Journal of the neurological Sciences, 1975, 25:303 308

Elsevier Scientific Publishing Company, Amsterdam

Printed in The Netherlands

Internuclear Ophthalmoplegia in Progressive Supranuclear Palsy F. L. MASTAGLIA AND K. M. R. G R A I N G E R D(Tartau,nt of Medicine, University of" Western Australia and The Neurological Service, Sir Charles Gairdner Hospital, Perth Medical Centre, Shenton Park, Western Australia, 6008 (Australia)

(Received 16 December, 1974)


The syndrome of progressive supranuclear palsy (PSP) (the Steele-Richardson Olszewski syndrome) is characterised by progressive impairment of voluntary eye movements, mild dementia, a variable degree ofpseudobulbar palsy, marked dystonia of the axial musculature, impaired postural reflexes and a variable degree of pyramidal and extrapyramidal motor dysfunction (Steele, Richardson and Olszewski 1964). The disturbance of ocular motility which is the hallmark of the condition is manifested as a progressive slowing and interruption of and a progressive reduction in the range of conjugate eye movements, initially in the vertical plane and subsequently in the horizontal plane, ultimately leading to virtually complete ophthalmoplegia. Eye movements induced by the oculocephalic manoeuvre or by caloric stimulation of the labyrinths are characteristically preserved, even when saccadic and pursuit movements are severely affected (Hoyt and Daroff 1971). This dissociation between volitional-pursuit and vestibulogenic eye movements indicates the supranuclear nature of the ophthalmoplegia, which has been attributed to involvement of descending cortical ocular motor pathways in the zona incerta, subthalamus, mid-brain reticular formation and peri-aqueductal gray matter (Steele et al. 1964; David, Mackey and Smith 1968; Dix, Harrison and Lewis 1971; Hoyt and Daroff 1971). Neuropathological observations have indicated that in some cases there may also be a nuclear component in the ophthalmoplegia (Blumenthal and Miller 1969; Ishino, Higashi, Kuroda, Yabuki, Hayahara and Otsuki 1974). We wish to draw attention to the occurrence of internuclear ophthalmoplegia (INO) in addition to the accepted form of supranuclear gaze palsy in some patients with PS P. This abnormality of ocular movement has been present in 4 out of 13 cases of PSP studied by the authors over the past 4 years. CL1N1CALOBSERVATIONS Each of the 4 patients showed the characteristic slowly progressive impairment of


1.-. I,+ MASI'A(}LIA, K. M. R. G R A I N G E R


Impairment o[ Case

1 2 3 4

A.R. E.C. M.S. L.P.

A qe ( yr )

49 68 72 73



Duration o f illness when I N O detected

4yr 10yr 2yr 8yr


R/L L R/'L R/L

Loss o[ conver~Tence ~,

4 + 4 ++~ + + + +++

saccadic and pursuit eye movements b'c vertical


+ -t- + ++~ +. + ++++

4 ~~ ++ + + +. -t-


~- + + (D) ++ + + + ++(D)

a I n t e r n u c l e a r o p h t h a l m o p l e g i a ; l a t e r a l i s a t i o n a c c o r d i n g to side of i m p a i r e d a d d u c t i o n . u G r a d e d from 0 to + + + q-. c Degree o f i m p a i r m e n t at t i m e of detection of I N O . d O p t o k i n e t i c n y s t a g m u s : d e g r e e of i m p a i r m e n t g r a d e d f r o m 0 to + + + + , D = h o r i z o n t a l dissociation.


voluntary eye movements (Table 1) as well as other major features of the condition (Mastaglia, Grainger, Kee. Sadka and Lefroy 1973). Saccadic and pursuit movements were severely affected in each case and in Cases 2, 3 and 4 were replaced by abnormally slow saccadic movements, particularly in the horizontal plane. In Case 1 voluntary saccadic movements had been completely lost while pursuit movements were markedly slowed, but remained smooth and uninterrupted. Convergence and vertical eye movements were severely impaired in each case when first seen. and became progressively more limited with the passage o f time. In each case the eyes remained orthotropic in the primary position (Fig. I). The INO was left-sided in Case 2 and bilateral in the other cases and was manifest as a variable degree of lag (Case 2) or limitation o f movement (Cases l, 3 and 4) of the adducting eye on lateral gaze. It was most marked in Case 1 in which the failure of adduction was readily apparent during horizontal pursuit movements as well as during volitionally-initiated lateral eye movements (Fig. 2). The failure of adduction was less marked in the other cases but could be detected when lateral eye movements were performed at maximal possible speed, as during the rapid alternate fixation manoeuvre for detecting ocular dysmetria (Cogan 1954). In Case 1 an asymmetric jerk nystagmus which was more marked in the abducting eye was present on lateral gaze to either side. In Case 4 a few beats of nystagmus confined to the abducting eye were noted at times towards the end of its excursion on lateral gaze. A sustained coarse jerk nystagmus was present syrmnetricaUy in both eyes on horizontal gaze to either side in Case 2. In each case horizontal ocular deviations produced by the ocuIocephalic ("doll's head") manoeuvre were brisk and uninterrupted and were not dissociated (Figs. 1 and 2). The fast component of optokinetic nystagmus (OKN) was severely impaired in Cases 1 and 4. The slow following component was retained and also demonstrated the dissociation of ocular movements in the horizontal plane in these cases. O K N was less severely disorganised in the other cases but observations on the t N O were not made during O K N testing. Conventional caloric tests were performed in Cases



Fig. 1. Case 3. A: eyes in the primary position; lid retraction (Collier's sign) is also seen; B, C: different stages of pursuit movement to the right showing lag in movement of the left eye in B and failure of full adduction in C; D: pursuit movement to the left showing mild ocular dissociation; E, F: ocular movements remain conjugate during the oculocephalic manoeuvre.

1, 2 and 3. Induced nystagmus was markedly depressed bilaterally in Case 1, poorly sustained and disorganised in Case 2 and showed a directional preponderance to the right in Case 3. Conjugate tonic ocular deviations were recorded in Case 3 but similar observations were not recorded in the other cases. As horizontal eye movements have become progressively more limited the INO in Case I has no longer been detectable for the past 2 years and has been less apparent in Cases 2 and 4.


The observed pattern of dissociation of horizontal eye movements in the present cases is characteristic of an internuclear ophthatmoplegia and suggests involvement of the medial longitudinal fasciculus (MLF) at some point rostral to the sixth nerve nuclei. While a similar pattern could theoretically result from a partial lesion of the oculomotor nuclei, the preservation of conjugate ocular deviations with vestibular stimulation makes this unlikely. In view of the associated impairment of convergence, the INO in these cases could be regarded as being of the anterior variety which, when due to a localised pathological process, is usually held to be indicative of a disturbance at mid-brain level (Smith and Cogan 1959; Cogan 1966). With a more diffuse pathological process such as that in


1;. L. MASTAGLIA, K. M. R. G R A ! N G E R

Fig. 2. Case 1. A : pursuit m o v e m e n t to the right showing impaired adduction of the left eye, B : pursuit m o v e m e n t to the left showing impaired adduction of the right eye : C : ocular m o v e m e n t s to the right remain conjugate during the oculocephalic manoeuvre.



PSP, the MLF and the corticofugal pathways concerned with vergence could well be involved at different levels, the former in the upper pons or mid-brain, the latter in the upper mid-brain or even more rostrally in the subthalamic region. INO has not previously been described in PSP. Pfaffenbach, Layton and Kearns (1972) commented on the presence of nystagmus or nystagmoid movements of the abducting eye during lateral gaze in 14 of their 44 cases but did not find other evidence of INO in those cases. Little information is available on the state of the M L F in cases of PSP which have been studied pathologically. Steele (1972)commented on loss of myelinated fibres from the MLF in some cases, but did not feel that this was a primary change. Pathological data are not yet available in any of the present cases. In 1 of our other cases which did not display INO during life the M L F was found to be normal at necropsy. In view of the extensive involvement of the upper brain-stem tegmentum in PSP (Steele et al. 1964; David et al. 1968; Behrman, Carroll, Janota and Matthews 1969 ; Steele 1972), it is perhaps not too surprising that the M L F should be involved in the multisystem degenerative process in some cases of this condition. Preservation of conjugate horizontal eye movements in response to vestibular stimulation is not usual in the INO which results from focal brain-stem lesions in man (Hoyt and Daroff 1971 ) or from focal experimental lesions of the M L F in monkeys (Shanzer 1964: Cohen 1971). This discrepancy between volitional-pursuit and reflex eye movements in the present cases is difficult to account for if, as is usually assumed, the M L F represents the final common pathway for all categories of conjugate horizontal eye movements. One possible explanation is that the involvement of the M L F is relatively mild and is more likely to be manifest during activation through a descending corticofugal pathway which is itself already severely affected at a more rostral level than during activation through relatively less affected vestibular pathways. An alternative explanation is that there are in fact separate pathways subserving volitionalpursuit and vestibulogenic eye movements in the MLF, and that these are differentially affected. The existence of extra-vestibular projections subserving cortically-initiated eye movements in the M L F has been postulated previously (Cohen 1971) bul has yet to be verified anatomically. It might be anticipated that such a differential involvement of fibres in the M L F would be more likely to occur in a degenerative condition such as PSP than in demyelinating, vascular or other focal destructive pathological processes.


The authors express their gratitude to Professor W. I. McDonald, Dr. J. D. Hood and Dr. M. R. Dix of the Institute of Neurology, Queen Square, for reviewing the manuscript and providing constructive suggestions and to Professor R. Lefroy for allowing them to examine Case 4. They are also grateful to Mr. R. Plummer of the Medical Illustrations Department of the Perth Medical Centre and to Mrs. Kay Cross for secretarial assistance.



Internuclear ophthalmoplegia has not previously been described in progressive supranuclear palsy. The present report draws attention to the occurrence of varying degrees of anterior internuclear ophthalmoplegia in 4 out of 13 cases of this condition studied over a 4-yr period. This finding suggests that the medial longitudinal fasciculus may be involved in the degenerative process in some cases of progressive supranuclear palsy.

REFERENCES BEHRMAN, S., J. D. CARROLL. I. JANOTA AND W. B. MATTHEWS (1969) Progressive supranuclear palsy Clinico-pathological study of four cases. Brain. 92 : 663-678. BLUMENTHAL, H. AND C. MILLER {19691 M o t o r nuclear involvement in progressive supranuclear palsy. Arch. Neurol. (Chic.), 20: 362-367. COGAN, D. G. (1954) Ocular dysmetria, flutter-like oscillations of the eyes and opsoclonus. 4rch. Ophthal • 51:318. CO(;AN, D. G. (1966) Neurolmfy ot the Ocular Muscles. Thomas. Springfield, Ill.. pp. ~4 91 COHEN, B. (1971) Vestibulo-ocular relations. In: P. BACH-Y-RITA. C. C. COLLINS AND I. |" HYDE (Eds. l. The Control o f Eve Movements, Academic Press. New York. London. pp. 105 148 DAVID, N. J., E. A. MACKEV AND J. L. SMITH [19681 Further observations in progressive supranuclear palsy, Neurolooy (Minneap. j, 18 : 349 356. Dtx, M. R., M. J. G. HARRISON AND P. D. LEWIS 11971) Progressive supranuclear palsy IThe Steele Richardson-Olszewski syndrome) -- A report of 9 cases with particular reference to the mechanism of the oculomotor disorder, J. neurol. Set.. 13 237-256. HOYT, W, F, AND R. B. DAROVV [1971) Supranuclear disorders of ocular control systems In: P. BACH-VRITA, C. C. COLLINS AND J. E. HYDE {Eds.~, The ControlofEve Movements. Academic Press, New York London, pp. 175--235. ISHtNO, H., H. HIGASHt, S. KURODA. S. YABUKI. T. HAVAHARa AND S. O~UKI {t974 i M o t o r nuclear involvement in progressive supranuclear palsy, J. neurol. Set., 22: 235-244. MaSTAGLtA, F. L., K. GRAINGER. F. KEE. M. SADr,A AND R. LEFROV (1973] Progressive suprzmuclear pals) (The Steele-Richardson-Olszewski syndromel Clinical and electrophysiological observations in I1 cases, Proc. Aust. Ass. Neurol. 10: 35~-4. PFAFFENBACH, D. D., O. O. LAYTON AND T. P. KEARNS t 1972) Ocular manifestations in progressive supranuclear palsy, Amer. J. Ophthal.. 74:1179-1184. SHANZER, S. (1964) Effects of semicircular canal stimulation in monkeys with lesions of the median longitudinal fasciculus, Fed. Proc. 2 3 : 4 1 4 (Abstr. 18771 SMITH, J. L. AND D. G. COGAN [1959} Internuclear ophthalmoplegia A review of 58 cases. Arch. Ophthal.. 61 : 6 8 7 ~ 9 4 . STEELE, J. C. (1972) Progressive supranuclear palsy, Brain. 95: 693-704. STEELE, J. C., J. C. RICHARDSON AND J. OLSZEWSKI (19641 Progressive supranuclear palsy..4rch. Neurol (Chic.), 10: 333-359.

Internuclear ophthalmoplegia in progressive supranuclear palsy.

Internuclear ophthalmoplegia has not previously been described in progressive supranuclear palsy. The present report draws attention to the occurrence...
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