lesion were clearly apparent. Therefore, it may also be that the course of the human CVTT, which is not known so far, passes slight-ly more ventrally than that of the cat, i.e. not in the ven-tral tegmentum but in the posterior basis pontis, at least just above the midpons level. Such a location at this spe-cifi c level does not preclude the possibility that the fur-ther course of the tract in the upper pons may be in the ventral tegmentum. Second, given that each CVTT is supposed to project to both third nuclei, it seems surpris-ing that this small unilateral pontine lesion resulted in such a coarse UBN, similar to that observed after large bilateral pontine lesions. It may be that the lesion in our patient was in fact located at the crossing level, thus af-fecting both CVTTs, i.e. just before and just after the decussation of each tract ( fi g. 3 ). In support of this hy-pothesis, it should be noted that the lesion was located slightly above the midpons level, which is precisely the decussation level described in the cat.

Nevertheless, the unilateral feature of our patient’s le-sion was well detected in lateral gaze since the UBN am-plitude was twice greater in right gaze than in left gaze and a clear torsional component existed in both directions of lateral gaze. While there is no obvious explanation for the fi rst fact, a torsional component is usual after unilateral vestibular damage [1] . Its opposite direction in right and left gaze (clockwise and counterclockwise, respectively, for the quick phases and from the point of view of the pa-tient) also supports the fact that both CVTTs were dam-aged and may explain why in the primary position (as well as in upgaze and downgaze) the torsional defi cit was bal-anced, with therefore no apparent torsion.

Role of the CVTT The upward VOR gain, in UBN in general, is known

to be decreased compared to the downward gain [12] . However, the vertical VOR gain has never previously been quantifi ed in cases of focal brainstem (pontine or caudal medullary) lesions with UBN [2] . In our patient, we are aware that we did not perform a perfect evaluation of the vertical ‘VOR’, but some points should be empha-sized in order to place this relative approximation in con-text. First, the VOR part in the OCR is largely predomi-nant [1] . Second, even though the pitch plane we used is not exactly that where a pure activity of the anterior and posterior canals may be tested [13] , the results of the up-ward and downward vestibular eye movements evaluated in this pitch plane are nevertheless a good refl ection of the activities of these canals [1] . Third, given that we tested the OCR using a relatively high peak velocity of the head, the measurement of peak eye velocity (required for the calculation of the gain) was reliable, since, at this head velocity, there was no longer any visible UBN in the zone of evaluation of the peak eye velocity, at least for upward eye movements (i.e. with no additional down-ward eye drift at this time of measurement). Fourth, it should especially be noted that the approximation in the determination of the velocity gain existed here for the two vertical vestibular eye movements and that a marked asymmetry was observed in the velocity of these move-ments, since the gain of the upward eye movement (0.48) was almost half that of the downward eye movement (0.94). It is therefore reasonable to assume, in particular with such asymmetry, that in our patient the upward eye movement gain was reduced compared to the downward gain. Thus, the existence of UBN after a putative CVTT lesion fi rst suggests that this tract transmits some upward eye position signals to the oculomotor nuclei. The concur-rent marked reduction in the velocity gain of the upward eye movement elicited by the OCR supports the hypoth-esis of a transmission of a part of the upward vestibular eye velocity signals through the CVTT in humans. In fact, this double role of the CVTT in the transmission of both eye position and vestibular eye velocity signals could be expected from a tract which belongs to the fi nal part of the central vestibulo-oculomotor connections [9] . Over-all, in our patient and probably in other cases of UBN due to pontine lesions, the nystagmus could be the result of a simple imbalance in the central vestibular connections between the two vertical systems, as previously hypoth-esized [12] : the CVTT failure would result in a relative hypoactivity in the fi nal upward vestibular pathways, compared to the undamaged downward system, with con-

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Eur Neurol 2005;54:186–190 190

sequently a continuous downward slow phase interrupted by upward quick phases, the latter being generated by the saccadic system to recenter the eyes.

From a theoretical point of view, the intermittent ex-ponential aspect of the nystagmus slow phase observed in our patient suggests an impairment of the neural integra-tor involved in gaze-holding. However, a similar aspect may also be observed in association with damage to cen-tral vestibular pathways, which also belong to the gaze-holding network [1] . Therefore, an exponential character-istic may exist after a CVTT lesion, but we do not know why this only occurred intermittently in our patient. Fi-nally, the marked attenuation of UBN and its intermit-tent disappearance in the extreme upgaze suggest that the main parts of the vertical gaze-holding integrator were not damaged in our patient and that pathways other than the CVTT contributed to this eye position being largely maintained (see next section).

Other Pathways Involved in Upward Vestibular Eye Movements It should be noted that the MLF is probably and the

BC possibly also involved in the transmission of upward excitatory vestibular signals [1, 2, 14] . However, what-ever the actual role of the BC, it would appear that up-ward vestibular signal transmission depends on both the MLF and the CVTT, whereas downward vestibular signal transmission appears to depend only upon the MLF [2] . This obvious asymmetry in central vestibular connec-tions between the two vertical directions has already been noted [1, 2] . The existence of several tracts involved in upward vestibular signal transmission could explain, in

our patient with an isolated (probably bilateral) CVTT impairment, why the velocity gain of the upward vestib-ular eye movements was not zero, being approximately half of the ideal gain (i.e. 1), and, furthermore, why a relative fi xation of the eyes could be observed in extreme upgaze. This may also explain in our case and in another pontine case [4] why UBN improved and eventually dis-appeared after a few months. An adaptive mechanism involving the undamaged tracts (MLF and/or BC) could have occurred, even though a simple restoration of the initially damaged CVTT axons cannot be ruled out in our case. Lastly, besides UBN due to pontine lesions damag-ing the CVTT, an analogous nystagmus may also result from caudal medullary lesions, but the mechanisms of this nystagmus appear to be different [2] . Further studies will be needed to determine precisely how the diverse eye movement mechanisms (eye position and eye velocity transmission) are shared by the different tracts involved in upward vestibular eye movements, and how adapta-tion occurs between these tracts in the event of one of them being damaged.

Conclusions

This unique case of UBN with a small pontine lesion suggests (1) that the human CVTT passes – at least just above the midpons level – through the paramedian and posterior part of the basis pontis, (2) that this tract decus-sates as in the cat at the upper pons level and (3) that it transmits to the third nucleus both upward eye position and eye velocity vestibular signals.

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