Journal ofNeurology, Neurosurgery, and Psychiatry 1990;53:67-71 67 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.53.1.67 on 1 January 1990. Downloaded from Vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)

J Bogousslavsky, J Miklossy, F Regli, R Janzer

Abstract Case report We report a clinico-pathological correla- A 60 year old housewife who was a smoker had tion study in a patient with basilar artery been investigated for ten years for arterial thrombosis, who developed tetraplegia hypertension, diabetes mellitus and elevated and combined up- and downgaze palsy blood cholesterol. Three weeks before admis- involving voluntary saccades and sion, she experienced transient dysarthria and visually-guided movements, but sparing dizziness and the day before had been unable to the oculocephalic responses. At necropsy, stand and experienced tingling in the left hand. apart from bilateral infarction in the One day later, she suffered acute rotatory basis pontis, there was a single unilateral vertigo with vomiting, diplopia, dysarthria, infarct selectively destroying the rostral and left-sided weakness and numbness. On interstitial nucleus of the medial longi- admission, the patient was well-oriented in tudinal fasciculus (riMLF) on the right. time and place but had severe dysarthria. Blood The posterior commissure and its pressure was 140/85 mm Hg. The visual fields nucleus, the nucleus of Cajal, the nucleus were normal. Eye movements were normal. of Darkschewitsch and the pontine The pupils could not be assessed, because of were spared. We suggest that previous cataract operations. She had a slight the unilateral riMLF lesion may have lower facial paresis on the left. The remainder disrupted bilateral upgaze excitatory and of the cranial nerves were normal. She had inhibitory inputs and unilateral down- a moderate left hemiparesis with decreased gaze excitatory inputs. The functional sensation for temperature and pain. The of inhibitory and excitatory upper limb showed dysmetria and dysdiado- vertical gaze circuitry, which remains chokinesia. Over 24 hours after admission, the speculative, may explain why a unilateral patient progressively worsened and developed lesion of the upper tegmentum a complete left hemiplegia, despite intravenous may be sufficient to generate an upgaze heparin therapy (30 000 Iu/24 h). Progressive palsy or a combined up- and downgaze weakness then developed on the right, and four palsy, while an isolated downgaze palsy days later she had a spastic tetraplegia with requires bilateral lesions. facial diplegia and severe lower cranial nerve

palsy. The clinical picture showed a typical http://jnnp.bmj.com/ for the horizontal is well known that vertical gaze palsy is locked-in syndrome, except It when related to mesencephalic dysfunction.'2 More eye movements which were unimpaired tested for voluntary and pursuit gaze. The recently, the critical area for the genesis of up- and downward saccades in the monkey and in patient could open and close her eyes on has been found to be located dorso- command, but there was a complete vertical humans and move- medial to the anterior pole ofthe , in gaze palsy for voluntary pursuit ments. Bedside vertical optokinetic testing an area now called the rostral interstitial on September 27, 2021 by guest. Protected copyright. nucleus of the medial longitudinal fasciculus with a drum showed no response, but the manoeuvre elicited a full Other upper midbrain structures vertical oculocephalic (riMLF)34. and downward response. This state implicated in vertical gaze include the posterior upward commissure, the interstitial nucleus of Cajal remained unchanged for four months. The the nucleus of Darkschewitsch.5 Classic- patient then developed palpebral ptosis and and adduction weakness in the right eye. It became ally, upgaze palsy has been related to uni- or more difficult to communicate with the patient bilateral upper midbrain lesions, while a Department of bilateral lesion is required to give rise to using her preserved eye movements. At the Neurology* and downgaze palsy.56 However, the respective role same time, the tetraplegia became flaccid, the Division of nucleus patient developed purposeless chewing Neuropathologyt of the riMLF, posterior commissure, 30 Centre nucleus of Darkschewitsch, and movements, and her weight dropped by kg. Hospitalier of Cajal, months after admission. Universitaire Vaudois, related structures has remain difficult to assess She died six Lausanne, Switzerland in in the absence of case reports with J Bogousslavsky* humans, J Miklossyt selective involvement of one or the other of Laboratory investigations F Regli* these structures. CT was checked three times and showed R Janzert Our report of a patient with combined up- a right occipital, left lenticular and right pon- Correspondence to: in association with an tine infarcts. Bilateral vertebral digital arterial Dr Bogousslavsky, and downgaze palsy Department of Neurology, upper midbrain infarct limited to the riMLF angiography ten days after admission showed CHUV, 1011 Lausanne, in progresive stenosis of the basilar artery from Switzerland. on the right side may provide further insight of vertical the last part of the middle third, with occlusion Received 24 February 1989. the understanding of the control Accepted 6 July 1989 gaze. of the distal third. auditory evoked 68 Bogousslavsky, Miklossy, Regli, Janzer J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.53.1.67 on 1 January 1990. Downloaded from Figure 1 Paraffin sections stainedfor myelin (Loyez), through the pons ...... :." atfour different levels (A: ..6 mesencephalic-pontine `.k1. junction; B: upper pons; C and D: midpons), showing the extent of the bilateral cystic infarction. Al, Bl, Cl and Dl are schematic representations of the lesion at the same levels.

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potentials showed no abnormality when per- weeks. After macroscopical examination, the formed three and four months after admission. brain was cut in 8 mm coronal slices. Blocks ECG and standard blood tests were normal. were taken from the left striatum, the left occipito-temporal, the right occipital region Neuropathologicalfindings and from the cerebellum. Ten pm paraffine The brain was fixed in 10%/ formalin for three sections were stained with hematoxyline- Vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinalfasciculus (riMLF) 69 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.53.1.67 on 1 January 1990. Downloaded from superior part of the were .s .- RiM'vLF.- stained alternatively with hematoxyline-eosine and Loyez stains. Forty gm frozen serial sec- tions from blocks of the thalamus and upper midbrain on both sides were stained with Oil red 0 and Sudan black. The brain weighed 1290 g. There was no sign of oedema or atrophy. The circle of Willis Nk showed severe atherosclerosis. The middle third of the basilar artery was totally occluded by an organised, recanalised thrombus which extended into the rostral segment of the artery. In the examination ofthe cerebral hemispheres there was revealed a small old cystic infarct (1-5 cm diameter) in the deep territory of the the R,N } left middle cerebral artery destroying supero-lateral part of the striatum and involv- ing the anterior-superior part of the internal capsule, and an old infarct in the territory ofthe right posterior cerebral artery destroying the posterior part of the lingual and fusiform gyri. The most important lesion was an infarct in the territory of the basilar artery, the appearance ofwhich corresponded to the dura- tion ofthe clinical history. The infarct involved ..< 7\\k large parts of the ventral pons, but the tegmen- tum of the pons was completely spared (fig 1). The medial longitudinal fasciculus, the trochlear and abducens nuclei and their fibres, as well as the paramedian pontine (PPRF) were intact on both sides. The caudal pons, medulla oblongata and cerebellum did not show any foci of infarction. At the meso-diencephalic junction, there was an infarct at the level of the central mesen- cephalic grey, and the right rostral interstitial nucleus of the mnedial longitudinal fasciculus (riMLF) was damaged (fig 2). The nucleus of Darkschewitsch, the interstitial nucleus of Cajal, the nucleus and fibres of the posterior commissure as well as the nuclei ofthe pretectal

region were completely spared. On the left side, http://jnnp.bmj.com/ the mesencephalic tegmentum was entirely spared. A more recent minute focus of infarct was

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.. . . on September 27, 2021 by guest. Protected copyright. A~~~~~~~~~~~~~~~~~~~~~~~~g.j~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~...... S Discussion Our patient had a severe infarct of the ventral pons due to basilar artery thrombosis. The

W*Me1 was completely spared, which explained the normal horizontal eye movements. On the other hand, a small focus of Figure 2 a: Coronal section of the upper midbrain at the level of the posterior the the spared left riMLF (dashed line). infarction was found in the mid-brain tegmen- commissure and demonstrating localisation of involved the Nissl stain. Magnification: 30 x . b: Same section on the right side, showing the riMLF tum on the right, which selectively entirely destroyed by the infarct. Arrows point to the inferior limit of the lesion. Same riMLF, and corresponded to the vertical gaze staining and magnifications as A. c: Coronal section adjacent to B, stained with Sudan A more recent small infarct black showing clearly the clearly defined infarct in the right riMLF. Magnification: 30 disturbances. x riMLF = rostral interstitial nucleus of the medial longitudinalfasciculus; RN = red involved part of the right nucleus. on the right, explaining the palpebral ptosis and adduction weakness in the right eye, eosine, cresyl violet, luxol fast blue-Van which developed shortly before death. Thus, Gieson, periodic acid-Schiff and Loyez stains. although our patient had other ischaemic Forty pm frozen sections were cut from blocks lesions than that in the upper midbrain teg- of the same regions and were stained with Oil mentum, it is the first case in which vertical red 0 and Sudan black. Ten pm serial paraffine gaze abnormalities can be correlated to selec- sections from the mesencephalon, pons and tive unilateral riMLF infarction. 70 Bogousslavsky, Miklossy, Regli, Janzer

The syndrome of combined up- and down- involvement of bilateral upgaze inhibitory J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.53.1.67 on 1 January 1990. Downloaded from gaze palsy shown by our patient has usually inputs and unilateral downgaze excitatory been related to bilateral involvement of the inputs from a unilateral riMLF lesion may thus upper midbrain tegmentum.6 Eleven infarct be sufficient to generate downgaze palsy, cases with pathological study have been re- because the uninvolved contralateral downgaze ported.4 7-16 However, in rare instances, inputs cannot compensate. Moreover, the it appears that a unilateral lesion confirmed preservation of contralateral downgaze inputs at necropsy at the same level may be sufficient explain why downgaze was usually only to generate combined vertical gaze palsy. paretic, in contrast to complete upgaze palsy, in Dereux'7 reported a patient with a unilateral the previously reported patients with a com- lesion involving the upper midbrain and peri- bined vertical gaze palsy and a unilateral lesion. aqueductal area. Garcin et al'8 reported the case On the other hand, this would also explain of a woman aged 65 with an upper brainstem why downgaze palsy from a unilateral riMLF infarct that was limited to the left side, who had involvement may not occur without associated a combined vertical gaze paresis, though upgaze palsy, because bilateral upgaze "slight upward and downward movements excitatory and inhibitory inputs are involved were still possible". Collier'9 described a concomitantly within the riMLF: woman aged 49 with up- and downgaze palsy The sparing of the vertical oculocephalic and a left thalamo-mesencephalic haemorr- response in our patient suggests that the hage. Molnari0 reported a man aged 72 with riMLF does not interfere with this reflex, upgaze palsy and "limitation of downgaze" which may be mediated at this level by the with a left paramedian thalamo-mesencephalic nucleus of Cajal and related structures.2230 infarct. Leigh and Zee2' reported a 38 year old 1 Henoch. Tuberculose der . Berlin Klin woman with upgaze palsy and decreased down- Wschr 1864;1:125-7. 2 Parinaud H. Paralyse des mouvements associes des yeux. ward saccades velocity and smooth pursuit Arch Neurol (Paris) 1883;5:145-72. with a left thalamic-midbrain haemorrhage. 3 Buttner-Ennever JA, Buttner U. A cell group associated with vertical eye movements in the rostral mesencephalic More recently, Ranalli and Sharpe22 reported a reticular formation of the monkey. Brain Res 1978;151: 64 year old man who had a right paramedian 31-47. 4 Buttner-Ennever JA, Buttner U, Cohen B, Baumgartner G. upper brainstem infarct and palsy of upward Vertical gaze paralysis and the rostral interstitial nucleus saccades, decreased amplitude and velocity of the medial longitudinal fasciculus. Brain 1982;105: 125-49. of downward saccades, decreased gain and 5 Pierrot-Deseilligny C. Circuits oculomoteurs centraux. Rev amplitude of vertical smooth pursuit and Neurol 1985;141:349-70. 6 Bogousslavsky J, Meienberg 0. Eye-movement disorders in vestibulo-ocular response, and inverted Bell's brain-stem and cerebellar stroke. Arch Neurol 1987; phenomenon on prolonged lid closure. In the 44:141-8. 7 Muskens LJJ. La base anatomique des positions forcees des first five cases, the neuropathological study did yeux soi-disant paralysies du regard. Rev Neurol 1933; not include microscopic details, but the region 40:287-96. 8 Schuster P. Beitrige zur Pathologie des Thalamus opticus. of the posterior commissure and riMLF was I. Mitteilung: Kasuistik. Gefissgebiet der A. thalamo- involved in all instances. In the sixth case, the geniculata, der A. thalamo-perforata, der A. tubero- thalamica und der A. lenticulo-optica. Arch Psychiat right riMLF, nucleus of Darkschewitsch, and Nervenkr 1936;105:358-432. part ofthe nucleus of Cajal and ofthe nucleus of 9 Angelergues R, De Ajuriaguerra J, Hecaen H. Paralysie de la verticalite due regard d'origine vasculaire: etude anatomo- the posterior commissure were involved, but clinique. Rev Neurol 1957;96:301-19.

the posterior commissure was spared. In our 10 Castaigne P, Buge A, Cambier J, Escourolle R, Brunet P, http://jnnp.bmj.com/ Degos JD. Demence thalamique d'origine vasculaire par patient, the right riMLF was selectively ramollissement bilateral, limite au territoire du pedicule involved in the upper midbrain, while the retro-mamillaire. A propos de 2 observations anatomo- cliniques. Rev Neurol 1966;1 14:89-107. posterior commissure and its nucleus, the 11 Segarra JM. Cerebral vascular disease and behaviour. I. The nucleus of Cajal and the nucleus of Dark- syndrome of the mesencephalic artery (basilar artery bifurcation). Arch Neurol 1970;22:408-18. schewitsch were completely spared. 12 Halmagyi GM, Evans WA, Halliman JM. Failure of down- Though our study suggests that selective ward gaze-the site and nature of the lesion. Arch Neurol 1976;35:22-6. involvement of riMLF on one side may 13 Trojanowski JQ, Lafontaine MH. Neuroanatomical generate a combined vertical gaze palsy, the correlates of selective downgaze paralysis. J Neurol Sci on September 27, 2021 by guest. Protected copyright. 1981;52:91-101. explanation of this remains unclear. Cases of 14 Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: unilateral midbrain lesion with upgaze'5 23-30 or selective paralysis of downward gaze. Neurology 1980; 30:605-10. combined up- and downgaze'722 palsy have 15 Pierrot-Deseilligny C, Chain F, Gray F, Serdaru M, been reported, but there is no single case with Escourolle R, Lhermitte F. Parinaud's syndrome. Elec- tro-oculographic and anatomical analyses of 6 vascular pathological verification in which downgaze cases with deductions about vertical gaze organization in palsy was due to a unilateral lesion. In patients the premotor structures. Brain 1982;105:667-96. 16 Lepore FE, Gulli V, Miller DC. Neuro-ophthalmological with isolated downgaze palsy and an apparently findings with neuropathological correlation in bilateral unilateral infarction on MRI31 a small con- thalamic mesencephalic infarction. J Clin Neuro-Ophthal- mol 1985;5:224-8. tralateral lesion cannot be excluded. 17 Dereux J. Paralysie verticale du regard. These Medecine, It is possible that inhibitory as well as Paris. L. Arnette 1926. 18 Garcin R, Bertrand I, Frumusan P. Etude anatomo-clinique excitatory upgaze fibres from the riMLF on d'un cas de syndrome de Parinaud et de myoclonies one side may decussate in the posterior com- rythmiques du voile du palais. Rev Neurol 1933;40: missure 812-20. and pass through the contralateral 19 Collier J. Nuclear ophthalmoplegia, with especial reference riMLF on their way to the oculomotor nuclear to retraction of the lids and ptosis and to lesions of the no posterior commissure. Brain 1927;50:488-98. complex. On the other hand, there is 20 Molnar L. Die lokal diagnostische Bedeutung der vertikalen experimental or clinical evidence that Blicklahmung. Beitrage zur Symnptomatologie und fibres decussate in Faseranatomie des meso-diencephalen Obergangs- downgaze the posterior gebietes. Archiv fur psychiatre und nervenkrankheiten commissure.520 This decussation is probably vereinigt mit Zeitschrift fur die gesamte neurologie und lower in the to psychiatre 1958-59;198:523-34. midbrain, close the oculomotor 21 Leigh RJ, Zee DS. The neurology ofeye movements. Philadel- nuclear complex.532 The combined phia: FA Davis Corporation 1983. Vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinalfasciculus (riMLF) 71 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.53.1.67 on 1 January 1990. Downloaded from

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